LENADOGENE NOLPARVOVEC for Leber hereditary optic neuropathy (ND4 mutation)

Inclusion criteria

• {"criterion_text":"- Aged 15 years or older at the time of vision loss onset\n- Willing and able to comply with the protocol, follow study instructions, attend study visits as required and complete all study assessments\n- Patient – and parent/legal guardian if the patient is under 18 years of age – has provided signed, written informed consent\n- Clinically manifested vision loss due to ND4 LHON in both eyes\n- BCVA of at least LogMAR +2.39, measured at the FrACT scale, in both eyes\n- Documented results of genotyping showing the presence of pathogenic LHON-associated mutation(s) in the ND4 mitochondrial gene and the absence of other pathogenic LHON-associated mutations in the patient’s mitochondrial DNA; absence of pathogenic mutations, other than the ND4 LHON-causing mutation(s), which are known to cause pathology of the optic nerve, retina or afferent visual system. Historic results of genetic analysis are acceptable upon Sponsor approval.\n- Vision loss duration from 6 months to 1.5 years in the first affected eye at the Inclusion visit (Day -1)\n- No limitations to OCT image collection that would prevent high quality, reliable images from being obtained in both eyes, as determined by the reading center\n- Clear ocular media and adequate pupillary dilation to permit thorough ocular examination, as assessed by the Investigator\n- Human immunodeficiency virus (HIV) negative serology\n- Female patients of childbearing potential must agree to use effective methods of birth control for up to 6 months after Treatment visit (Day 0). Male patients must agree to use condoms with their female partners for up to 6 months after Treatment visit (Day 0)."}

Exclusion criteria

• {"criterion_text":"- Any known allergy or hypersensitivity to GS010 or any of its constituents\n- Contraindication to IVT in any eye according to the Investigator’s clinical judgment and international guidelines (Avery, 2014)\n- Prior intraocular surgery or procedure or IVT, which occurred 6 months prior to inclusion and is considered of clinical relevance per Investigator assessment, or planned intraocular surgery or procedure\n- Presence of optic neuropathy from any cause except LHON, as determined by the Investigator\n- History of recurrent uveitis (idiopathic or immune-related) or active intraocular inflammation, as determined by the Investigator\n- Indication of a unilateral treatment with GS010, as determined by the Investigator: • Unilateral or asymmetric ND4 LHON disease: only one eye affected with a vision loss due to ND4 LHON, and the fellow eye with preserved BCVA (LogMAR 0 or close to 0); • Amblyopia: unilateral treatment of the functional eye with a vision loss due to ND4 LHON; • Patient’s desire for unilateral treatment\n- Ingestion of idebenone less than 7 days prior to the Inclusion visit (Day -1)\n- Inability to tolerate the anti-inflammatory regimen\n- Presence of ocular disease (excluding LHON), or systemic disease, or condition (including medications and laboratory test abnormalities) that could compromise patient safety or interfere with assessment of efficacy and safety, as determined by the Investigator\n- Use of any investigational drug, or device, within 90 days, or 5 half-lives, preceding the Inclusion visit (Day-1), whichever is longer, or plans to participate in another study of an investigational drug or device during the study period\n- Previous treatment with ocular gene therapy in either eye.\n- Pregnancy or breast-feeding"}

Primary endpoints

• {"endpoint_text":"- BCVA change from baseline to 1.5 years post-treatment in the study eyes.","definition_or_measurement_approach":"Change in best corrected visual acuity (BCVA) from baseline to 1.5 years post-treatment in the study eyes; measured as BCVA change (LogMAR) at 1.5 years post-treatment."}

Secondary endpoints

• {"endpoint_text":"- BCVA responder rates from baseline to 1.5 years post-treatment in the study eyes, defined as an improvement of at least -0.2 LogMAR.","definition_or_measurement_approach":"Responder defined as improvement of at least -0.2 LogMAR from baseline to 1.5 years in study eyes."}
• {"endpoint_text":"- BCVA change from baseline to 1.5 years post-treatment in both eyes.","definition_or_measurement_approach":"Change in BCVA from baseline to 1.5 years post-treatment measured in both eyes."}
• {"endpoint_text":"- Difference between ARM H and ARM L in BCVA change from baseline to 1.5 years post-treatment in the study eyes.","definition_or_measurement_approach":"Comparison of BCVA change from baseline to 1.5 years between high-dose (ARM H) and low-dose (ARM L) treatment arms in study eyes."}
• {"endpoint_text":"- Frequency and severity of ocular adverse events (AEs).","definition_or_measurement_approach":"Collection and grading of ocular AEs by frequency and severity per study safety reporting."}
• {"endpoint_text":"- Frequency and severity of ocular AEs of special interest (AESIs) post-GS010 administration: o Intraocular inflammation; evolution with time and response to corticosteroid. o Increase in intraocular pressure (IOP); evolution with time and response to IOP lowering treatment.","definition_or_measurement_approach":"Monitoring occurrences, time course and treatment response for intraocular inflammation and IOP increases after GS010 administration."}
• {"endpoint_text":"- Frequency and severity of non-ocular AEs.","definition_or_measurement_approach":"Collection and grading of non-ocular adverse events by frequency and severity per study safety reporting."}

France

Earliest CTIS Part Ii Submission Date

22-10-2025

Latest Decision Or Authorization Date

11-05-2026

Processing Time Days

201

Number Of Sites

1

Number Of Participants

14

Primary sponsor

Full Name

Gensight Biologics

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Clinipace GmbH

Responsibilities

sponsorDuties codes: [12]

Name

Expert Monitor Pharma

Responsibilities

sponsorDuties code: 1 (monitoring)

Third parties

• {"country":"Germany","full_name":"Clinipace GmbH","duties_or_roles":"sponsorDuties codes: [12]","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Accovion","duties_or_roles":"sponsorDuties codes: [12]","organisation_type":"Pharmaceutical company"}
• {"country":"Portugal","full_name":"Association For Innovation And Biomedical Research On Light And Image","duties_or_roles":"Central Reading center for OCT (Optical Coherence Tomography) (sponsorDuties code: 15)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"France","full_name":"Voisin Consulting Life Sciences","duties_or_roles":"sponsorDuties codes: [6, 8]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Welocalize Inc.","duties_or_roles":"Translation services (sponsorDuties code: 15)","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"sponsorDuties code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Unisphere Travel Ltd. Inc.","duties_or_roles":"Patient's travel and reimbursement management (sponsorDuties code: 15)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"Accovion GmbH","duties_or_roles":"sponsorDuties code: 5","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Expert Monitor Pharma","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Exystat","duties_or_roles":"sponsorDuties codes: [10, 3, 6, 7]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"OcuSciences, Inc","duties_or_roles":"Reading Center (sponsorDuties code: 15)","organisation_type":"Industry"}