RESTORE: RESCUE and REVERSE Long-term Follow-up

Sponsor

GenSight Biologics (Industry)

Overall Status

Completed

CT.gov ID

NCT03406104

Collaborator

(none)

Enrollment

Locations

Arms

53.8

Actual Duration (Months)

8.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Leber Hereditary Optic Neuropathy	Genetic: GS010 Other: Sham	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

61 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

intra patient comparaisonintra patient comparaison

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jan 9, 2018

Actual Primary Completion Date :

Jul 4, 2022

Actual Study Completion Date :

Jul 4, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GS010 Lenadogene nolparvovec Intravitreal occular unilateral Injection	Genetic: GS010 Lenadogene nolparvovec Intravitreal occular unilateral Injection
Sham Comparator: Sham Sham Intravitreal occular unilateral Injection	Other: Sham Lenadogene nolparvovec Intravitreal occular unilateral Injection

Arm

Intervention/Treatment

Experimental: GS010

Lenadogene nolparvovec Intravitreal occular unilateral Injection

Genetic: GS010

Lenadogene nolparvovec Intravitreal occular unilateral Injection

Sham Comparator: Sham

Sham Intravitreal occular unilateral Injection

Other: Sham

Lenadogene nolparvovec Intravitreal occular unilateral Injection

Outcome Measures

Primary Outcome Measures

Adverse events (AEs) or serious adverse events (SAEs) (ocular or systemic) [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

Secondary Outcome Measures

Best-Corrected Visual Acuity (BCVA) reported with LogMAR [Up to 5-Year post-treatment]
Change in best BCVA reported with LogMAR
HumphreyTM visual field (HVF) 30-2 parameters [Up to 5-Year post-treatment]
Change of parameters measured with HVF 30-2
Spectral domain optical coherence tomography (SD-OCT) parameters [Up to 5-Year post-treatment]
Change of parameters measured with SD-OCT
Responder Analysis [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 [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 [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 [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) [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) [Up to 5-Year post-treatment]
QOL as measured with SF-36v2 subject-rated instrument

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Doheny Eye Center UCLA	Pasadena	California	United States	91105
2	Emory University Hospital	Atlanta	Georgia	United States	30322
3	Wills Eye Institute	Philadelphia	Pennsylvania	United States	19107
4	CHNO Les Quinze Vingts	Paris		France	75012
5	LMU Klinikum der Universität München / Friedrich-Baur-Institut	Munich		Germany	80336
6	Ospedale Bellaria	Bologna		Italy	40139
7	Moorfields Eye Hospital	London	Greater London	United Kingdom	EC1V 2PD