A Phase 3 interventional study of 2.0 mg OPT-302 and 0.5 mg ranibizumab in Neovascular Age-related Macular Degeneration, sponsored by Opthea Limited. Terminated at 191 sites in 24 countries. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2025-07-22.
Sponsored by Opthea Limited · Phase 3, Interventional, and Treatment
A 2-year, phase 3, multicentre, randomised, parallel-group, sham-controlled, double-masked study. Primary efficacy will be determined at Week 52.
1,459 studies on the registry are indexed under Macular Degeneration; 238 are open to participants now.
This study's enrollment of 986 is above the median of 56 across 985 interventional studies indexed under Macular Degeneration.
Browse Macular Degeneration studies →Opthea Limited is the lead sponsor of 5 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Main Exclusion Criteria:
Any current (or history of a) social, psychological, or medical condition that precludes enrolment into the study.
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.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
0.5 mg ranibizumab intravitreal injection administered at 4-weekly intervals. 2.0 mg OPT-302 intravitreal injection administered at 4-weekly intervals.
Biological: 2.0 mg OPT-302 · Biological: 0.5 mg ranibizumab
0.5 mg ranibizumab intravitreal injection administered at 4-weekly intervals. 2.0 mg OPT-302 intravitreal injection administered at 4-weekly intervals for three treatments, and then at 8-weekly intervals, with sham intravitreal injection administered at visits when OPT-302 is not.
Biological: 2.0 mg OPT-302 · Biological: 0.5 mg ranibizumab
0.5 mg ranibizumab intravitreal injection administered at 4-weekly intervals. Sham intravitreal injection administered at 4-weekly intervals.
Biological: 0.5 mg ranibizumab · Procedure: Sham
intravitreal injection
intravitreal injection
intravitreal injection
Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) Letters
To determine the efficacy of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 0.5 mg ranibizumab, in participants with neovascular age-related macular degeneration (nAMD), in terms of change in ETDRS BCVA letter score in the study eye from Baseline to Week 52. The primary analysis presented used mixed model for repeated measures in the overall population. (A positive outcome measure means an improvement in ETDRS BCVA letter score from baseline; a negative outcome measure means a deterioration in ETDRS BCVA letter score from baseline)
Time frame: Baseline to Week 52
Participants Gaining 15 or More ETDRS BCVA Letters
To determine the effects of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 0.5 mg ranibizumab, in participants with neovascular age-related macular degeneration (nAMD), in terms of proportion of participants gaining 15 or more letters in ETDRS BCVA in the study eye from Baseline to Week 52.
Time frame: Baseline to Week 52
Participants Gaining 10 More ETDRS BCVA Letters
To determine the effects of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 0.5 mg ranibizumab, in participants with neovascular age-related macular degeneration (nAMD), in terms of proportion of participants gaining 10 or more letters in ETDRS BCVA in the study eye from Baseline to Week 52.
Time frame: Baseline to Week 52
Change in Choroidal Neovascularisation (CNV) Area by Fluorescein Angiography (FA)
To determine the effects of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 0.5 mg ranibizumab, in participants with neovascular age-related macular degeneration (nAMD), in terms of change in CNV area as measured by FA in the study eye from Baseline to Week 52.
Time frame: Baseline to Week 52
Participants With Absence of Both Sub-retinal Fluid and Intra-retinal Cysts by SD-OCT
To determine the effects of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 0.5 mg ranibizumab, in participants with neovascular age-related macular degeneration (nAMD), in terms of proportion of participants with absence of both sub-retinal fluid and intra-retinal cysts by SD-OCT in the study eye at Week 52.
Time frame: at Week 52
Participants 50 years or older with active subfoveal CNV lesion or juxtafoveal CNV lesion with foveal involvement that is secondary to AMD in the study eye with an ETDRS BCVA score between 60 and 25 (inclusive) letters in the study eye.
| Milestone | 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Sham |
|---|---|---|---|
| Started | 329 | 326 | 331 |
| Treated | 328 | 326 | 331 |
| Completed | 167 | 168 | 171 |
| Not completed | 162 | 158 | 160 |
| Withdrew: Adverse event | 13 | 10 | 5 |
| Withdrew: Death | 5 | 13 | 8 |
| Withdrew: Lack of efficacy | 1 | 2 | 3 |
| Withdrew: Lost to follow-up | 7 | 2 | 7 |
| Withdrew: Physician decision | 4 | 1 | 2 |
| Withdrew: Withdrawal by subject | 26 | 25 | 25 |
| Withdrew: Study terminated by sponsor | 105 | 105 | 110 |
| Withdrew: Randomized in error | 1 | 0 | 0 |
To determine the efficacy of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 0.5 mg ranibizumab, in participants with neovascular age-related macular degeneration (nAMD), in terms of change in ETDRS BCVA letter score in the study eye from Baseline to Week 52. The primary analysis presented used mixed model for repeated measures in the overall population. (A positive outcome measure means an improvement in ETDRS BCVA letter score from baseline; a negative outcome measure means a deterioration in ETDRS BCVA letter score from baseline)
| Letters read | 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Sham |
|---|---|---|---|
| Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) Letters | 13.20 ± 0.728 | 12.41 ± 0.731 | 14.30 ± 0.719 |
To determine the effects of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 0.5 mg ranibizumab, in participants with neovascular age-related macular degeneration (nAMD), in terms of proportion of participants gaining 15 or more letters in ETDRS BCVA in the study eye from Baseline to Week 52.
| Participants | 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Sham |
|---|---|---|---|
| Participants Gaining 15 or More ETDRS BCVA Letters | 159 | 135 | 164 |
To determine the effects of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 0.5 mg ranibizumab, in participants with neovascular age-related macular degeneration (nAMD), in terms of proportion of participants gaining 10 or more letters in ETDRS BCVA in the study eye from Baseline to Week 52.
| Participants | 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Sham |
|---|---|---|---|
| Participants Gaining 10 More ETDRS BCVA Letters | 198 | 182 | 202 |
To determine the effects of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 0.5 mg ranibizumab, in participants with neovascular age-related macular degeneration (nAMD), in terms of change in CNV area as measured by FA in the study eye from Baseline to Week 52.
| mm^2 | 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Sham |
|---|---|---|---|
| Change in Choroidal Neovascularisation (CNV) Area by Fluorescein Angiography (FA) | -3.359 ± 0.3483 | -3.901 ± 0.3972 | -3.238 ± 0.3588 |
To determine the effects of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 0.5 mg ranibizumab, in participants with neovascular age-related macular degeneration (nAMD), in terms of proportion of participants with absence of both sub-retinal fluid and intra-retinal cysts by SD-OCT in the study eye at Week 52.
| Participants | 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Sham |
|---|---|---|---|
| Participants With Absence of Both Sub-retinal Fluid and Intra-retinal Cysts by SD-OCT | 33 | 22 | 22 |
Collected over From Baseline to Week 100. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 5/328 (1.5%) | 65/328 (19.8%) | 290/328 (88.4%) |
| 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 13/327 (4%) | 60/327 (18.3%) | 261/327 (79.8%) |
| 0.5 mg Ranibizumab With Sham | 8/330 (2.4%) | 52/330 (15.8%) | 265/330 (80.3%) |
| Event | 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Sham |
|---|---|---|---|
| Atrial fibrillationCardiac disorders | 0/328 | 6/327 | 2/330 |
| EndophthalmitisInfections and infestations | 4/328 | 1/327 | 1/330 |
| Rib fractureInjury, poisoning and procedural complications | 4/328 | 1/327 | 0/330 |
| Cardiac failure congestiveCardiac disorders | 2/328 | 3/327 | 1/330 |
| PneumoniaInfections and infestations | 2/328 | 3/327 | 2/330 |
| FallInjury, poisoning and procedural complications | 2/328 | 3/327 | 2/330 |
| CataractEye disorders | 3/328 | 0/327 | 0/330 |
| Acute myocardial infarctionCardiac disorders | 3/328 | 2/327 | 2/330 |
| Ischaemic strokeNervous system disorders | 2/328 | 2/327 | 3/330 |
| Myocardial infarctionCardiac disorders | 0/328 | 2/327 | 1/330 |
| Event | 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Sham |
|---|---|---|---|
| NasopharyngitisInfections and infestations | 57/328 | 42/327 | 39/330 |
| Conjunctival haemorrhageEye disorders | 32/328 | 42/327 | 24/330 |
| CataractEye disorders | 39/328 | 33/327 | 14/330 |
| COVID-19Infections and infestations | 32/328 | 27/327 | 38/330 |
| Intraocular pressure increasedInvestigations | 35/328 | 29/327 | 16/330 |
| Eye painEye disorders | 32/328 | 19/327 | 20/330 |
| Neovascular age-related macular degenerationEye disorders | 22/328 | 19/327 | 27/330 |
| HypertensionVascular disorders | 19/328 | 21/327 | 27/330 |
| HeadacheNervous system disorders | 21/328 | 22/327 | 25/330 |
| Urinary tract infectionInfections and infestations | 22/328 | 23/327 | 20/330 |
Modified Intent-to-Treat (mITT) dataset comprised all randomised participants with at least one dose of study medication. Participants were analysed according to the study medication to which they were randomised for all efficacy analyses.
| Age, Categorical(Participants) | 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Sham | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 31 | 38 | 35 | 104 |
| >=65 years | 297 | 288 | 296 | 881 |
| Age, Continuous(years) | 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Sham | Total |
|---|---|---|---|---|
| Mean | 75.3 ± 8.28 | 75.8 ± 8.62 | 75.1 ± 8.52 | 75.4 ± 8.47 |
| Sex: Female, Male(Participants) | 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Sham | Total |
|---|---|---|---|---|
| Female | 184 | 169 | 179 | 532 |
| Male | 144 | 157 | 152 | 453 |
| Ethnicity (NIH/OMB)(Participants) | 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Sham | Total |
|---|---|---|---|---|
| Hispanic or Latino | 10 | 10 | 5 | 25 |
| Not Hispanic or Latino | 117 | 121 | 123 | 361 |
| Unknown or Not Reported | 201 | 195 | 203 | 599 |
| Race (NIH/OMB)(Participants) | 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Sham | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 1 | 1 |
| Asian | 44 | 42 | 48 | 134 |
| Native Hawaiian or Other Pacific Islander | 0 | 1 | 1 | 2 |
| Black or African American | 1 | 0 | 1 | 2 |
| White | 277 | 273 | 274 | 824 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 6 | 10 | 6 | 22 |
| Early Treatment Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA) Letters(letters read) | 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Sham | Total |
|---|---|---|---|---|
| Mean | 52.1 ± 9.45 | 52.1 ± 8.83 | 52.5 ± 9.13 | 52.23 ± 9.14 |
| Choroidal Neovascularisation (CNV) Area by Fluorescein Angiography (FA)(mm^2) | 0.5 mg Ranibizumab With Standard Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Extended Dosing 2.0 mg OPT-302 | 0.5 mg Ranibizumab With Sham | Total |
|---|---|---|---|---|
| Mean | 6.256 ± 2.8634 | 6.576 ± 3.2278 | 6.286 ± 3.1770 | 6.373 ± 3.0894 |
Showing the first 100 of 191 sites across 24 countries. Choose a country and city above to see the rest.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Mar 2021 to primary completion in Mar 2025, 48 months.
Results were first posted in Jul 2025, 3 months after primary completion.
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This study is terminated, as verified in Jun 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Sozinibercept
Opthea Limited