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

NCT ID: NCT03293524

Last Updated: 2025-08-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

98 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-12

Study Completion Date

2024-07-23

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The goal of this clinical trial is to assess the safety and efficacy of GS010, a gene therapy, in improving the retina functional \& structural outcomes in subjects with LHON due to the G11778A ND4 mitochondrial mutation when vision loss duration is present up to one year.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

GS-LHON-CLIN-05 is a Phase III, global, multi-center randomized, double-masked for the primary analysis, placebo-controlled, clinical study. As LHON is a neurodegenerative disease, the goal is to administer GS010 as soon as possible upon confirmation of the LHON diagnosis and the causative mutation.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Leber Hereditary Optic Neuropathy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment Arm 1

Subjects will be randomized to treatment arm 1 or treatment arm 2 in a 1:1 allocation. Subjects in treatment arm 1 will receive intravitreal GS010 in both eyes.

Group Type EXPERIMENTAL

GS010

Intervention Type GENETIC

GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). GS010 will be administrated via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) as a single baseline intravitreal injection.

Treatment Arm 2

Subjects will be randomized to treatment arm 1 or treatment arm 2 in a 1:1 allocation. Subjects in treatment arm 2 will receive GS010 in one eye and placebo intravitreal injection in the other eye.

Group Type PLACEBO_COMPARATOR

GS010

Intervention Type GENETIC

GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). GS010 will be administrated via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) as a single baseline intravitreal injection.

Placebo

Intervention Type DRUG

The placebo is a BSS, sterile, apyrogenic solution and used for ocular surgery. The placebo will be administered via intravitreal injection in a volume of 90 μL.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

GS010

GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). GS010 will be administrated via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) as a single baseline intravitreal injection.

Intervention Type GENETIC

Placebo

The placebo is a BSS, sterile, apyrogenic solution and used for ocular surgery. The placebo will be administered via intravitreal injection in a volume of 90 μL.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Lenadogene nolparvovec

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

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.


* 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.

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).
Minimum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

GenSight Biologics

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Nancy Newman, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University Hospital Atlanta, Georgia, United States, 30322

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Doheny Eye Center UCLA Pasadena

Pasadena, California, United States

Site Status

University of Colorado Health Eye Center

Aurora, Colorado, United States

Site Status

Emory Healthcare - The Emory Clinic

Atlanta, Georgia, United States

Site Status

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

Wills Eye Institute - Ocular Oncology Service

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt Eye Institute

Nashville, Tennessee, United States

Site Status

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status

CHNO Les Quinze Vingts

Paris, , France

Site Status

IRCCS Istituto delle Scienze Neurologiche di Bologna UOC Clinica Neurologica

Bologna, , Italy

Site Status

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Moorfields Eye Hospital

London, Greater London, United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Belgium France Italy Spain Taiwan United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

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)

Related Links

Access external resources that provide additional context or updates about the study.

http://www.gensight-biologics.com

GenSight Biologics website

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2017-002187-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-LHON-CLIN-05

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Gene Therapy for Gyrate Atrophy
NCT00001735 COMPLETED PHASE1