Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) and Non-interventional Arm With Untreated Patients

Opus Genetics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: LCA5

Treatments: Biological: AAV8.hLCA5

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05616793

FD-R-008174 (Other Grant/Funding Number)

OPGx-LCA5-1001

Details and patient eligibility

About

The goals of this clinical trial are assess the natural course of LCA5-IRD over 6 months and 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. Funding Source- FDA Office of Orphan Products Development (OOPD).

Full description

This is a non-randomized, open-label, phase 1/2 dose-escalation study evaluating untreated patients for 6 months and with 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).

Concurrently, 16 untreated patients will be assessed for 6 months prior to treatment to study the natural course of LCA5-IRD.

Enrollment: 22 estimated patients

Sex: All

Ages: 4+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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22 participants in 4 patient groups

Dose Group 1

Experimental group

Description:

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).

Treatment:

Biological: AAV8.hLCA5

Dose Group 2

Experimental group

Description:

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).

Treatment:

Biological: AAV8.hLCA5

Dose Group 3

Experimental group

Description:

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).

Treatment:

Biological: AAV8.hLCA5

Part B Observational

No Intervention group

Description:

Part B will occur concurrently with Dose Groups 1-3. Sixteen patients will be assessed for 6 months to assess the natural course of LCA5-IRD, then will be treated with OPGx-001 which will be described in a future protocol amendment.