LCA5
Conditions
Keywords
LCA, Retinal Degeneration, IRD, adeno associated virus, gene therapy, LCA5
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).
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.
Interventions
BIOLOGICALAAV8.hLCA5
Adeno-associated virus vector expressing human LCA5 gene
Sponsors
Opus Genetics, Inc
University of Pennsylvania
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
4 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of cross-sectional spectral domain optical coherence tomography images | 2 years | Qualitative Assessment of SD-OCT image |
| Assessment of Natural course of LCA5-IRD | 6 months | Change from baseline in MLoMT |
| Incidence of Dose Limiting Toxicities | 2 years | Number of DLT events |
| Number of adverse events related to OPGx-001 | 2 years | Number of AEs related to IP |
| Incidence of adverse events related to OPGx-001 | 2 years | Incidence of AEs related to IP |
| Severity of adverse events related to OPGx-001 | 2 years | Severity of AEs related to IP |
| Number of procedure-related adverse events | 2 years | Number of AEs related to IP administration |
| Incidence of procedure-related adverse events | 2 years | Incidence of AEs related to IP administration |
| Severity of procedure-related adverse events | 2 years | Severity of AEs related to IP administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline over time in Dark-adapted full-field sensitivity testing | 2 years | FST |
| Change from baseline over time in visual functioning questionnaire | 1 year | Assessed by the Modified National Eye Institute Visual Functioning Questionnaire |
| Change from baseline over time in Multi-luminance Orientation and Mobility Test | 2 years | Number of objects identified |
| Change from baseline over time in best corrected visual acuity (BCVA) | 2 years | Measured using LogMAR scale |
Countries
United States
Contacts
CONTACTTomas Aleman, M.D.
CONTACTMariejel Weber
Outcome results
None listed