RESCUE and REVERSE Long-term Follow-up

Phase 3

Completed

Conditions: Leber Hereditary Optic Neuropathy

Interventions: Other: Sham Intravitreal Injection
Genetic: GS010

Registration Number: NCT03406104

Lead Sponsor: GenSight Biologics

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 62

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham-treated Eyes	Sham Intravitreal Injection	Sham Intravitreal ocular unilateral Injection Each participant will have one eye randomly selected to receive GS010 and the other eye will receive a sham injection. Eyes receiving sham injection will undergo the same preparatory procedures as eyes receiving GS010 injection, including pupillary dilation, topical anti-infection and topical anesthetic procedures. Sham intravitreal injection will be performed by applying pressure to the eye at the location of a typical intravitreal injection procedure using the blunt end of a syringe without a needle.
GS010-treated Eyes	GS010	Lenadogene nolparvovec Intravitreal ocular unilateral Injection Each participant will have one eye randomly selected to receive a single injection of GS010 and the other eye will receive a sham injection. GS010-treated Eyes: GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). Participants will receive a single dose of GS010 in one of their randomly selected eyes, via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) plus 0.001% Pluronic F68®.

Primary Outcome Measures

Name	Time	Method
Ocular Adverse Events (AEs)	from year 2 to year 5 post treatment	Number of Eyes with Ocular Adverse events related to study treatment or study procedures as judged by the investigator reported from year 2 to year 5 post treatment

Secondary Outcome Measures

Name	Time	Method
Visual Acuity	Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment	Change from Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment, expressed in LogMAR. On chart visual acuity: Visual acuity inferior or equal to LogMAR +1.6 Off chart visual acuity: Visual acuity superior to LogMar +1.7 Normal vision LogMar: 0 and less than 0
Responder Analysis: Clinically Relevant Recovery	Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment	CRR clinically relevant recovery from Nadir defined as i/ for eyes on chart at Nadir, an improvement of at least -0.2 LogMar from Nadir and ii/ for eyes off chart at Nadir eyes that became on chart. Off chart visual acuity expressed in LogMar: more than +1.7 On chart visual acuity expressed in LogMar: less than 1.6 Normal vision LogMar: 0 and less than 0

Trial Locations

Locations (7): Emory University Hospital
🇺🇸
Atlanta, Georgia, United States
Wills Eye Institute
🇺🇸
Philadelphia, Pennsylvania, United States
Doheny Eye Center UCLA
🇺🇸
Pasadena, California, United States
LMU Klinikum der Universität München / Friedrich-Baur-Institut
🇩🇪
Munich, Germany
CHNO Les Quinze Vingts
🇫🇷
Paris, France
Ospedale Bellaria
🇮🇹
Bologna, Italy
Moorfields Eye Hospital
🇬🇧
London, Greater London, United Kingdom