Clinical Trial Results:
Long-term Follow-up of ND4 LHON Subjects Treated With GS010 Ocular
Gene Therapy in the RESCUE or REVERSE Phase III Clinical Trials
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Summary
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EudraCT number |
2017-002153-11 |
Trial protocol |
DE GB IT FR |
Global end of trial date |
25 May 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Mar 2024
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First version publication date |
06 Mar 2024
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GS-LHON-CLIN-06
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03406104 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Gensight Biologics
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Sponsor organisation address |
74 Faubourg Saint Antoine, Paris, France, 75012
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Public contact |
Szilvia Fabian, Gensight Biologics, sfabian@GENSIGHT-BIOLOGICS.COM
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Scientific contact |
Magali Taiel, Gensight Biologics, mtaiel@GENSIGHT-BIOLOGICS.COM
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Jan 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
25 May 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
25 May 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the long-term safety of intravitreal GS010 administration up to
5 years post-treatment in subjects who were treated in the RESCUE or
REVERSE studies.
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Protection of trial subjects |
This study was conducted in compliance with the protocol, Good Clinical Practice (GCP) Integrated Addendum to International Council for Harmonisation (ICH) E6 R1 as set forth in the ICH guidelines on GCP (ICH E6 R2 March 2018), European Union General Data Protection Regulation (2016/679), and applicable local regulatory requirements
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Dec 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 5
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Country: Number of subjects enrolled |
France: 16
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Country: Number of subjects enrolled |
Germany: 9
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Country: Number of subjects enrolled |
Italy: 1
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Country: Number of subjects enrolled |
United States: 31
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Worldwide total number of subjects |
62
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EEA total number of subjects |
26
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
7
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Adults (18-64 years) |
55
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The trial recruited subjects previously treated with GS010 and Sham during 2 Phase III studies—RESCUE and REVERSE. The study followed subjects for an additional 3 years, for a total of 5 years post-injection. The study included 5 visits at 2, 2.5, 3, 4, and 5 years after the investigational medicinal product (IMP) injection. | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Not applicable as no screening period | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
from 2 to 5 Years (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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GS010 arm | ||||||||||||||||||||||||
Arm description |
Subjects with Leber Hereditary Optic Neuropathy (LHON) who participated in the RESCUE and REVERSE clinical trials were administered gene therapy with the investigational medicinal product (IMP), GS010, by a single intravitreal (IVT) injection in a single randomly-selected eye, while the fellow eye received a sham IVT injection. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
GS010 (rAAV2/2-ND4)
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Investigational medicinal product code |
GS010
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Other name |
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Pharmaceutical forms |
Suspension for suspension for injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
GS010 (rAAV2/2-ND4) Drug Product is a sterile suspension of concentrated and purified virus vector formulated in Balanced Saline Solution (BSS) plus 0.001% Pluronic F68®. GS010 is stored at ≤ -70°C.
GS010 was administered via standard intravitreal injection under local (i.e. topical) anesthesia.
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Investigational medicinal product name |
Sham injection
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intraocular use
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Dosage and administration details |
Sham IVT injection will be performed by applying pressure to the eye at the location of a typical procedure using the blunt end of a syringe without a needle.
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Arm title
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Sham IVT arm | ||||||||||||||||||||||||
Arm description |
Subjects with Leber Hereditary Optic Neuropathy (LHON) who participated in the RESCUE and REVERSE clinical trials were administered gene therapy with the investigational medicinal product (IMP), GS010, by a single intravitreal (IVT) injection in a single randomly-selected eye, while the fellow eye received a sham IVT injection. | ||||||||||||||||||||||||
Arm type |
sham injection | ||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
from 2 to 5 Years
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Modified Intent-to-treat population
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Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All efficacy analyses were conducted on the modified intent-to-treat population and additionally in subset
populations, as appropriate.The modified intent-to-treat (mITT) population consisted of all subjects who received the IMP in
RESCUE or REVERSE Phase III studies, consented to be enrolled in this LTFU study, and
provided visual acuity data at Visit 2 (Year 2.5).
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End points reporting groups
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Reporting group title |
GS010 arm
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Reporting group description |
Subjects with Leber Hereditary Optic Neuropathy (LHON) who participated in the RESCUE and REVERSE clinical trials were administered gene therapy with the investigational medicinal product (IMP), GS010, by a single intravitreal (IVT) injection in a single randomly-selected eye, while the fellow eye received a sham IVT injection. | ||
Reporting group title |
Sham IVT arm
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Reporting group description |
Subjects with Leber Hereditary Optic Neuropathy (LHON) who participated in the RESCUE and REVERSE clinical trials were administered gene therapy with the investigational medicinal product (IMP), GS010, by a single intravitreal (IVT) injection in a single randomly-selected eye, while the fellow eye received a sham IVT injection. | ||
Subject analysis set title |
Modified Intent-to-treat population
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
All efficacy analyses were conducted on the modified intent-to-treat population and additionally in subset
populations, as appropriate.The modified intent-to-treat (mITT) population consisted of all subjects who received the IMP in
RESCUE or REVERSE Phase III studies, consented to be enrolled in this LTFU study, and
provided visual acuity data at Visit 2 (Year 2.5).
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End point title |
Ocular Adverse Events (AEs) [1] | |||||||||
End point description |
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
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End point type |
Primary
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End point timeframe |
from 2 to 5 years
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistical analyses. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Visual Acuity | ||||||||||||
End point description |
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
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End point type |
Secondary
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End point timeframe |
Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Responder Analysis: clinically relevant recovery | |||||||||
End point description |
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
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End point type |
Secondary
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End point timeframe |
Nadir to 5 Years post-treatment, Assessed at Baseline in RESCUE and REVERSE studies to year 5 post-treatment
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| No statistical analyses for this end point | ||||||||||
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End point title |
Eyes on chart | |||||||||
End point description |
Definition: visual acuity inferior or equal to LogMar +1.6 at 5 Years post-treatment
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End point type |
Secondary
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End point timeframe |
Year 5 post-treatment
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
from 2 to 5 years
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
All subjects
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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17 Sep 2018 |
Purposes and Rationale for Amendment
1. Based on REVERSE (Study GS-LHON-CLIN-03B) available efficacy data, contrast sensitivity measured with the Pelli-Robson chart constitutes additional and complementary key information to better assess patients’ benefit from GS010. Therefore, contrast sensitivity assessments have been added every year through the GS-LHON-CLIN-06 long-term follow up study.
2. Another purpose of the amendment is to add comparisons between all GS010-treated eyes and all sham-treated eyes at years 2, 2.5, 3, 4, and 5 for the secondary endpoints “visual improvement as measured by LogMAR” and “change of ganglion cell layer thickness/volume and topographical map and other parameters measured by SD-OCT.” The addition of these comparisons will make the efficacy analysis more complete and provide additional insight into the long-term efficacy of GS010.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
