Safety and Tolerability of KH631 Gene Therapy in Participants With Neovascular Age-related Macular Degeneration

A Phase I, Open-label, Multicenter, Dose-Escalating Study to Evaluate the Safety and Tolerability of KH631 Gene Therapy in Participants With Neovascular Age-related Macular Degeneration

VAN-2201 is Phase I clinical trial to assess the safety and tolerability of KH631 in subjects with neovascular AMD. KH631 is gene therapy designed to deliver a protein which targets and blocks VEGF via an adeno-associated viral vector. The standard of care for patients with neovascular AMD are anti-VEGF treaments, which have demonstrated improvement in vision and reduction in fluid. A one time placement of a product which inhibits VEGF has the potential to reduce the patient burden of regular intraocular injections.

Study Overview

• Status: Active, not recruiting
• Conditions: Age-Related Macular Degeneration
• Intervention / Treatment: Drug: KH631

Detailed Description

The VAN-2201 clinical trial is a multicenter, open-label, dose-escalating clinical study. The primary objective of the study will be to establish a safe and tolerable dose range in subjects with neovascular AMD. Five dose cohorts are planned to be included in the study, with approximately five subjects per cohort. Subjects who meet the eligibility criteria (i.e. all the inclusion and no exclusion criteria) will be enrolled to receive KH631. KH631 will be delivered at the dose level according to the cohort via intraocular injection. Subjects will be seen monthly until the primary outcome measurement at 24 weeks and through week 52. The subjects will be continued to followed with regular visits until they complete the 104 week visit.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Kanghong Investigative Site
  • Illinois
    • Lemont, Illinois, United States, 60439
      • Kanghong Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Kanghong Investigative Site
  • Nevada
    • Reno, Nevada, United States, 89502
      • Kanghong Investigative Site
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08034
      • Kanghong Investigative Site
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Kanghong Investigative Site
  • Texas
    • Dallas, Texas, United States, 75231
      • Kanghong Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 81 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males and Females ages 50 to 85 (inclusive) with a study eye which meets the following criteria:

a. Previously received IVT treatment of anti-VEGF for neovascular AMD, with documented response to anti-VEGF therapy during the first 2 weeks of screening b. active macular CNV lesion secondary to AMD evidenced by SD-OCT c. Have a ETDRS BCVA letter score of 63 to 19 (approximately 20/63 to 20/400 Snellen equivalent) in the study eye at Screening for the first subject in each cohort (sentinel subject), followed by ETDRS BCVA letter score of 73 to 19 (approximately 20/40 to 20/400 Snellen equivalent) for the rest of the subjects each cohort; d. Pseudophakia in the study eye, with ocular media to permit high quality fundus imaging at screening and allow planned vitrectomy and subretinal injection; e. Are willing and able to sign the study written informed consent form (ICF).

Exclusion Criteria:

1. Have had any prior ocular or systemic treatment (investigational or approved) or surgery for the treatment of neovascular AMD except IVT anti-VEGF
2. Retinal pigment epithelial tears or rips at screening
3. Any history or presence of vitreous hemorrhage;
4. Have any condition preventing visual acuity improvement;
5. Have any other cause of CNV; prior pars plana vitrectomy or scleral buckling or retinal detachment surgery; macular hole, Epiretinal membrane or vitreo-macular traction; full thickness macular hole;
6. History of intraocular or periocular surgery in the prior 3 months;
7. Prior trabeculectomy or other filtration surgery ;
8. Any use of long-acting intraocular steroids, including implants, within six months prior;

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; KH631 One-Time Intraocular Injection Dose Level 1	Drug: KH631; KH631: AAV vector containing a coding sequence for an anti-VEGF protein
Experimental: KH631 Dose 2; KH631 One-Time Intraocular Injection Dose Level 2	Drug: KH631; KH631: AAV vector containing a coding sequence for an anti-VEGF protein
Experimental: KH631 Dose 3; KH631 One-Time Intraocular Injection Dose Level 3	Drug: KH631; KH631: AAV vector containing a coding sequence for an anti-VEGF protein
Experimental: KH631 Dose 4; KH631 One-Time Intraocular Injection Dose Level 4	Drug: KH631; KH631: AAV vector containing a coding sequence for an anti-VEGF protein
Experimental: KH631 Dose 5; KH631 One-Time Intraocular Injection Dose Level 5	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 (Type, Severity and Incidence of ocular and systemic AEs and SAEs)	type, severity and incidence of ocular and systemic AEs and SAEs	52 Weeks
Best Corrected Visual Acuity	Change in Best Corrected Visual Acuity	52 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rescue Injections	Mean Number of Rescue Injections	104 Weeks
Safety (type, severity and incidence of ocular and systemic AEs and SAEs)	type, severity and incidence of ocular and systemic AEs and SAEs	104 Weeks
Best Corrected Visual Acuity	Change in Best Corrected Visual Acuity	104 Weeks

Collaborators and Investigators

• Sponsor: Chengdu Origen Biotechnology Co., Ltd.
• Investigators: Study Director: Avner Ingerman, MD, MSc, Vanotech Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: December 10, 2022
• First Submitted That Met QC Criteria: December 10, 2022
• First Posted (Actual): December 20, 2022

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 25, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration
• Other Study ID Numbers: VAN-2201

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