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

NCT05616793 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OPGx-LCA5-1001FD-R-008174
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

LCA5

Keywords

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

Outcome Measures

Primary Outcomes (15)

• 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 Outcomes (4)

• Change from baseline over time in Multi-luminance Orientation and Mobility Test

  2 years

• Change from baseline over time in Dark-adapted full-field sensitivity testing

  2 years

• Change from baseline over time in best corrected visual acuity (BCVA)

  2 years

• Change from baseline over time in visual functioning questionnaire

  1 year

Other Outcomes (9)

• Microperimetry

  1 year

• Kinetic perimetry

  1 year

• Virtual Reality Orientation and Mobility Test (VR-O&M)

  1 year

Study Arms (4)

Dose Group 1

EXPERIMENTAL

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

Dose Group 2

EXPERIMENTAL

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

Dose Group 3

EXPERIMENTAL

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

Part B Observational

NO INTERVENTION

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.

Interventions

AAV8.hLCA5 BIOLOGICAL

Adeno-associated virus vector expressing human LCA5 gene

Dose Group 1; Dose Group 2; Dose Group 3

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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).
• 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 (Part A only).

You may not qualify if:

• 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).
• 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 (Part A only).
• 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.

Sponsors & Collaborators

• Opus Genetics, Inc: lead
• University of Pennsylvania: collaborator

Study Sites (2)

University of Pennsylvania Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

RECRUITING

MeSH Terms

Conditions

Retinal Degeneration

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Central Study Contacts

Tomas Aleman, M.D.

CONTACT

1 (215) 662-6396; ct.gov_inquiries@opusgtx.com

Mariejel Weber

CONTACT

1 (215) 662-6396; mariejel.weber@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 Record Dates

• First Submitted: November 7, 2022
• First Posted: November 15, 2022
• Study Start: June 15, 2023
• Primary Completion (Estimated): June 15, 2028
• Study Completion (Estimated): June 15, 2028
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)