A Dose Escalation Study of IBI302 in Patients With Wet Age-related Macular Degeneration

Study Overview
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Brief Summary
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This study is designed for single-center, open-label, dose escalation phase I trial to evaluate the safety and tolerability of a single intravitreal injection of IBI302 in patients with wet AMD.

Official Title
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A Dose Escalation Phase I Clinical Study to Evaluate the Tolerability and Safety of IBI302 in Patients With Wet Age-related Macular Degeneration (AMD)

Conditions
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Neovascular Age-related Macular Degeneration

Intervention / Treatment
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* Drug: IBI302
* Drug: IBI302
* Drug: IBI302
* Drug: IBI302
* Drug: IBI302
* Drug: IBI302


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patient ≥ 50 yrs. of age. Active subfoveal CNV secondary to wet AMD, with lesion size ≤ 12 optic discs in the study eye. BCVA score of 10-73 letters using ETDRS charts (in 4 meters) in the study eye. Central macular sub-field thickness according to OCT of at least 250 micron. Clear stereoscopic fundus photography is obtained while the lens or other media is clear. Female subjects of childbearing age or male subjects with childbearing age female partner agree to take effective contraceptive measures from the screening period to 3 months after the end of treatment. Willing and able to sign informed consent form and comply with visit and study procedures per protocol. Exclusion Criteria: Presence of other causes of CNV other than wet AMD in the study eye. Presence of active diabetic retinopathy in the study eye. Presence of uncontrolled glaucoma in the study eye (defined as IOP≥30mmHg despite the standardized treatment). Prior retinal detachment in the study eye. Prior any treatment of following in the study eye: Anti-VEGF therapy within 6 months prior to screening; Anti-complement therapy; Laser photocoagulation; Photodynamic therapy; Transpupillary thermotherapy Intraocular surgery; Intraocular or periocular glucocorticoid injection therapy within 6 months prior to enrollment; Presence of any non-AMD disease that may affect visual acuity in the study eye Prior anti-VEGF therapy within 1 month before study drug administration or plan of above anti-VEGF therapy in the non-study eye during the whole study. Oral steroid drugs within 1 month before study drug administration. Presence of active intraocular or periocular inflammation or infection. Diabetic patients have any of the following conditions: Microvascular and macrovascular complications; HbA1c>7.5% when screening; Receiving more than two oral hypoglycemic agents; Receiving insulin or GLP-1 receptor agonist; Hypertension (defined as systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg despite standard treatment); Presence of any following laboratory abnormality: PLT<100×109/L, INR≥1.5ULN, APTT≥ 10 seconds more than ULN; ALT or AST >2ULN; Cr or Ur>1.5ULN; Large or medium surgery, or unhealed surgical incisions, ulcers or fractures within 1 month before study drug administration.

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cohort 1 IBI302 treated with first dose level of IBI302<br> | Drug: IBI302<br>* 0.05mg/eye;Intraocular injection<br>|
| Experimental: cohort 2 IBI302 treated with second dose level of IBI302<br> | Drug: IBI302<br>* 0.15mg/eye;Intraocular injection<br>|
| Experimental: cohort 3 IBI302 treated with third dose level of IBI302<br> | Drug: IBI302<br>* 0.5mg/eye;Intraocular injection<br>|
| Experimental: cohort 4 IBI302 treated with fourth dose level of IBI302<br> | Drug: IBI302<br>* 1mg/eye;Intraocular injection<br>|
| Experimental: cohort 5 IBI302 treated with fifth dose level of IBI302<br> | Drug: IBI302<br>* 2mg/eye;Intraocular injection<br>|
| Experimental: cohort 6 IBI302 treated with sixth dose level of IBI302<br> | Drug: IBI302<br>* 4mg/eye;Intraocular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety evaluation indicators | Decreasing of BCVA; b) Changes in intraocular pressure compared with baseline; c) Incidence, relatedness and severity of all adverse events, treatment emergent adverse events and serious adverse events; | Baseline to Day43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy evaluation indicators | Changes in central subfield thickness by OCT compared with baseline; b) Changes in CNV area by FA compared with baseline; c) Changes in BCVA compared with baseline. | Baseline to Day43 | 
| Immunogenicity evaluation indicators | Positive rate of anti-drug antibody and neutralizing antibody | Baseline to Day43 | 
| The area under the drug-time curve from 0 to time t (AUC0-t) |  | Baseline to Day43 | 
| The area under the curve at the time of 0-infinity (AUC0-∞) |  | Baseline to Day43 | 
| The peak concentration (Cmax) |  | Baseline to Day43 | 
| The peak time (Tmax) |  | Baseline to Day43 | 
| Clearance rate (CL) |  | Baseline to Day43 | 
| Half-life (t1/2) |  | Baseline to Day43 | 
| Free and total VEGF concentration |  | Baseline to Day43 |