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

Primary Purpose

Leber Hereditary Optic Neuropathy

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
GS010
Sham
Sponsored by
GenSight Biologics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leber Hereditary Optic Neuropathy focused on measuring 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

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Doheny Eye Center UCLA
  • Emory University Hospital
  • Wills Eye Institute
  • CHNO Les Quinze Vingts
  • LMU Klinikum der Universität München / Friedrich-Baur-Institut
  • Ospedale Bellaria
  • Moorfields Eye Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

GS010

Sham

Arm Description

Lenadogene nolparvovec Intravitreal occular unilateral Injection

Sham Intravitreal occular unilateral Injection

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Best-Corrected Visual Acuity (BCVA) reported with LogMAR
Change in best BCVA reported with LogMAR
HumphreyTM visual field (HVF) 30-2 parameters
Change of parameters measured with HVF 30-2
Spectral domain optical coherence tomography (SD-OCT) parameters
Change of parameters measured with SD-OCT
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)
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
Visual improvement
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
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)
QOL as measured with VFQ-25 subject-rated instrument
Quality of Life: 36-Item Short Form Health Survey, version 2 (SF-36-v2)
QOL as measured with SF-36v2 subject-rated instrument

Full Information

First Posted
January 15, 2018
Last Updated
July 25, 2022
Sponsor
GenSight Biologics
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1. Study Identification

Unique Protocol Identification Number
NCT03406104
Brief Title
RESCUE and REVERSE Long-term Follow-up
Acronym
RESTORE
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

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
January 9, 2018 (Actual)
Primary Completion Date
July 4, 2022 (Actual)
Study Completion Date
July 4, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GenSight Biologics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
intra patient comparaison
Masking
None (Open Label)
Allocation
Randomized
Enrollment
61 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GS010
Arm Type
Experimental
Arm Description
Lenadogene nolparvovec Intravitreal occular unilateral Injection
Arm Title
Sham
Arm Type
Sham Comparator
Arm Description
Sham Intravitreal occular unilateral Injection
Intervention Type
Genetic
Intervention Name(s)
GS010
Intervention Description
Lenadogene nolparvovec Intravitreal occular unilateral Injection
Intervention Type
Other
Intervention Name(s)
Sham
Intervention Description
Lenadogene nolparvovec Intravitreal occular unilateral Injection
Primary Outcome Measure Information:
Title
Adverse events (AEs) or serious adverse events (SAEs) (ocular or systemic)
Description
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
Time Frame
Up to 5-Year post-treatment
Secondary Outcome Measure Information:
Title
Best-Corrected Visual Acuity (BCVA) reported with LogMAR
Description
Change in best BCVA reported with LogMAR
Time Frame
Up to 5-Year post-treatment
Title
HumphreyTM visual field (HVF) 30-2 parameters
Description
Change of parameters measured with HVF 30-2
Time Frame
Up to 5-Year post-treatment
Title
Spectral domain optical coherence tomography (SD-OCT) parameters
Description
Change of parameters measured with SD-OCT
Time Frame
Up to 5-Year post-treatment
Title
Responder Analysis
Description
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 Frame
Up to 5-Year post-treatment
Title
Time course of the response
Description
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
Time Frame
Up to 5-Year post-treatment
Title
Visual improvement
Description
Visual improvement as measured by LogMAR by analysis of covariance (ANCOVA)
Time Frame
Up to 5-Year post-treatment
Title
Change of ganglion cell layer (GCL) thickness/volume and topographical map and other parameters measured by SD-OCT
Description
Change of GCL thickness/volume and topographical map and other parameters measured by SD-OCT using a mixed model of ANCOVA
Time Frame
Up to 5-Year post-treatment
Title
Quality of Life: Visual Functioning Questionnaire 25 (VFQ-25)
Description
QOL as measured with VFQ-25 subject-rated instrument
Time Frame
Up to 5-Year post-treatment
Title
Quality of Life: 36-Item Short Form Health Survey, version 2 (SF-36-v2)
Description
QOL as measured with SF-36v2 subject-rated instrument
Time Frame
Up to 5-Year post-treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nancy Newman, MD
Organizational Affiliation
Emory University Hospital Atlanta, Georgia, United States, 30322
Official's Role
Principal Investigator
Facility Information:
Facility Name
Doheny Eye Center UCLA
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
Emory University Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Wills Eye Institute
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
CHNO Les Quinze Vingts
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
LMU Klinikum der Universität München / Friedrich-Baur-Institut
City
Munich
ZIP/Postal Code
80336
Country
Germany
Facility Name
Ospedale Bellaria
City
Bologna
ZIP/Postal Code
40139
Country
Italy
Facility Name
Moorfields Eye Hospital
City
London
State/Province
Greater London
ZIP/Postal Code
EC1V 2PD
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
34108929
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.
Results Reference
derived

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RESCUE and REVERSE Long-term Follow-up

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