RESCUE and REVERSE Long-term Follow-up

Study Overview
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Brief Summary
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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.

Official Title
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Long-term Follow-up of ND4 LHON Subjects Treated With GS010 Ocular Gene Therapy in the RESCUE or REVERSE Phase III Clinical Trials (RESTORE)

Conditions
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Leber Hereditary Optic Neuropathy

Intervention / Treatment
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* Genetic: GS010
* Other: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria 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 Non-Inclusion Criteria 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

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: intra patient comparaison
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GS010<br>Lenadogene nolparvovec Intravitreal occular unilateral Injection | Genetic: GS010<br>* Lenadogene nolparvovec Intravitreal occular unilateral Injection<br>|
| Sham Comparator: Sham<br>Sham Intravitreal occular unilateral Injection | Other: Sham<br>* Lenadogene nolparvovec Intravitreal occular unilateral Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AEs) or serious adverse events (SAEs) (ocular or systemic) | AEs or SAEs (ocular or systemic) related to IMP or administration procedure, as judged by the Investigator, reported during the long-term follow-up visits (2, 2.5, 3, 4, and 5 years) from the period of 96 weeks up to 5 years post-treatment and summarized descriptively by type, frequency (number, percentage), severity, causal relationship, and seriousness | Up to 5-Year post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best-Corrected Visual Acuity (BCVA) reported with LogMAR | Change in best BCVA reported with LogMAR | Up to 5-Year post-treatment | 
| HumphreyTM visual field (HVF) 30-2 parameters | Change of parameters measured with HVF 30-2 | Up to 5-Year post-treatment | 
| Spectral domain optical coherence tomography (SD-OCT) parameters | Change of parameters measured with SD-OCT | Up to 5-Year post-treatment | 
| Responder Analysis | Response status of eyes treated with GS010 IVT injection compared to eyes treated with sham IVT injection (An improvement of at least 15 ETDRS letters/Eyes that lose less than the 15 ETDRS letters) | Up to 5-Year post-treatment | 
| Time course of the response | Time course of the response in eyes treated with GS010 IVT injection compared to eyes treated with sham IVT injection, for the BCVA reported with LogMAR, for parameters measured with HVF 30-2 and SD-OCT | Up to 5-Year post-treatment | 
| Visual improvement | Visual improvement as measured by LogMAR by analysis of covariance (ANCOVA) | Up to 5-Year post-treatment | 
| Change of ganglion cell layer (GCL) thickness/volume and topographical map and other parameters measured by SD-OCT | Change of GCL thickness/volume and topographical map and other parameters measured by SD-OCT using a mixed model of ANCOVA | Up to 5-Year post-treatment | 
| Quality of Life: Visual Functioning Questionnaire 25 (VFQ-25) | QOL as measured with VFQ-25 subject-rated instrument | Up to 5-Year post-treatment | 
| Quality of Life: 36-Item Short Form Health Survey, version 2 (SF-36-v2) | QOL as measured with SF-36v2 subject-rated instrument | Up to 5-Year post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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