Evaluation of IBI302 Injection in nAMD or DME

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and safety of intravitreal IBI302 in the treatment of subjects with neovascular age-related macular degeneration (only in Phase I) or diabetic macular edema.

Official Title
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A Dose Escalation Study to Evaluate the Safety and Tolerability of IBI302 Intravitreal Injection in Subjects With Neovascular Age-related Macular Degeneration and Diabetic Macular Edema AND A Multi-center, Randomized, Double-blind, Active-controlled Study to Evaluate the Efficacy and Safety of IBI302 in Subjects With Diabetic Macular Edema

Conditions
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Neovascular Age-related Macular Degeneration, Diabetic Macular Edema

Intervention / Treatment
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* Biological: Intravitreal injection of IBI302(dose 1)
* Biological: Intravitreal injection of IBI302(dose 2)
* Biological: Intravitreal injection of IBI302(dose 3)
* Drug: Intravitreal injection of Aflibercept


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Willing and able to sign informed consent form and comply with visit and study procedures per protocol; Male or female patiensubjects ≥ 18 yrs. of age; For AMD subjects, active subfoveal or parafoveal CNV secondary to neovascular AMD; the vision decreased by nAMD; For DME subjects, Type 1 or type 2 diabetes mellitus, decrease in vision determined to be primarily the result of DME in the study eye; the CST measurement of ≥ 280 μm in the study eye; BCVA ETDRS letter score of 24-73 in the study eye; Exclusion criteria Concomitant diseases that may cause subjects fail to respond to the treatment or confuse the interpretation of the study results; Presence of uncontrolled glaucoma in the study eye ; Presence of active intraocular or periocular inflammation or infection; Prior any treatment of following in the study eye: Anti-VEGF therapy or anti-complement therapy; Laser photocoagulation; History of vitreoretinal surgery; Glucocorticoid treatment(intravitreal or peribulbar) ; BCVA score <19 letters in the fellow eye; Anti-VEGF therapy in the fellow eye within 30 days of day 0; Presence of any systemic disease: including but not limited to active infections (such as active viral hepatitis); unstable angina; cerebrovascular accident or transient cerebral ischemia (within 6 months prior to screening); myocardial infarction (within 6 months prior to screening; serious arrhythmia requiring medical treatment; liver, kidney or metabolic diseases; uncontrolled clinical disease(such as diabetes mellitus, hypertension) 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 90 days of day 0, or attempted to participate in other drug trials during the study; Other conditions unsuitable for enrollment judged by investigatiors.

Ages Eligible for Study
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Minimum Age: 18 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: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aflibercept<br>only phase II | Drug: Intravitreal injection of Aflibercept<br>* Aflibercept intravitreal injection given as protocol<br>|
| Experimental: IBI302<br> | Biological: Intravitreal injection of IBI302(dose 1)<br>* IBI302(dose 1) intravitreal injection given as protocol<br>Biological: Intravitreal injection of IBI302(dose 2)<br>* IBI302(dose 2) intravitreal injection given as protocol<br>Biological: Intravitreal injection of IBI302(dose 3)<br>* IBI302(dose 3) intravitreal injection given as protocol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of ocular and non-ocular adverse events. | To evaluate the number of subjects with ocular and non-ocular adverse events, treatment emergent adverse event, adverse event of special interest, serious adverse events; number of subjects with clinical significant abnormal laboratory values, electrocardiograms (pre and post infusions), abnormal vital signs, ophthalmic and physical examinations. | Up to week 20 | 
| DLT in each group |  | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of BCVA from baseline by visit | 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. | through study completion，an average of 20 weeks | 
| Change of CST from baseline by visit | Central subfield thickness（CST） was defined as the distance between the internal limiting member and the Bruch's member using OCT, as assessed by the central reading. | through study completion，an average of 20 weeks | 
| Area under the concentration time curve (AUC) and Maximum plasma concentration (Cmax) |  | through study completion，an average of 20 weeks | 
| The ADA and neutralizing antibody | Blood samples were obtained for measurement of anti-drug antibodies (ADAs) to IBI302 by a validated enzyme-linked immunosorbent assay (ELISA). | through study completion，an average of 20 weeks |