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

NCT03293524 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-LHON-CLIN-052017-002187-40
• Study Type: interventional
• Target: 98
• Locations: 7 countries
• Sites: 13

Brief Summary

The goal of this clinical trial is to assess the efficacy and safety of GS010 gene therapy - (lenadogene nolparvovec) in subjects with LHON due to the G11778A ND4 mitochondrial mutation with a vision loss up to one year.

Conditions

Leber Hereditary Optic Neuropathy

Keywords

Leber Hereditary Optic Atrophy; Leber Hereditary Optic Neuropathy; LHON; Eye Diseases; Hereditary Eye Diseases; Inherited retinal dystrophies or degeneration; Gene Therapy; Intravitreal Injections; Mitochondrial Disease; AAV2 Vectors; Hereditary Optic Atrophy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline of the Best Corrected Visual Acuity (BCVA) Reported With Log of the Minimal Angle of Resolution (LogMAR) at 1.5 Years Post-treatment, in the Second Affected/Not-yet Affected Eyes

  The primary efficacy endpoint was the change from baseline of BCVA reported with LogMAR at 1.5-year post-treatment, in the second-affected/not-yet-affected eyes of ND4 LHON patients with vision loss up to one year. LogMAR BCVA was used to represent BCVA.

  at 1.5 years post-treatment, in the second-affected/not-yet affected eyes

Secondary Outcomes (6)

• Change From Baseline of the BCVA Reported With LogMAR at 5 Years Post-treatment, in the Second Affected/Not-yet Affected Eyes

  at 5 years post-treatment, in the second-affected/not-yet affected eyes

• Proportion of Patients Who Switched From Off-chart Eyes to On-chart Eyes at 5 Years Post-treatment

  From baseline to 5 years post-treatment

• Responder Analyses - Improvements From Nadir (Gainer Eyes) at 5 Years

  From nadir to 5 years post-treatment

• Responder Analyses - Clinically Relevant Recovery From Nadir at 5 Years

  From nadir to 5 years post-treatment

• Responder Analyses- Clinically Relevant Benefit at 5 Years

  From baseline nadir to 5 years post-treatment

Study Arms (2)

GS010-GS010

EXPERIMENTAL

Patients received single IVT injection of GS010 in both their first-affected eye and their second-affected/not-yet-affected eye at a droplet digital polymerase chain reaction (ddPCR) dose of 1.2/1.3E11 vg in 90 μL for each eye. Treatment could be performed either on a single day (1 IVT injection in each eye on Day 0) or on 2 consecutive days (1st IVT injection on Day -1 and 2nd IVT injection on Day 0).

Genetic: GS010

GS010-Placebo

PLACEBO COMPARATOR

Patients received single IVT injection of GS010 in their first-affected eye and placebo IVT injection in their second-affected/not-yet-affected eye. Patients received IVT lenadogene nolparvovec in their first-affected eye (ddPCR dose of 1.2/1.3E11 vg in a volume of 90 μL) and placebo IVT injection (volume of 90 μL) in their second-affected/not-yet-affected eye. Treatment could be performed either on a single day (1 IVT injection in each eye on Day 0) or on 2 consecutive days (1st IVT injection on Day -1 and 2nd IVT injection on Day 0).

Genetic: GS010; Drug: Placebo

Interventions

GS010 GENETIC

GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). GS010 was administrated via intravitreal injection containing 1.2/1.3E11 vg in 90 μL balanced sterile saline solution (BSSS).

Also known as: Lenadogene nolparvovec

GS010-GS010; GS010-Placebo

Placebo DRUG

The placebo is a balanced sterile saline solution (BSSS) used for IVT. The placebo was administered via intravitreal injection in a volume of 90 μL.

GS010-Placebo

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:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• GenSight Biologics: lead

Study Sites (13)

Doheny Eye Center UCLA Pasadena

Pasadena, California, 91105, United States

Location

University of Colorado Health Eye Center

Aurora, Colorado, 80045, United States

Location

Emory Healthcare - The Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

Department of Ophthalmology, Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Departments of Neurology and Ophthalmology, Wills Eye Hospital and Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Vanderbilt Eye Institute

Nashville, Tennessee, 37232, United States

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

CHNO Les Quinze Vingts

Paris, Paris, 75012, France

Location

IRCCS Istituto delle Scienze Neurologiche di Bologna (ISNB) Clinica Neurologica

Bologna, 40139, Italy

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Moorfields Eye Hospital

London, Greater London, EC1V 2PD, United Kingdom

Location

Related Publications (1)

• 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

Related Links

• GenSight Biologics website

MeSH Terms

Conditions

Optic Atrophy, Hereditary, Leber; Eye Diseases; Eye Diseases, Hereditary; Mitochondrial Diseases; Optic Atrophies, Hereditary

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Chief Medical Officer
• Organization: GenSight Biologics

mtaiel@gensight-biologics.com

33 176217233

Study Officials

• Nancy Newman, MD

  Emory University Hospital Atlanta, Georgia, United States, 30322

  PRINCIPAL INVESTIGATOR

• Patrick Yu-Wai-Man, PhD

  John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, CB2 0PY, United Kingdom

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Study treatments were masked and the allocation to treatment groups was not known to the investigator or other persons involved in the conduct of the study, except the site pharmacies personnel to allow for preparation of investigational products before administration, in cases of emergencies and the data safety monitoring board (DSMB). To ensure that the double-masking design of the study was maintained, GS010 and placebo were identical in appearance and storage conditions.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: Each participant had an eye designated as first-affected eye, and a fellow eye designated as either second-affected eye or not-yet-affected eye at the Screening Visit based on non-equal vision loss duration. In participants reporting simultaneous onset of vision loss in both eyes, the second-affected eye was randomly selected between both eyes. All participants received GS010 in their first-affected eye and were randomized in a 1:1 ratio to receive either GS010 (GS010- GS010 treatment arm) or placebo (GS010-Placebo treatment arm) in the second-affected/not-yet-affected eye.

Study Record Dates

• First Submitted: September 19, 2017
• First Posted: September 26, 2017
• Study Start: March 12, 2018
• Primary Completion: July 23, 2024
• Study Completion: July 23, 2024
• Last Updated: April 16, 2026
• Results First Posted: April 16, 2026

Record last verified: 2026-03

Locations

TW (1); GB (1); US (7); FR (1); IT (1); ES (1); BE (1)