Safety and Tolerability of KH631 Gene Therapy in Subjects With Neovascular Age-related Macular Degeneration (nAMD)

Study Overview
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Brief Summary
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KH631 is a adeno-associated virus (AAV) vector-based gene therapy for subretinal injection. The long-term, stable therapeutic protein after one time injection for nAMD could potentially reduce the treatment burden and maintain vision.

Official Title
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A Phase I/II, Open-label, Multiple-cohort, Dose-escalation Study to Evaluate the Safety and Tolerability of KH631 Gene Therapy in Subjects With Neovascular Age-related Macular Degeneration (nAMD)

Conditions
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Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: KH631


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Are willing and able to sign the study written informed consent form (ICF); 2. Men and women ≥ 50 and ≤85 years of age, diagnosed with nAMD at the Screening visit; 3. Subjects must be under active anti-VEGF treatment for nAMD and received a minimum of 3 injections within 6 months prior to screening; 4. Response to anti-VEGF therapy(Response is defined as reduction in CRT≥50μm or at least 30% reduction in fluid by OCT compared to disease at the worst); 5. BCVA between ≤20/63 and ≥20/400(≤63 and ≥19 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) for the first patient in each cohort followed by BCVA between ≤20/40 and ≥20/400(≤73 and ≥19 ETDRS letters) for the rest of the cohort; 6. Must be pseudophakic(at least 3 months after intraocular lens implantation) in the study eye; 7.Female subjects must have been postmenopausal for at least 1 year. Exclusion Criteria: 1.Any other cause of CNV, including pathologic myopia, etc, or other diseases except nAMD have an influence on the test of macular or affect the central visual acuity; 2.Presence of an implant, refractive media opacity affects fundus examination or narrow pupil of the study eye; 3.Active or history of retinal detachment in the study eye; 4.Uncontrolled glaucoma or ocular hypertension; 5.Have taken the drug known to have retinal toxicity; 6.History of intraocular surgery; 7.Uncontrolled hypertension despite medication at the screening visit.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KH631 Dose 1<br>dose1:Administered by Subretinal injection. Dosage form: injection solution. Dose: 200uL. Frequency of administration: one time injection. | Drug: KH631<br>* KH631: AAV vector containing a coding sequence for an anti-VEGF protein<br>|
| Experimental: KH631 Dose 2<br>dose2:Administered by Subretinal injection. Dosage form: injection solution. Dose: 200uL. Frequency of administration: one time injection. | Drug: KH631<br>* KH631: AAV vector containing a coding sequence for an anti-VEGF protein<br>|
| Experimental: KH631 Dose 3<br>dose3:Administered by Subretinal injection. Dosage form: injection solution. Dose: 200uL. Frequency of administration: one time injection. | Drug: KH631<br>* KH631: AAV vector containing a coding sequence for an anti-VEGF protein<br>|
| Experimental: KH631 Dose 4<br>dose4:Administered by Subretinal injection. Dosage form: injection solution. Dose: 200uL. Frequency of administration: one time injection. | Drug: KH631<br>* KH631: AAV vector containing a coding sequence for an anti-VEGF protein<br>|
| Experimental: KH631 Dose 5<br>dose5:Administered by Subretinal injection. Dosage form: injection solution. Dose: 200uL. Frequency of administration: one time injection. | Drug: KH631<br>* KH631: AAV vector containing a coding sequence for an anti-VEGF protein<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | incidence of AEs and SAEs | 24 weeks | 
| Change in best corrected visual acuity | BCVA | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | incidence of AEs and SAEs | 104 weeks | 
| Change in best corrected visual acuity | BCVA | 104 weeks | 
| Change in central retinal thickness | CRT | 104 weeks | 
| Change in area of retinal leakage | Leakage measured by FFA | 104 weeks | 
| Rescue injections | Mean number of rescue injections | 104 weeks |