Clinical trial NCT05616793: Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: LCA5
Keywords: LCA
Retinal Degeneration
IRD
adeno associated virus
gene therapy
LCA5
Lead sponsor: Opus Genetics, Inc
Sponsor class: INDUSTRY
Collaborators: name: University of Pennsylvania
First posted: 2022-11-15
Enrollment: 15
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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. Funding Source- FDA Office of Orphan Products Development (OOPD).

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities
timeFrame: 1 year
measure: Number of adverse events related to OPGx-001
timeFrame: 1 year
measure: Number of procedure-related adverse events
timeFrame: 1 year
measure: Change in retinal thickness
timeFrame: 1 year
Secondary outcomes:
measure: Change from baseline to month 12 in retinal sensitivity
timeFrame: 1 year
measure: Change from baseline to month 12 in best corrected visual acuity (BCVA)
timeFrame: 1 year
measure: Change from baseline to month 12 in oculomotor control and fixation stability
timeFrame: 1 year
measure: Change from baseline to month 12 transient pupillary light reflexes (TPLR)
timeFrame: 1 year
measure: Change from baseline to month 12 in visual functioning questionnaire
timeFrame: 1 year
measure: Mesopic, low-contrast visual acuity (MLCVA)
timeFrame: 1 year
Other outcomes:
measure: Microperimetry
timeFrame: 1 year
measure: Kinetic perimetry
timeFrame: 1 year
measure: Virtual Reality Orientation and Mobility Test (VR-O&M)
timeFrame: 1 year
measure: Frequency doubling technology (FDT) perimetry (sFDT-CA)
timeFrame: 1 year
measure: Light-adapted transient pupillary light reflex (LA-TPLR)
timeFrame: 1 year
measure: Sweep visual evoked potentials (sVEPs)
timeFrame: 1 year
measure: Chromatic referential looking
timeFrame: 1 year
measure: Full-field chromatic sensitivity testing (FST)
timeFrame: 1 year
measure: Portable chromatic pupillometry Portable chromatic pupillometry
timeFrame: 1 year
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania Perelman School of Medicine
state: Pennsylvania
Study officials:
References: