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NCT Number: NCT03293524

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 efficacy and safety of GS010 gene therapy - (lenadogene nolparvovec) in subjects with LHON due to the G11778A ND4 mitochondrial mutation with a vision loss up to one year.

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Key information

Conditions

Leber Hereditary Optic Neuropathy Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cranial Nerve Diseases Eye Diseases Eye Diseases, Hereditary Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Metabolic Diseases Mitochondrial Diseases Nervous System Diseases Neurodegenerative Diseases Nutritional and Metabolic Diseases Optic Atrophies, Hereditary Optic Atrophy Optic Atrophy, Hereditary, Leber Optic Nerve Diseases

Age range

15 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Universitair Ziekenhuis Gent, Ghent, Belgium

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About this study

The REFLECT study is a Phase 3, international, multi-center, randomized, double-masked, placebo-controlled, clinical trial. The primary objective is to assess the efficacy of intravitreal (IVT) of GS010 compared to IVT of placebo in second-affected/not-yet-affected eyes at 1.5 years post-treatment, by analyzing the change from baseline of the visual acuity in ND4 LHON subjects with vision loss up to one year.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Main Selection Criteria:

  • Age 15 years or older on the date of signed informed consent.
  • Clinically manifested vision loss due to ND4 LHON, to any extent, in at least one eye.
  • Vision loss duration of ≤ 365 days (i.e. ≤ 1 year) in each affected eye at Inclusion Visit (Visit 2).

Main Non-Selection Criteria:

  • Contraindication to intravitreal injection in any eye.
  • Subjects refusing to discontinue idebenone.
  • Previous vitrectomy in either eye.
  • Narrow angle in any eye contra-indicating pupillary dilation.
  • 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.
  • History of recurrent uveitis (idiopathic or immune-related) or active ocular inflammation.

Main Inclusion Criteria:

  • 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 Exclusion Criteria:

  • 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).

Treatment and study plan

GS010

Genetic

GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). GS010 was administrated via intravitreal injection containing 1.2/1.3E11 vg in 90 μL balanced sterile saline solution (BSSS).

Other names: Lenadogene nolparvovec

Placebo

Drug

The placebo is a balanced sterile saline solution (BSSS) used for IVT. The placebo was administered via intravitreal injection in a volume of 90 μL.

Primary outcomes

  1. Change From Baseline of the Best Corrected Visual Acuity (BCVA) Reported With Log of the Minimal Angle of Resolution (LogMAR) at 1.5 Years Post-treatment, in the Second Affected/Not-yet Affected Eyes

    Time frame: at 1.5 years post-treatment, in the second-affected/not-yet affected eyes

    The primary efficacy endpoint was the change from baseline of BCVA reported with LogMAR at 1.5-year post-treatment, in the second-affected/not-yet-affected eyes of ND4 LHON patients with vision loss up to one year. LogMAR BCVA was used to represent BCVA.

Secondary outcomes

  1. Change From Baseline of the BCVA Reported With LogMAR at 5 Years Post-treatment, in the Second Affected/Not-yet Affected Eyes

    Time frame: at 5 years post-treatment, in the second-affected/not-yet affected eyes

    Change from baseline of BCVA reported with LogMAR at 5 years post-treatment, in the second-affected/not-yet-affected eyes of ND4 LHON patients with vision loss up to one year. LogMAR BCVA was used to represent BCVA.

  2. Proportion of Patients Who Switched From Off-chart Eyes to On-chart Eyes at 5 Years Post-treatment

    Time frame: From baseline to 5 years post-treatment

    Proportion of patients with both eyes off-chart, defined as those patients unable to read letter on the ETDRS chart, who had at least one eye on-chart, defined as those patients able to read letters on the ETDRS chart (at either 4 meters or 1 meter) at 5 years

  3. Responder Analyses - Improvements From Nadir (Gainer Eyes) at 5 Years

    Time frame: From nadir to 5 years post-treatment

    Proportion of patients with an improvement of at least -0.3 LogMAR (≥ +15 ETDRS letters) from nadir to year 5 in at least one eye. Nadir was defined for each eye of each subject as the worst value observed from baseline to year 5

  4. Responder Analyses - Clinically Relevant Recovery From Nadir at 5 Years

    Time frame: From nadir to 5 years post-treatment

    Proportion of patients with clinically relevant recovery (CRR) from nadir that was defined as patient with a CRR in at least one eye - Patient with at least one eye which was on chart at nadir, and which had an improvement of at least -0.2 LogMAR from nadir, or which was off-chart at nadir but became on-chart

  5. Responder Analyses- Clinically Relevant Benefit at 5 Years

    Time frame: From baseline nadir to 5 years post-treatment

    Proportion of patients who had clinically relevant stabilization (CRS), defined as eyes with LogMAR BCVA < 1 at baseline and at 5 years post-treatment or had a clinically relevant recovery (CRR) from nadir. The best response observed in either eye was considered.

  6. Quality of Life Questionnaire: VFQ-25 - Composite Score

    Time frame: From baseline to 5 years post-treatment

    Change from baseline to 5 years follow up in the Visual Function Questionnaire (VFQ-25) composite score. The VFQ-25 is a patient-reported outcome instrument assessing vision-related quality of life and consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs plus an additional single-item general health rating question. Each item was converted to a 0-100 scale for scoring, where 100 represents the best possible score on the measure and 0 represents the worst. Items within each subscale were averaged to create 12 subscale scores (11 subscales related to vision + 1 subscale related to general health). The vision-related subscale scores (excluding the general health rating question) were then averaged to calculate the composite score.

Sponsors and collaborators

Lead sponsor

GenSight Biologics

Industry

Registry information

Official study title

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

Acronym: REFLECT

Important dates

Study start
2018
Primary completion
2024
Study completion
2024
First posted
Sep 26, 2017
Registry last updated
Apr 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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