A Study of Longer Interval of IVT 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-controlled study to evaluate the longer interval of intravitreal injection of IBI302 in subjects with neovascular age-related macular degeneration.

Official Title
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A Multi-center, Randomized, Double-masked, Active-controlled Study to Evaluate the Longer Interval of Intravitreal (IVT) Injection of IBI302 in Subjects With Neovascular Age-related Macular Degeneration (nAMD)

Conditions
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Neovascular Age-related Macular Degeneration

Intervention / Treatment
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* Biological: dose 1 IBI302
* Drug: Aflibercept
* Biological: dose 2 IBI302


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to sign informed consent from and comply with visit and study procedures per protocol. Male or female patients≥50 yrs. of age. Active subfoveal or parafoveal CNV secondary to neovascular AMD on FFA or OCT. The CNV area≥50% lesion area on FFA in the study eye at screening visit. BCVA score of 24-78 letters using ETDRS charts in the study eye at the baseline. Exclusion Criteria: Concomitant diseases that may cause subjects fail to respond to the treatment or confuse the interpretation of the study results. Subretinal hemorrhage>50% total lesion area and/or involvement in the macular foveal, fibrosis or atrophy area>50% total lesion area and/or involved of macular fovea; Presence of uncontrolled glaucoma in the study eye(defined as IOP≥25mmHg, or judged by the investigators at the screening or baseline visit) Presence of active intraocular or periocular inflammation or infection; Prior any treatment of following in the study eye: Anti-VEGF(Vascular Endothelial Growth Factor) therapy or anti-complement therapy within 3 months prior to screening; Laser photocoagulation within 3 months prior to screening; Photodynamic therapy or vitreoretinal surgery; Intraocular glucocorticoid injection within 6 months prior to enrollment; Presence of any systemic disease: including but not limited tractive infections (such as active viral hepatitis); unstable angina; cerebrovascular accident or transient cerebral ischemia (within 6 months prior to selection); myocardial infarction (within 6 months prior to selection); serious arrhythmia requiring medical treatment; liver, kidney or metabolic diseases; or malignant tumor; History of severe hypersensitivity/allergy to active ingredients or any excipients of the study drug, or fluorescein and povidone iodine; Pregnant or lactating women or women preparing to become pregnant or breastfeeding during the study period; Participated in any clinical study of any other drug within three months prior to enrollment, or attempted to participate in other drug trials during the study; Other conditions unsuitable for enrollment judged by investigators

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBI302 dose 2 group<br>Drug: Aflibercept 8mg/eye;Intraocular injection | Biological: dose 2 IBI302<br>* After 4 loading monthly intravitreal injections of dose 2 IBI302，the following IBI302 IVT is given as descript in protocol<br>|
| Active Comparator: Aflibercept<br>Drug: Aflibercept 2mg/eye;Intraocular injection | Drug: Aflibercept<br>* Three consecutive monthly intravitreal injections of 2.0mg Aflibercept followed by injection every other month<br>|
| Experimental: IBI302 dose 1 group<br>Drug: Aflibercept 6.4mg/eye;Intraocular injection | Biological: dose 1 IBI302<br>* After 4 loading monthly intravitreal injections of dose 1 IBI302，the following IBI302 IVT is given as descript in protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of BCVA from baseline | 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. | Baseline to week 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Loss >0,≥5,10，15 Letters From the Baseline BCVA in the Study Eye Over Time | 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 loss in BCVA letter score from baseline indicates a decline in visual acuity. | Baseline to week 52 | 
| Change of Central Subfield Thickness in the Study Eye from baseline | Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane using optical coherence tomography (OCT), as assessed by the central reading center. | Baseline to week 52 | 
| Change of Total Area of Choroidal Neovascularization (CNV) Lesion/Total Area of Choroidal Neovascularization Leakage in the Study Eye from Baseline | The total area of the choroidal neovascularization lesion/Total Area of Choroidal Neovascularization Leakage in the study eye was evaluated by a central reading center using fundus fluorescein angiography (FFA). | From Baseline to week 52 | 
| Percentage of Participants in different dosage of IBI302 Arm on Once Every 8-Weeks, 12-Weeks,Treatment Intervals |  | At Week 20,40,52 | 
| Safety Summary of the Overall Number of Participants With at Least One Adverse Event by Event Type, in All Participants | This safety summary reports the number and percentage of participants who experienced at least one adverse event (AE) during the study. AEs are categorized as any AEs, ocular AEs occurring in the study eye or fellow eye, systemic AEs, serious AEs, AEs related to treatment with study drug, AEs of special interest. The investigator independently assessed the seriousness and severity for each AE. Severity was graded according to the following grading scale: Mild = Discomfort noticed, but no disruption of normal daily activity; Moderate = Discomfort sufficient to reduce or affect normal daily activity; Severe = Incapacitating with inability to work or to perform normal daily activity. | From Baseline to week 52 | 
| Percentage of Participants Gaining ≥0,5,10,15 Letters From the Baseline BCVA in the Study Eye Over Time | 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 letter score from baseline indicates an improvement in visual acuity. | From Baseline to week 52 | 
| Immunogenicity end points | Production of anti-drug antibodies in serum. | From Baseline to week 52 |