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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Age-Related Macular Degeneration
• Intervention / Treatment: Drug: KH631

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Qiang Zheng; Phone Number: 86 13880331037; Email: zhengqiang@cnkh.com
• Study Contact Backup: Name: Shanshan Ji; Phone Number: 86 18188058101; Email: 022078@cnkh.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Tongren Hospital, Capital Medical University
    • Contact: Wenbin Wei, PhD; Phone Number: 86 13701255115; Email: tr_weiwenbin@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
KH631 protein in aqueous fluid and blood	Exploratory	104 weeks
VEGF-A in aqueous fluid and blood	Exploratory	104 weeks

Collaborators and Investigators

• Sponsor: Chengdu Origen Biotechnology Co., Ltd.
• Investigators: Principal Investigator: Wenbin Wei, PhD, Beijing Tongren Hospital Affiliated to Capital Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2023
• Primary Completion (Estimated): December 28, 2026
• Study Completion (Estimated): December 28, 2026

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: January 3, 2023
• First Posted (Actual): January 5, 2023

Study Record Updates

• Last Update Posted (Estimated): November 27, 2024
• Last Update Submitted That Met QC Criteria: November 26, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration
• Other Study ID Numbers: KH631-40101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No