Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD)

Phase 1

Recruiting

• Conditions: LCA5
• Interventions: Biological: AAV8.hLCA5

• Registration Number: NCT05616793
• Lead Sponsor: Opus Genetics, Inc

Brief Summary

The goal of this clinical trial is to evaluate the safety and preliminary efficacy of subretinal gene therapy with OPGx-001 in patients with inherited retinal degeneration due to biallelic mutations in the LCA5 gene.

Detailed Description

This is a non-randomized, open-label, phase 1/2 dose-escalation study evaluating three doses of OPGx-001 for the treatment of LCA5-IRD.

Enrollment will begin with a low-dose of OPGx-001 delivered via single, unilateral subretinal injection (Cohort 1) and proceed to an intermediate dose (Cohort 2) and subsequent high dose (Cohort 3). Escalation to each next cohort will proceed only after review of all data and upon recommendation by an independent data monitoring committee (IDMC).

Study Timeline

• Study First Submitted: 2022-11-07
• Study First Submitted QC: 2022-11-07
• Study First Posted: 2022-11-15
• Study Start: 2023-06-15
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-26
• Last Update Posted: 2024-07-01
• Primary Completion: 2024-12-30
• Study Completion: 2028-01-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 15

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. Participants must be at least 13 years of age at consent.
4. Carry disease-causing biallelic LCA5 gene mutations determined by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory.
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.

Exclusion Criteria

1. Individuals of childbearing potential (male and female) who are pregnant or unwilling to use effective contraception for the duration of the study, including barrier methods for the first year after investigational product (IP) administration.
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.
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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Group 1	AAV8.hLCA5	A single, unilateral, subretinal injection of low dose (1E10 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of a low dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents).
Dose Group 2	AAV8.hLCA5	A single, unilateral, subretinal injection of an intermediate dose (3E10 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of an intermediate dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents).
Dose Group 3	AAV8.hLCA5	A single, unilateral, subretinal injection of high dose (1E11 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of a high dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents).

Primary Outcome Measures

Name	Time	Method
Number of procedure-related adverse events	1 year
Incidence of Dose Limiting Toxicities	1 year
Number of adverse events related to OPGx-001	1 year
Change in retinal thickness	1 year	Measured by OCT; changes from baseline in total retinal thickness and outer retinal thickness (in microns)

Secondary Outcome Measures

Name	Time	Method
Change from baseline to month 12 in retinal sensitivity	1 year	Measured by full-field stimulus testing (FST)
Change from baseline to month 12 in oculomotor control and fixation stability	1 year
Change from baseline to month 12 transient pupillary light reflexes (TPLR)	1 year	In dark-adapted subjects
Change from baseline to month 12 in best corrected visual acuity (BCVA)	1 year
Mesopic, low-contrast visual acuity (MLCVA)	1 year
Change from baseline to month 12 in visual functioning questionnaire	1 year

Trial Locations

Locations (1)

University of Pennsylvania Perelman School of Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States