Study of IBI333 in Subjects With Neovascular Age-related Macular Degeneration

Study Overview
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Brief Summary
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This study is designed for multi-center, open-label, dose escalation phase I trial to evaluate the safety and tolerability of a single and multiple intravitreal injection of IBI333 in subjects with neovascular age-related macular degeneration (nAMD).

Official Title
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A Dose Escalation Phase I Clinical Study to Evaluate the Tolerability and Safety of IBI333 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: IBI333


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 patients ≥ 50 yrs. of age. Active CNV lesions secondary to neovascular AMD. BCVA score of 19-78 letters using ETDRS charts in the study eye. Female subjects of childbearing age or male subjects with childbearing age female partner agree to take effective contraceptive measures from the screening period to 6 months after the end of treatment. Exclusion Criteria: Concomitant diseases that may cause subjects fail to respond to the treatment or confuse the interpretation of the study results; Tractional retinal detachment, pre-retinal fibrosis, vitreomacular traction, or epiretinal membrane involving the fovea or disrupting the macular structure in the study eye; Active ocular or periocular inflammation/infection in either eye; Prior any treatment of following in the study eye: Anti-VEGF therapy within 90 days prior to screening; Intraocular glucocorticoid injection within 180 days prior to screening; Laser photocoagulation or photodynamic therapy within 90 days prior to screening; Intraocular surgery within 90 days prior to screening; Laser posterior capsulotomy, laser trabeculectomy or laser peripheral iridectomy within 30 days prior to screening; Glycated hemoglobin (HbA1c) > 8% within 28 days prior to screening; Uncontrolled hypertension (defined as systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg); Systemic administration of steroids within 30 days prior to screening; Systemic administration of anti-VEGF drugs within 90 days prior to screening; History of severe hypersensitivity/allergic to active ingredients or any excipients of the study drug, or fluorescein and povidone iodine; Participated in any clinical study of any other drug within 90 days 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: :treated with different doses of single intravitreal injections of IBI333<br>Biological: IBI333 Dose 1 IBI333 of single IVT injections， Biological: IBI333 Dose 2 IBI333 of single IVT injections | Biological: IBI333<br>* Intravitreal injection of IBI333<br>|
| Experimental: treated with different doses of multiple intravitreal injections of IBI333<br>Biological: IBI333 Dose 3 IBI333 of multiple IVT injections， Biological: IBI333 Dose 4 IBI333 of multiple IVT injections | Biological: IBI333<br>* Intravitreal injection of IBI333<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerance indicators | Incidence, relatedness and severity of all adverse events (AE), treatment emergent adverse events (TEAE) and serious adverse events (SAE); Incidence of dose limiting toxicity; | Through study completion, a maximum of 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The area under the curve (AUC) of serum concentration of the drug after the administration. |  | Through study completion, a maximum of 24 weeks | 
| Maximum concentration (Cmax) of the drug after the administration. |  | Through study completion, a maximum of 24 weeks | 
| Time at which maximum concentration (Tmax) occurs for the drug after the administration. |  | Through study completion, a maximum of 24 weeks | 
| The half-life (t1/2) of drug after the administration . |  | Through study completion, a maximum of 24 weeks | 
| Number of participants with anti-drug antibodies or neutralizing antibodies . |  | Through study completion, a maximum of 24 weeks | 
| Changes of BCVA measured by ETDRS chart from baseline. |  | Through study completion, a maximum of 24 weeks | 
| Changes of CST measured by spectral domain optical coherence tomography (SD-OCT) from baseline. |  | Through study completion, a maximum of 24 weeks | 
| Proportion of subjects without intraretinal or subretinal fluid on SD-OCT. |  | Through study completion, a maximum of 24 weeks | 
| Change of height of pigment epithelial detachment from baseline on SD-OCT. |  | Through study completion, a maximum of 24 weeks |