RESCUE and REVERSE Long-term Follow-up (RESTORE)

• ClinicalTrials.gov Identifier: NCT03406104
• Recruitment Status: Completed
• First Posted: January 23, 2018
• Last Update Posted: July 27, 2022
• Sponsor: GenSight Biologics
• Information provided by (Responsible Party): GenSight Biologics

Tracking Information

• First Submitted Date: January 15, 2018
• First Posted Date: January 23, 2018
• Last Update Posted Date: July 27, 2022
• Actual Study Start Date: January 9, 2018
• Actual Primary Completion Date: July 4, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 15, 2018)

Adverse events (AEs) or serious adverse events (SAEs) (ocular or systemic) [ Time Frame: Up to 5-Year post-treatment ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 15, 2018)

• Best-Corrected Visual Acuity (BCVA) reported with LogMAR [ Time Frame: Up to 5-Year post-treatment ]
  Change in best BCVA reported with LogMAR
• HumphreyTM visual field (HVF) 30-2 parameters [ Time Frame: Up to 5-Year post-treatment ]
  Change of parameters measured with HVF 30-2
• Spectral domain optical coherence tomography (SD-OCT) parameters [ Time Frame: Up to 5-Year post-treatment ]
  Change of parameters measured with SD-OCT
• Responder Analysis [ Time Frame: Up to 5-Year post-treatment ]
  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)
• Time course of the response [ Time Frame: Up to 5-Year post-treatment ]
  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
• Visual improvement [ Time Frame: Up to 5-Year post-treatment ]
  Visual improvement as measured by LogMAR by analysis of covariance (ANCOVA)
• Change of ganglion cell layer (GCL) thickness/volume and topographical map and other parameters measured by SD-OCT [ Time Frame: Up to 5-Year post-treatment ]
  Change of GCL thickness/volume and topographical map and other parameters measured by SD-OCT using a mixed model of ANCOVA
• Quality of Life: Visual Functioning Questionnaire 25 (VFQ-25) [ Time Frame: Up to 5-Year post-treatment ]
  QOL as measured with VFQ-25 subject-rated instrument
• Quality of Life: 36-Item Short Form Health Survey, version 2 (SF-36-v2) [ Time Frame: Up to 5-Year post-treatment ]
  QOL as measured with SF-36v2 subject-rated instrument

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

intra patient comparaison

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Leber Hereditary Optic Neuropathy

Intervention

• Genetic: GS010
  Lenadogene nolparvovec Intravitreal occular unilateral Injection
• Other: Sham
  Lenadogene nolparvovec Intravitreal occular unilateral Injection

Study Arms

• Experimental: GS010
  Lenadogene nolparvovec Intravitreal occular unilateral Injection
  Intervention: Genetic: GS010
• Sham Comparator: Sham
  Sham Intravitreal occular unilateral Injection
  Intervention: Other: Sham

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 21, 2020): 61
• Original Estimated Enrollment (submitted: January 15, 2018): 74
• Actual Study Completion Date: July 4, 2022
• Actual Primary Completion Date: July 4, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 15 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, Italy, United Kingdom, United States

Administrative Information

• NCT Number: NCT03406104
• Other Study ID Numbers: GS-LHON-CLIN-06; 2017-002153-11 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: GenSight Biologics
• Original Responsible Party: Same as current
• Current Study Sponsor: GenSight Biologics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Nancy Newman, MD; Emory University Hospital Atlanta, Georgia, United States, 30322

• PRS Account: GenSight Biologics
• Verification Date: July 2022