RESCUE and REVERSE Long-term Follow-up

NCT ID: NCT03406104

Last Updated: 2025-09-09

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

62 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-09

Study Completion Date

2022-07-04

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Leber Hereditary Optic Neuropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

intra patient comparaison
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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®.

Group Type EXPERIMENTAL

GS010

Intervention Type GENETIC

Lenadogene nolparvovec Intravitreal ocular unilateral Injection

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.

Group Type SHAM_COMPARATOR

Sham Intravitreal Injection

Intervention Type OTHER

Lenadogene nolparvovec Intravitreal ocular unilateral Injection

Interventions

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GS010

Lenadogene nolparvovec Intravitreal ocular unilateral Injection

Intervention Type GENETIC

Sham Intravitreal Injection

Lenadogene nolparvovec Intravitreal ocular unilateral Injection

Intervention Type OTHER

Other Intervention Names

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Lenadogene Nolparvovec

Eligibility Criteria

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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
Minimum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GenSight Biologics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nancy Newman, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University Hospital Atlanta, Georgia, United States, 30322

Locations

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Doheny Eye Center UCLA

Pasadena, California, United States

Site Status

Emory University Hospital

Atlanta, Georgia, United States

Site Status

Wills Eye Institute

Philadelphia, Pennsylvania, United States

Site Status

CHNO Les Quinze Vingts

Paris, , France

Site Status

LMU Klinikum der Universität München / Friedrich-Baur-Institut

Munich, , Germany

Site Status

Ospedale Bellaria

Bologna, , Italy

Site Status

Moorfields Eye Hospital

London, Greater London, United Kingdom

Site Status

Countries

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United States France Germany Italy United Kingdom

References

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Yu-Wai-Man P, Newman NJ, Biousse V, Carelli V, Moster ML, Vignal-Clermont C, Klopstock T, Sadun AA, Sergott RC, Hage R, Degli Esposti S, La Morgia C, Priglinger C, Karanja R, Taiel M, Sahel JA; LHON Study Group. Five-Year Outcomes of Lenadogene Nolparvovec Gene Therapy in Leber Hereditary Optic Neuropathy. JAMA Ophthalmol. 2025 Feb 1;143(2):99-108. doi: 10.1001/jamaophthalmol.2024.5375.

Reference Type DERIVED
PMID: 39699886 (View on PubMed)

Carelli V, Newman NJ, Yu-Wai-Man P, Biousse V, Moster ML, Subramanian PS, Vignal-Clermont C, Wang AG, Donahue SP, Leroy BP, Sergott RC, Klopstock T, Sadun AA, Rebolleda Fernandez G, Chwalisz BK, Banik R, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA; the LHON Study Group. Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G>A MT-ND4 Mutation. Ophthalmol Ther. 2023 Feb;12(1):401-429. doi: 10.1007/s40123-022-00611-x. Epub 2022 Nov 30.

Reference Type DERIVED
PMID: 36449262 (View on PubMed)

Newman NJ, Yu-Wai-Man P, Carelli V, Biousse V, Moster ML, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA. Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison. Front Neurol. 2021 May 24;12:662838. doi: 10.3389/fneur.2021.662838. eCollection 2021.

Reference Type DERIVED
PMID: 34108929 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2017-002153-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NCT02652767 RESCUE

Identifier Type: OTHER

Identifier Source: secondary_id

NCT02652780 REVERSE

Identifier Type: OTHER

Identifier Source: secondary_id

GS-LHON-CLIN-06

Identifier Type: -

Identifier Source: org_study_id

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