KH658 Gene Therapy for Age-Related Macular Degeneration

Not currently recruiting at 2 trial locations

Overseen By Avner Ingerman

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Chengdu Origen Biotechnology Co., Ltd.

Must be taking: Anti-VEGF

Must not be taking: Long-acting steroids

Disqualifiers: Retinal tears, Vitreous hemorrhage, Uncontrolled glaucoma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new gene therapy called KH658 for individuals with neovascular age-related macular degeneration (AMD), a condition that impairs vision due to abnormal blood vessel growth in the eye. The trial aims to determine if KH658 is safe and well-tolerated. This therapy seeks to reduce the need for frequent eye injections by delivering a protein that blocks VEGF, a factor involved in blood vessel formation. Ideal participants have previously received anti-VEGF treatments and noticed an improvement in vision. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Is there any evidence suggesting that KH658 is likely to be safe for humans?

Research shows that gene therapy for wet age-related macular degeneration (AMD) holds promise. KH658 is a gene therapy designed to block VEGF, a protein that causes abnormal blood vessel growth in the eye. This treatment aims to be a one-time solution, potentially reducing the need for regular eye injections.

Previous studies have focused on the safety of these gene therapies. Although detailed safety data for KH658 is not yet available, similar gene therapies have generally been well-tolerated in early research. Participants in similar trials have not reported serious side effects. However, since this is an early-stage study, the full safety profile is still being assessed.

In summary, while KH658 is still under study, other gene therapies in this area have shown potential safety and may help improve vision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AMD?

Unlike the standard treatments for age-related macular degeneration that often involve repeated injections into the eye, KH658 offers a one-time delivery directly into the suprachoroidal space. This gene therapy aims to address the root cause of the condition by potentially altering the genetic factors involved in disease progression. Researchers are excited because this novel delivery method could reduce the treatment burden on patients and offer more sustained benefits compared to current therapies.

What evidence suggests that KH658 gene therapy might be an effective treatment for age-related macular degeneration?

Research has shown that gene therapy for wet age-related macular degeneration (AMD) holds promise. KH658, the investigational treatment in this trial, delivers a protein that inhibits VEGF, a molecule that causes blood vessels in the eye to grow and leak, worsening vision. Current treatments require regular injections to block VEGF, but KH658 might provide a long-term solution with a single treatment. Studies have demonstrated that continuous delivery of anti-VEGF can effectively control the disease. This therapy could reduce the need for frequent eye injections, potentially easing life for those with neovascular AMD. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people who have neovascular Age-related Macular Degeneration (AMD) and responded to previous anti-VEGF treatments. They must have active macular lesions, a certain level of vision as measured by the ETDRS score, and be willing to consent to the study.

Inclusion Criteria

Have an ETDRS BCVA letter score of 63 to 25 in the study eye at Screening for the first subject in each cohort, followed by ETDRS BCVA letter score of 73 to 25 for the rest of the subjects in each cohort

Are willing and able to sign the study written informed consent form (ICF)

I am between 50 and 85 years old and my eye meets the study requirements.

Exclusion Criteria

Retinal pigment epithelial tears or rips at screening

Intraocular implant

I have had or currently have bleeding in the eye.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time suprachoroidal space delivery of KH658 gene therapy at varying dose levels

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in visual acuity and need for rescue injections

52 weeks

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• KH658

Trial Overview

KH658 gene therapy is being tested in this Phase I trial. It's designed to deliver a protein that blocks VEGF using a viral vector, potentially reducing the need for regular eye injections currently used in standard AMD care.

How Is the Trial Designed?

Group I: KH658 Dose 3 Experimental Treatment 1 Intervention

KH658 One-Time Suprachroidal Space delivery Dose Level 3

Group II: KH658 Dose 2 Experimental Treatment 1 Intervention

KH658 One-Time Suprachroidal Space delivery Dose Level 2

Group III: KH658 Dose 1 Experimental Treatment 1 Intervention

KH658 One-Time Suprachroidal Space delivery Dose Level 1

Who Is Running the Clinical Trial?

Chengdu Origen Biotechnology Co., Ltd.

Lead Sponsor

Trials

4

Recruited

120+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06825858

Study Details | NCT06825858 | A Phase I, Open-label, ...

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

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12562165/

Gene Therapy for Wet Age-Related Macular Degeneration

Gene therapy for wet AMD has shown particularly promising results. Based on cohort size, efficacy, and stage of advancement, Ixo-vec (ADVM-022), ...

3.

firstwordpharma.com

firstwordpharma.com/story/5956224

Chengdu Origen and Vanotech Announce First Patient ...

This multi-center, open-label, dose-escalation clinical trial in the US will assess the safety, tolerability and efficacy of KH658 as a single suprachoroidal ...

4.

clinicaltrialsarena.com

clinicaltrialsarena.com/news/chengdu-vanotech-trial/

Chengdu Origen and Vanotech dose first subject in wet ...

“KH658 is designed to deliver anti-VEGF continuously to the retina, with the potential to provide sustained levels that can control the disease.

5.

modernretina.com

modernretina.com/view/first-patient-dosed-in-van-2401-phase-1-clinical-trial

First patient dosed in VAN-2401 phase 1 clinical trial

The VAN-2401 clinical trial is for the evaluation of KH658 for the treatment for patients with wet age-related macular degeneration (wet AMD).

6.

trialfinder.panfoundation.org

trialfinder.panfoundation.org/en-US/trial/listing/501995

Safety and Tolerability of KH658 Gene Therapy in Subjects With ...

A Phase I/II Study to Evaluate the Tolerability, Safety and Efficacy of KH658 Gene Therapy in Subjects With Neovascular Age-related Macular Degeneration (nAMD).

7.

scge.mcw.edu

scge.mcw.edu/platform/data/report/clinicalTrials/NCT06458595

Gene Therapy Trial Report

Safety and Tolerability of KH658 Gene Therapy in Subjects With Neovascular Age-related Macular Degeneration (nAMD) ; NCTID, NCT06458595 (View at clinicaltrials.

8.

app.trialscreen.org

app.trialscreen.org/trials/phase-1-2-safety-tolerability-kh658-gene-therapy-subjects-neovascular-age-trial-nct06458595

Safety and Tolerability of KH658 Gene Therapy in Subjects ...

Participants may potentially benefit from improved vision and retinal anatomy if the KH658 gene therapy is effective in treating their wet age-related macular ...