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Phase 3 N=98 Randomized Double-blind Treatment

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

Leber Hereditary Optic Neuropathy

Enrolled (actual)
98
Serious AEs
11.2%
Results posted
Apr 2026
Primary outcome: Primary: Change From Baseline of the Best Corrected Visual Acuity (BCVA) Reported With Log of the Minimal Angle of Resolution (LogMAR) at 1.5 Years Post-treatment, in the Second Affected/Not-yet Affected Eyes — -0.09; -0.04 logMAR — p== 0.608

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
GS010 (Genetic); Placebo (Drug)
Age
Pediatric, Adult, Older Adult · 15+ yrs
Sex
All
Sponsor
GenSight Biologics
Primary completion
Jul 2024

Outcome Measures

OutcomeResultp-value
PRIMARY
Change From Baseline of the Best Corrected Visual Acuity (BCVA) Reported With Log of the Minimal Angle of Resolution (LogMAR) at 1.5 Years Post-treatment, in the Second Affected/Not-yet Affected Eyes
-0.09; -0.04 = 0.608
SECONDARY
Change From Baseline of the BCVA Reported With LogMAR at 5 Years Post-treatment, in the Second Affected/Not-yet Affected Eyes
-0.13; -0.05 = 0.5086
SECONDARY
Proportion of Patients Who Switched From Off-chart Eyes to On-chart Eyes at 5 Years Post-treatment
61.54; 33.33
SECONDARY
Responder Analyses - Improvements From Nadir (Gainer Eyes) at 5 Years
68.8; 66.0 = 0.7605
SECONDARY
Responder Analyses - Clinically Relevant Recovery From Nadir at 5 Years
75.0; 60.0 = 0.1352
SECONDARY
Responder Analyses- Clinically Relevant Benefit at 5 Years
75.0; 62.0 = 0.1995
SECONDARY
Quality of Life Questionnaire: VFQ-25 - Composite Score
11.8; 15.0 = 0.3605

Summary

The goal of this clinical trial is to assess the efficacy and safety of GS010 gene therapy - (lenadogene nolparvovec) in subjects with LHON due to the G11778A ND4 mitochondrial mutation with a vision loss up to one year.

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).
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03293524). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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