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.
Name: GS010
Description: GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). GS010 will be administrated via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) as a single baseline intravitreal injection.Type: GeneticTreatment Arm 1 Treatment Arm 2
Name: Placebo
Description: The placebo is a BSS, sterile, apyrogenic solution and used for ocular surgery. The placebo will be administered via intravitreal injection in a volume of 90 μL.Type: DrugTreatment Arm 2
Description: The primary endpoint will be the BCVA reported with LogMAR at 1-Year post-treatment in second affected/not yet affected eyes. The change from baseline in second affected/not yet affected eyes receiving GS010 and placebo will be the primary response of interest. LogMAR BCVA will be used for statistical purposes.
Measure: Best-Corrected Visual Acuity (BCVA) reported using Log of the Minimal Angle of Resolution (LogMAR) - 1 year Time: at 1-Year post baseline treatmentDescription: LogMAR BCVA at each timepoint of the follow-up period and at 2-years post-treatment, for second affected/not yet affected eyes receiving GS010 versus placebo and also for first affected eyes receiving GS010. The change from baseline of the LogMAR BCVA will be used for statistical analyses.
Measure: Best-Corrected Visual Acuity (BCVA) reported with LogMAR - 2 years Time: at 2-Years post baseline treatmentDescription: Response status over time and at 1 and 2-years post baseline treatment. Response status will be assessed for second affected/not yet affected eyes receiving GS010 versus placebo and also for first affected eyes receiving GS010. Definitions of responder eyes include: Eyes whose LogMAR BCVA improves (i.e. decreases) by ≥ 0.3 LogMAR (equivalent to a gain of ≥ 15 ETDRS letters) compared to baseline. Eyes whose LogMAR BCVA does not increase (i.e. worsen) by ≥ 0.3 LogMAR (equivalent to eye that lose ≤ 15 ETDRS letters) compared to baseline. Eyes whose LogMAR visual acuity is < 1.0 (i.e. better than LogMAR 1.0, equivalent to better than Snellen acuity of 20/200).
Measure: Responder Analysis Time: at 1-Year and 2-Years post baseline treatmentDescription: Parameters measured with SD-OCT over time and at 1 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
Measure: Spectral-Domain - Optical Coherence Tomography (SD-OCT) parameter Time: at 1-Year and 2-Years post baseline treatmentDescription: Parameters measured with HVF 30-2 over time and at 1 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
Measure: Humphrey Visual Field (HVF) parameter Time: at 1-Year and 2-Years post baseline treatmentDescription: Parameters measured with Pelli Robson Low Vision Contrast Sensitivity over time and at 1 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
Measure: Pelli Robson Low Vision Contrast Sensitivity parameter Time: at 1-Year and 2-Years post baseline treatmentDescription: Visual Functioning Questionnaire-25 at 1 and 2-years post-treatment
Measure: Quality of Life: Visual Functioning Questionnaire-25 Time: at 1-Year and 2-Years post baseline treatmentDescription: 36-Item Short Form Health Survey, version 2 Questionnaire at 1 and 2-years post-treatment.
Measure: Quality of Life: 36-Item Short Form Health Survey, version 2 Questionnaire Time: at 1-Year and 2-Years post baseline treatmentDescription: Adverse events (AEs) and serious adverse events (SAEs), including those that are treatment-emergent and non-treatment-emergent, throughout the study period and at each study visit. Incidence and severity of systemic and local (ocular) AEs and SAEs will be determined at each clinical site and for the entire study cohort.
Measure: Adverse events (AEs) and serious adverse events (SAEs) Time: up to 2-Years post baseline treatmentDescription: Results of physical examinations
Measure: Physical examinations Time: At 2-Years post baseline treatmentDescription: Results of Electrocardiograms (ECGs)
Measure: Electrocardiograms Time: At 2-Years post baseline treatmentDescription: Results of laboratory tests from blood collection
Measure: Laboratory results Time: At 2-Years post baseline treatmentDescription: Results of immune response evaluations Time course of the humoral immune response measured with Neutralizing Antibodies (Nab) against Adeno-associated virus vector 2 (AAV2) Time course of the cellular immune response against AAV2
Measure: Immune response evaluations Time: Up to 2-Years post baseline treatmentDescription: Results of bio-dissemination testing up to 4-weeks post-treatment
Measure: Blood Bio-dissemination of AAV2 Vector DNA Time: up to 4 weeks post-treatmentAllocation: Randomized
Parallel Assignment
There is one SNP
Efficacy and Safety of Bilateral Intravitreal Injection of GS010: A Randomized, Double-Masked, Placebo-Controlled Trial in Subjects Affected With G11778A ND4 Leber Hereditary Optic Neuropathy for Up to One Year. --- G11778A ---
Efficacy & Safety Study of Bilateral IVT Injection of GS010 in LHON Subjects Due to the ND4 Mutation for up to 1 Year 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. --- G11778A ---
- Presence of known/documented mutations, other than the G11778A ND4 LHON-causing mutation, which are known to cause pathology of the optic nerve, retina or afferent visual system. --- G11778A ---
- 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. --- G11778A ---