Gene Therapy for Age-Related Macular Degeneration

Recruiting at7 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Trial Summary

What is the purpose of this trial?

This trial is testing a new gene therapy called KH631 for patients with a severe eye condition known as neovascular AMD. The therapy uses a harmless virus to deliver a protein that blocks a harmful substance in the eye. This could help improve vision and reduce the need for frequent eye injections.

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.

What data supports the effectiveness of the treatment KH631 for age-related macular degeneration?

Preclinical studies in non-human primates showed that a single low-dose injection of KH631 prevented the formation and progression of severe lesions in the eye and maintained its effects for over 96 weeks, suggesting it could be an effective long-term treatment for age-related macular degeneration. ^{1 2 3 4 5}

Is KH631 gene therapy safe for humans?

KH631, a gene therapy for age-related macular degeneration, has been tested in preclinical studies on non-human primates, showing promising safety results with no major safety concerns reported. However, human safety data is not provided in the available research. ^{1 3 4 5 6}

How does the treatment KH631 differ from other treatments for age-related macular degeneration?

KH631 is unique because it uses gene therapy to provide a long-term solution for age-related macular degeneration by delivering a single subretinal injection that enables sustained expression of anti-VEGF proteins, reducing the need for frequent injections. ^{1 2 4 7 8}

Research Team

Avner Ingerman, MD, MSc

Principal Investigator

Vanotech Ltd.

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• KH631 (Gene Therapy)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of KH631, a novel rAAV8 gene therapy product for neovascular age-related macular degeneration. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Gene therapy for retinal and choroidal diseases. [2019]

3. Netherlands 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. [2022]

4. United States 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. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Review of gene therapies for age-related macular degeneration. [2023]

6. England 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. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Engineering of PEDF-Expressing Primary Pigment Epithelial Cells by the SB Transposon System Delivered by pFAR4 Plasmids. [2022]

8. Singapore pubmed.ncbi.nlm.nih.gov

Gene therapy in age related macular degeneration and hereditary macular disorders. [2022]