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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 10 December 2019
Main ID:  EUCTR2017-002187-40-GB
Date of registration: 18/01/2018
Prospective Registration: Yes
Primary sponsor: GENSIGHT BIOLOGICS
Public title: Efficacy and Safety of Bilateral Intravitreal Injection of GS010
Scientific title: Efficacy and Safety of Bilateral Intravitreal Injection of GS010: A Randomized, Double-Masked, Placebo-Controlled Trial in Subjects Affected with G11778A ND4 Leber Hereditary Optic Neuropathy for Up to One Year - REFLECT
Date of first enrolment: 30/03/2018
Target sample size: 90
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002187-40
Study type:  Interventional clinical trial of medicinal product
Study design: 
Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: yes
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: yes
Other: no
Number of treatment arms in the trial: 2
 
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
Belgium France Italy Netherlands Spain United Kingdom
Contacts
Name: Regulatory Affairs Director   
Address:  74 rue du Faubourg Saint-Antoine 75012 PARIS France
Telephone: 33176217233
Email: ipengue@gensight-biologics.com
Affiliation:  GENSIGHT-BIOLOGICS
Name: Regulatory Affairs Director   
Address:  74 rue du Faubourg Saint-Antoine 75012 PARIS France
Telephone: 33176217233
Email: ipengue@gensight-biologics.com
Affiliation:  GENSIGHT-BIOLOGICS
Key inclusion & exclusion criteria
Inclusion criteria:
1. Age 15 years or older on the date of signed informed consent.
2. Clinically manifested vision loss due to ND4 LHON, to any extent, in at
least one eye.
3. Vision loss duration of = 365 days (i.e. = 1 year) in each affected eye
at Inclusion Visit
(Visit 2).
4. Female subjects (if of childbearing potential) must agree to use
effective methods of birth control for up to 6 months after Treatment Visit(s) 3 and male subjects must agree to use condoms for up to 6 months after Treatment Visit(s) 3.
5. Ability to obtain adequate pupillary dilation to permit thorough ocular
examination and visual testing.
6. Subject – and parent/legal guardian if the subject is under 18 years of
age – has provided signed, written informed consent.
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 76
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion criteria:
1. Any known allergy or hypersensitivity to GS010 or its constituents.
2. Contraindication to intravitreal injection in any eye.
3. Intravitreal drug delivery to any eye within 30 days prior to the
Screening Visit (Visit 1).
4. Previous vitrectomy in either eye.
5. Narrow angle in any eye contra-indicating pupillary dilation.
6. Presence of disorders or diseases of the eye or adnexa, excluding
LHON, which may interfere with visual or ocular assessments, including SD-OCT, during the study period.
7. Presence of known/documented mutations, other than the G11778A
ND4 LHON-causing mutation, which are known to cause pathology of the optic nerve, retina or afferent visual system.
8. Presence of systemic or ocular/vision diseases, disorders or
pathologies, other than LHON, known to cause or be associated with vision loss, or whose associated treatment(s) or
therapy(ies) is/are known to cause or be associated with vision loss.
9. Presence of optic neuropathy from any cause except LHON.
10. Presence of illness or disease that, in the opinion of the Investigator,
include symptoms and/or the associated treatments that can alter visual function, for instance cancers or pathology of the central nervous system, including Multiple Sclerosis (diagnosis of Multiple Sclerosis must be based on the 2010 Revisions to the McDonald Criteria [Polman 2011]).
11. History of recurrent uveitis (idiopathic or immune-related) or active
ocular inflammation.
12. Participation in another clinical trial and receiving an IMP within 90 days prior to the Screening Visit (Visit 1). Exception: subjects remain eligible if they completed a clinical trial with idebenone as an IMP less than 90 days prior to Visit 1 AND completely discontinued idebenone at least 7 days prior to Visit 2.
13. Previous treatment with ocular gene therapy in either eye.
14. Subjects refusing to discontinue idebenone.
15. Subjects who have undergone ocular surgery of clinical relevance
(per Investigator assessment) within 90 days preceding the Screening
Visit (Visit 1).
16. Female Subjects who are, or who intend to breast feed during the initial six months' postadministration of GS010.
17. Subjects who unable to tolerate (e.g. the immune modulating
regimen) or unable or unwilling to comply with all the protocol
requirements.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Therapeutic area: Diseases [C] - Eye Diseases [C11]
Leber Hereditary Optic Neuropathy due to mutations in the mitochondrial NADH Dehydrogenase 4 gene
MedDRA version: 20.1 Level: LLT Classification code 10062951 Term: Leber's hereditary optic atrophy neuropathy System Organ Class: 100000004850
Intervention(s)

Product Name: Recombinant AAV vector serotype 2 containing the human wild type mitochondrial ND4 gene
Product Code: GS010
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: lenadogene nolparvovec
CAS Number: 1640969-63-6
Current Sponsor code: GS010
Other descriptive name: Recombinant Adeno-Associated Viral vector, serotype 2 (rAAV2/2) containing the human wild-type mitochondrial NADH Dehydrogenase 4 gene (ND4)
Concentration unit: vector genomes (vg)/mL
Concentration type: not less then
Concentration number: 1E12-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravitreal use

Primary Outcome(s)

Main Objective: To assess the efficacy of intravitreal GS010 compared to placebo
intravitreal injection in second affected/not yet affected eyes, at 1.5-Year
post-treatment, analyzing the change from baseline of the best-corrected
visual acuity (BCVA) reported with the Log of the Minimal Angle of
Resolution (LogMAR), in ND4 LHON subjects with vision loss up to one
year.
Primary end point(s): The primary efficacy endpoint will be the change from baseline (Visit 2) BCVA reported with LogMAR at 1.5-Year post-treatment in second affected/not yet affected eyes of ND4 LHON subjects with vision loss up to one year. The change from baseline (Visit 2) in second affected/not yet affected eyes receiving GS010 and placebo will be the primary response of interest. LogMAR BCVA will be used to represent BCVA.

Secondary Objective: Assess safety and tolerability of bilateral and unilateral intravitreal injection of GS010
Compare time course of the BCVA LogMAR response in second affected/not yet affected eyes treated with GS010 compared to placebo treatment
Assess the efficacy of intravitreal GS010 compared to placebo intravitreal injection in second affected/not yet affected eyes
Compare the time course of the response in second affected/not yet affected eyes treated with GS010 compared to placebo treatment and to estimate the magnitude of the treatment effect at 1.5 and 2-years post treatment
Verify whether a difference exists at 1.5 and 2-years post-treatment, between first affected eyes and second affected/not yet affected eyes treated with GS010, using both an intra-subject and inter-subject analysis
Assess rate of responders in first affected eyes treated with GS010
Assess humoral and cellular immune responses
Assess impact of bilateral intravitreal GS010 administration on Quality of Life
Timepoint(s) of evaluation of this end point: at 1.5-Year post-treatment in second affected/not yet affected eyes of ND4 LHON subjects
Secondary Outcome(s)

Secondary end point(s): Change from baseline in LogMAR BCVA at each timepoint of the follow-up period and at 2-years post-treatment.
Response status at each timepoint of the follow-up period and at 2-years post-treatment.

Timepoint(s) of evaluation of this end point: BCVA : each timepoint of the follow-up period and at 2-years post-treatment,
Response status at each timepoint of the follow-up period and at 2-years post-treatment.
Secondary ID(s)
GS-LHON-CLIN-05
2017-002187-40-BE
NCT03293524
Source(s) of Monetary Support
GENSIGHT-BIOLOGICS
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date:
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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