A Study to Evaluate the Efficacy and Safety of IBI302 in Subjects With nAMD

Study Overview
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Brief Summary
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The study is designed for multi-center,randomized,double-masked,active-contralled study to evaluate effective and security of intravitreal injection of IBI302 in subjects with neovascular age-related macular degeneration.

Official Title
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A Phase 3, Randomized, Double-masked, Active-Controlled Study to Evaluate the Efficacy and Safety of Intravitreal IBI302(Efdamrofusp Alfa) in Subjects With Neovascular Age-Related Macular Degeneration

Conditions
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Neovascular Age-related Macular Degeneration

Intervention / Treatment
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* Drug: Aflibercept Ophthalmic
* Biological: IBI302


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent must be obtained prior to study participation; Male or female ≥ 50 years of age at the time of signing the informed consent; Active subfoveal CNV secondary to nAMD, or active CNV with intra/subretinal fluid involving the fovea; BCVA of 19 to 78 ETDRS letters (inclusive) in the study eye at baseline. Exclusion Criteria: Ocular disease: Any concurrent intraocular condition/systemic disease in the study eye at screening or baseline that, in the judgment of the investigator, may cause the participant fail to respond to the treatment or confuse the interpretation of study results; Total lesion area(including blood, atrophy, fibrosis, PED and neovascularization)> 12 optic disc area (DA) on FFA; Subretinal hemorrhage area > 50% of the total lesion area, or subretinal hemorrhage area involving macular fovea ≥ 1 DA; Fibrosis or atrophy area > 50% of the total lesion area, or involving the fovea; Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥ 25 mmHg after standard treatment); Presence of active intraocular or periocular infection or inflammation; Ocular treatment: Anti-VEGF or anti-complement therapy in the study eye within 90 days prior to baseline; Fundus laser photo-coagulation in the study eye within 90 days prior to baseline; Photodynamic Therapy (PDT) in the study eye within 90 days prior to baseline; History of vitreoretinal surgery, penetrating keratoplasty in the study eye; General condition or treatment: Uncontrolled hypertension (defined as systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg after standard treatment); HbA1c > 8% within 28 days prior to baseline; Systemic anti-VEGF drug and anti-complement drug therapy within 90 days prior to baseline; History of hypersensitivity to any component of the test article, control article, or clinically relevant sensitivity to fluorescein dye, povidone-iodine; Pregnant or lactating women; Inappropriate for the study (e.g., substance abuse, inability or unwillingness to follow the trial protocol), as judged by the investig.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aflibercept<br>Drug: Aflibercept 2mg/eye; Intraocular injection | Drug: Aflibercept Ophthalmic<br>* 2mg Aflibercept will be administered by intravitreal injection into the study eye once every 4 weeks for 3 consecutive monthes, folloesd by once every 8 weeks(Q8W).<br>|
| Experimental: IBI302 dose 8mg<br>Drug: IBI302 8mg/eye; Intraocular injection | Biological: IBI302<br>* 8 mg IBI302 will be administered by intraitreal injection into the study eye at intervals as specified in the study protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in Best corrected visual acuity ( BCVA ) in the study eye. | Change from Baseline in BCVA as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at week 44, 48, 52. | At week 44, 48, 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of participants with absence intraretinal fluid (IRF) and absence subretinal fluid (SRF) in the fovea at Week 16 | The intraretinal fluid and subretinal fluid is measured by optical coherence tomography (OCT) in the central subfield(center 1 millimeter) | At week 16 | 
| Change from baseline in BCVA at Week 52 and 100 | Best corrected visual acuity (BCVA) was measured on early treatment diabetic retinopathy study(ETDRS) chart at a starting distance of 4 meters. The BCVAletter score ranges from 0 to 100(best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. | Upto Week 100 | 
| Change from baseline in central subfield thickness (CST) measured by optical coherence tomography (OCT) at Week 52 and 100 | Central subfield thickness was defined as the distance between the internal limiting member and the Bruch's member using OCT, as assessed by the central reading center. | Upto Week 100 | 
| Change from baseline in area of CNV on fundus fluorescence angiography (FFA) at Week 52 and 100 | the area of the choroidal neovascularization lesion in the study eye was measured by a central reading center using FFA | Upto Week 100 | 
| Proportion of participants on a q8W, q12W, and q16W treatment intervals at Week 52 and 100 | Percentages are based on number of participants randomized to the IBI302 group who have not discontinued the study at week 52 and 100. the treatment interval at a givven visit is defined as the treatment interval decision followed at that visit. | Upto Week 100 | 
| Incidence, relatedness to the study drug and severity of ocular and Non-ocular adverse events (AE), treatment emergent adverse events (TEAE) and serious adverse events (SAE). | All AEs were recorded and the investigator made an assessment of seriousness,severity, and causality of each AE. | Upto Week 100 |