NCT04757636: COAST

OPT-302 With Aflibercept in Neovascular Age-related Macular Degeneration (nAMD)

Terminated Phase 3 Results posted Last updated 5 August 2025

What this trial tests

Phase 3 trial testing 2.0 mg OPT-302 in Neovascular Age-related Macular Degeneration in 998 participants. Terminated before completion.

Timeline

12 March 2021

Primary endpoint
31 March 2025

31 March 2025

Quick facts

Lead sponsor	Opthea Limited
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	998
Start date	12 March 2021
Primary completion	31 March 2025
Estimated completion	31 March 2025
Sites	209 locations across Italy, Colombia, Taiwan, Poland, South Korea, Philippines, Croatia, Denmark

Drugs / interventions tested

• 2.0 mg OPT-302 — full drug profile →
• 2.0 aflibercept — full drug profile →
• Sham

Conditions studied

• Neovascular Age-related Macular Degeneration — all drugs for Neovascular Age-related Macular Degeneration →

Sponsor

Opthea Limited — full company profile →

Who can join

50 and older, any sex, with Neovascular Age-related Macular Degeneration. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Change in Early Treatment Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) Letters Primary · Baseline to Week 52

To determine the efficacy of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 2.0 mg aflibercept, 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)

Group	Value	95% CI
2.0 mg Aflibercept With Standard Dosing 2.0 mg OPT-302	13.48	± 0.729
2.0 mg Aflibercept With Extended Dosing 2.0 mg OPT-302	12.82	± 0.728
2.0 mg Aflibercept With Sham	13.66	± 0.728

Proportion of Participants Gaining 15 or More ETDRS BCVA Letters Secondary · Baseline to Week 52

To determine the effects of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 2.0 mg aflibercept, 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. The secondary analysis presented used multiple imputation analysis assuming missing at random in the overall population.

Group	Value	95% CI
2.0 mg Aflibercept With Standard Dosing 2.0 mg OPT-302	167
2.0 mg Aflibercept With Extended Dosing 2.0 mg OPT-302	156
2.0 mg Aflibercept With Sham	162

Proportion of Participants Gaining 10 or More ETDRS BCVA Letters Secondary · Baseline to Week 52

To determine the effects of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 2.0 mg aflibercept, 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. The secondary analysis presented used multiple imputation analysis assuming missing at random in the overall population.

Group	Value	95% CI
2.0 mg Aflibercept With Standard Dosing 2.0 mg OPT-302	204
2.0 mg Aflibercept With Extended Dosing 2.0 mg OPT-302	197
2.0 mg Aflibercept With Sham	204

Change in Choroidal Neovascularisation (CNV) Area by Fluorescein Angiography (FA) Secondary · Baseline to Week 52

To determine the effects of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 2.0 mg aflibercept, 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. The secondary analysis presented used mixed model for repeated measures in the overall population.

Group	Value	95% CI
2.0 mg Aflibercept With Standard Dosing 2.0 mg OPT-302	-4.91	± 0.165
2.0 mg Aflibercept With Extended Dosing 2.0 mg OPT-302	-4.92	± 0.166
2.0 mg Aflibercept With Sham	-4.61	± 0.166

Proportion of Participants With Absence of Both Sub-retinal Fluid and Intra-retinal Cysts by SD-OCT Secondary · at Week 52

To determine the effects of intravitreal 2.0 mg OPT-302 when administered in combination with intravitreal 2.0 mg aflibercept, 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. The secondary analysis presented used multiple imputation analysis assuming missing at random in the overall population.

Group	Value	95% CI
2.0 mg Aflibercept With Standard Dosing 2.0 mg OPT-302	30
2.0 mg Aflibercept With Extended Dosing 2.0 mg OPT-302	32
2.0 mg Aflibercept With Sham	29

Adverse events — posted to ClinicalTrials.gov

Time frame: From Baseline to Week 100. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

2.0 mg Aflibercept With Standard Dosing 2.0 mg OPT-302

Serious: 71/333 (21%)

Deaths: 9/333

2.0 mg Aflibercept With Extended Dosing 2.0 mg OPT-302

Serious: 61/330 (18%)

Deaths: 12/330

2.0 mg Aflibercept With Sham

Serious: 68/330 (21%)

Deaths: 6/330

Serious adverse events (173 terms)

Reaction	System	2.0 mg Aflibercept With St…	2.0 mg Aflibercept With Ex…	2.0 mg Aflibercept With Sham
Pneumonia	Infections and infestations	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—
Endophthalmitis	Infections and infestations	—	—	—
Cardiac failure	Cardiac disorders	—	—	—
Cholecystitis	Hepatobiliary disorders	—	—	—
Sepsis	Infections and infestations	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Visual acuity reduced	Eye disorders	—	—	—
Cataract	Eye disorders	—	—	—
Retinal haemorrhage	Eye disorders	—	—	—
Rhegmatogenous retinal detachment	Eye disorders	—	—	—
Cataract traumatic	Injury, poisoning and procedural complications	—	—	—
Coronary artery disease	Cardiac disorders	—	—	—
Supraventricular tachycardia	Cardiac disorders	—	—	—
Aortic valve stenosis	Cardiac disorders	—	—	—
Atrial flutter	Cardiac disorders	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—
Death	General disorders	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—
Head injury	Injury, poisoning and procedural complications	—	—	—
Subdural haematoma	Injury, poisoning and procedural complications	—	—	—
Femur fracture	Injury, poisoning and procedural complications	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—
Prostate cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—

Other adverse events (16 terms — click to expand)

Reaction	System	2.0 mg Aflibercept With St…	2.0 mg Aflibercept With Ex…	2.0 mg Aflibercept With Sham
Cataract	Eye disorders	—	—	—
COVID-19	Infections and infestations	—	—	—
Intraocular pressure increased	Investigations	—	—	—
Hypertension	Vascular disorders	—	—	—
Neovascular age-related macular degeneration	Eye disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Conjunctival haemorrhage	Eye disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Vitreous detachment	Eye disorders	—	—	—
Visual acuity reduced	Eye disorders	—	—	—
Eye pain	Eye disorders	—	—	—
Retinal degeneration	Eye disorders	—	—	—
Influenza	Infections and infestations	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—

Most-reported serious reactions: Pneumonia, Acute myocardial infarction, Atrial fibrillation, Endophthalmitis, Cardiac failure, Cholecystitis, Sepsis, Urinary tract infection.

Data from ClinicalTrials.gov NCT04757636 adverse events section.

Sponsor's own description

A 2-year phase 3, multicentre, randomised, parallel-group, sham-controlled, double-masked study. Primary efficacy will be determined at Week 52.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration.
   Khachigian LM, Liew G, Teo KYC, Wong TY, et al · · 2023 · cited 61× · PMID 36810060 · DOI 10.1186/s12967-023-03937-7
2. An update on long-acting therapies in chronic sight-threatening eye diseases of the posterior segment: AMD, DMO, RVO, uveitis and glaucoma.
   Ghanchi F, Bourne R, Downes SM, Gale R, et al · · 2022 · cited 35× · PMID 34974541 · DOI 10.1038/s41433-021-01766-w
3. Ocular Delivery of Therapeutic Agents by Cell-Penetrating Peptides.
   Nhàn NTT, Maidana DE, Yamada KH. · · 2023 · cited 25× · PMID 37048144 · DOI 10.3390/cells12071071
4. Exploring new horizons in neovascular age-related macular degeneration: novel mechanisms of action and future therapeutic avenues.
   Shirian JD, Shukla P, Singh RP. · · 2025 · cited 16× · PMID 39379521 · DOI 10.1038/s41433-024-03373-x
5. Recent Developments in Gene Therapy for Neovascular Age-Related Macular Degeneration: A Review.
   Finocchio L, Zeppieri M, Gabai A, Toneatto G, et al · · 2023 · cited 14× · PMID 38137442 · DOI 10.3390/biomedicines11123221
6. Vascular Endothelial Growth Factor C and D Signaling Pathways as Potential Targets for the Treatment of Neovascular Age-Related Macular Degeneration: A Narrative Review.
   Leitch IM, Gerometta M, Eichenbaum D, Finger RP, et al · · 2024 · cited 10× · PMID 38824253 · DOI 10.1007/s40123-024-00973-4
7. Beyond the injection: delivery systems reshaping retinal disease management.
   Rowe LW, Akotoye C, Harris A, Ciulla TA. · · 2025 · cited 6× · PMID 40319468 · DOI 10.1080/14656566.2025.2496424
8. The Landscape of Vascular Endothelial Growth Factor Inhibition in Retinal Diseases.
   Lin JB, Apte RS. · · 2025 · cited 3× · PMID 39836404 · DOI 10.1167/iovs.66.1.47