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

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

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).

Study Overview

• Status: Recruiting
• Conditions: LCA5
• Intervention / Treatment: Biological: AAV8.hLCA5

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Tomas Aleman, M.D.; Phone Number: 1 (215) 662-6396; Email: ct.gov_inquiries@opusgtx.com
• Study Contact Backup: Name: Mariejel Weber; Phone Number: 1 (215) 662-6396; Email: mariejel.weber@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania Perelman School of Medicine
      • Principal Investigator: Tomas Aleman, MD
      • Contact: Mariejel Weber; Phone Number: +12156626396; Email: mariejel.weber@pennmedicine.upenn.edu
  • Texas
    • Dallas, Texas, United States, 75231
      • Recruiting
      • Retina Foundation of the Southwest
      • Contact: Martin Klein; Phone Number: 214-363-3911; Email: mklein@retinafoundation.org
      • Principal Investigator: Mark Penessi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Group 1; 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).	Biological: AAV8.hLCA5; Adeno-associated virus vector expressing human LCA5 gene
Experimental: Dose Group 2; 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).	Biological: AAV8.hLCA5; Adeno-associated virus vector expressing human LCA5 gene
Experimental: Dose Group 3; 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).	Biological: AAV8.hLCA5; Adeno-associated virus vector expressing human LCA5 gene
No Intervention: Part B Observational; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose Limiting Toxicities	Number of DLT events	2 years
Number of adverse events related to OPGx-001	Number of AEs related to IP	2 years
Incidence of adverse events related to OPGx-001	Incidence of AEs related to IP	2 years
Severity of adverse events related to OPGx-001	Severity of AEs related to IP	2 years
Number of procedure-related adverse events	Number of AEs related to IP administration	2 years
Incidence of procedure-related adverse events	Incidence of AEs related to IP administration	2 years
Severity of procedure-related adverse events	Severity of AEs related to IP administration	2 years
Assessment of cross-sectional spectral domain optical coherence tomography images	Qualitative Assessment of SD-OCT image	2 years
Assessment of Natural course of LCA5-IRD	Change from baseline in MLoMT	6 months
Assessment of Natural course of LCA5-IRD	Change from baseline in FST	6 months
Assessment of Natural course of LCA5-IRD	Change from baseline in BCVA	6 months
Assessment of Natural course of LCA5-IRD	Change from baseline in FCP/Microperimetry	6 months
Assessment of Natural course of LCA5-IRD	Change from baseline in SD-OCT	6 months
Assessment of Natural course of LCA5-IRD	Change from baseline in pupillometry	6 months
Assessment of Natural course of LCA5-IRD	Number of adverse events	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline over time in Multi-luminance Orientation and Mobility Test	Number of objects identified	2 years
Change from baseline over time in Dark-adapted full-field sensitivity testing	FST	2 years
Change from baseline over time in best corrected visual acuity (BCVA)	Measured using LogMAR scale	2 years
Change from baseline over time in visual functioning questionnaire	Assessed by the Modified National Eye Institute Visual Functioning Questionnaire	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microperimetry	Mean sensitivity, in dB	1 year
Kinetic perimetry	Field extent, in degrees	1 year
Virtual Reality Orientation and Mobility Test (VR-O&M)	Performance over a range of light levels	1 year
Frequency doubling technology (FDT) perimetry (sFDT-CA)		1 year
Light-adapted transient pupillary light reflex (LA-TPLR)		1 year
Sweep visual evoked potentials (sVEPs)		1 year
Chromatic referential looking	In dark-adapted patients	1 year
Full-field chromatic sensitivity testing (FST)	In free view	1 year
Portable chromatic pupillometry Portable chromatic pupillometry		1 year

Collaborators and Investigators

• Sponsor: Opus Genetics, Inc
• Collaborators: University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2023
• Primary Completion (Estimated): June 15, 2028
• Study Completion (Estimated): June 15, 2028

Study Registration Dates

• First Submitted: November 7, 2022
• First Submitted That Met QC Criteria: November 7, 2022
• First Posted (Actual): November 15, 2022

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: gene therapy; Retinal Degeneration; LCA; IRD; adeno associated virus; LCA5
• Additional Relevant MeSH Terms: Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases; Retinal Degeneration
• Other Study ID Numbers: OPGx-LCA5-1001; FD-R-008174 (Other Grant/Funding Number: Funding Source- FDA Office of Orphan Product Development (OOPD) Grant)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No