A Phase 3 interventional study of Brolucizumab 6 mg and Aflibercept 2 mg in Neovascular Age-related Macular Degeneration, sponsored by Novartis Pharmaceuticals. Completed at 65 sites in 2 countries. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2021-01-05.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 3, Interventional, and Treatment
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Among 20 studies testing brolucizumab in Macular Degeneration — none open to participants now, 1 under way, none of them phase 3. brolucizumab · Macular Degeneration.
Among the 20 studies testing brolucizumab in Macular Degeneration, this one is the 9th largest by enrollment, is one of 2 that started in 2018, is one of 11 in phase 3, and was the 4th registered.
1,459 studies on the registry are indexed under Macular Degeneration; 236 are open to participants now.
Browse Macular Degeneration studies →None of the 20 studies testing brolucizumab in Macular Degeneration is open now. The open studies under Macular Degeneration, anywhere →
brolucizumab: first FDA approval 2019 (BEOVU), first EMA approval 2020. What it is approved for, and how studies give it, is on its page →
Of the 165 Macular Degeneration studies recruiting now, 116 (70%) set no upper age limit and 5 (3%) stop at 75 or younger; 19 take children under 18; 35 take healthy volunteers.
This study: 50 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
20 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 1 · Phase 2 3 · Phase 3 11 · Phase 4 5
First in 2010; this study’s year is marked. 2 started in 2018.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 151 is above the median of 56 across 985 interventional studies indexed under Macular Degeneration.
Median enrollment 101 across the 20 interventional studies. Of the 16 that completed or were terminated, 14 (88%) have results posted.
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15 of 20 have an industry lead sponsor. The 7 most frequent:
This study is registered under Novartis Pharmaceuticals, one of the names counted as Novartis. Under that name alone:
Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.
Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.
81 studies in Macular Degeneration by Novartis: 1 open now, 1 under way, none of them phase 3. Of 79 finished, 41 (52%) have results posted.
Among the 81 studies in Macular Degeneration by Novartis, this one is the 27th largest by enrollment of the 56 interventional ones that give a count, is one of 2 that started in 2018, is one of 23 in phase 3, and was the 42nd registered.
Novartis’s Macular Degeneration studies by the year they started, since 2003.
1 of the studies testing brolucizumab in Macular Degeneration that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT04932980Berner AugenklinikComparison of Rapid Aflibercept and Brolucizumab T&E in wAMD | 2027-06 |
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Among the 20 studies testing brolucizumab in Macular Degeneration, from their registry updates:
Nothing recorded among them since 2026-09-25.
Among Novartis’s 81 in Macular Degeneration:
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The purpose of this extension study was to assess the safety and efficacy of the new formulation of brolucizumab 6 mg ophthalmic solution when given to the same patients who received brolucizumab in the core trial CRTH258A2301 (also known as CRTH258-C002). The medical condition treated in the core and extension trials was neo-vascular age-related macular degeneration (nAMD).
Subjects in the United States who had completed the 96 week core trial, CRTH258A2301 (also referred as CRTH258-C002), were eligible to participate in the extension trial provided the core trial Visit 26 at week 96, was less than or equal to 12 weeks from the Baseline Visit in the extension trial, CRTH258A2301E1.
Subjects who were treated with aflibercept during the core trial and met the eligibility requirements of this extension trial continued to receive aflibercept in this extension trial in order to maintain the masking during the extension trial. No hypothesis testing or descriptive analyses were planned.
Subjects who were treated in the core trial with brolucizumab 3mg or brolucizumab 6 mg, and met the eligibility requirements of this extension trial, received the new formulation of brolucizumab 6 mg solution in the extension trial.
Enrolled subjects were to receive three intravitreal (IVT) ophthalmic injections. The study eye was the same eye that received the treatment in the core study. The extension trial consisted of 7 study visits at 4 week intervals over a period of 24 weeks.
Assessment of the efficacy and safety of brolucizumab 6 mg was based on a within-patient comparison with the last 6 months of corresponding core-study efficacy and safety data serving as the reference. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorized to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorized to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brolucizumab 6 mg solution for IVT injection, single injection at Day 1 (baseline), Week 8, and Week 16 or Week 20
Drug: Brolucizumab 6 mg
Aflibercept 2 mg solution for IVT injection, single injection at Day 1 (baseline), Week 8 and Week 16 to maintain the masking of the extension trial only.
Drug: Aflibercept 2 mg
Administered as opthalmic solution for an intravitreal injection to the study eye
Also known as: RTH258
Administered as an opthalmic solution for intravitreal injection to the study eye
Also known as: EYELEA
Number of Participants With Ocular and Non-Ocular Treatment Emergent Adverse Events
Number of participants with ocular and non-ocular treatment emergent events with the new formulation brolucizumab 6 mg in this extension trial up to week 24 vs. the corresponding last 6 months of brolucizumab treatment in the Core trial \>= 2%. Safety assessment of the new formulation brolucizumab 6 mg was based on a within-patient comparison with the last 6 months of corresponding Core safety data. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
Time frame: Up to Week 24
Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit
Best-corrected visual acuity for the study eye was tested at all study visits in a sitting position using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. Outcome measure was prespecified for brolucizumab arm only. Neither patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data presented descriptively for only brolucizumab in line with study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
Time frame: Extension Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
Change in BCVA From Extension Baseline at Each Post-baseline Visit
Best-corrected visual acuity for the study eye was tested at all study visits in a sitting position using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
Time frame: Extension baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
Patients With Positive q12w Treatment Status at Week 20
The estimate for the proportion of patients with a positive q12w treatment status at Week 24 was derived from Kaplan Meier time-to-event analyses for the event 'first q8w-need'. The outcome of the Kaplan-Meier analysis was estimated probability for maintaining on q12w up to the Disease Activity Assessment (DAA) at exWeek 20. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
Time frame: Week 20
Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit
Measurement of the central subfield thickness of the retina was assessed using Optical Coherence Tomography (OCT) at each visit for the study eye. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
Time frame: Extension Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
Percentage of Subjects With Positive Anti-drug Antibody (ADA) Status for Brolucuzumab 6 mg in Extension
Positive integrated anti-drug antibodies (ADA) status is defined as induced ADA status with ADA negative at pre-dose and a post-dose titer value of greater than or equal to 30 at any time point or boosted ADA status with ADA positive at pre-dose and a post-dose titer value increase by more than 3-fold (1 dilution) at any time point. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
Time frame: Extension Baseline, Week 8, Week 16, Week 24
150 subjects who completed the 96 week CORE trial (RTH258-C001) were eligible to continue in the extension. 62 CORE sub. were treated w/ brolucizumab 3mg \& 45 CORE sub. w/ brolucizumab 6mg. These 107 sub. were treated in the extension w/ new formulation 6 mg brolucizumab. 43 subjects treated with aflibercept 2 mg in the CORE continued aflibercept.
| Milestone | Brolucizumab - Overall Extension Study | Aflibercept |
|---|---|---|
| Started | 107 | 43 |
| Completed | 106 | 42 |
| Not completed | 1 | 1 |
| Withdrew: Death | 1 | 0 |
| Withdrew: Adverse event | 0 | 1 |
Number of participants with ocular and non-ocular treatment emergent events with the new formulation brolucizumab 6 mg in this extension trial up to week 24 vs. the corresponding last 6 months of brolucizumab treatment in the Core trial \>= 2%. Safety assessment of the new formulation brolucizumab 6 mg was based on a within-patient comparison with the last 6 months of corresponding Core safety data. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
| Participants | Brolucizumab - Overall Extension Study | Brolucizumab Overall Last 6 Months From Core Study |
|---|---|---|
| Ocular AEs | 20 | 25 |
| Non-Ocular AEs | 51 | 50 |
Best-corrected visual acuity for the study eye was tested at all study visits in a sitting position using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. Outcome measure was prespecified for brolucizumab arm only. Neither patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data presented descriptively for only brolucizumab in line with study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
| Number of Participants | Brolucizumab 6 mg - 3 mg in Core Study | Brolucizumab 6 mg - 6 mg in Core Study | Brolucizumab - Overall Extension Study |
|---|---|---|---|
| exWeek 4 (>=15 letters loss) | 2 | 0 | 2 |
| exWeek 8 (>=15 letters loss) | 4 | 0 | 4 |
| exWeek 12 (>=15 letters loss) | 4 | 0 | 4 |
| exWeek 16 (>=15 letters loss) | 6 | 0 | 6 |
| exWeek 20 (>=15 letters loss) | 4 | 0 | 4 |
| exWeek 24 (>=15 letters loss) | 3 | 0 | 3 |
Best-corrected visual acuity for the study eye was tested at all study visits in a sitting position using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
| Letter read | Brolucizumab 6 mg - 3 mg in Core Study | Brolucizumab 6 mg - 6 mg in Core Study | Brolucizumab - Overall Extension Study |
|---|---|---|---|
| exWeek 4 | -1.3 ± 6.26 | 0.5 ± 3.81 | -0.5 ± 5.42 |
| exWeek 8 | -1.7 ± 6.90 | -0.4 ± 4.29 | -1.2 ± 5.96 |
| exWeek 12 | -2.7 ± 7.73 | -0.3 ± 5.17 | -1.7 ± 6.84 |
| exWeek 16 | -3.9 ± 8.42 | 0.8 ± 5.36 | -1.9 ± 7.63 |
| exWeek 20 | -3.4 ± 7.66 | 0.5 ± 7.34 | -1.8 ± 7.75 |
| exWeek 24 | -2.0 ± 8.17 | 0.3 ± 6.79 | -1.0 ± 7.67 |
The estimate for the proportion of patients with a positive q12w treatment status at Week 24 was derived from Kaplan Meier time-to-event analyses for the event 'first q8w-need'. The outcome of the Kaplan-Meier analysis was estimated probability for maintaining on q12w up to the Disease Activity Assessment (DAA) at exWeek 20. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
| Percentage of patients | Brolucizumab 6 mg - 3 mg in Core Study | Brolucizumab 6 mg- 6 mg in Core Study | Brolucizumab - Overall Extension Study |
|---|---|---|---|
| Patients With Positive q12w Treatment Status at Week 20 | 63.3 | 63.1 | 63.3 |
Measurement of the central subfield thickness of the retina was assessed using Optical Coherence Tomography (OCT) at each visit for the study eye. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
| micrometer | Brolucizumab 6 mg - 3 mg in Core Study | Brolucizumab 6 mg- 6 mg in Core Study | Brolucizumab - Overall Extension Study |
|---|---|---|---|
| exWeek 4 | -19.2 ± 39.29 | -17.5 ± 40.76 | -18.5 ± 39.74 |
| exWeek 8 | -6.3 ± 25.47 | -18.9 ± 31.74 | -11.6 ± 28.82 |
| exWeek 12 | -17.9 ± 43.07 | -28.9 ± 48.80 | -22.5 ± 45.66 |
| exWeek 16 | -7.8 ± 31.94 | -11.7 ± 39.83 | -9.4 ± 35.35 |
| exWeek 20 | -10.1 ± 59.04 | -15.3 ± 46.20 | -12.3 ± 53.84 |
| exWeek 24 | -19.8 ± 37.67 | -24.6 ± 42.10 | -21.8 ± 39.47 |
Positive integrated anti-drug antibodies (ADA) status is defined as induced ADA status with ADA negative at pre-dose and a post-dose titer value of greater than or equal to 30 at any time point or boosted ADA status with ADA positive at pre-dose and a post-dose titer value increase by more than 3-fold (1 dilution) at any time point. Outcome measure was prespecified for brolucizumab arm only. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).
| Percentage of participants | Brolucizumab - Overall Extension Study |
|---|---|
| Percentage of Subjects With Positive Anti-drug Antibody (ADA) Status for Brolucuzumab 6 mg in Extension | 54 |
Collected over From first treatment in the extension study, through study completion, to an average of 24 weeks. Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 6 months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Brolucizumab 6mg Overall Extension Study | 1/107 (0.9%) | 7/107 (6.5%) | 12/107 (11.2%) |
| Brolucizumab Overall Last 6 Months Core Study | 0/107 (0%) | 7/107 (6.5%) | 14/107 (13.1%) |
| Aflibercept 2 mg | 0/43 (0%) | 10/43 (23.3%) | 13/43 (30.2%) |
| Event | Brolucizumab 6mg Overall Extension Study | Brolucizumab Overall Last 6 Months Core Study | Aflibercept 2 mg |
|---|---|---|---|
| SyncopeNervous system disorders | 0/107 | 0/107 | 3/43 |
| Anaemia macrocyticBlood and lymphatic system disorders | 0/107 | 0/107 | 1/43 |
| LymphadenopathyBlood and lymphatic system disorders | 0/107 | 0/107 | 1/43 |
| Left ventricular failureCardiac disorders | 0/107 | 0/107 | 1/43 |
| PyrexiaGeneral disorders | 0/107 | 0/107 | 1/43 |
| CholelithiasisHepatobiliary disorders | 0/107 | 0/107 | 1/43 |
| Necrotising fasciitisInfections and infestations | 0/107 | 0/107 | 1/43 |
| OsteomyelitisInfections and infestations | 0/107 | 0/107 | 1/43 |
| PneumoniaInfections and infestations | 1/107 | 0/107 | 1/43 |
| SepsisInfections and infestations | 0/107 | 0/107 | 1/43 |
| Event | Brolucizumab 6mg Overall Extension Study | Brolucizumab Overall Last 6 Months Core Study | Aflibercept 2 mg |
|---|---|---|---|
| Urinary tract infectionInfections and infestations | 4/107 | 6/107 | 6/43 |
| Cataract - Fellow eyeEye disorders | 1/107 | 1/107 | 3/43 |
| Neovascular age-related macular degeneration - Fellow eyeEye disorders | 2/107 | 2/107 | 3/43 |
| NasopharyngitisInfections and infestations | 5/107 | 4/107 | 3/43 |
| HaematuriaRenal and urinary disorders | 0/107 | 1/107 | 3/43 |
The Extension safety set includes all subjects who entered the extension study and received at least one injection of study treatment in this extension study.
| Age, Continuous(years) | Brolucizumab - Overall Extension Study | Aflibercept | Total |
|---|---|---|---|
| Mean | 80.6 ± 8.63 | 77.9 ± 9.20 | 79.8 ± 8.85 |
| Sex: Female, Male(Participants) | Brolucizumab - Overall Extension Study | Aflibercept | Total |
|---|---|---|---|
| Female | 69 | 22 | 91 |
| Male | 38 | 21 | 59 |
| Ethnicity (NIH/OMB)(Participants) | Brolucizumab - Overall Extension Study | Aflibercept | Total |
|---|---|---|---|
| Hispanic or Latino | 11 | 6 | 17 |
| Not Hispanic or Latino | 95 | 37 | 132 |
| Unknown or Not Reported | 1 | 0 | 1 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Ran from Jan 2018 to primary completion in Sep 2018, 7 months.
Results were first posted in Apr 2020, 1 year 7 months after primary completion. A results delay was requested in Feb 2019.
Of 77 industry-sponsored phase 3 interventional studies under Macular Degeneration, half reached primary completion within 24 months of starting (the median), counting those still running; a quarter within 20 and three quarters within 33. This study's 7 months is below that.
Counting every sponsor, half of 83 studies reached it within 24 months; a quarter within 20 and three quarters within 35.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Mar 2020. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Brolucizumab