Efficacy & Safety Study of Bilateral IVT Injection of GS010 in LHON Subjects Due to the ND4 Mutation for up to 1 Year (REFLECT)

GenSight Biologics

Status and phase: Completed; Phase 3

Conditions: Leber Hereditary Optic Neuropathy

Treatments: Drug: Placebo; Genetic: GS010

Study type: Interventional

Funder types: Industry

Identifiers

NCT03293524

GS-LHON-CLIN-05

2017-002187-40 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 98 patients

Sex: All

Ages: 15+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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98 participants in 2 patient groups, including a placebo group

Treatment Arm 1

Experimental group

Description:

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.

Treatment:

Genetic: GS010

Treatment Arm 2

Placebo Comparator group

Description:

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.

Treatment:

Genetic: GS010

Drug: Placebo