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

Sponsor

Opus Genetics, Inc (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05616793

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
LCA5	Biological: AAV8.hLCA5	Phase 1/Phase 2

Detailed Description

This is a non-randomized, open-label, phase 1/2 dose-escalation study evaluating two 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 Design

Study Type:

Interventional

Anticipated Enrollment :

9 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Anticipated Study Start Date :

Jan 31, 2023

Anticipated Primary Completion Date :

Aug 30, 2024

Anticipated Study Completion Date :

Sep 30, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Group 1 Single, unilateral subretinal administration of a low dose of OPGx-001 to adult participants at least 18 years of age	Biological: AAV8.hLCA5 Adeno-associated virus vector expressing human LCA5 gene
Experimental: Dose Group 2 Single, unilateral subretinal administration of an intermediate dose of OPGx-001 to adult participants at least 18 years of age	Biological: AAV8.hLCA5 Adeno-associated virus vector expressing human LCA5 gene
Experimental: Dose Group 3 Single, unilateral subretinal administration of a high dose of OPGx-001 to adult participants at least 18 years of age	Biological: AAV8.hLCA5 Adeno-associated virus vector expressing human LCA5 gene

Arm

Intervention/Treatment

Experimental: Dose Group 1

Single, unilateral subretinal administration of a low dose of OPGx-001 to adult participants at least 18 years of age

Biological: AAV8.hLCA5

Adeno-associated virus vector expressing human LCA5 gene

Experimental: Dose Group 2

Single, unilateral subretinal administration of an intermediate dose of OPGx-001 to adult participants at least 18 years of age

Biological: AAV8.hLCA5

Adeno-associated virus vector expressing human LCA5 gene

Experimental: Dose Group 3

Single, unilateral subretinal administration of a high dose of OPGx-001 to adult participants at least 18 years of age

Biological: AAV8.hLCA5

Adeno-associated virus vector expressing human LCA5 gene

Outcome Measures

Primary Outcome Measures

Incidence of dose limiting toxicities [1 year]
Number of adverse events related to OPGx-001 [1 year]
Number of procedure-related adverse events [1 year]
Change in retinal thickness (as measured by OCT) [1 year]
Changes from baseline in total retinal thickness and outer retinal thickness (in microns)

Secondary Outcome Measures

Change from baseline to month 12 in retinal sensitivity as measured by full-field stimulus testing (FST) [1 year]
Change from baseline to month 12 in best corrected visual acuity (BCVA) [1 year]
Change from baseline to month 12 in oculomotor control and fixation stability [1 year]
Change from baseline to month 12 in dark-adapted transient pupillary light reflexes (TPLR) [1 year]
Change from baseline to month 12 in visual functioning questionnaire [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Are willing and able to provide written informed consent (ICF) and, where appropriate, willing to sign an assent prior to any study procedures.
Are willing to adhere to the clinical protocol and able to perform testing procedures.
Participants must be at least 18 years of age at consent.
Carry disease-causing biallelic LCA5 gene mutations determined by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory.
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
Show evidence of detectable photoreceptors by Spectral Domain Optical Coherence Tomography (SD-OCT)
Participant is a good candidate for surgery per investigator judgement
Participant agrees to follow direction of investigator regarding restrictions post-surgery.

Exclusion Criteria:

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.
Pre-existing eye conditions or complicating systemic diseases that would preclude the planned surgery. This includes individuals who are immunocompromised.
History of intraocular surgery for either eye within 6 months prior to planned IP administration.
Have previously received gene therapy.
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.
History of disease which may preclude the participant from participation, or which may interfere with outcome measure testing or test results.
Incapable of performing visual function testing (e.g., FST testing) for reasons other than poor vision.
Any absolute contraindication to a course of oral steroids.
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.