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Report for Clinical Trial NCT03293524

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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

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.

NCT03293524 Leber Hereditary Optic Neuropathy
MeSH:Optic Nerve Diseases Optic Atrophy, Hereditary, Optic Atrophy, Hereditary, Leber
HPO:Leber optic atrophy

2 Interventions

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: Genetic
Group Labels: 2

Treatment 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: Drug
Group Labels: 1

Treatment Arm 2


Primary Outcomes

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 treatment

Secondary Outcomes

Description: 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 treatment

Description: 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 treatment

Description: 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 treatment

Description: 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 treatment

Description: 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 treatment

Description: 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 treatment

Description: 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 treatment

Other Outcomes

Description: 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 treatment

Description: Results of physical examinations

Measure: Physical examinations

Time: At 2-Years post baseline treatment

Description: Results of Electrocardiograms (ECGs)

Measure: Electrocardiograms

Time: At 2-Years post baseline treatment

Description: Results of laboratory tests from blood collection

Measure: Laboratory results

Time: At 2-Years post baseline treatment

Description: 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 treatment

Description: 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-treatment

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 G11778A

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 ---



HPO Nodes


HPO: