Efficacy & Safety Study of Bilateral IVT Injection of GS010 in LHON Subjects Due to the ND4 Mutation for up to 1 Year (REFLECT)

March 27, 2026 updated by: GenSight Biologics

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 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
98

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Expanded Access

Expanded Access

A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved by the U.S. Food and Drug Administration (FDA). Also called compassionate use. There are different expanded access types.
No longer available

No longer available

  • Available: Expanded access is currently available for this investigational treatment, and patients who are not participants in the clinical study may be able to gain access to the drug, biologic, or medical device being studied.
  • No longer available: Expanded access was available for this intervention previously but is not currently available and will not be available in the future.
  • Temporarily not available: Expanded access is not currently available for this intervention but is expected to be available in the future.
  • Approved for marketing: The intervention has been approved by the U.S. Food and Drug Administration for use by the public.
 outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Ghent, Belgium, 9000
        • Universitair Ziekenhuis Gent
  • France
    • Paris
      • Paris, Paris, France, 75012
        • CHNO Les Quinze Vingts
  • Italy
      • Bologna, Italy, 40139
        • IRCCS Istituto delle Scienze Neurologiche di Bologna (ISNB) Clinica Neurologica
  • Spain
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
  • Taiwan
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital
  • United Kingdom
    • Greater London
      • London, Greater London, United Kingdom, EC1V 2PD
        • Moorfields Eye Hospital
  • United States
    • California
      • Pasadena, California, United States, 91105
        • Doheny Eye Center UCLA Pasadena
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Health Eye Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory Healthcare - The Emory Clinic
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts Eye and Ear Infirmary
    • New York
      • New York, New York, United States, 10029
        • Department of Ophthalmology, Icahn School of Medicine at Mount Sinai
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Departments of Neurology and Ophthalmology, Wills Eye Hospital and Thomas Jefferson University
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Eye Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

15 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: GS010-GS010

Patients received single IVT injection of GS010 in both their first-affected eye and their second-affected/not-yet-affected eye at a droplet digital polymerase chain reaction (ddPCR) dose of 1.2/1.3E11 vg in 90 μL for each eye.

Treatment could be performed either on a single day (1 IVT injection in each eye on Day 0) or on 2 consecutive days (1st IVT injection on Day -1 and 2nd IVT injection on Day 0).
Genetic: GS010
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 Comparator: GS010-Placebo

Patients received single IVT injection of GS010 in their first-affected eye and placebo IVT injection in their second-affected/not-yet-affected eye.

Patients received IVT lenadogene nolparvovec in their first-affected eye (ddPCR dose of 1.2/1.3E11 vg in a volume of 90 μL) and placebo IVT injection (volume of 90 μL) in their second-affected/not-yet-affected eye.

Treatment could be performed either on a single day (1 IVT injection in each eye on Day 0) or on 2 consecutive days (1st IVT injection on Day -1 and 2nd IVT injection on Day 0).
Genetic: GS010
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
Drug: Placebo
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
at 1.5 years post-treatment, in the second-affected/not-yet affected eyes

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
at 5 years post-treatment, in the second-affected/not-yet affected eyes
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
From baseline to 5 years post-treatment
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
From nadir to 5 years post-treatment
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
From nadir to 5 years post-treatment
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.
From baseline nadir to 5 years post-treatment
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.
From baseline to 5 years post-treatment

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Adverse events (AEs) and serious adverse events (SAEs)
Time Frame: up to 2-Years post baseline treatment
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.
up to 2-Years post baseline treatment
Physical examinations
Time Frame: At 2-Years post baseline treatment
Results of physical examinations
At 2-Years post baseline treatment
Electrocardiograms
Time Frame: At 2-Years post baseline treatment
Results of Electrocardiograms (ECGs)
At 2-Years post baseline treatment
Laboratory results
Time Frame: At 2-Years post baseline treatment
Results of laboratory tests from blood collection
At 2-Years post baseline treatment
Immune response evaluations
Time Frame: Up to 2-Years post baseline treatment

Results of immune response evaluations

  1. Time course of the humoral immune response measured with Neutralizing Antibodies (Nab) against Adeno-associated virus vector 2 (AAV2)
  2. Time course of the cellular immune response against AAV2
Up to 2-Years post baseline treatment
Blood Bio-dissemination of AAV2 Vector DNA
Time Frame: up to 4 weeks post-treatment
Results of bio-dissemination testing up to 4-weeks post-treatment
up to 4 weeks post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GenSight Biologics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Nancy Newman, MD, Emory University Hospital Atlanta, Georgia, United States, 30322
  • Principal Investigator: Patrick Yu-Wai-Man, PhD, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, CB2 0PY, United Kingdom

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 12, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 23, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 23, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 19, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 21, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 26, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 16, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 27, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GS-LHON-CLIN-05
  • 2017-002187-40 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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