Efficacy & Safety Study of Bilateral IVT Injection of GS010 in LHON Subjects Due to the ND4 Mutation for up to 1 Year (REFLECT)
Leber Hereditary Optic Neuropathy
About this trial
This is an interventional treatment trial for Leber Hereditary Optic Neuropathy focused on measuring 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
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).
Sites / Locations
- Doheny Eye Center UCLA Pasadena
- University of Colorado Health Eye Center
- Emory Healthcare - The Emory Clinic
- Massachusetts Eye and Ear Infirmary
- Icahn School of Medicine at Mount Sinai
- Wills Eye Institute - Ocular Oncology Service
- Vanderbilt Eye Institute
- Universitair Ziekenhuis Gent
- CHNO Les Quinze Vingts
- IRCCS Istituto delle Scienze Neurologiche di Bologna UOC Clinica Neurologica
- Hospital Universitario Ramon y Cajal
- Taipei Veterans General Hospital
- Moorfields Eye Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Treatment Arm 1
Treatment Arm 2
Subjects will be randomized to treatment arm 1 or treatment arm 2 in a 1:1 allocation. Subjects in treatment arm 1 will receive intravitreal GS010 in both eyes.
Subjects will be randomized to treatment arm 1 or treatment arm 2 in a 1:1 allocation. Subjects in treatment arm 2 will receive GS010 in one eye and placebo intravitreal injection in the other eye.