Gene Therapy for Age-Related Macular Degeneration
Recruiting in Palo Alto (17 mi)
+7 other 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.
12345Is 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.
13456How 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.
12478Eligibility 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.
+5 more
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
Participant Groups
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.
5Treatment groups
Experimental Treatment
Group I: KH631 Dose 5Experimental Treatment1 Intervention
KH631 One-Time Intraocular Injection Dose Level 5
Group II: KH631 Dose 4Experimental Treatment1 Intervention
KH631 One-Time Intraocular Injection Dose Level 4
Group III: KH631 Dose 3Experimental Treatment1 Intervention
KH631 One-Time Intraocular Injection Dose Level 3
Group IV: KH631 Dose 2Experimental Treatment1 Intervention
KH631 One-Time Intraocular Injection Dose Level 2
Group V: KH631 Dose 1Experimental Treatment1 Intervention
KH631 One-Time Intraocular Injection Dose Level 1
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Kanghong Investigative SiteDallas, TX
Kanghong Investigative SiteKaty, TX
Kanghong Investigative SiteReno, NV
Kanghong Investigative SiteGermantown, TN
More Trial Locations
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Who Is Running the Clinical Trial?
Chengdu Origen Biotechnology Co., Ltd.Lead Sponsor
References
Preclinical evaluation of KH631, a novel rAAV8 gene therapy product for neovascular age-related macular degeneration. [2023]The upregulation of vascular endothelial growth factor (VEGF) is strongly associated with the development of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD). Currently, the standard treatment for nAMD involves frequent intravitreal injections of anti-VEGF agents, which inhibit the growth of new blood vessels and prevent leakage. However, this treatment regimen places a significant burden on patients, their families, and healthcare providers due to the need for repeated visits to the clinic for injections. Gene therapy, which enables the sustained expression of anti-VEGF proteins after a single injection, can dramatically reduce the treatment burden. KH631 is a recombinant adeno-associated virus 8 vector that encodes a human VEGF receptor fusion protein, and it is being developed as a long-term treatment for nAMD. In preclinical studies using non-human primates, subretinal administration of KH631 at a low dose of 3 × 108 vg/eye resulted in remarkable retention of the transgene product in the retina and prevented the formation and progression of grade IV CNV lesions. Furthermore, sustained transgene expression was observed for more than 96 weeks. These findings suggest that a single subretinal injection of KH631 has the potential to offer a one-time, low-dose treatment for nAMD patients.
Gene therapy for retinal and choroidal diseases. [2019]The eye is a small compartment separated from the systemic circulation by the blood-ocular barriers, providing advantages for intraocular gene transfer - an approach which is being investigated for several types of retinal and choroidal diseases. A compelling application is gene replacement for homozygous loss-of-function mutations in genes differentially expressed in photoreceptors or retinal pigmented epithelial (RPE) cells that result in retinal degeneration. Considerable progress has been made in this area, including demonstration of return of visual function in RPE65 (-/-) dogs after subretinal injection of adeno-associated viral vectors encoding RPE65, providing groundwork for a clinical trial in patients with Leber's Congenital Amaurosis. Proof of principle has been provided for intraocular gene transfer of ribozymes for dominantly inherited retinal degenerations. Survival factor gene therapy shows promise for treatments that may be used in multiple retinal degenerations. Transduction of intraocular and/or periocular cells with constructs that encode antiangiogenic proteins provides a new approach for sustained local delivery treatment of retinal and choroidal neovascularisation. While considerable investigation remains to work out critical details, there is substantial evidence suggesting that in the near future, gene therapy-based treatments will be an important addition to what is currently offered to patients with retinal and/or choroidal diseases.
Phase 2a Randomized Clinical Trial: Safety and Post Hoc Analysis of Subretinal rAAV.sFLT-1 for Wet Age-related Macular Degeneration. [2022]We present the results of a Phase 2a randomized controlled trial investigating the safety, and secondary endpoints of subretinal rAAV.sFLT-1 gene therapy in patients with active wet age-related macular degeneration (wAMD).
Three-Year Follow-Up of Phase 1 and 2a rAAV.sFLT-1 Subretinal Gene Therapy Trials for Exudative Age-Related Macular Degeneration. [2020]To assess the safety and the 3-year results of combined phase 1 and 2a randomized controlled trials of rAAV.sFLT-1 gene therapy (GT) for wet age-related macular degeneration.
Review of gene therapies for age-related macular degeneration. [2023]Gene therapies aim to deliver a therapeutic payload to specified tissues with underlying protein deficiency. Since the 1990s, gene therapies have been explored as potential treatments for chronic conditions requiring lifetime care and medical management. Ocular gene therapies target a range of ocular disorders, but retinal diseases are of particular importance due to the prevalence of retinal disease and the current treatment burden of such diseases on affected patients, as well as the challenge of properly delivering these therapies to the target tissue. The purpose of this review is to provide an update on the most current data available for five different retinal gene therapies currently undergoing clinical trials for use against age-related macular degeneration (AMD) and the development of novel delivery routes for the administration of such therapies. Research has been performed and compiled from PubMed and the select authors of this manuscript on the treatment and effectiveness of five current retinal gene therapies: Luxturna, ADVM-022, RGX-314, GT-005, and HMR59. We present the available data of current clinical trials for the treatment of neovascular and dry age-related macular degeneration with different AAV-based gene therapies. We also present current research on the progress of developing novel routes of administration for ocular gene therapies. Retinal gene therapies offer the potential for life-changing treatment for chronic conditions like age-related macular degeneration with a single administration. In doing so, gene therapies change the landscape of treatment options for these chronic conditions for both patient and provider.
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]Neovascular, or wet, age-related macular degeneration causes central vision loss and represents a major health problem in elderly people, and is currently treated with frequent intraocular injections of anti-VEGF protein. Gene therapy might enable long-term anti-VEGF therapy from a single treatment. We tested the safety of rAAV.sFLT-1 in treatment of wet age-related macular degeneration with a single subretinal injection.
Engineering of PEDF-Expressing Primary Pigment Epithelial Cells by the SB Transposon System Delivered by pFAR4 Plasmids. [2022]Neovascular age-related macular degeneration (nvAMD) is characterized by choroidal blood vessels growing into the subretinal space, leading to retinal pigment epithelial (RPE) cell degeneration and vision loss. Vessel growth results from an imbalance of pro-angiogenic (e.g., vascular endothelial growth factor [VEGF]) and anti-angiogenic factors (e.g., pigment epithelium-derived factor [PEDF]). Current treatment using intravitreal injections of anti-VEGF antibodies improves vision in about 30% of patients but may be accompanied by side effects and non-compliance. To avoid the difficulties posed by frequent intravitreal injections, we have proposed the transplantation of pigment epithelial cells modified to overexpress human PEDF. Stable transgene integration and expression is ensured by the hyperactive Sleeping Beauty transposon system delivered by pFAR4 miniplasmids, which have a backbone free of antibiotic resistance markers. We demonstrated efficient expression of the PEDF gene and an optimized PEDF cDNA sequence in as few as 5 × 103 primary cells. At 3 weeks post-transfection, PEDF secretion was significantly elevated and long-term follow-up indicated a more stable secretion by cells transfected with the optimized PEDF transgene. Analysis of transgene insertion sites in human RPE cells showed an almost random genomic distribution. The results represent an important contribution toward a clinical trial aiming at a non-viral gene therapy of nvAMD.
Gene therapy in age related macular degeneration and hereditary macular disorders. [2022]In ophthalmology, administration of the therapeutic agent can be difficult due to the tight barriers in the eye. Multiple injections may be needed to allow the therapeutic agent to reach adequate levels in retina and choroidea which may increase the risk of complications including endophthalmitis, cataract and haemorrhages. Optimal methods for the delivery of therapeutic agents to the posterior segments of the eye have not yet been developed. Gene therapy offers an alternative where the therapeutic protein or proteins can be induced in the target tissue for a prolonged period of time after a single injection. The eye is a promising target for gene therapy due to its small size and tissue boundaries preventing leakage of the therapeutic material to other tissues or systemic circulation. However, most of the work in ocular gene therapy is still at the preclinical phase; only three vectors have reached phase 1/2 clinical trials. This review summarizes basic principles and current status of gene therapy in age related macular degeneration and hereditary macular disorders.