Main
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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:
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EUCTR |
Last refreshed on:
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10 December 2019 |
Main ID: |
EUCTR2017-002187-40-GB |
Date of registration:
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18/01/2018 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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Efficacy and Safety of Bilateral Intravitreal Injection of GS010
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Scientific title:
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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:
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30/03/2018 |
Target sample size:
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90 |
Recruitment status: |
Authorised-recruitment may be ongoing or finished |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002187-40 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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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
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): no
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Belgium
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France
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Italy
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Netherlands
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Spain
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United Kingdom
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Contacts
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Name:
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Regulatory Affairs Director
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Address:
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74 rue du Faubourg Saint-Antoine
75012
PARIS
France |
Telephone:
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33176217233 |
Email:
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ipengue@gensight-biologics.com |
Affiliation:
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GENSIGHT-BIOLOGICS |
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Name:
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Regulatory Affairs Director
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Address:
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74 rue du Faubourg Saint-Antoine
75012
PARIS
France |
Telephone:
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33176217233 |
Email:
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ipengue@gensight-biologics.com |
Affiliation:
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GENSIGHT-BIOLOGICS |
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Key inclusion & exclusion criteria
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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
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Health Condition(s) or Problem(s) studied
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Therapeutic area: Diseases [C] - Eye Diseases [C11]
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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
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Intervention(s)
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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
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Primary Outcome(s)
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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.
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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.
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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
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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
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Secondary Outcome(s)
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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.
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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.
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Secondary ID(s)
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GS-LHON-CLIN-05
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2017-002187-40-BE
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NCT03293524
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Source(s) of Monetary Support
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GENSIGHT-BIOLOGICS
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Ethics review
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Status: Approved
Approval date:
Contact:
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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