RESCUE and REVERSE Long-term Follow-up (RESTORE)

February 27, 2026 updated by: GenSight Biologics

Long-term Follow-up of ND4 LHON Subjects Treated With GS010 Ocular Gene Therapy in the RESCUE or REVERSE Phase III Clinical Trials (RESTORE)

The goal of this clinical trial is to assess the long-term safety and efficacy of GS010, a gene therapy, and assess the quality of life in subjects with LHON due to the G11778A ND4 mitochondrial mutation and who were treated in the Rescue or Reverse studies.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Seven investigational centers from the RESCUE and REVERSE studies also participated in the RESTORE study, located in the European union and in the USA.

Primary objectives: to assess the long term safety of intravitreal injection up to 5 years of post treatment in subjects who were treated in the RESCUE or REVERSE studies.

Secondary objectives: (1) to assess the long-term efficacy of intravitreal GS010 administration up to 5 years post-treatment in subjects who were treated in the RESCUE or REVERSE studies; and (2) to assess the quality of life (QoL) in subjects who were treated with GS010 in the RESCUE or REVERSE studies for up to 5 years post-treatment.

Methodology: This was a Phase III prospective long-term follow-up (LTFU) clinical study of subjects previously treated with GS010 and Sham during 2 Phase III studies-RESCUE and REVERSE. The LTFU study followed subjects for an additional 3 years, for a total of 5 years post-injection. The LTFU study included 5 visits at 2, 2.5, 3, 4, and 5 years after the investigational medicinal product (IMP) injection. Safety, efficacy, and QoL variables were assessed during each of the 5 LTFU visits, and descriptive summaries and statistical testing were used for the analysis of the data.

This report presents the final analysis of results at Year 5 after treatment administration in RESCUE and REVERSE.

Number of analysed subjects: all subjects completing RECUE and REVERSE studies who provided consent for the RESTORE study: 62 subjects.

Study Type

Interventional

Enrollment (Actual)

62

Phase

  • Phase 3

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

  • France
      • Paris, France, 75012
        • CHNO Les Quinze Vingts
  • Germany
      • Munich, Germany, 80336
        • LMU Klinikum der Universität München / Friedrich-Baur-Institut
  • Italy
      • Bologna, Italy, 40139
        • Ospedale Bellaria
  • 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
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Wills 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

Ages Eligible for Study

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

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • Subject was treated with GS010 IVT injection in either of the RESCUE or REVERSE Phase III clinical studies
  • Subject of legal consent age has provided informed consent; subjects that are not of legal consent age have undergone their country-approved clinical trial enrollment consent process

Exclusion Criteria

  • Subject is unwilling or unable to comply with the protocol requirements
  • Subject has any medical or psychological condition that, in the opinion of the Investigator, may compromise his or her safe participation in the study
  • Subject is taking or intending to take idebenone during the long-term follow-up study period

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GS010-treated Eyes
Lenadogene nolparvovec Intravitreal ocular unilateral Injection Each participant will have one eye randomly selected to receive a single injection of GS010 and the other eye will receive a sham injection. GS010-treated Eyes: GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). Participants will receive a single dose of GS010 in one of their randomly selected eyes, via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) plus 0.001% Pluronic F68®.
Genetic: GS010
Lenadogene nolparvovec Intravitreal ocular unilateral Injection
Other Names:
  • Lenadogene Nolparvovec
Sham Comparator: Sham-treated Eyes
Sham Intravitreal ocular unilateral Injection Each participant will have one eye randomly selected to receive GS010 and the other eye will receive a sham injection. Eyes receiving sham injection will undergo the same preparatory procedures as eyes receiving GS010 injection, including pupillary dilation, topical anti-infection and topical anesthetic procedures. Sham intravitreal injection will be performed by applying pressure to the eye at the location of a typical intravitreal injection procedure using the blunt end of a syringe without a needle.
Other: Sham Intravitreal Injection
Lenadogene nolparvovec Intravitreal ocular unilateral Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ocular Adverse Events (AEs)
Time Frame: from year 2 to year 5 post treatment
Number of Eyes with Ocular Adverse events related to study treatment or study procedures as judged by the investigator reported from year 2 to year 5 post treatment
from year 2 to year 5 post treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Visual Acuity
Time Frame: Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment

Change from Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment, expressed in LogMAR.

On chart visual acuity: Visual acuity inferior or equal to LogMAR +1.6 Off chart visual acuity: Visual acuity superior to LogMar +1.7

Normal vision LogMar: 0 and less than 0
Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment
Responder Analysis: Clinically Relevant Recovery
Time Frame: Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment

CRR clinically relevant recovery from Nadir defined as i/ for eyes on chart at Nadir, an improvement of at least -0.2 LogMar from Nadir and ii/ for eyes off chart at Nadir eyes that became on chart.

Off chart visual acuity expressed in LogMar: more than +1.7 On chart visual acuity expressed in LogMar: less than 1.6 Normal vision LogMar: 0 and less than 0
Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Eyes on Chart
Time Frame: Year 5 post-treatment
Definition: Visual acuity inferior or equal to LogMAR +1.6 at 5 Years post treatment
Year 5 post-treatment

Collaborators and Investigators

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

Sponsor

GenSight Biologics

Investigators

  • Principal Investigator: Nancy Newman, MD, Emory University Hospital Atlanta, Georgia, United States, 30322

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

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)

January 9, 2018

Primary Completion (Actual)

July 4, 2022

Study Completion (Actual)

July 4, 2022

Study Registration Dates

First Submitted

January 15, 2018

First Submitted That Met QC Criteria

January 15, 2018

First Posted (Actual)

January 23, 2018

Study Record Updates

Last Update Posted (Actual)

March 2, 2026

Last Update Submitted That Met QC Criteria

February 27, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-LHON-CLIN-06
  • 2017-002153-11 (EudraCT Number)
  • NCT02652767 RESCUE (Other Identifier: clin.trial.gov)
  • NCT02652780 REVERSE (Other Identifier: clin.trial.gov)

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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