Gene therapy for inherited retinal degeneration caused by LCA5 mutations

An Open Label, Dose Exploration, Safety and Tolerability Study of a Subretinal Injection of an OPGx-001 Gene Vector to Participants With LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) With OCncurrent Non-Interventional Follow-Up of Untreated Patients

This study is testing a new gene therapy to see if it can help improve vision in people with inherited retinal degeneration caused by LCA5 gene mutations.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 22 (estimated)
• Ages: 4 Years and up
• Sex: All
• Sponsor: Opus Genetics, Inc (Industry-sponsored)
• Locations: 2 sites (Philadelphia, Pennsylvania and 1 other locations)
• Trial ID: NCT05616793 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and preliminary efficacy of a gene therapy called OPGx-001 delivered via subretinal injection in patients with inherited retinal degeneration due to mutations in the LCA5 gene. It is a non-randomized, open-label study that will escalate doses across three cohorts, starting with a low dose and moving to intermediate and high doses based on safety data reviewed by an independent monitoring committee. The goal is to assess how well this treatment can improve vision in affected individuals.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 13 and older with biallelic mutations in the LCA5 gene and visual acuity worse than 20/80.

Not a fit: Patients with other forms of retinal degeneration or those without detectable photoreceptors may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this therapy could significantly improve vision and quality of life for patients with LCA5-associated retinal degeneration.

How similar studies have performed: Other studies using gene therapy for inherited retinal diseases have shown promising results, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Are willing and able to provide written informed consent (ICF) and, where appropriate, willing to sign an assent prior to any study procedures.
2. Are willing to adhere to the clinical protocol and able to perform testing procedures.
3. In part A participants must be 13 years of age or older at consent, for Part B, participants must be 4 years of age or older at consent with the ability to conduct the MLoMT.
4. Carry disease-causing biallelic LCA5 gene mutations determined by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory (historic testing up to 15 years from date of consent can be considered).
5. Visual acuity: BCVA \< 20/80 on the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity chart (modified for low vision participants) in the eye to be treated
6. Show evidence of detectable photoreceptors by Spectral Domain Optical Coherence Tomography (SD-OCT)
7. Participant is a good candidate for surgery per investigator judgement
8. Participant agrees to follow direction of investigator regarding restrictions post-surgery (Part A only).

Exclusion Criteria:

1. Women who are pregnant or individuals (women of childbearing potential and men) unwilling to use effective contraception for the duration of the study, including barrier methods for the first year after investigational product (IP) administration (Part A only).
2. Pre-existing eye conditions or complicating systemic diseases that would preclude the planned surgery. This includes individuals who are immunocompromised.
3. History of intraocular surgery for either eye within 6 months prior to planned IP administration (Part A only).
4. Have previously received gene therapy.
5. Have used any investigational drug or device within 90 days or 5 estimated half-lives of treatment, whichever is longer or plan to participate in another study of drug or device during the study period.
6. History of disease which may preclude the participant from participation, or which may interfere with outcome measure testing or test results.
7. Incapable of performing visual function testing (e.g., FST testing) for reasons other than poor vision.
8. Any absolute contraindication to a course of oral steroids.
9. Any other condition that would not allow the potential participant to complete follow-up examinations during the study and, in the opinion of the Investigator, makes the potential participant unsuitable for the study.

Where this trial is running

Philadelphia, Pennsylvania and 1 other locations

• University of Pennsylvania Perelman School of Medicine — Philadelphia, Pennsylvania, United States (Recruiting)
• Retina Foundation of the Southwest — Dallas, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Tomas Aleman, M.D.

Conditions LCA5; LCA; Retinal Degeneration; IRD; adeno associated virus; gene therapy