A Phase 3 interventional study of Faricimab and Aflibercept in Macular Edema and Branch Retinal Vein Occlusion, sponsored by Hoffmann-La Roche. Completed at 150 sites in 22 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-08-06.
Sponsored by Hoffmann-La Roche · Phase 3, Interventional, and Treatment
This is a Phase III, multicenter, randomized, double-masked, active comparator-controlled, parallel-group study evaluating the efficacy, safety, and pharmacokinetics of faricimab administered by intravitreal (IVT) injection at 4-week intervals until Week 24, followed by a double-masked period of study without active control to evaluate faricimab administered according to a personalized treatment interval (PTI) dosing regimen in participants with macular edema due to branch retinal vein occlusion (BRVO).
841 studies on the registry are indexed under Macular Edema; 56 are open to participants now.
This study's enrollment of 553 is above the median of 50 across 619 interventional studies indexed under Macular Edema.
Browse Macular Edema studies →Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.
Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Ocular Exclusion Criteria for Study Eye:
Ocular Exclusion Criteria for Both Eyes:
In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm A will receive faricimab 6 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants will receive faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure will be administered during study visits at which no faricimab treatment is administered (according to the PTI dosing regimen).
Drug: Faricimab · Procedure: Sham Procedure
In Part 1 (Day 1 through Week 24), participants randomly assigned to Arm B will receive aflibercept 2 milligrams (mg) by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections). In Part 2 (from Week 24 to Week 72), participants will receive faricimab 6 mg by IVT injection according to a personalized treatment interval (PTI) dosing regimen. To preserve masking for Part 2, a sham procedure will be administered during study visits at which no faricimab treatment is administered (according to the PTI dosing regimen).
Drug: Faricimab · Drug: Aflibercept · Procedure: Sham Procedure
Faricimab will be administered by intravitreal (IVT) injection as specified in each treatment arm.
Also known as: VABYSMO®, faricimab-svoa, RO6867461, RG7716
Aflibercept 2 mg will be administered by IVT injection once every 4 weeks (Q4W) from Day 1 through Week 20 (a total of 6 injections).
Also known as: Eylea
The sham is a procedure that mimics an intravitreal (IVT) injection, but involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.
Part 1: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye at Week 24
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), and randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
Time frame: From Baseline through Week 24
Part 1: Change From Baseline in BCVA in the Study Eye at Specified Timepoints Through Week 24
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), and randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye at Week 24
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline and Week 24
Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Percentage of Participants Gaining >0 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 24
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Percentage of Participants Achieving ≥84 Letters in BCVA (20/20 Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Percentage of Participants Achieving ≥69 Letters in BCVA (20/40 or Better Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Percentage of Participants With ≤38 Letters in BCVA (20/200 or Worse Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 24
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (\>38 and ≤38 letters) and region (U.S. and Canada, Asia, and rest of the world). All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Change From Baseline in Central Subfield Thickness in the Study Eye at Specified Timepoints Through Week 24
Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline CST (continuous), and randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Percentage of Participants With Absence of Macular Edema in the Study Eye at Specified Timepoints Through Week 24
Absence of diabetic macular edema was defined as achieving a central subfield thickness of \<325 microns in the study eye. Central subfield thickness was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 24
Intraretinal fluid was measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Percentage of Participants With Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24
Subretinal fluid was measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 24
Intraretinal fluid and subretinal fluid were measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
Part 1: Change From Baseline in National Eye Institute 25-Item Visual Functioning Questionnaire (NEI VFQ-25) Composite Score at Week 24
The NEI VFQ-25 captures a patient's perception of vision-related functioning and vision-related quality of life. The core measure includes 25 items that comprise 11 vision-related subscales and 1 item on general health. The composite score ranges from 0 to 100, with higher scores indicating better vision-related functioning. For the ANCOVA analysis, the model uses the non-missing change from baseline in BCVA at Weeks 24 as the response variables adjusted for the treatment group, baseline NEI VFQ-25 Composite Score (continuous), baseline BCVA score (≥55 and ≤54 letters) and region (U.S. and Canada, Asia, and the rest of the world). Observed NEI VFQ-25 assessments were used regardless of the occurrence of intercurrent events. Missing data were not imputed. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline and Week 24
Parts 1 and 2: Change From Baseline in BCVA in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), and randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Parts 1 and 2: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Parts 1 and 2: Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Parts 1 and 2: Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Parts 1 and 2: Percentage of Participants Gaining >0 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Parts 1 and 2: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Parts 1 and 2: Percentage of Participants Achieving ≥84 Letters in BCVA (20/20 Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Parts 1 and 2: Percentage of Participants Achieving ≥69 Letters in BCVA (20/40 or Better Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Parts 1 and 2: Percentage of Participants With ≤38 Letters in BCVA (20/200 or Worse Snellen Equivalent) in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (\>38 and ≤38 letters) and region (U.S. and Canada, Asia, and rest of the world). All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Parts 1 and 2: Change From Baseline in NEI VFQ-25 Questionnaire Composite Score at Specified Timepoints Through Week 72
The NEI VFQ-25 captures a patient's perception of vision-related functioning and vision-related quality of life. The core measure includes 25 items that comprise 11 vision-related subscales and 1 item on general health. The composite score ranges from 0 to 100, with higher scores indicating better vision-related functioning. For the MMRM analysis, the model adjusted for the treatment group, visit, visit-by-treatment group interaction, baseline NEI VFQ-25 Composite Score continuous), baseline BCVA score (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and the rest of the world). Observed NEI VFQ-25 assessments were used regardless of the occurrence of intercurrent events. Missing data were implicitly imputed. Invalid BCVA values were excluded. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline and Weeks 24, 48, and 72
Parts 1 and 2: Change From Baseline in Central Subfield Thickness in the Study Eye at Specified Timepoints Through Week 72
Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline CST (continuous), and randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Parts 1 and 2: Percentage of Participants With Absence of Macular Edema in the Study Eye at Specified Timepoints Through Week 72
Absence of diabetic macular edema was defined as achieving a central subfield thickness of \<325 microns in the study eye. Central subfield thickness was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Parts 1 and 2: Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye at Specified Timepoints Through Week 72
Intraretinal fluid was measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Parts 1 and 2: Percentage of Participants With Absence of Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 72
Subretinal fluid was measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Parts 1 and 2: Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye at Specified Timepoints Through Week 72
Intraretinal fluid and subretinal fluid were measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Part 2: Change From Week 24 in BCVA in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), and randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
Time frame: Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Part 2: Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Week 24 in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Part 2: Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Week 24 in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Part 2: Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Week 24 in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Part 2: Percentage of Participants Avoiding a Loss of >0 Letters in BCVA From Week 24 in the Study Eye at Specified Timepoints Through Week 72
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
Time frame: Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, and 72
Part 2: Percentage of Participants on Different Treatment Intervals at Week 68
In Part 2 of the study, participants in both the faricimab Q4W and aflibercept Q4W arms in Part 1 received 6 mg faricimab intravitreal injections administered according to a personalized treatment interval (PTI) dosing regimen in intervals between Q4W and Q16W. At faricimab dosing visits, treatment intervals were maintained or adjusted (i.e., increased by 4 weeks or decreased by 4, 8, or 12 weeks), based on central subfield thickness (CST) and BCVA values.
Time frame: Week 68
Part 2: Number of Study Drug Injections Received in the Study Eye From Week 24 Through Week 72
Time frame: From Week 24 to Week 72
Incidence and Severity of Ocular Adverse Events in the Study Eye, With Severity Determined According to Adverse Event Severity Grading Scale
This analysis of adverse events (AEs) only includes ocular AEs that occurred in the study eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. Ocular AEs of special interest included the following: Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation (IOI).
Time frame: Part 1: From first dose up to Week 24; Part 2: from Week 24 through Week 72
Incidence of Ocular Adverse Events in the Fellow Eye
This analysis of adverse events (AEs) only includes ocular AEs that occurred in the fellow eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. Ocular AEs of special interest included the following: Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation (IOI).
Time frame: Part 1: From first dose up to Week 24; Part 2: from Week 24 through Week 72
Incidence of Non-Ocular Adverse Events
This analysis of adverse events (AEs) only includes non-ocular (systemic) AEs. Investigators sought information on adverse events (AEs) at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. The non-ocular AE of special interest was: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.
Time frame: Part 1: From first dose up to Week 24; Part 2: from Week 24 through Week 72
Plasma Concentration of Faricimab Over Time
Time frame: Predose at Day 1 (Baseline), Weeks 4, 24, 28, 52, and 72
Number of Participants With Anti-Drug Antibodies (ADAs) to Faricimab at Baseline and Post-Baseline During the Study
Anti-drug antibodies (ADAs) against fariciamb were detected in plasma using a validated bridging enzyme-linked immunosorbent assay (ELISA). The number of participants with treatment-emergent ADA-positive samples includes post-baseline evaluable participants with at least one treatment-induced (defined as having an ADA-negative sample or missing sample at baseline and any positive post-baseline sample) or treatment-boosted (defined as having an ADA-positive sample at baseline and any positive post-baseline sample with a titer that is equal to or greater than 4-fold baseline titer) ADA-positive sample during the study treatment period. Treatment-unaffected ADA-positive is a post-baseline sample with a titer that is lower than 4-fold the ADA-positive baseline titer (faricimab arm) or the ADA-positive titer prior to first faricimab injection (aflibercept arm).
Time frame: Predose at Day 1 (Baseline), Weeks 4, 24, 28, 52, and 72
A total of 768 patients were screened; 9 of these patients were rescreened and randomized in the study. A total of 215 patients failed screening due to not meeting the inclusion criteria. A total of 553 patients with BRVO were randomized 1:1 into the study: 276 to the faricimab Q4W arm and 277 to the aflibercept Q4W arm.
| Milestone | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Started | 276 | 277 |
| Received at least one dose of study drug | 276 | 274 |
| Completed | 271 | 274 |
| Not completed | 5 | 3 |
| Withdrew: Protocol violation | 0 | 3 |
| Withdrew: Lost to follow-up | 2 | 0 |
| Withdrew: Adverse event | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 |
| Withdrew: Death | 1 | 0 |
| Milestone | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Started | 271 | 274 |
| Completed | 245 | 244 |
| Not completed | 26 | 30 |
| Withdrew: Withdrawal by subject | 13 | 12 |
| Withdrew: Lost to follow-up | 7 | 6 |
| Withdrew: Adverse event | 0 | 4 |
| Withdrew: Physician decision | 0 | 4 |
| Withdrew: Patient missed week 72 visit due to sae | 1 | 1 |
| Withdrew: Death | 1 | 2 |
| Withdrew: Non-compliance with study drug | 2 | 1 |
| Withdrew: Patient could not return to hospital due to covid-19 epidemic | 1 | 0 |
| Withdrew: Patient refused to continue study | 1 | 0 |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), and randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
| ETDRS Letters | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Part 1: Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye at Week 24 | 16.9 (15.7 to 18.1) | 17.5 (16.3 to 18.6) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), and randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
| ETDRS Letters | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | 11.5 (10.5 to 12.5) | 12.4 (11.4 to 13.4) |
| Week 8 | 13.7 (12.6 to 14.7) | 15.1 (14.1 to 16.2) |
| Week 12 | 15.1 (14.0 to 16.2) | 15.9 (14.8 to 17.0) |
| Week 16 | 15.5 (14.4 to 16.6) | 16.5 (15.4 to 17.7) |
| Week 20 | 16.3 (15.2 to 17.4) | 17.3 (16.1 to 18.4) |
| Week 24 | 16.9 (15.7 to 18.1) | 17.5 (16.3 to 18.6) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Part 1: Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye at Week 24 | 56.1 (50.4 to 61.9) | 60.4 (54.7 to 66.0) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | 34.3 (28.9 to 39.8) | 36.9 (31.5 to 42.3) |
| Week 8 | 41.2 (35.6 to 46.9) | 46.7 (41.0 to 52.3) |
| Week 12 | 51.0 (45.3 to 56.7) | 52.1 (46.3 to 57.8) |
| Week 16 | 53.6 (47.8 to 59.3) | 56.4 (50.8 to 62.1) |
| Week 20 | 56.1 (50.3 to 61.8) | 58.9 (53.3 to 64.6) |
| Week 24 | 56.1 (50.4 to 61.9) | 60.4 (54.7 to 66.0) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | 57.5 (51.8 to 63.3) | 59.2 (53.6 to 64.9) |
| Week 8 | 69.1 (63.8 to 74.5) | 69.0 (63.6 to 74.4) |
| Week 12 | 75.0 (69.9 to 80.1) | 74.8 (69.7 to 79.8) |
| Week 16 | 72.1 (66.9 to 77.3) | 76.6 (71.6 to 81.5) |
| Week 20 | 75.3 (70.3 to 80.4) | 79.1 (74.3 to 83.9) |
| Week 24 | 77.5 (72.6 to 82.4) | 77.3 (72.4 to 82.2) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | 75.7 (70.7 to 80.7) | 79.1 (74.4 to 83.9) |
| Week 8 | 84.0 (79.7 to 88.3) | 88.1 (84.3 to 91.9) |
| Week 12 | 87.0 (83.1 to 90.9) | 87.0 (83.1 to 91.0) |
| Week 16 | 85.9 (81.8 to 89.9) | 88.8 (85.1 to 92.5) |
| Week 20 | 88.4 (84.6 to 92.2) | 90.3 (86.8 to 93.7) |
| Week 24 | 90.9 (87.6 to 94.3) | 89.6 (86.0 to 93.1) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | 90.2 (86.8 to 93.6) | 93.2 (90.3 to 96.1) |
| Week 8 | 92.7 (89.7 to 95.8) | 96.8 (94.7 to 98.8) |
| Week 12 | 94.9 (92.4 to 97.5) | 94.2 (91.5 to 97.0) |
| Week 16 | 93.8 (91.1 to 96.6) | 94.9 (92.4 to 97.5) |
| Week 20 | 94.9 (92.4 to 97.5) | 96.0 (93.8 to 98.3) |
| Week 24 | 96.4 (94.2 to 98.6) | 95.3 (92.9 to 97.8) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | 99.3 (98.3 to 100.0) | 98.9 (97.7 to 100.0) |
| Week 8 | 99.3 (98.3 to 100.0) | 98.9 (97.7 to 100.0) |
| Week 12 | 99.3 (98.3 to 100.0) | 98.9 (97.7 to 100.0) |
| Week 16 | 99.3 (98.3 to 100.0) | 98.6 (97.2 to 99.9) |
| Week 20 | 99.6 (98.9 to 100.0) | 98.6 (97.2 to 99.9) |
| Week 24 | 99.6 (98.9 to 100.0) | 98.6 (97.2 to 99.9) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | 98.5 (97.1 to 99.9) | 98.9 (97.7 to 100.0) |
| Week 8 | 98.5 (97.1 to 100.0) | 98.9 (97.7 to 100.0) |
| Week 12 | 98.5 (97.1 to 99.9) | 98.9 (97.7 to 100.0) |
| Week 16 | 98.5 (97.1 to 99.9) | 98.2 (96.7 to 99.7) |
| Week 20 | 99.3 (98.3 to 100.0) | 98.6 (97.2 to 99.9) |
| Week 24 | 99.6 (98.9 to 100.0) | 98.2 (96.7 to 99.7) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | 97.1 (95.1 to 99.1) | 98.6 (97.2 to 99.9) |
| Week 8 | 97.8 (96.1 to 99.5) | 98.6 (97.2 to 99.9) |
| Week 12 | 97.8 (96.1 to 99.5) | 98.9 (97.7 to 100.0) |
| Week 16 | 97.8 (96.1 to 99.5) | 98.2 (96.7 to 99.7) |
| Week 20 | 98.5 (97.1 to 99.9) | 97.8 (96.2 to 99.5) |
| Week 24 | 98.6 (97.2 to 100.0) | 97.5 (95.7 to 99.3) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | 8.7 (5.5 to 11.9) | 8.6 (5.5 to 11.8) |
| Week 8 | 14.1 (10.3 to 18.0) | 15.5 (11.5 to 19.5) |
| Week 12 | 15.6 (11.7 to 19.6) | 20.2 (15.7 to 24.6) |
| Week 16 | 17.4 (13.3 to 21.6) | 22.0 (17.4 to 26.5) |
| Week 20 | 20.7 (16.2 to 25.2) | 23.8 (19.0 to 28.5) |
| Week 24 | 22.9 (18.2 to 27.6) | 23.8 (19.1 to 28.5) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | 55.6 (50.6 to 60.5) | 62.3 (57.3 to 67.3) |
| Week 8 | 63.9 (59.3 to 68.6) | 70.3 (65.7 to 74.9) |
| Week 12 | 69.0 (64.4 to 73.6) | 69.2 (64.4 to 74.0) |
| Week 16 | 72.2 (67.7 to 76.8) | 72.1 (67.5 to 76.8) |
| Week 20 | 73.3 (69.1 to 77.6) | 76.1 (71.7 to 80.5) |
| Week 24 | 73.7 (69.3 to 78.1) | 76.5 (71.9 to 81.0) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (\>38 and ≤38 letters) and region (U.S. and Canada, Asia, and rest of the world). All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | 3.6 (2.0 to 5.3) | 1.5 (0.1 to 2.9) |
| Week 8 | 3.2 (1.3 to 5.0) | 1.9 (0.5 to 3.3) |
| Week 12 | 2.3 (0.8 to 3.8) | 1.5 (0.2 to 2.8) |
| Week 16 | 2.3 (0.8 to 3.8) | 1.9 (0.4 to 3.3) |
| Week 20 | 2.3 (0.8 to 3.8) | 1.9 (0.4 to 3.3) |
| Week 24 | 2.3 (0.8 to 3.8) | 1.9 (0.4 to 3.3) |
Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline CST (continuous), and randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
| microns | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | -283.9 (-290.1 to -277.8) | -281.1 (-287.2 to -274.9) |
| Week 8 | -299.4 (-305.2 to -293.7) | -296.9 (-302.6 to -291.2) |
| Week 12 | -304.4 (-309.7 to -299.1) | -298.8 (-304.1 to -293.5) |
| Week 16 | -306.1 (-311.5 to -300.8) | -301.4 (-306.7 to -296.1) |
| Week 20 | -307.3 (-312.5 to -302.1) | -302.2 (-307.4 to -297.0) |
| Week 24 | -311.4 (-316.4 to -306.4) | -304.4 (-309.3 to -299.4) |
Absence of diabetic macular edema was defined as achieving a central subfield thickness of \<325 microns in the study eye. Central subfield thickness was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | 88.8 (85.1 to 92.5) | 88.1 (84.4 to 91.9) |
| Week 8 | 94.5 (91.9 to 97.2) | 93.2 (90.3 to 96.1) |
| Week 12 | 96.4 (94.2 to 98.5) | 92.1 (89.0 to 95.2) |
| Week 16 | 95.3 (92.8 to 97.7) | 93.6 (90.7 to 96.4) |
| Week 20 | 96.0 (93.7 to 98.3) | 94.6 (92.1 to 97.2) |
| Week 24 | 95.3 (92.8 to 97.7) | 93.9 (91.2 to 96.6) |
Intraretinal fluid was measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | 46.1 (40.2 to 51.9) | 54.8 (49.0 to 60.6) |
| Week 8 | 53.8 (48.2 to 59.4) | 57.4 (51.6 to 63.1) |
| Week 12 | 65.3 (59.7 to 70.8) | 56.6 (50.8 to 62.4) |
| Week 16 | 69.9 (64.6 to 75.3) | 72.9 (67.8 to 78.1) |
| Week 20 | 67.1 (61.6 to 72.6) | 66.4 (60.9 to 71.9) |
| Week 24 | 72.5 (67.3 to 77.7) | 66.0 (60.5 to 71.6) |
Subretinal fluid was measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | 76.1 (71.1 to 81.1) | 72.9 (67.8 to 78.1) |
| Week 8 | 93.1 (90.2 to 96.1) | 91.4 (88.1 to 94.6) |
| Week 12 | 96.4 (94.2 to 98.6) | 97.1 (95.2 to 99.1) |
| Week 16 | 95.3 (92.8 to 97.8) | 96.4 (94.2 to 98.6) |
| Week 20 | 98.2 (96.6 to 99.8) | 97.8 (96.1 to 99.5) |
| Week 24 | 91.3 (88.0 to 94.6) | 90.3 (86.9 to 93.7) |
Intraretinal fluid and subretinal fluid were measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Week 4 | 37.8 (32.1 to 43.4) | 40.8 (35.2 to 46.4) |
| Week 8 | 50.9 (45.3 to 56.5) | 54.1 (48.4 to 59.9) |
| Week 12 | 63.8 (58.2 to 69.4) | 56.3 (50.5 to 62.1) |
| Week 16 | 67.1 (61.6 to 72.6) | 72.6 (67.4 to 77.8) |
| Week 20 | 66.0 (60.5 to 71.5) | 66.0 (60.5 to 71.6) |
| Week 24 | 66.3 (60.8 to 71.9) | 61.0 (55.3 to 66.7) |
The NEI VFQ-25 captures a patient's perception of vision-related functioning and vision-related quality of life. The core measure includes 25 items that comprise 11 vision-related subscales and 1 item on general health. The composite score ranges from 0 to 100, with higher scores indicating better vision-related functioning. For the ANCOVA analysis, the model uses the non-missing change from baseline in BCVA at Weeks 24 as the response variables adjusted for the treatment group, baseline NEI VFQ-25 Composite Score (continuous), baseline BCVA score (≥55 and ≤54 letters) and region (U.S. and Canada, Asia, and the rest of the world). Observed NEI VFQ-25 assessments were used regardless of the occurrence of intercurrent events. Missing data were not imputed. 95% CI is a rounding of 95.03% CI.
| score on a scale | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) |
|---|---|---|
| Part 1: Change From Baseline in National Eye Institute 25-Item Visual Functioning Questionnaire (NEI VFQ-25) Composite Score at Week 24 | 5.6 (4.5 to 6.7) | 5.9 (4.8 to 7.1) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), and randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
| ETDRS Letters | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | 11.5 (10.5 to 12.5) | 12.4 (11.4 to 13.4) |
| Week 8 | 13.7 (12.6 to 14.7) | 15.1 (14.1 to 16.2) |
| Week 12 | 15.1 (14.0 to 16.1) | 15.9 (14.8 to 17.0) |
| Week 16 | 15.5 (14.4 to 16.6) | 16.5 (15.4 to 17.6) |
| Week 20 | 16.3 (15.1 to 17.4) | 17.2 (16.1 to 18.4) |
| Week 24 | 16.8 (15.6 to 17.9) | 17.5 (16.3 to 18.6) |
| Week 28 | 16.5 (15.3 to 17.6) | 17.3 (16.2 to 18.4) |
| Week 32 | 17.2 (16.0 to 18.4) | 17.5 (16.3 to 18.7) |
| Week 36 | 17.3 (16.1 to 18.4) | 18.0 (16.8 to 19.2) |
| Week 40 | 17.3 (16.1 to 18.4) | 17.7 (16.6 to 18.9) |
| Week 44 | 18.1 (16.8 to 19.3) | 17.7 (16.5 to 18.9) |
| Week 48 | 18.0 (16.8 to 19.3) | 18.2 (17.0 to 19.4) |
| Week 52 | 18.0 (16.7 to 19.3) | 18.4 (17.1 to 19.7) |
| Week 56 | 17.3 (16.0 to 18.6) | 18.1 (16.8 to 19.4) |
| Week 60 | 18.0 (16.7 to 19.3) | 18.6 (17.3 to 19.8) |
| Week 64 | 17.9 (16.6 to 19.2) | 18.6 (17.3 to 19.9) |
| Week 68 | 18.1 (16.8 to 19.4) | 18.8 (17.5 to 20.1) |
| Week 72 | 18.4 (17.1 to 19.7) | 18.8 (17.5 to 20.1) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | 34.3 (28.9 to 39.8) | 36.9 (31.5 to 42.3) |
| Week 8 | 41.2 (35.6 to 46.9) | 46.7 (41.0 to 52.3) |
| Week 12 | 51.0 (45.3 to 56.7) | 52.1 (46.3 to 57.8) |
| Week 16 | 53.6 (47.8 to 59.3) | 56.4 (50.8 to 62.1) |
| Week 20 | 56.1 (50.3 to 61.8) | 58.9 (53.3 to 64.6) |
| Week 24 | 56.1 (50.4 to 61.9) | 60.4 (54.7 to 66.0) |
| Week 28 | 55.8 (50.0 to 61.5) | 61.8 (56.2 to 67.4) |
| Week 32 | 59.0 (53.3 to 64.6) | 61.4 (55.8 to 67.1) |
| Week 36 | 61.2 (55.5 to 66.8) | 62.5 (56.9 to 68.1) |
| Week 40 | 60.8 (55.2 to 66.4) | 61.1 (55.4 to 66.7) |
| Week 44 | 65.5 (60.1 to 71.0) | 58.9 (53.4 to 64.5) |
| Week 48 | 64.1 (58.5 to 69.6) | 60.7 (55.1 to 66.3) |
| Week 52 | 61.2 (55.6 to 66.8) | 64.0 (58.4 to 69.5) |
| Week 56 | 57.9 (52.3 to 63.5) | 63.6 (58.1 to 69.2) |
| Week 60 | 62.6 (57.1 to 68.1) | 62.9 (57.4 to 68.4) |
| Week 64 | 61.9 (56.3 to 67.4) | 65.4 (59.9 to 70.9) |
| Week 68 | 63.0 (57.5 to 68.4) | 64.7 (59.2 to 70.2) |
| Week 72 | 62.3 (56.7 to 67.8) | 66.9 (61.5 to 72.3) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | 57.5 (51.8 to 63.3) | 59.2 (53.6 to 64.9) |
| Week 8 | 69.1 (63.8 to 74.5) | 69.0 (63.6 to 74.4) |
| Week 12 | 75.0 (69.9 to 80.1) | 74.8 (69.7 to 79.8) |
| Week 16 | 72.1 (66.9 to 77.3) | 76.6 (71.6 to 81.5) |
| Week 20 | 75.3 (70.3 to 80.4) | 79.1 (74.3 to 83.9) |
| Week 24 | 77.5 (72.6 to 82.4) | 77.3 (72.4 to 82.2) |
| Week 28 | 76.1 (71.1 to 81.1) | 76.6 (71.6 to 81.5) |
| Week 32 | 77.5 (72.6 to 82.4) | 78.4 (73.6 to 83.2) |
| Week 36 | 75.7 (70.7 to 80.7) | 78.7 (74.0 to 83.5) |
| Week 40 | 77.5 (72.7 to 82.4) | 76.2 (71.3 to 81.2) |
| Week 44 | 80.4 (75.8 to 85.1) | 76.6 (71.7 to 81.5) |
| Week 48 | 79.7 (75.0 to 84.4) | 79.4 (74.7 to 84.2) |
| Week 52 | 80.8 (76.2 to 85.4) | 80.2 (75.5 to 84.8) |
| Week 56 | 75.7 (70.7 to 80.7) | 78.0 (73.2 to 82.9) |
| Week 60 | 79.3 (74.6 to 84.0) | 80.5 (75.9 to 85.2) |
| Week 64 | 78.9 (74.2 to 83.7) | 78.7 (73.9 to 83.5) |
| Week 68 | 78.9 (74.2 to 83.7) | 77.3 (72.4 to 82.2) |
| Week 72 | 80.4 (75.8 to 85.0) | 79.5 (74.7 to 84.2) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | 75.7 (70.7 to 80.7) | 79.1 (74.4 to 83.9) |
| Week 8 | 84.0 (79.7 to 88.3) | 88.1 (84.3 to 91.9) |
| Week 12 | 87.0 (83.1 to 90.9) | 87.0 (83.1 to 91.0) |
| Week 16 | 85.9 (81.8 to 89.9) | 88.8 (85.1 to 92.5) |
| Week 20 | 88.4 (84.6 to 92.2) | 90.3 (86.8 to 93.7) |
| Week 24 | 90.9 (87.6 to 94.3) | 89.6 (86.0 to 93.1) |
| Week 28 | 89.1 (85.5 to 92.8) | 87.8 (84.0 to 91.6) |
| Week 32 | 89.5 (85.9 to 93.1) | 87.7 (83.9 to 91.6) |
| Week 36 | 88.4 (84.6 to 92.1) | 90.6 (87.2 to 94.0) |
| Week 40 | 90.2 (86.7 to 93.7) | 90.6 (87.2 to 94.0) |
| Week 44 | 89.1 (85.5 to 92.8) | 88.4 (84.7 to 92.2) |
| Week 48 | 88.4 (84.6 to 92.2) | 90.3 (86.8 to 93.8) |
| Week 52 | 89.9 (86.4 to 93.4) | 88.5 (84.7 to 92.2) |
| Week 56 | 88.0 (84.3 to 91.8) | 87.0 (83.1 to 91.0) |
| Week 60 | 89.9 (86.3 to 93.4) | 88.1 (84.3 to 91.9) |
| Week 64 | 90.6 (87.1 to 94.0) | 87.7 (83.9 to 91.6) |
| Week 68 | 89.5 (85.9 to 93.1) | 87.1 (83.1 to 91.0) |
| Week 72 | 89.8 (86.3 to 93.4) | 87.4 (83.5 to 91.3) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | 90.2 (86.8 to 93.6) | 93.2 (90.3 to 96.1) |
| Week 8 | 92.7 (89.7 to 95.8) | 96.8 (94.7 to 98.8) |
| Week 12 | 94.9 (92.4 to 97.5) | 94.2 (91.5 to 97.0) |
| Week 16 | 93.8 (91.1 to 96.6) | 94.9 (92.4 to 97.5) |
| Week 20 | 94.9 (92.4 to 97.5) | 96.0 (93.8 to 98.3) |
| Week 24 | 96.4 (94.2 to 98.6) | 95.3 (92.9 to 97.8) |
| Week 28 | 95.3 (92.9 to 97.8) | 95.0 (92.4 to 97.5) |
| Week 32 | 96.0 (93.8 to 98.3) | 95.0 (92.4 to 97.5) |
| Week 36 | 94.2 (91.5 to 96.9) | 94.6 (92.0 to 97.2) |
| Week 40 | 94.6 (91.9 to 97.2) | 95.7 (93.3 to 98.0) |
| Week 44 | 95.3 (92.9 to 97.7) | 94.6 (92.0 to 97.2) |
| Week 48 | 94.6 (92.0 to 97.2) | 96.1 (93.8 to 98.3) |
| Week 52 | 93.8 (91.1 to 96.6) | 94.6 (92.1 to 97.2) |
| Week 56 | 93.1 (90.2 to 96.1) | 95.3 (92.9 to 97.8) |
| Week 60 | 94.6 (91.9 to 97.2) | 94.2 (91.5 to 97.0) |
| Week 64 | 94.9 (92.4 to 97.5) | 94.2 (91.5 to 97.0) |
| Week 68 | 93.5 (90.6 to 96.4) | 93.9 (91.1 to 96.7) |
| Week 72 | 94.6 (91.9 to 97.2) | 93.9 (91.1 to 96.7) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | 99.3 (98.3 to 100.0) | 98.9 (97.7 to 100.0) |
| Week 8 | 99.3 (98.3 to 100.0) | 98.9 (97.7 to 100.0) |
| Week 12 | 99.3 (98.3 to 100.0) | 98.9 (97.7 to 100.0) |
| Week 16 | 99.3 (98.3 to 100.0) | 98.6 (97.2 to 99.9) |
| Week 20 | 99.6 (98.9 to 100.0) | 98.6 (97.2 to 99.9) |
| Week 24 | 99.6 (98.9 to 100.0) | 98.6 (97.2 to 99.9) |
| Week 28 | 99.6 (98.9 to 100.0) | 98.6 (97.2 to 99.9) |
| Week 32 | 99.6 (98.9 to 100.0) | 98.6 (97.2 to 99.9) |
| Week 36 | 99.6 (98.9 to 100.0) | 98.6 (97.2 to 100.0) |
| Week 40 | 98.9 (97.7 to 100.0) | 98.6 (97.2 to 100.0) |
| Week 44 | 99.3 (98.3 to 100.0) | 98.6 (97.2 to 100.0) |
| Week 48 | 99.3 (98.3 to 100.0) | 98.2 (96.7 to 99.8) |
| Week 52 | 98.6 (97.2 to 100.0) | 98.2 (96.7 to 99.8) |
| Week 56 | 98.9 (97.7 to 100.0) | 98.2 (96.7 to 99.8) |
| Week 60 | 99.3 (98.3 to 100.0) | 98.2 (96.7 to 99.8) |
| Week 64 | 98.9 (97.7 to 100.0) | 97.9 (96.2 to 99.5) |
| Week 68 | 98.9 (97.7 to 100.0) | 98.2 (96.7 to 99.8) |
| Week 72 | 98.9 (97.7 to 100.0) | 98.2 (96.7 to 99.8) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | 98.5 (97.1 to 99.9) | 98.9 (97.7 to 100.0) |
| Week 8 | 98.5 (97.1 to 100.0) | 98.9 (97.7 to 100.0) |
| Week 12 | 98.5 (97.1 to 99.9) | 98.9 (97.7 to 100.0) |
| Week 16 | 98.5 (97.1 to 99.9) | 98.2 (96.7 to 99.7) |
| Week 20 | 99.3 (98.3 to 100.0) | 98.6 (97.2 to 99.9) |
| Week 24 | 99.6 (98.9 to 100.0) | 98.2 (96.7 to 99.7) |
| Week 28 | 99.6 (98.9 to 100.0) | 98.2 (96.7 to 99.7) |
| Week 32 | 99.3 (98.3 to 100.0) | 98.2 (96.7 to 99.7) |
| Week 36 | 99.6 (98.9 to 100.0) | 98.6 (97.2 to 100.0) |
| Week 40 | 98.9 (97.7 to 100.0) | 98.6 (97.2 to 100.0) |
| Week 44 | 99.3 (98.3 to 100.0) | 98.2 (96.7 to 99.8) |
| Week 48 | 98.9 (97.7 to 100.0) | 98.2 (96.7 to 99.8) |
| Week 52 | 98.6 (97.2 to 100.0) | 98.2 (96.7 to 99.8) |
| Week 56 | 98.9 (97.7 to 100.0) | 97.9 (96.2 to 99.5) |
| Week 60 | 98.9 (97.7 to 100.0) | 98.2 (96.7 to 99.8) |
| Week 64 | 98.6 (97.2 to 99.9) | 97.1 (95.2 to 99.1) |
| Week 68 | 98.6 (97.2 to 100.0) | 97.9 (96.2 to 99.5) |
| Week 72 | 98.2 (96.6 to 99.8) | 97.9 (96.2 to 99.5) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | 97.1 (95.1 to 99.1) | 98.6 (97.2 to 99.9) |
| Week 8 | 97.8 (96.1 to 99.5) | 98.6 (97.2 to 99.9) |
| Week 12 | 97.8 (96.1 to 99.5) | 98.9 (97.7 to 100.0) |
| Week 16 | 97.8 (96.1 to 99.5) | 98.2 (96.7 to 99.7) |
| Week 20 | 98.5 (97.1 to 99.9) | 97.8 (96.2 to 99.5) |
| Week 24 | 98.6 (97.2 to 100.0) | 97.5 (95.7 to 99.3) |
| Week 28 | 98.2 (96.6 to 99.8) | 97.5 (95.7 to 99.3) |
| Week 32 | 98.6 (97.2 to 99.9) | 97.8 (96.2 to 99.5) |
| Week 36 | 98.2 (96.7 to 99.7) | 97.5 (95.7 to 99.3) |
| Week 40 | 97.1 (95.2 to 99.0) | 97.5 (95.6 to 99.3) |
| Week 44 | 98.6 (97.2 to 99.9) | 97.8 (96.1 to 99.5) |
| Week 48 | 97.1 (95.2 to 99.0) | 97.9 (96.2 to 99.5) |
| Week 52 | 97.1 (95.2 to 99.1) | 97.5 (95.7 to 99.3) |
| Week 56 | 97.5 (95.6 to 99.3) | 97.5 (95.7 to 99.3) |
| Week 60 | 97.8 (96.1 to 99.5) | 96.8 (94.7 to 98.8) |
| Week 64 | 97.1 (95.1 to 99.1) | 96.8 (94.7 to 98.8) |
| Week 68 | 97.1 (95.1 to 99.1) | 97.1 (95.2 to 99.1) |
| Week 72 | 97.1 (95.1 to 99.1) | 96.8 (94.7 to 98.8) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | 8.7 (5.5 to 11.9) | 8.6 (5.5 to 11.8) |
| Week 8 | 14.1 (10.3 to 18.0) | 15.5 (11.5 to 19.5) |
| Week 12 | 15.6 (11.7 to 19.6) | 20.2 (15.7 to 24.6) |
| Week 16 | 17.4 (13.3 to 21.6) | 22.0 (17.4 to 26.5) |
| Week 20 | 20.7 (16.2 to 25.2) | 23.8 (19.0 to 28.5) |
| Week 24 | 22.9 (18.2 to 27.6) | 23.8 (19.1 to 28.5) |
| Week 28 | 24.0 (19.2 to 28.8) | 25.6 (20.7 to 30.4) |
| Week 32 | 25.1 (20.3 to 29.8) | 23.4 (18.8 to 28.0) |
| Week 36 | 25.1 (20.2 to 29.9) | 25.2 (20.4 to 30.0) |
| Week 40 | 26.9 (22.0 to 31.8) | 22.0 (17.4 to 26.5) |
| Week 44 | 26.8 (21.8 to 31.8) | 24.8 (20.0 to 29.7) |
| Week 48 | 29.0 (24.0 to 34.1) | 25.2 (20.3 to 30.1) |
| Week 52 | 26.8 (21.9 to 31.7) | 25.6 (20.7 to 30.4) |
| Week 56 | 26.1 (21.2 to 31.0) | 22.0 (17.3 to 26.6) |
| Week 60 | 27.6 (22.6 to 32.6) | 25.6 (20.8 to 30.4) |
| Week 64 | 30.1 (25.0 to 35.3) | 24.5 (19.7 to 29.3) |
| Week 68 | 29.4 (24.2 to 34.6) | 25.9 (21.0 to 30.8) |
| Week 72 | 29.4 (24.3 to 34.5) | 24.8 (20.0 to 29.7) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | 55.6 (50.6 to 60.5) | 62.3 (57.3 to 67.3) |
| Week 8 | 63.9 (59.3 to 68.6) | 70.3 (65.7 to 74.9) |
| Week 12 | 69.0 (64.4 to 73.6) | 69.2 (64.4 to 74.0) |
| Week 16 | 72.2 (67.7 to 76.8) | 72.1 (67.5 to 76.8) |
| Week 20 | 73.3 (69.1 to 77.6) | 76.1 (71.7 to 80.5) |
| Week 24 | 73.7 (69.3 to 78.1) | 76.5 (71.9 to 81.0) |
| Week 28 | 73.3 (68.7 to 77.9) | 75.4 (70.7 to 80.0) |
| Week 32 | 76.9 (72.6 to 81.2) | 75.4 (70.7 to 80.1) |
| Week 36 | 76.2 (71.8 to 80.6) | 77.9 (73.3 to 82.5) |
| Week 40 | 75.5 (71.0 to 79.9) | 76.8 (72.3 to 81.3) |
| Week 44 | 76.9 (72.4 to 81.4) | 76.1 (71.4 to 80.7) |
| Week 48 | 77.2 (72.7 to 81.8) | 79.3 (75.0 to 83.7) |
| Week 52 | 78.7 (74.3 to 83.1) | 80.4 (76.1 to 84.7) |
| Week 56 | 76.2 (71.5 to 80.9) | 79.0 (74.5 to 83.5) |
| Week 60 | 80.2 (75.8 to 84.5) | 79.0 (74.5 to 83.5) |
| Week 64 | 77.6 (73.0 to 82.2) | 81.1 (76.8 to 85.5) |
| Week 68 | 77.6 (73.0 to 82.2) | 80.4 (76.0 to 84.9) |
| Week 72 | 78.0 (73.5 to 82.4) | 79.0 (74.4 to 83.6) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (\>38 and ≤38 letters) and region (U.S. and Canada, Asia, and rest of the world). All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | 3.6 (2.0 to 5.3) | 1.5 (0.1 to 2.9) |
| Week 8 | 3.2 (1.3 to 5.0) | 1.9 (0.5 to 3.3) |
| Week 12 | 2.3 (0.8 to 3.8) | 1.5 (0.2 to 2.8) |
| Week 16 | 2.3 (0.8 to 3.8) | 1.9 (0.4 to 3.3) |
| Week 20 | 2.3 (0.8 to 3.8) | 1.9 (0.4 to 3.3) |
| Week 24 | 2.3 (0.8 to 3.8) | 1.9 (0.4 to 3.3) |
| Week 28 | 2.0 (0.6 to 3.5) | 1.9 (0.4 to 3.3) |
| Week 32 | 2.4 (0.8 to 4.0) | 1.9 (0.4 to 3.3) |
| Week 36 | 1.9 (0.5 to 3.4) | 1.5 (0.2 to 2.8) |
| Week 40 | 2.3 (0.8 to 3.7) | 1.5 (0.2 to 2.8) |
| Week 44 | 2.7 (1.0 to 4.4) | 1.5 (0.2 to 2.8) |
| Week 48 | 2.4 (0.8 to 4.0) | 2.2 (0.6 to 3.9) |
| Week 52 | 3.1 (1.3 to 4.9) | 2.6 (0.9 to 4.3) |
| Week 56 | 2.7 (1.0 to 4.4) | 2.6 (0.9 to 4.3) |
| Week 60 | 2.1 (0.6 to 3.6) | 2.6 (0.9 to 4.3) |
| Week 64 | 3.1 (1.3 to 4.9) | 2.2 (0.6 to 3.9) |
| Week 68 | 2.1 (0.6 to 3.6) | 1.8 (0.3 to 3.3) |
| Week 72 | 2.1 (0.6 to 3.6) | 2.2 (0.5 to 3.9) |
The NEI VFQ-25 captures a patient's perception of vision-related functioning and vision-related quality of life. The core measure includes 25 items that comprise 11 vision-related subscales and 1 item on general health. The composite score ranges from 0 to 100, with higher scores indicating better vision-related functioning. For the MMRM analysis, the model adjusted for the treatment group, visit, visit-by-treatment group interaction, baseline NEI VFQ-25 Composite Score continuous), baseline BCVA score (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and the rest of the world). Observed NEI VFQ-25 assessments were used regardless of the occurrence of intercurrent events. Missing data were implicitly imputed. Invalid BCVA values were excluded. 95% CI is a rounding of 95.03% CI.
| score on a scale | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 24 | 5.6 (4.5 to 6.6) | 5.9 (4.9 to 7.0) |
| Week 48 | 6.4 (5.3 to 7.5) | 6.3 (5.2 to 7.4) |
| Week 72 | 6.0 (4.8 to 7.3) | 7.8 (6.6 to 9.0) |
Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline CST (continuous), and randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
| microns | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | -287.3 (-293.5 to -281.1) | -284.3 (-290.4 to -278.2) |
| Week 8 | -302.9 (-308.7 to -297.2) | -300.2 (-306.0 to -294.5) |
| Week 12 | -307.8 (-313.1 to -302.6) | -301.9 (-307.1 to -296.7) |
| Week 16 | -309.3 (-314.6 to -304.0) | -304.5 (-309.8 to -299.3) |
| Week 20 | -310.6 (-315.5 to -305.6) | -304.2 (-309.1 to -299.3) |
| Week 24 | -314.5 (-319.5 to -309.6) | -307.6 (-312.5 to -302.7) |
| Week 28 | -294.0 (-302.2 to -285.8) | -285.1 (-293.3 to -276.9) |
| Week 32 | -308.3 (-314.6 to -302.0) | -303.2 (-309.4 to -297.0) |
| Week 36 | -304.1 (-310.6 to -297.6) | -298.8 (-305.2 to -292.4) |
| Week 40 | -296.7 (-304.4 to -288.9) | -285.8 (-293.7 to -278.0) |
| Week 44 | -309.2 (-315.9 to -302.5) | -301.6 (-308.3 to -294.9) |
| Week 48 | -309.4 (-315.3 to -303.5) | -302.8 (-308.7 to -296.9) |
| Week 52 | -302.2 (-308.6 to -295.7) | -302.4 (-308.8 to -296.0) |
| Week 56 | -294.0 (-302.6 to -285.5) | -288.0 (-296.6 to -279.4) |
| Week 60 | -309.5 (-315.1 to -303.9) | -306.2 (-311.9 to -300.6) |
| Week 64 | -311.1 (-316.3 to -305.9) | -305.9 (-311.1 to -300.7) |
| Week 68 | -311.2 (-316.3 to -306.1) | -307.9 (-313.0 to -302.8) |
| Week 72 | -310.5 (-315.7 to -305.4) | -307.2 (-312.3 to -302.0) |
Absence of diabetic macular edema was defined as achieving a central subfield thickness of \<325 microns in the study eye. Central subfield thickness was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | 88.8 (85.1 to 92.5) | 88.1 (84.4 to 91.9) |
| Week 8 | 94.5 (91.9 to 97.2) | 93.2 (90.3 to 96.1) |
| Week 12 | 96.4 (94.2 to 98.5) | 92.1 (89.0 to 95.2) |
| Week 16 | 95.3 (92.8 to 97.7) | 93.6 (90.7 to 96.4) |
| Week 20 | 96.0 (93.7 to 98.3) | 94.6 (92.1 to 97.2) |
| Week 24 | 95.6 (93.3 to 98.0) | 94.3 (91.6 to 96.9) |
| Week 28 | 89.1 (85.5 to 92.8) | 86.0 (82.0 to 90.0) |
| Week 32 | 94.6 (91.9 to 97.2) | 92.5 (89.4 to 95.5) |
| Week 36 | 93.8 (91.1 to 96.5) | 90.7 (87.3 to 94.0) |
| Week 40 | 89.5 (85.9 to 93.0) | 84.2 (79.9 to 88.4) |
| Week 44 | 96.0 (93.7 to 98.3) | 92.1 (88.9 to 95.2) |
| Week 48 | 94.9 (92.4 to 97.5) | 91.4 (88.1 to 94.6) |
| Week 52 | 92.4 (89.3 to 95.5) | 91.4 (88.2 to 94.6) |
| Week 56 | 89.5 (85.9 to 93.1) | 86.3 (82.3 to 90.3) |
| Week 60 | 94.2 (91.5 to 96.9) | 93.9 (91.1 to 96.7) |
| Week 64 | 95.3 (92.8 to 97.8) | 93.9 (91.1 to 96.7) |
| Week 68 | 94.9 (92.4 to 97.5) | 92.4 (89.4 to 95.5) |
| Week 72 | 94.2 (91.5 to 96.9) | 94.2 (91.5 to 97.0) |
Intraretinal fluid was measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | 46.1 (40.2 to 51.9) | 54.8 (49.0 to 60.6) |
| Week 8 | 53.8 (48.2 to 59.4) | 57.4 (51.6 to 63.1) |
| Week 12 | 65.3 (59.7 to 70.8) | 56.6 (50.8 to 62.4) |
| Week 16 | 69.9 (64.6 to 75.3) | 72.9 (67.8 to 78.1) |
| Week 20 | 67.1 (61.6 to 72.6) | 66.4 (60.9 to 71.9) |
| Week 24 | 73.9 (68.9 to 79.0) | 69.3 (63.9 to 74.7) |
| Week 28 | 54.4 (48.7 to 60.2) | 47.6 (41.8 to 53.5) |
| Week 32 | 68.1 (62.6 to 73.6) | 65.0 (59.4 to 70.6) |
| Week 36 | 60.9 (55.1 to 66.6) | 56.0 (50.2 to 61.7) |
| Week 40 | 50.8 (45.0 to 56.6) | 48.1 (42.3 to 53.9) |
| Week 44 | 70.3 (64.9 to 75.6) | 63.9 (58.3 to 69.6) |
| Week 48 | 76.1 (71.1 to 81.1) | 67.9 (62.5 to 73.3) |
| Week 52 | 55.8 (50.0 to 61.7) | 56.7 (50.9 to 62.5) |
| Week 56 | 58.4 (52.6 to 64.1) | 58.9 (53.2 to 64.6) |
| Week 60 | 75.0 (69.9 to 80.1) | 72.6 (67.4 to 77.7) |
| Week 64 | 75.8 (70.9 to 80.7) | 69.7 (64.3 to 75.1) |
| Week 68 | 69.9 (64.5 to 75.3) | 68.6 (63.2 to 74.1) |
| Week 72 | 72.8 (67.6 to 78.0) | 72.9 (67.7 to 78.1) |
Subretinal fluid was measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | 76.1 (71.1 to 81.1) | 72.9 (67.8 to 78.1) |
| Week 8 | 93.1 (90.2 to 96.1) | 91.4 (88.1 to 94.6) |
| Week 12 | 96.4 (94.2 to 98.6) | 97.1 (95.2 to 99.1) |
| Week 16 | 95.3 (92.8 to 97.8) | 96.4 (94.2 to 98.6) |
| Week 20 | 98.2 (96.6 to 99.8) | 97.8 (96.1 to 99.5) |
| Week 24 | 91.3 (88.0 to 94.6) | 90.3 (86.9 to 93.7) |
| Week 28 | 93.5 (90.7 to 96.4) | 91.0 (87.6 to 94.3) |
| Week 32 | 96.4 (94.2 to 98.6) | 97.1 (95.2 to 99.1) |
| Week 36 | 97.1 (95.1 to 99.1) | 96.0 (93.7 to 98.3) |
| Week 40 | 96.8 (94.7 to 98.8) | 95.7 (93.3 to 98.1) |
| Week 44 | 97.5 (95.7 to 99.3) | 95.7 (93.3 to 98.0) |
| Week 48 | 97.1 (95.1 to 99.1) | 94.6 (91.9 to 97.2) |
| Week 52 | 98.2 (96.6 to 99.8) | 97.1 (95.2 to 99.1) |
| Week 56 | 95.3 (92.8 to 97.8) | 95.0 (92.4 to 97.5) |
| Week 60 | 95.7 (93.3 to 98.1) | 96.0 (93.8 to 98.3) |
| Week 64 | 98.2 (96.7 to 99.7) | 96.8 (94.7 to 98.8) |
| Week 68 | 97.5 (95.6 to 99.3) | 97.5 (95.7 to 99.3) |
| Week 72 | 96.4 (94.2 to 98.6) | 94.9 (92.4 to 97.5) |
Intraretinal fluid and subretinal fluid were measured in the study eye using optical coherence tomography (OCT) in the central subfield (center 1 mm) by a central reading center. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Week 4 | 37.8 (32.1 to 43.4) | 40.8 (35.2 to 46.4) |
| Week 8 | 50.9 (45.3 to 56.5) | 54.1 (48.4 to 59.9) |
| Week 12 | 63.8 (58.2 to 69.4) | 56.3 (50.5 to 62.1) |
| Week 16 | 67.1 (61.6 to 72.6) | 72.6 (67.4 to 77.8) |
| Week 20 | 66.0 (60.5 to 71.5) | 66.0 (60.5 to 71.6) |
| Week 24 | 67.4 (61.9 to 72.9) | 64.3 (58.6 to 69.9) |
| Week 28 | 53.0 (47.2 to 58.7) | 46.9 (41.1 to 52.8) |
| Week 32 | 67.4 (61.9 to 72.9) | 64.6 (59.0 to 70.2) |
| Week 36 | 60.5 (54.8 to 66.3) | 54.2 (48.4 to 59.9) |
| Week 40 | 50.4 (44.6 to 56.2) | 47.3 (41.5 to 53.2) |
| Week 44 | 69.6 (64.2 to 74.9) | 63.6 (57.9 to 69.2) |
| Week 48 | 74.7 (69.6 to 79.8) | 65.4 (59.8 to 70.9) |
| Week 52 | 55.5 (49.6 to 61.3) | 55.6 (49.8 to 61.4) |
| Week 56 | 58.0 (52.2 to 63.8) | 57.8 (52.0 to 63.6) |
| Week 60 | 73.9 (68.8 to 79.1) | 70.4 (65.1 to 75.7) |
| Week 64 | 75.4 (70.5 to 80.4) | 69.3 (64.0 to 74.7) |
| Week 68 | 68.9 (63.4 to 74.3) | 68.3 (62.8 to 73.7) |
| Week 72 | 70.7 (65.3 to 76.0) | 71.1 (65.8 to 76.4) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The Mixed Model of Repeated Measures (MMRM) analysis included the categorical covariates of treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), and randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\] as fixed effects. An unstructured covariance structure was used. Missing data were implicitly imputed by MMRM model assuming missing at random. Treatment policy strategy (i.e., all observed values used) was applied to all intercurrent events (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). 95% CI is a rounding of 95.03% CI.
| ETDRS Letters | Arm A: Faricimab Q4W to Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W to Faricimab PTI (Part 2) |
|---|---|---|
| Week 28 | -0.3 (-0.8 to 0.3) | -0.1 (-0.6 to 0.5) |
| Week 32 | 0.5 (-0.1 to 1.0) | 0.0 (-0.6 to 0.5) |
| Week 36 | 0.5 (-0.2 to 1.2) | 0.6 (-0.1 to 1.2) |
| Week 40 | 0.3 (-0.4 to 1.1) | 0.4 (-0.3 to 1.2) |
| Week 44 | 1.1 (0.3 to 1.9) | 0.3 (-0.5 to 1.1) |
| Week 48 | 1.1 (0.3 to 2.0) | 0.7 (-0.1 to 1.6) |
| Week 52 | 1.1 (0.2 to 2.0) | 0.9 (0.0 to 1.8) |
| Week 56 | 0.4 (-0.5 to 1.4) | 0.6 (-0.3 to 1.6) |
| Week 60 | 1.0 (0.1 to 2.0) | 1.1 (0.1 to 2.0) |
| Week 64 | 0.9 (0.0 to 1.9) | 1.2 (0.2 to 2.2) |
| Week 68 | 1.2 (0.2 to 2.1) | 1.3 (0.4 to 2.2) |
| Week 72 | 1.5 (0.5 to 2.5) | 1.3 (0.3 to 2.3) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W to Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W to Faricimab PTI (Part 2) |
|---|---|---|
| Week 28 | 85.5 (81.4 to 89.6) | 84.1 (79.8 to 88.3) |
| Week 32 | 89.1 (85.5 to 92.7) | 87.7 (83.9 to 91.5) |
| Week 36 | 89.5 (85.9 to 93.1) | 88.4 (84.7 to 92.2) |
| Week 40 | 89.5 (85.9 to 93.0) | 88.0 (84.2 to 91.8) |
| Week 44 | 89.9 (86.3 to 93.4) | 86.3 (82.2 to 90.3) |
| Week 48 | 89.5 (85.9 to 93.1) | 86.6 (82.6 to 90.6) |
| Week 52 | 89.9 (86.3 to 93.4) | 87.7 (83.9 to 91.6) |
| Week 56 | 88.0 (84.3 to 91.8) | 86.6 (82.6 to 90.6) |
| Week 60 | 88.8 (85.1 to 92.5) | 87.0 (83.0 to 90.9) |
| Week 64 | 89.5 (85.9 to 93.1) | 86.6 (82.6 to 90.6) |
| Week 68 | 88.4 (84.7 to 92.1) | 87.0 (83.0 to 90.9) |
| Week 72 | 88.4 (84.7 to 92.1) | 87.0 (83.0 to 90.9) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W to Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W to Faricimab PTI (Part 2) |
|---|---|---|
| Week 28 | 84.8 (80.6 to 89.0) | 82.3 (77.8 to 86.7) |
| Week 32 | 88.8 (85.1 to 92.5) | 85.9 (81.8 to 89.9) |
| Week 36 | 87.3 (83.4 to 91.2) | 87.0 (83.0 to 90.9) |
| Week 40 | 87.7 (83.8 to 91.5) | 86.3 (82.2 to 90.3) |
| Week 44 | 88.8 (85.1 to 92.5) | 85.5 (81.4 to 89.7) |
| Week 48 | 88.4 (84.7 to 92.2) | 85.2 (81.0 to 89.3) |
| Week 52 | 88.4 (84.7 to 92.2) | 85.2 (81.0 to 89.3) |
| Week 56 | 86.2 (82.2 to 90.2) | 83.4 (79.0 to 87.7) |
| Week 60 | 86.9 (83.0 to 90.9) | 83.4 (79.0 to 87.7) |
| Week 64 | 86.9 (83.0 to 90.9) | 85.2 (81.0 to 89.4) |
| Week 68 | 86.6 (82.6 to 90.6) | 85.5 (81.4 to 89.7) |
| Week 72 | 86.6 (82.6 to 90.6) | 85.5 (81.4 to 89.7) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W to Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W to Faricimab PTI (Part 2) |
|---|---|---|
| Week 28 | 74.6 (69.5 to 79.7) | 73.6 (68.5 to 78.8) |
| Week 32 | 80.0 (75.4 to 84.7) | 77.2 (72.3 to 82.1) |
| Week 36 | 79.7 (75.0 to 84.4) | 79.0 (74.2 to 83.8) |
| Week 40 | 78.6 (73.8 to 83.4) | 78.3 (73.5 to 83.1) |
| Week 44 | 83.3 (79.0 to 87.7) | 76.9 (71.9 to 81.9) |
| Week 48 | 82.6 (78.2 to 87.0) | 79.4 (74.6 to 84.1) |
| Week 52 | 81.5 (77.0 to 86.0) | 79.4 (74.6 to 84.1) |
| Week 56 | 76.4 (71.5 to 81.3) | 78.3 (73.5 to 83.1) |
| Week 60 | 79.0 (74.2 to 83.7) | 77.2 (72.3 to 82.1) |
| Week 64 | 77.9 (73.0 to 82.8) | 76.1 (71.1 to 81.1) |
| Week 68 | 78.2 (73.4 to 83.1) | 76.5 (71.6 to 81.5) |
| Week 72 | 77.5 (72.7 to 82.4) | 77.6 (72.7 to 82.5) |
Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. The weighted percentage of participants was estimated based on the Cochran-Mantel Haenszel (CMH) weights stratified by randomization stratification factors \[baseline BCVA (≥55 and ≤54 letters), and region (U.S. and Canada, Asia, and rest of the world)\]. All observed values were used regardless of the occurrence of an intercurrent event (discontinuation of treatment due to AEs or lack of efficacy, use of prohibited therapy). Missing assessments were imputed by last observation carried forward. 95% CI is a rounding of 95.03% CI.
| Percentage of participants | Arm A: Faricimab Q4W to Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W to Faricimab PTI (Part 2) |
|---|---|---|
| Week 28 | 46.4 (40.6 to 52.3) | 51.3 (45.4 to 57.1) |
| Week 32 | 55.4 (49.6 to 61.2) | 54.2 (48.3 to 60.0) |
| Week 36 | 55.1 (49.2 to 60.9) | 52.7 (46.9 to 58.6) |
| Week 40 | 56.2 (50.4 to 62.0) | 55.2 (49.4 to 61.1) |
| Week 44 | 62.4 (56.7 to 68.0) | 56.0 (50.1 to 61.8) |
| Week 48 | 63.8 (58.2 to 69.4) | 56.6 (50.9 to 62.4) |
| Week 52 | 59.8 (54.1 to 65.5) | 58.5 (52.7 to 64.3) |
| Week 56 | 57.2 (51.5 to 63.0) | 57.4 (51.5 to 63.2) |
| Week 60 | 58.0 (52.1 to 63.8) | 60.3 (54.5 to 66.0) |
| Week 64 | 62.0 (56.3 to 67.7) | 56.6 (50.8 to 62.5) |
| Week 68 | 60.9 (55.1 to 66.6) | 58.8 (53.1 to 64.6) |
| Week 72 | 63.0 (57.4 to 68.7) | 58.1 (52.3 to 63.9) |
In Part 2 of the study, participants in both the faricimab Q4W and aflibercept Q4W arms in Part 1 received 6 mg faricimab intravitreal injections administered according to a personalized treatment interval (PTI) dosing regimen in intervals between Q4W and Q16W. At faricimab dosing visits, treatment intervals were maintained or adjusted (i.e., increased by 4 weeks or decreased by 4, 8, or 12 weeks), based on central subfield thickness (CST) and BCVA values.
| Percentage of participants | Arm A: Faricimab Q4W to Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W to Faricimab PTI (Part 2) |
|---|---|---|
| Once Every 4 Weeks (Q4W) | 22.6 (17.4 to 27.8) | 25.0 (19.6 to 30.4) |
| Once Every 8 Weeks (Q8W) | 13.3 (9.1 to 17.5) | 18.0 (13.2 to 22.9) |
| Once Every 12 Weeks (Q12W) | 11.7 (7.7 to 15.7) | 9.4 (5.8 to 13.1) |
| Once Every 16 Weeks (Q16W) | 52.4 (46.2 to 58.6) | 47.5 (41.3 to 53.8) |
| Injections | Arm A: Faricimab Q4W to Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W to Faricimab PTI (Part 2) |
|---|---|---|
| Part 2: Number of Study Drug Injections Received in the Study Eye From Week 24 Through Week 72 | 4.0 (1 to 12) | 4.0 (1 to 12) |
This analysis of adverse events (AEs) only includes ocular AEs that occurred in the study eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. Ocular AEs of special interest included the following: Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation (IOI).
| Participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) | Arm A: Faricimab Q4W to Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W to Faricimab PTI (Part 2) |
|---|---|---|---|---|
| Adverse Event (AE) | 45 | 56 | 76 | 81 |
| AE by Severity: Mild | 40 | 47 | 50 | 64 |
| AE by Severity: Moderate | 4 | 8 | 25 | 16 |
| AE by Severity: Severe | 0 | 1 | 1 | 1 |
| AE by Severity: Missing | 1 | 0 | 0 | 0 |
| Serious Adverse Event (SAE) | 3 | 2 | 4 | 3 |
| AE Leading to Withdrawal from Study Treatment | 0 | 0 | 0 | 1 |
| Treatment Related AEs | 1 | 3 | 7 | 8 |
| Treatment Related SAEs | 0 | 0 | 0 | 0 |
| Any AE of Special Interest (AESI) | 1 | 2 | 1 | 1 |
| AESI: Drop in Visual Acuity Score ≥30 | 1 | 2 | 1 | 1 |
This analysis of adverse events (AEs) only includes ocular AEs that occurred in the fellow eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. Ocular AEs of special interest included the following: Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation (IOI).
| Participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) | Arm A: Faricimab Q4W to Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W to Faricimab PTI (Part 2) |
|---|---|---|---|---|
| Adverse Event (AE) | 25 | 21 | 37 | 30 |
| Serious Adverse Event (SAE) | 0 | 0 | 0 | 0 |
| Any AE of Special Interest (AESI) | 0 | 0 | 0 | 0 |
This analysis of adverse events (AEs) only includes non-ocular (systemic) AEs. Investigators sought information on adverse events (AEs) at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. The non-ocular AE of special interest was: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.
| Participants | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) | Arm A: Faricimab Q4W to Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W to Faricimab PTI (Part 2) |
|---|---|---|---|---|
| Adverse Event (AE) | 94 | 99 | 136 | 126 |
| Serious Adverse Event (SAE) | 9 | 16 | 25 | 23 |
| AE Leading to Withdrawal from Study Treatment | 1 | 0 | 0 | 3 |
| Any AE of Special Interest (AESI) | 0 | 0 | 0 | 0 |
| microgram per millilitre (μg/mL) | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) |
|---|---|---|
| Baseline | 0.0000 ± 0.0000 | — |
| Week 4 | 0.0215 ± 0.0160 | — |
| Week 24 | 0.0220 ± 0.0181 | 0.0005 ± 0.0006 |
| Week 28 | 0.0040 ± 0.0072 | 0.0025 ± 0.077 |
| Week 52 | 0.0061 ± 0.0110 | 0.0097 ± 0.0156 |
| Week 72 | 0.0076 ± 0.0109 | 0.0087 ± 0.0146 |
Anti-drug antibodies (ADAs) against fariciamb were detected in plasma using a validated bridging enzyme-linked immunosorbent assay (ELISA). The number of participants with treatment-emergent ADA-positive samples includes post-baseline evaluable participants with at least one treatment-induced (defined as having an ADA-negative sample or missing sample at baseline and any positive post-baseline sample) or treatment-boosted (defined as having an ADA-positive sample at baseline and any positive post-baseline sample with a titer that is equal to or greater than 4-fold baseline titer) ADA-positive sample during the study treatment period. Treatment-unaffected ADA-positive is a post-baseline sample with a titer that is lower than 4-fold the ADA-positive baseline titer (faricimab arm) or the ADA-positive titer prior to first faricimab injection (aflibercept arm).
| Participants | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) | All Faricimab Participants |
|---|---|---|---|
| Baseline (BL): Total ADA-Positive | 3 | 4 | 7 |
| Post-BL: Total ADA-Positive | 33 | 23 | 56 |
| Post-BL: Treatment-Emergent ADA-Positive | 32 | 21 | 53 |
| Post-BL: Treatment-Unaffected ADA-Positive | 1 | 2 | 3 |
Collected over Part 1: From first dose up to Week 24; Part 2: from Week 24 through Week 72. Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm A: Faricimab Q4W (Part 1) | 1/276 (0.4%) | 12/276 (4.3%) | 62/276 (22.5%) |
| Arm B: Aflibercept Q4W (Part 1) | 0/274 (0%) | 17/274 (6.2%) | 69/274 (25.2%) |
| Arm A: Faricimab Q4W to Faricimab PTI (Part 2) | 1/270 (0.4%) | 29/270 (10.7%) | 92/270 (34.1%) |
| Arm B: Aflibercept Q4W to Faricimab PTI (Part 2) | 2/267 (0.7%) | 26/267 (9.7%) | 87/267 (32.6%) |
| Event | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) | Arm A: Faricimab Q4W to Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W to Faricimab PTI (Part 2) |
|---|---|---|---|---|
| Cerebral infarctionNervous system disorders | 3/276 | 0/274 | 0/270 | 1/267 |
| Retinal ischaemiaEye disorders | 2/276 | 0/274 | 0/270 | 2/267 |
| Cerebrovascular accidentNervous system disorders | 1/276 | 1/274 | 0/270 | 2/267 |
| Ischaemic strokeNervous system disorders | 0/276 | 0/274 | 0/270 | 2/267 |
| Myocardial infarctionCardiac disorders | 1/276 | 0/274 | 2/270 | 1/267 |
| Angina unstableCardiac disorders | 0/276 | 0/274 | 2/270 | 0/267 |
| Hip fractureInjury, poisoning and procedural complications | 0/276 | 0/274 | 2/270 | 0/267 |
| Intervertebral disc protrusionMusculoskeletal and connective tissue disorders | 0/276 | 0/274 | 2/270 | 0/267 |
| Acute myocardial infarctionCardiac disorders | 0/276 | 2/274 | 0/270 | 1/267 |
| Coronary artery diseaseCardiac disorders | 0/276 | 2/274 | 0/270 | 1/267 |
| Event | Arm A: Faricimab Q4W (Part 1) | Arm B: Aflibercept Q4W (Part 1) | Arm A: Faricimab Q4W to Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W to Faricimab PTI (Part 2) |
|---|---|---|---|---|
| COVID-19Infections and infestations | 10/276 | 16/274 | 32/270 | 25/267 |
| HypertensionVascular disorders | 20/276 | 7/274 | 14/270 | 8/267 |
| Intraocular pressure increasedInvestigations | 1/276 | 8/274 | 13/270 | 8/267 |
| Conjunctival haemorrhageEye disorders | 8/276 | 10/274 | 11/270 | 10/267 |
| NasopharyngitisInfections and infestations | 6/276 | 6/274 | 7/270 | 10/267 |
| Macular oedemaEye disorders | 1/276 | 2/274 | 10/270 | 5/267 |
| Back painMusculoskeletal and connective tissue disorders | 2/276 | 10/274 | 5/270 | 4/267 |
| Upper respiratory tract infectionInfections and infestations | 4/276 | 5/274 | 6/270 | 9/267 |
| CataractEye disorders | 2/276 | 1/274 | 9/270 | 9/267 |
| Vitreous detachmentEye disorders | 4/276 | 2/274 | 7/270 | 9/267 |
ITT Population: All global participants who were randomized in the study, according to the assigned treatment.
| Age, Continuous(Years) | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) | Total |
|---|---|---|---|
| Mean | 64.3 ± 10.7 | 63.8 ± 10.6 | 64.1 ± 10.7 |
| Sex: Female, Male(Participants) | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) | Total |
|---|---|---|---|
| Female | 133 | 147 | 280 |
| Male | 143 | 130 | 273 |
| Ethnicity (NIH/OMB)(Participants) | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) | Total |
|---|---|---|---|
| Hispanic or Latino | 47 | 51 | 98 |
| Not Hispanic or Latino | 224 | 224 | 448 |
| Unknown or Not Reported | 5 | 2 | 7 |
| Race (NIH/OMB)(Participants) | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 3 | 0 | 3 |
| Asian | 90 | 94 | 184 |
| Native Hawaiian or Other Pacific Islander | 1 | 0 | 1 |
| Black or African American | 6 | 7 | 13 |
| White | 172 | 172 | 344 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 4 | 4 | 8 |
| Region of Enrollment(Participants) | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) | Total |
|---|---|---|---|
| Rest of the World | 129 | 128 | 257 |
| Asia | 85 | 85 | 170 |
| USA and Canada | 62 | 64 | 126 |
| Number of Participants by the Eye (Left or Right) Chosen as the Study Eye(Participants) | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) | Total |
|---|---|---|---|
| Left Eye | 140 | 127 | 267 |
| Right Eye | 136 | 150 | 286 |
| Best Corrected Visual Acuity (BCVA) Letter Score in the Study Eye(ETDRS Letters) | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) | Total |
|---|---|---|---|
| Mean | 57.50 ± 13.04 | 57.64 ± 12.15 | 57.57 ± 12.59 |
| Number of Participants by the BCVA Letter Score Categories in the Study Eye(Participants) | Arm A: Faricimab Q4W (Part 1), Faricimab PTI (Part 2) | Arm B: Aflibercept Q4W (Part 1), Faricimab PTI (Part 2) | Total |
|---|---|---|---|
| ≤54 Letters (20/80 or Worse) | 89 | 90 | 179 |
| ≥55 Letters (20/80 or Better) | 187 | 187 | 374 |
Showing the first 100 of 150 sites across 22 countries.
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