Clinical trial NCT03293524: Efficacy & Safety Study of Bilateral IVT Injection of GS010 in LHON Subjects Due to the ND4 Mutation for up to 1 Year
Official 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Leber Hereditary Optic Neuropathy
Keywords: Heredity Optic Atrophy
Leber Hereditary Optic Atrophy
Leber Hereditary Optic Neuropathy
LHON
Eye Diseases
Hereditary Eye Diseases
Inherited retinal dystrophies or degeneration
Inborn Genetic Disease
Gene Therapy
Intravitreal Injections
Mitochondrial Disease
AAV2 Vectors
Nervous System Diseases
Neurodegenerative Disease
Heredodegenerative Disorders of the Nervous System
Atrophy
Pathological Conditions, Anatomical
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Lead sponsor: GenSight Biologics
Sponsor class: INDUSTRY
First posted: 2017-09-26
Enrollment: 90
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to assess the safety and efficacy of GS010, a gene therapy, in improving the retina functional \& structural outcomes in subjects with LHON due to the G11778A ND4 mitochondrial mutation when vision loss duration is present up to one year.

Detailed description: GS-LHON-CLIN-05 is a Phase III, global, multi-center randomized, double-masked for the primary analysis, placebo-controlled, clinical study. As LHON is a neurodegenerative disease, the goal is to administer GS010 as soon as possible upon confirmation of the LHON diagnosis and the causative mutation.

Eligibility criteria: Main Selection Criteria:

* Age 15 years or older on the date of signed informed consent.
* Clinically manifested vision loss due to ND4 LHON, to any extent, in at least one eye.
* Vision loss duration of ≤ 365 days (i.e. ≤ 1 year) in each affected eye at Inclusion Visit (Visit 2).

Main Non-Selection Criteria:

* Contraindication to intravitreal injection in any eye.
* Subjects refusing to discontinue idebenone.
* Previous vitrectomy in either eye.
* Narrow angle in any eye contra-indicating pupillary dilation.
* 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.
* History of recurrent uveitis (idiopathic or immune-related) or active ocular inflammation.

Main Inclusion Criteria:

* Vision loss duration of ≤ 365 days (i.e. ≤ 1 year) in each affected eye at Inclusion Visit (Visit 2).
* Each eye of the subject must maintain at least Hand Motion (HM) visual acuity, as defined by the study's SOP for visual acuity testing.
* Documented results of genotyping showing the presence of the G11778A mutation in the ND4 gene and the absence of the other primary LHON-associated mutations (ND1 or ND6) in the subject's mitochondrial DNA.

Main Exclusion Criteria:

* Light Perception (LP) or No Light Perception (NLP) visual acuity in any eye, as defined by the study's standard operating procedure (SOP) for visual acuity testing.
* Presence of active infectious conjunctivitis, keratitis, scleritis or endophthalmitis in either eye.
* Presence of alcoholism, alcohol dependence, or alcohol or drug abuse (excluding nicotine).

Primary outcomes:
measure: Best-Corrected Visual Acuity (BCVA) reported using Log of the Minimal Angle of Resolution (LogMAR) - 1 year
timeFrame: at 1.5 Year post baseline treatment
Secondary outcomes:
measure: Best-Corrected Visual Acuity (BCVA) reported with LogMAR - 2 years
timeFrame: at 1.5-Year and 2-Years post baseline treatment
measure: Responder Analysis
timeFrame: at 1.5-Year and 2-Years post baseline treatment
measure: Spectral-Domain - Optical Coherence Tomography (SD-OCT) parameter
timeFrame: at 1.5-Year and 2-Years post baseline treatment
measure: Humphrey Visual Field (HVF) parameter
timeFrame: at 1.5-Year and 2-Years post baseline treatment
measure: Pelli Robson Low Vision Contrast Sensitivity parameter
timeFrame: at 1.5-Year and 2-Years post baseline treatment
measure: Quality of Life: Visual Functioning Questionnaire-25
timeFrame: at 1.5-Year and 2-Years post baseline treatment
measure: Quality of Life: 36-Item Short Form Health Survey, version 2 Questionnaire
timeFrame: at 1.5-Year and 2-Years post baseline treatment
Other outcomes:
measure: Adverse events (AEs) and serious adverse events (SAEs)
timeFrame: up to 2-Years post baseline treatment
measure: Physical examinations
timeFrame: At 2-Years post baseline treatment
measure: Electrocardiograms
timeFrame: At 2-Years post baseline treatment
measure: Laboratory results
timeFrame: At 2-Years post baseline treatment
measure: Immune response evaluations
timeFrame: Up to 2-Years post baseline treatment
measure: Blood Bio-dissemination of AAV2 Vector DNA
timeFrame: up to 4 weeks post-treatment
Locations:
city: Pasadena
country: United States
facility: Doheny Eye Center UCLA Pasadena
state: California
city: Aurora
country: United States
facility: University of Colorado Health Eye Center
state: Colorado
city: Atlanta
country: United States
facility: Emory Healthcare - The Emory Clinic
state: Georgia
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Philadelphia
country: United States
facility: Wills Eye Institute - Ocular Oncology Service
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Eye Institute
state: Tennessee
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Paris
country: France
facility: CHNO Les Quinze Vingts
city: Bologna
country: Italy
facility: IRCCS Istituto delle Scienze Neurologiche di Bologna UOC Clinica Neurologica
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
state: Greater London
Study officials:
affiliation: Emory University Hospital Atlanta, Georgia, United States, 30322
name: Nancy Newman, MD
role: PRINCIPAL_INVESTIGATOR
References: