Efficacy Study of GS010 for the Treatment of Vision Loss up to 6 Months From Onset in LHON Due to the ND4 Mutation

NCT02652767 | Completed Phase 3 Results DMC

• 2 other identifiers: GS-LHON-CLIN-03A2015-001265-11
• Study Type: interventional
• Target: 39
• Locations: 5 countries
• Sites: 7

Brief Summary

The goal of this clinical trial is to assess the effectiveness of GS010, a gene therapy, in improving the visual outcome in participants with Leber Hereditary Optic Neuropathy (LHON) due to the G11778A ND4 mitochondrial mutation when vision loss is present for six months or less.

Conditions

Optic, Atrophy, Hereditary, Leber

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 48

  Visual acuity was derived from the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Visual acuity is measured in "logarithm of the minimal angle of resolution" (LogMAR), which was derived from the number of letters participants could read on the ETDRS chart. 1 ETDRS line = 5 letters 1 ETDRS line = 0.1 LogMAR A lower LogMAR score denotes better visual acuity. A positive change from baseline indicates a worsening in symptoms. Change = (Week 48 score - Baseline score).

  Baseline and Week 48

Secondary Outcomes (11)

• Change From Baseline in ETDRS Visual Acuity (Quantitative Score)

  Baseline; Week 72 and Week 96

• Number of Eye Responders to Treatment

  Baseline; Week 48; Week 72 and Week 96

• Number of Subject Responders to Treatment

  Week 48; Week 72 and Week 96

• Change From Baseline in GCL Macular Volume

  Baseline; Week 48; Week 72 and Week 96

• Change From Baseline in RNFL Temporal Quadrant Thickness

  Baseline; Week 48; Week 72 and Week 96

Study Arms (2)

GS010-treated Eyes

EXPERIMENTAL

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®.

Biological: GS010

Sham-treated Eyes

SHAM COMPARATOR

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.

Device: Sham Intravitreal Injection

Interventions

GS010 BIOLOGICAL

Both eyes of each participant will receive standard antiseptic preparation, administration of topical local ocular anesthetic agents and will undergo pupillary dilation. Administration of an intra-ocular pressure lowering agent will precede treatment for every participant. 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®.

Also known as: Lenadogene Nolparvovec, rAAV2/2-ND4

GS010-treated Eyes

Sham Intravitreal Injection DEVICE

Both eyes of each participant will receive standard antiseptic preparation, administration of topical local ocular anesthetic agents and will undergo pupillary dilation. Administration of an intra-ocular pressure lowering agent will precede treatment for every participant. Sham-treated Eyes: One eye of each participant will undergo sham injection. 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.

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:

• Selection Criteria:
• Participants must meet all the following criteria at the Screening Visit (Visit 1) in order to be included into the study.
• Age 15 years or older.
• Onset of vision loss based on medically documented history or participant testimony, in at least one eye for ≤180 days in duration and if both eyes are affected the duration of vision loss in both eyes must be ≤180 days in duration.
• Each eye of the participant maintaining visual ability to allow at least for counting of the examiner's fingers at any distance.
• Female participants (if of childbearing potential) must agree to use effective methods of birth control up to 6 months after intravitreal (IVT) injection and male participants must agree to use condoms for up to 6 months after IVT injection.
• Ability to obtain adequate pupillary dilation to permit thorough ocular examination and testing.
• Signed written informed consent.
• Documented results of genotyping showing the presence of the G11778A mutation in the ND4 gene and the absence of the other primary Leber Hereditary Optical Neuropathy (LHON)-associated mutations (ND1 or ND6) in the participant's mitochondrial DNA.
• Review of all selection criteria to ensure continued compliance.
• Have a negative test for infection with human immunodeficiency virus.
• Have a negative pregnancy test for women of childbearing potential (a woman who is 2 years post-menopausal or surgically sterile is not considered to be of childbearing potential).

You may not qualify if:

• Non-Selection Criteria:
• Participants who meet at least one of the following criteria at the Screening Visit (Visit 1) will not be included into the study.
• Any known allergy or hypersensitivity to GS010 or its constituents.
• Contraindication to IVT injection.
• IVT drug delivery to either eye within 30 days prior to the Screening Visit (Visit 1).
• Previous vitrectomy in either eye.
• Narrow angle in either eye contra-indicating pupillary dilation.
• Presence of disorders of the ocular media, such as the cornea and lens, which may interfere with visual acuity and other ocular assessments during the study period.
• Vision disorders, other than LHON, involving visual disability or with the potential to cause further vision loss during the trial period.
• Causes of optic neuropathy other than LHON and glaucoma.
• Participants with known mutations of other genes involved in pathological retinal or optic nerve conditions.
• Presence of ocular or systemic disease, other than LHON, whose pathology or associated treatments might affect the retina or the optic nerve.
• History of amblyopia associated with a Snellen visual acuity equivalent of worse than 20/80 (equivalent to 6/24 at 6 meters, decimal acuity 0.25, LogMAR +0.6) in the affected eye.
• Presence of ocular conditions, which in the opinion of the Investigator will prevent good quality SD-OCT imaging from being obtained.
• Presence, in either eye, of uncontrolled glaucoma, defined as an intra-ocular pressure (IOP) greater than 25 mmHg, despite maximal medical therapy with IOP-lowering agents.

Sponsors & Collaborators

• GenSight Biologics: lead

Study Sites (7)

Doheny Eye Center, University of California, Los Angeles

Los Angeles, California, 91105, United States

Location

Department of Ophthalmology, Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Neuro Ophthalmologic Associates, Wills Eye Hospital, Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Centre National Hospitalier d'Ophtalmologie des Quinze-VingtCentre National Hospitalier d'Ophtalmologie des Quinze-Vingt

Paris, Paris, France

Location

Department of Neurology, University of Munich, Friedrich-Baur-Institute

Munich, 80336, Germany

Location

IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Ospedale Bellaria

Bologna, Bologna, Italy

Location

Moorfields Eye Hospital NHS Foundation Trust

London, EC1V 2PD, United Kingdom

Location

Related Publications (3)

• 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

• Newman NJ, Yu-Wai-Man P, Carelli V, Moster ML, Biousse V, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Barboni P, DeBusk AA, Girmens JF, Rudolph G, Karanjia R, Taiel M, Blouin L, Smits G, Katz B, Sahel JA; LHON Study Group. Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset. Ophthalmology. 2021 May;128(5):649-660. doi: 10.1016/j.ophtha.2020.12.012. Epub 2021 Jan 12.

  PMID: 33451738 DERIVED

Related Links

• National Library of Medicine's Genetics Home Reference for Leber Hereditary Optic Neuropathy
• National Library of Medicine's Genes and Gene Therapy

MeSH Terms

Conditions

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

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 CMO
• Organization: GenSight Biologics

mtaiel@gensight-biologics.com

1 76 21 72 26

Study Officials

• Nancy J. Newman, MD

  Department of Ophthalmology, Emory University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: January 7, 2016
• First Posted: January 12, 2016
• Study Start: February 23, 2016
• Primary Completion: August 7, 2018
• Study Completion: July 4, 2019
• Last Updated: March 2, 2026
• Results First Posted: January 28, 2020

Record last verified: 2026-02

Locations

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