RESCUE and REVERSE Long-term Follow-up

NCT03406104 | Completed Phase 3 Results FDA Drug

• 4 other identifiers: GS-LHON-CLIN-062017-002153-11NCT02652767 RESCUENCT02652780 REVERSE
• Study Type: interventional
• Target: 62
• Locations: 5 countries
• Sites: 7

Brief Summary

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.

Conditions

Leber Hereditary Optic Neuropathy

Keywords

Heredity Optic Atrophy; Leber Hereditary Optic Atrophy; Leber Hereditary Optic Neuropathy; LHON; Eye Diseases; Hereditary Eye Diseases; Inborn Genetic Disease; Gene Therapy; Intravitreal Injections; Mitochondrial Disease; AAV2 Vectors; Nervous System Diseases; Neurodegenerative Disease; Heredodegenerative Disorders of the Nervous System

Outcome Measures

Primary Outcomes (1)

• Ocular Adverse Events (AEs)

  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 Outcomes (2)

• Visual Acuity

  Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment

• Responder Analysis: Clinically Relevant Recovery

  Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment

Other Outcomes (1)

• Eyes on Chart

  Year 5 post-treatment

Study Arms (2)

GS010-treated Eyes

EXPERIMENTAL

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

Sham-treated Eyes

SHAM COMPARATOR

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

Interventions

GS010 GENETIC

Lenadogene nolparvovec Intravitreal ocular unilateral Injection

Also known as: Lenadogene Nolparvovec

GS010-treated Eyes

Sham Intravitreal Injection OTHER

Lenadogene nolparvovec Intravitreal ocular unilateral Injection

Sham-treated Eyes

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GenSight Biologics: lead

Study Sites (7)

Doheny Eye Center UCLA

Pasadena, California, 91105, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Wills Eye Institute

Philadelphia, Pennsylvania, 19107, United States

Location

CHNO Les Quinze Vingts

Paris, 75012, France

Location

LMU Klinikum der Universität München / Friedrich-Baur-Institut

Munich, 80336, Germany

Location

Ospedale Bellaria

Bologna, 40139, Italy

Location

Moorfields Eye Hospital

London, Greater London, EC1V 2PD, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 39699886 DERIVED

• 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.

  PMID: 36449262 DERIVED

• 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.

  PMID: 34108929 DERIVED

MeSH Terms

Conditions

Optic Atrophy, Hereditary, Leber; Eye Diseases; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Mitochondrial Diseases; Nervous System Diseases; Neurodegenerative Diseases

Interventions

salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Optic Atrophies, Hereditary; Optic Atrophy; Optic Nerve Diseases; Cranial Nerve Diseases; Heredodegenerative Disorders, Nervous System; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Magali TAIEL Chief Medical Officer
• Organization: Gensight Biologics

mtaiel@gensight-biologics.com

0762891252

Study Officials

• Nancy Newman, MD

  Emory University Hospital Atlanta, Georgia, United States, 30322

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: intra patient comparaison

Study Record Dates

• First Submitted: January 15, 2018
• First Posted: January 23, 2018
• Study Start: January 9, 2018
• Primary Completion: July 4, 2022
• Study Completion: July 4, 2022
• Last Updated: March 2, 2026
• Results First Posted: January 25, 2024

Record last verified: 2026-02

Locations

DE (1); FR (1); IT (1); GB (1); US (3)