Gene Therapy for Age-Related Macular Degeneration

Recruiting at 7 trial locations

Overseen By Sponsor Clinical Contact

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, others

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

Compensation: Varies

Number of Visits: 53

Duration: 1 day

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new gene therapy for individuals with neovascular age-related macular degeneration (AMD). The research aims to test the safety of KH631, a one-time eye injection that might reduce the need for regular anti-VEGF shots, which help improve vision by reducing fluid in the eye. Participants will receive different doses to determine the optimal and safest amount. This study suits those who have previously responded well to anti-VEGF treatments for neovascular AMD and continue to experience active symptoms. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you have only received anti-VEGF treatments for neovascular AMD before participating.

Is there any evidence suggesting that KH631 is likely to be safe for humans?

Research has shown that patients generally handle gene therapies like KH631 well in other studies. KH631 uses a harmless virus to deliver a protein that blocks VEGF, a substance causing abnormal blood vessel growth in the eye. Previous studies have examined the use of these viruses in gene therapy, and they are usually considered safe, with mild side effects such as temporary redness or discomfort in the eye.

Although KH631 remains in the early testing stages, with limited safety data available, it builds on existing treatments for age-related macular degeneration (AMD) that target VEGF. These existing treatments have been well-studied for safety and are known to improve vision and reduce fluid in the eye.

In summary, while complete safety data for KH631 is still being gathered, the early stage of the study focuses primarily on ensuring safety. Researchers are carefully monitoring for any potential side effects as they proceed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about KH631 for age-related macular degeneration because it utilizes gene therapy, a novel approach compared to traditional treatments like anti-VEGF injections. Unlike these standard treatments, which often require repeated administration, KH631 is designed as a one-time intraocular injection, potentially offering a more convenient and lasting solution. This gene therapy aims to address the underlying causes of vision loss by delivering genetic material directly to the eye, which could lead to more sustained improvements in vision and overall eye health.

What evidence suggests that KH631 might be an effective treatment for neovascular AMD?

Research has shown that KH631, a new gene therapy, could be promising for treating neovascular age-related macular degeneration (AMD). In early animal tests, KH631 greatly reduced the need for regular eye injections, with decreases of 96% and 85% in high-dose trials. These injections are important for improving vision and reducing fluid in the eye. The therapy uses a harmless virus to deliver a protein that blocks VEGF, a substance contributing to AMD. Initial studies suggest that KH631 might effectively treat AMD with just one injection. Participants in this trial will receive one of several dose levels of KH631 to evaluate its safety and effectiveness. ^{1 2 6 7 8}

Who Is on the Research Team?

Avner Ingerman, MD, MSc

Principal Investigator

Vanotech Ltd.

Are You a Good Fit for This Trial?

This trial is for men and women aged 50 to 85 with neovascular Age-related Macular Degeneration (AMD) who've had some improvement from previous anti-VEGF treatments. They must have a certain level of vision in the affected eye and be able to undergo high-quality imaging. Those with recent eye surgery, other causes of CNV, or long-term intraocular steroid use can't participate.

Inclusion Criteria

Males and Females ages 50 to 85 with a study eye meeting specific criteria: a. Previously received IVT treatment of anti-VEGF for neovascular AMD with documented response during the first 2 weeks of screening b. active macular CNV lesion secondary to AMD evidenced by SD-OCT c. ETDRS BCVA letter score of 63 to 19 at Screening for the first subject in each cohort, followed by 73 to 19 for the rest of the subjects each cohort d. Pseudophakia in the study eye with ocular media permitting high-quality fundus imaging and planned vitrectomy and subretinal injection e. Willing and able to sign the study written informed consent form

Exclusion Criteria

Retinal pigment epithelial tears or rips at screening

I have not had eye surgery or specific eye conditions like a macular hole.

I have had bleeding inside my 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 intraocular injection of KH631 at the assigned dose level

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with regular visits

104 weeks

Monthly visits until week 52, then regular visits until week 104

What Are the Treatments Tested in This Trial?

Interventions

• KH631

Trial Overview KH631 gene therapy is being tested for safety and tolerability in this Phase I trial. It's designed as a one-time treatment delivering a protein that blocks VEGF, which could potentially reduce the need for regular eye injections currently used to treat neovascular AMD.

How Is the Trial Designed?

Group I: KH631 Dose 5 Experimental Treatment 1 Intervention

KH631 One-Time Intraocular Injection Dose Level 5

Group II: KH631 Dose 4 Experimental Treatment 1 Intervention

KH631 One-Time Intraocular Injection Dose Level 4

Group III: KH631 Dose 3 Experimental Treatment 1 Intervention

KH631 One-Time Intraocular Injection Dose Level 3

Group IV: KH631 Dose 2 Experimental Treatment 1 Intervention

KH631 One-Time Intraocular Injection Dose Level 2

Group V: KH631 Dose 1 Experimental Treatment 1 Intervention

KH631 One-Time Intraocular Injection Dose Level 1

Who Is Running the Clinical Trial?

Chengdu Origen Biotechnology Co., Ltd.

Lead Sponsor

Trials

4

Recruited

120+

Published Research Related to This Trial

Intraocular gene transfer shows promise for treating retinal diseases, with successful restoration of visual function observed in RPE65 (-/-) dogs after gene therapy, paving the way for potential clinical trials in humans.

Gene therapy approaches, including gene replacement and antiangiogenic protein delivery, are being developed to address various retinal degenerations, indicating a future where these therapies could significantly enhance treatment options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for retinal and choroidal diseases. Campochiaro, PA.[2019]

The gene therapy rAAV.sFLT-1 was found to be safe and well tolerated in a phase 1 trial involving nine patients with wet age-related macular degeneration, with no drug-related adverse events reported.

A significant portion of the treatment group (67%) did not require any rescue injections after the therapy, suggesting that a single subretinal injection could provide long-term benefits compared to the frequent injections currently needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy with recombinant adeno-associated vectors for neovascular age-related macular degeneration: 1 year follow-up of a phase 1 randomised clinical trial. Rakoczy, EP., Lai, CM., Magno, AL., et al.[2022]

Gene therapy presents a promising solution for delivering therapeutic agents to the eye, potentially reducing the need for multiple injections that can lead to complications like endophthalmitis and cataracts.

Currently, gene therapy for eye conditions such as age-related macular degeneration is mostly in the preclinical stage, with only three vectors having advanced to phase 1/2 clinical trials, indicating that more research is needed to establish its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy in age related macular degeneration and hereditary macular disorders. Kinnunen, K., Yla-Herttuala, S.[2022]

The rAAV.sFLT-1 gene therapy for wet age-related macular degeneration was well tolerated in a small group of elderly patients, with no serious adverse events directly linked to the treatment, despite some reported adverse events.

While the study did not find statistically significant improvements in visual acuity, a notable percentage of patients receiving gene therapy maintained their baseline vision over three years, suggesting potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Year Follow-Up of Phase 1 and 2a rAAV.sFLT-1 Subretinal Gene Therapy Trials for Exudative Age-Related Macular Degeneration. Rakoczy, EP., Magno, AL., Lai, CM., et al.[2020]

Retinal gene therapies, particularly for age-related macular degeneration (AMD), are showing promise in clinical trials, with five therapies (Luxturna, ADVM-022, RGX-314, GT-005, and HMR59) being evaluated for their effectiveness against this common condition.

These therapies could potentially provide long-lasting treatment with a single administration, significantly changing the treatment landscape for chronic retinal diseases and reducing the ongoing burden of care for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of gene therapies for age-related macular degeneration. Khanani, AM., Thomas, MJ., Aziz, AA., et al.[2023]

KH631, a gene therapy using a recombinant adeno-associated virus vector, shows promise as a long-term treatment for neovascular age-related macular degeneration (nAMD) by enabling sustained expression of anti-VEGF proteins after a single injection.

In preclinical studies with non-human primates, a low dose of KH631 effectively prevented the formation and progression of severe choroidal neovascularization lesions for over 96 weeks, significantly reducing the treatment burden compared to frequent anti-VEGF injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of KH631, a novel rAAV8 gene therapy product for neovascular age-related macular degeneration. Ke, X., Jiang, H., Li, Q., et al.[2023]

In a Phase 2a trial with 32 patients suffering from wet age-related macular degeneration, the gene therapy rAAV.sFLT-1 was found to be safe, with mainly self-resolving ocular adverse events and no serious safety concerns linked to the treatment.

Patients receiving rAAV.sFLT-1 showed a median improvement in visual acuity compared to the control group, with 57% maintaining or improving vision, and they required fewer ranibizumab retreatments, suggesting that this gene therapy could be a promising option for managing wAMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2a Randomized Clinical Trial: Safety and Post Hoc Analysis of Subretinal rAAV.sFLT-1 for Wet Age-related Macular Degeneration. Constable, IJ., Pierce, CM., Lai, CM., et al.[2022]

Transplanting pigment epithelial cells that overexpress the anti-angiogenic factor PEDF could provide a new treatment for neovascular age-related macular degeneration (nvAMD), potentially reducing the need for frequent and invasive anti-VEGF injections.

The study demonstrated successful and stable expression of the PEDF gene in primary retinal pigment epithelial cells, suggesting a promising approach for long-term therapy in nvAMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering of PEDF-Expressing Primary Pigment Epithelial Cells by the SB Transposon System Delivered by pFAR4 Plasmids. Thumann, G., Harmening, N., Prat-Souteyrand, C., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10638048/

Preclinical evaluation of KH631, a novel rAAV8 gene therapy ... Safety and efficacy of conbercept in neovascular age-related macular degeneration: results from a 12-month randomized phase 2 study: AURORA study.

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

Gene Therapy for Wet Age-Related Macular Degeneration Given the promising outcome of KH631, the phase 1 dose escalation study (NCT05672121) is underway to establish its safety and efficacy in humans ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05657301

Safety and Tolerability of KH631 Gene Therapy in ... Safety and Tolerability of KH631 Gene Therapy in Participants With Neovascular Age-related Macular Degeneration. ClinicalTrials.gov ID NCT05657301. Sponsor ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0039625724000493

Gene and cell therapy for age-related macular degeneration Preliminary results showed a reduction of 96% and 85% in the mean annual frequency of anti-VEGF injections in the high-dose (6×1011 viral genomes (vg)/eye) and ...

5. cgtlive.com cgtlive.com/view/first-patient-dosed-kh631-gene-therapy-phase-1-trial-wet-amd

First Patient Dosed With KH631 Gene Therapy in Phase 1 ... Heier, MD, will assess KH631's safety, tolerability, and efficacy as a 1-time treatment. In preclinical studies of wet AMD disease models, the ...

6. trialx.com trialx.com/clinical-trials/listings/236657/safety-and-tolerability-of-kh631-gene-therapy-in-subjects-with-neovascular-age-related-macular-degeneration-namd/?&radius=50

Safety and Tolerability of KH631 Gene Therapy in Subjects ... Clinical trial for Age-Related Macular Degeneration , Safety and Tolerability of KH631 Gene Therapy in Subjects With Neovascular Age-related ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05672121

NCT05672121 | Safety and Tolerability of KH631 Gene ... Safety and Tolerability of KH631 Gene Therapy in Subjects With Neovascular Age-related Macular Degeneration (nAMD). ClinicalTrials.gov ID NCT05672121. Sponsor ...

8. ctv.veeva.com ctv.veeva.com/study/safety-and-tolerability-of-kh631-gene-therapy-in-participants-with-neovascular-age-related-macular-d

Safety and Tolerability of KH631 Gene Therapy in Participants ... VAN-2201 is Phase I clinical trial to assess the safety and tolerability of KH631 in subjects with neovascular AMD. KH631 is gene therapy ...