A Phase I, Open-label, Multicenter, Dose-Escalating Study to Evaluate the Safety and Tolerability of KH658 Gene Therapy in Participants With Neovascular Age-related Macular Degeneration

VAN-2401 is Phase I clinical trial to assess the safety and tolerability of KH658 in subjects with neovascular AMD. KH658 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 ocular injections.

Study Overview

• Status: Active, not recruiting
• Conditions: Age-Related Macular Degeneration
• Intervention / Treatment: Drug: KH658

• Study Type: Interventional
• Enrollment (Estimated): 9
• 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
  • Tennessee
    • Memphis, Tennessee, United States, 38138
      • Kanghong Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 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 25 in the study eye at Screening for the first subject in each cohort (sentinel subject), followed by ETDRS BCVA letter score of 73 to 25 for the rest of the subjects each cohort; d. 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 (SLT or MIGS are permitted); 8. corneal transplant; 9. Any use of long-acting intraocular steroids, including implants, within six months prior; 10. Uncontrolled glaucoma; 11. Intraocular implant 12. Participated as a subject in any interventional clinical trial within 1 month prior; 13. Have received any gene or cell therapy product at any time in the past (either eye or systemically); 14. Have active intraocular inflammation in either eye at Screening or a history of uveitis in either eye 15.Have active ocular or periocular infection in either eye; 16. Have presence or history of scleromalacia in either eye;

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KH658 Dose 1; KH658 One-Time Suprachroidal Space delivery Dose Level 1	Drug: KH658; KH658: AAV vector containing a coding sequence for an anti-VEGF protein
Experimental: KH658 Dose 2; KH658 One-Time Suprachroidal Space delivery Dose Level 2	Drug: KH658; KH658: AAV vector containing a coding sequence for an anti-VEGF protein
Experimental: KH658 Dose 3; KH658 One-Time Suprachroidal Space delivery Dose Level 3	Drug: KH658; KH658: 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	52 Weeks
Safety	Change in Best Corrected Visual Acuity	52 Weeks
Safety	type, severity and incidence of ocular and systemic AEs and SAEs	24Weeks
Rescue Injections	Mean Number of Rescue Injections	24Weeks
Rescue Injections	Mean Number of Rescue Injections	52Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Change in Best Corrected Visual Acuity	24 Weeks

Collaborators and Investigators

• Sponsor: Chengdu Origen Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: February 8, 2025
• First Submitted That Met QC Criteria: February 8, 2025
• First Posted (Actual): February 13, 2025

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Age-Related Macular Degeneration
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration
• Other Study ID Numbers: VAN-2401

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
• product manufactured in and exported from the U.S.: No