RESCUE and REVERSE Long-term Follow-up

Leber Hereditary Optic Neuropathy Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03406104
• Other study ID #: GS-LHON-CLIN-06
• Secondary ID: 2017-002153-11NC
• Status: Completed
• Phase: Phase 3
• Start date: January 9, 2018
• Est. completion date: July 4, 2022

Study information

• Verified date: January 2024
• Source: GenSight Biologics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: July 4, 2022
• Est. primary completion date: July 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leber Hereditary Optic Neuropathy
• Optic Atrophy, Hereditary, Leber
• Optic Nerve Diseases

Intervention

Genetic:
• GS010
Lenadogene nolparvovec Intravitreal ocular unilateral Injection

Other:
• Sham Intravitreal Injection
Lenadogene nolparvovec Intravitreal ocular unilateral Injection

Locations

Country	Name	City	State
France	CHNO Les Quinze Vingts	Paris
Germany	LMU Klinikum der Universität München / Friedrich-Baur-Institut	Munich
Italy	Ospedale Bellaria	Bologna
United Kingdom	Moorfields Eye Hospital	London	Greater London
United States	Emory University Hospital	Atlanta	Georgia
United States	Doheny Eye Center UCLA	Pasadena	California
United States	Wills Eye Institute	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
GenSight Biologics

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Eyes on Chart	Definition: Visual acuity inferior or equal to LogMAR +1.6 at 5 Years post treatment	Year 5 post-treatment
Primary	Ocular Adverse Events (AEs)	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	from year 2 to year 5 post treatment
Secondary	Visual Acuity	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	Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment
Secondary	Responder Analysis: Clinically Relevant Recovery	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	Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment