Clinical Trial: Efficacy Study of GS010 for Treatment of Vision Loss From 7 Months to 1 Year From Onset in LHON Due to the ND4 Mutation

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Randomized, Double-Masked, Sham-Controlled Clinical Trial to Evaluate the Efficacy of a Single Intravitreal Injection of GS010 in Subjects Affected for More Than 6 Months and To 12 Months by LHON Due

Brief Summary: The goal of this clinical trial is to assess the effectiveness of GS010, a gene therapy, in improving the visual outcome in patients with LHON due to the G11778A ND4 mitochondrial mutation when vision loss is present for more than six months and up to one year.

Detailed Summary:
Sponsor: GenSight Biologics

Current Primary Outcome: ETDRS visual acuity, utilizing derived LogMAR acuity [ Time Frame: 48 weeks after GS010/sham injection ]

The primary endpoint will be the ETDRS visual acuity (quantitative score) at Week 48 after intravitreal injection. The subjects' LogMAR scores, which are derived from the number of letters they read on the ETDRS chart, will be used for statistical analysis purposes. The change from baseline in each eye will be the primary response of interest.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • ETDRS visual acuity, utilizing derived LogMAR acuity [ Time Frame: 96 weeks after GS010/sham injection ]
    ETDRS visual acuity (quantitative score) over the follow-up period and at Week 96 after intravitreal injection. Change from baseline of the LogMAR scores will be used for statistical analysis purposes.
  • Responder Analysis: Improvement from Baseline by 15 ETDRS letters or having Visual Acuity >20/200 at 48 and 96 weeks [ Time Frame: 48 and 96 weeks after GS010/sham injection ]
    Response status to treatment at Week 48 and 96 after intravitreal injection will be determined. Responder will be defined by an improvement of at least 15 letters in the visual acuity score obtained with ETDRS or being greater than a Snellen acuity equivalent of 20/200. The number of GS010-treated eyes that qualify as responders will be compared to the number of sham-treated eyes that qualify as responders.
  • High Resolution Spectral Domain Optical Coherence Tomography to measure the optic nerve retinal nerve fiber layer (RNFL) thickness and the thickness/volume of the retinal layers of the macula [ Time Frame: 48 and 96 weeks after GS010/sham injection ]
    Measure of parameters of high resolution SD-OCT of the posterior pole and optic nerve at Week 48 and Week 96.Total average and quadrant thickness of the RNFL will be evaluated. The various layers of the retina, including the retinal ganglion cell layer and inner plexiform layer, will be analyzed and the thickness/volume will be evaluated.
  • Humphrey Visual Field 30-2 [ Time Frame: 48 and 96 weeks after GS010/sham injection ]
    Measure of the standardized automated visual fields obtained with HVF Analyzer II. Mean Deviation (MD) in decibels of sensitivity will be used at Week 48 and Week 96.
  • Pelli-Robson Contrast Sensitivity [ Time Frame: 48 and 96 weeks after GS010/sham injection ]
    Measure of contrast sensitivity with the Pelli-Robson chart at Week 48 and Week 96.
  • Farnsworth-Munsell Color 100 Hue Vision Test [ Time Frame: 48 and 96 weeks after GS010/sham injection ]
    Measure of color vision with the Farnsworth-Munsell 100 Hue color vision test at Week 48 and Week 96.
  • Adverse Events and Serious Adverse Events [ Time Frame: Continuous over 96 week study period ]
    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.
  • Immune Responses [ Time Frame: 96 week study period ]

    Results of immune response evaluations:

    Time course of neutralizing antibodies against AAV2 vector and cellular immune response against AAV2 vector and ND4 protein.

  • Blood Bio-dissemination of AAV2 Vector DNA [ Time Frame: Two weeks post GS010 administration ]
    Blood bio-dissemination two weeks after injection of GS010. The presence of AAV2 vector DNA in the blood of subjects will be tested for and quantified utilizing quantitative PCR.


Original Secondary Outcome: Same as current

Information By: GenSight Biologics

Dates:
Date Received: January 7, 2016
Date Started: January 2016
Date Completion: January 2019
Last Updated: February 22, 2017
Last Verified: February 2017