Clinical trial NCT03406104: RESCUE and REVERSE Long-term Follow-up
Official title: Long-term Follow-up of ND4 LHON Subjects Treated With GS010 Ocular Gene Therapy in the RESCUE or REVERSE Phase III Clinical Trials (RESTORE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Leber Hereditary Optic Neuropathy
Keywords: 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
Lead sponsor: GenSight Biologics
Sponsor class: INDUSTRY
First posted: 2018-01-23
Enrollment: 62
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: intra patient comparaison
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Seven investigational centers from the RESCUE and REVERSE studies also participated in the RESTORE study, located in the European union and in the USA.

Primary objectives: to assess the long term safety of intravitreal injection up to 5 years of post treatment in subjects who were treated in the RESCUE or REVERSE studies.

Secondary objectives: (1) to assess the long-term efficacy of intravitreal GS010 administration up to 5 years post-treatment in subjects who were treated in the RESCUE or REVERSE studies; and (2) to assess the quality of life (QoL) in subjects who were treated with GS010 in the RESCUE or REVERSE studies for up to 5 years post-treatment.

Methodology: This was a Phase III prospective long-term follow-up (LTFU) clinical study of subjects previously treated with GS010 and Sham during 2 Phase III studies-RESCUE and REVERSE. The LTFU study followed subjects for an additional 3 years, for a total of 5 years post-injection. The LTFU study included 5 visits at 2, 2.5, 3, 4, and 5 years after the investigational medicinal product (IMP) injection. Safety, efficacy, and QoL variables were assessed during each of the 5 LTFU visits, and descriptive summaries and statistical testing were used for the analysis of the data.

This report presents the final analysis of results at Year 5 after treatment administration in RESCUE and REVERSE.

Number of analysed subjects: all subjects completing RECUE and REVERSE studies who provided consent for the RESTORE study: 62 subjects.

Eligibility criteria: 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

Primary outcomes:
measure: Ocular Adverse Events (AEs)
timeFrame: from year 2 to year 5 post treatment
Secondary outcomes:
measure: Visual Acuity
timeFrame: Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment
measure: Responder Analysis: Clinically Relevant Recovery
timeFrame: Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment
Other outcomes:
measure: Eyes on Chart
timeFrame: Year 5 post-treatment
Locations:
city: Pasadena
country: United States
facility: Doheny Eye Center UCLA
state: California
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Philadelphia
country: United States
facility: Wills Eye Institute
state: Pennsylvania
city: Paris
country: France
facility: CHNO Les Quinze Vingts
city: Munich
country: Germany
facility: LMU Klinikum der Universität München / Friedrich-Baur-Institut
city: Bologna
country: Italy
facility: Ospedale Bellaria
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
state: Greater London
Study officials:
affiliation: Emory University Hospital Atlanta, Georgia, United States, 30322
name: Nancy Newman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.