Efficacy & Safety Study of Bilateral IVT Injection of GS010 in LHON Subjects Due to the ND4 Mutation for up to 1 Year
- Conditions
- Leber Hereditary Optic Neuropathy
- Interventions
- Genetic: GS010Drug: Placebo
- Registration Number
- NCT03293524
- Lead Sponsor
- GenSight Biologics
- Brief Summary
The goal of this clinical trial is to assess the safety and efficacy of GS010, a gene therapy, in improving the retina functional \& structural outcomes in subjects with LHON due to the G11778A ND4 mitochondrial mutation when vision loss duration is present up to one year.
- Detailed Description
GS-LHON-CLIN-05 is a Phase III, global, multi-center randomized, double-masked for the primary analysis, placebo-controlled, clinical study. As LHON is a neurodegenerative disease, the goal is to administer GS010 as soon as possible upon confirmation of the LHON diagnosis and the causative mutation.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 90
- Vision loss duration of ≤ 365 days (i.e. ≤ 1 year) in each affected eye at Inclusion Visit (Visit 2).
- Each eye of the subject must maintain at least Hand Motion (HM) visual acuity, as defined by the study's SOP for visual acuity testing.
- Documented results of genotyping showing the presence of the G11778A mutation in the ND4 gene and the absence of the other primary LHON-associated mutations (ND1 or ND6) in the subject's mitochondrial DNA.
Main
- Light Perception (LP) or No Light Perception (NLP) visual acuity in any eye, as defined by the study's standard operating procedure (SOP) for visual acuity testing.
- Presence of active infectious conjunctivitis, keratitis, scleritis or endophthalmitis in either eye.
- Presence of alcoholism, alcohol dependence, or alcohol or drug abuse (excluding nicotine).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Arm 1 GS010 Subjects will be randomized to treatment arm 1 or treatment arm 2 in a 1:1 allocation. Subjects in treatment arm 1 will receive intravitreal GS010 in both eyes. Treatment Arm 2 Placebo Subjects will be randomized to treatment arm 1 or treatment arm 2 in a 1:1 allocation. Subjects in treatment arm 2 will receive GS010 in one eye and placebo intravitreal injection in the other eye. Treatment Arm 2 GS010 Subjects will be randomized to treatment arm 1 or treatment arm 2 in a 1:1 allocation. Subjects in treatment arm 2 will receive GS010 in one eye and placebo intravitreal injection in the other eye.
- Primary Outcome Measures
Name Time Method Best-Corrected Visual Acuity (BCVA) reported using Log of the Minimal Angle of Resolution (LogMAR) - 1 year at 1.5 Year post baseline treatment The primary efficacy endpoint will be the change from baseline (Visit 2) BCVA reported with LogMAR at 1.5 years post-treatment in second affected/not yet affected eyes of ND4 LHON subjects with vision loss up to one year. The change from baseline (Visit 2) in second affected/not yet affected eyes receiving GS010 and placebo will be the primary response of interest. LogMAR BCVA will be used to represent BCVA.
- Secondary Outcome Measures
Name Time Method Best-Corrected Visual Acuity (BCVA) reported with LogMAR - 2 years at 1.5-Year and 2-Years post baseline treatment Change from baseline in LogMAR BCVA at each timepoint of the follow-up period and at 2 years post-treatment.
Spectral-Domain - Optical Coherence Tomography (SD-OCT) parameter at 1.5-Year and 2-Years post baseline treatment Parameters measured with SD-OCT over time and at 1.5 and 2-years post baseline treatment. The change from baseline will be the response. Analysis will be performed mainly for second affected/not yet affected eyes treated with GS010 versus placebo and also for first affected eyes receiving GS010 as well
Humphrey Visual Field (HVF) parameter at 1.5-Year and 2-Years post baseline treatment Parameters measured with HVF 30-2 over time and at 1.5 and 2-years post baseline treatment. The change from baseline will be the response. Analysis will be performed mainly for second affected/not yet affected eyes treated with GS010 versus placebo and also for first affected eyes receiving GS010 as well
Pelli Robson Low Vision Contrast Sensitivity parameter at 1.5-Year and 2-Years post baseline treatment Parameters measured with Pelli Robson Low Vision Contrast Sensitivity over time and at 1.5 and 2-years post baseline treatment. The change from baseline will be the response. Analysis will be performed mainly for second affected/not yet affected eyes treated with GS010 versus placebo and also for first affected eyes receiving GS010 as well
Quality of Life: Visual Functioning Questionnaire-25 at 1.5-Year and 2-Years post baseline treatment Visual Functioning Questionnaire-25 at 1.5 and 2-years post-treatment
Responder Analysis at 1.5-Year and 2-Years post baseline treatment Response status at each timepoint of the follow-up period and at 2 years post-treatment. Definitions of responder eyes include:
1. Eyes whose LogMAR BCVA improves (i.e. decreases) by ≥ 0.3 LogMAR (equivalent to a gain of ≥ 15 ETDRS letters) compared to baseline.
2. Eyes whose LogMAR BCVA does not increase (i.e. worsen) by ≥ 0.3 LogMAR (equivalent to eyes that lose ≤ 15 ETDRS letters) compared to baseline.
3. Eyes whose LogMAR visual acuity is \< 1.0 (i.e. better than LogMAR 1.0, equivalent to better than Snellen acuity of 20/200).Quality of Life: 36-Item Short Form Health Survey, version 2 Questionnaire at 1.5-Year and 2-Years post baseline treatment 36-Item Short Form Health Survey, version 2 Questionnaire at 1 and 2-years post-treatment.
Trial Locations
- Locations (13)
Massachusetts Eye and Ear Infirmary
🇺🇸Boston, Massachusetts, United States
University of Colorado Health Eye Center
🇺🇸Aurora, Colorado, United States
CHNO Les Quinze Vingts
🇫🇷Paris, France
Doheny Eye Center UCLA Pasadena
🇺🇸Pasadena, California, United States
Emory Healthcare - The Emory Clinic
🇺🇸Atlanta, Georgia, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Wills Eye Institute - Ocular Oncology Service
🇺🇸Philadelphia, Pennsylvania, United States
Vanderbilt Eye Institute
🇺🇸Nashville, Tennessee, United States
Moorfields Eye Hospital
🇬🇧London, Greater London, United Kingdom
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
IRCCS Istituto delle Scienze Neurologiche di Bologna UOC Clinica Neurologica
🇮🇹Bologna, Italy
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium