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

Browse trials for

• Optic Atrophy, Hereditary, Leber 44
• Eye Diseases 388
• Eye Diseases, Hereditary 39
• Mitochondrial Diseases 189

Keywords

• Leber Hereditary Optic Atrophy
• Leber Hereditary Optic Neuropathy
• LHON
• Eye Diseases
• Hereditary Eye Diseases
• Inherited retinal dystrophies or degeneration
• Gene Therapy
• Intravitreal Injections
• Mitochondrial Disease
• AAV2 Vectors
• Hereditary Optic Atrophy

Optic Atrophy, Hereditary, Leber

44 studies on the registry are indexed under Optic Atrophy, Hereditary, Leber; 9 are open to participants now.

This study's enrollment of 98 is above the median of 36 across 31 interventional studies indexed under Optic Atrophy, Hereditary, Leber.

Lead sponsor

GenSight Biologics is the lead sponsor of 9 studies on the registry; 1 is open to participants now.

Study arms

• Experimental
  GS010-GS010

  Patients received single IVT injection of GS010 in both their first-affected eye and their second-affected/not-yet-affected eye at a droplet digital polymerase chain reaction (ddPCR) dose of 1.2/1.3E11 vg in 90 μL for each eye. Treatment could be performed either on a single day (1 IVT injection in each eye on Day 0) or on 2 consecutive days (1st IVT injection on Day -1 and 2nd IVT injection on Day 0).

  Genetic: GS010

• Placebo comparator
  GS010-Placebo

  Patients received single IVT injection of GS010 in their first-affected eye and placebo IVT injection in their second-affected/not-yet-affected eye. Patients received IVT lenadogene nolparvovec in their first-affected eye (ddPCR dose of 1.2/1.3E11 vg in a volume of 90 μL) and placebo IVT injection (volume of 90 μL) in their second-affected/not-yet-affected eye. Treatment could be performed either on a single day (1 IVT injection in each eye on Day 0) or on 2 consecutive days (1st IVT injection on Day -1 and 2nd IVT injection on Day 0).

  Genetic: GS010 · Drug: Placebo

Interventions

• GeneticGS010

  GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). GS010 was administrated via intravitreal injection containing 1.2/1.3E11 vg in 90 μL balanced sterile saline solution (BSSS).

  Also known as: Lenadogene nolparvovec

• DrugPlacebo

  The placebo is a balanced sterile saline solution (BSSS) used for IVT. The placebo was administered via intravitreal injection in a volume of 90 μL.

Primary outcomes

1. 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

   The primary efficacy endpoint was the change from baseline of BCVA reported with LogMAR at 1.5-year post-treatment, in the second-affected/not-yet-affected eyes of ND4 LHON patients with vision loss up to one year. LogMAR BCVA was used to represent BCVA.

   Time frame: at 1.5 years post-treatment, in the second-affected/not-yet affected eyes

Secondary outcomes

1. Change From Baseline of the BCVA Reported With LogMAR at 5 Years Post-treatment, in the Second Affected/Not-yet Affected Eyes

   Change from baseline of BCVA reported with LogMAR at 5 years post-treatment, in the second-affected/not-yet-affected eyes of ND4 LHON patients with vision loss up to one year. LogMAR BCVA was used to represent BCVA.

   Time frame: at 5 years post-treatment, in the second-affected/not-yet affected eyes

2. Proportion of Patients Who Switched From Off-chart Eyes to On-chart Eyes at 5 Years Post-treatment

   Proportion of patients with both eyes off-chart, defined as those patients unable to read letter on the ETDRS chart, who had at least one eye on-chart, defined as those patients able to read letters on the ETDRS chart (at either 4 meters or 1 meter) at 5 years

   Time frame: From baseline to 5 years post-treatment

3. Responder Analyses - Improvements From Nadir (Gainer Eyes) at 5 Years

   Proportion of patients with an improvement of at least -0.3 LogMAR (≥ +15 ETDRS letters) from nadir to year 5 in at least one eye. Nadir was defined for each eye of each subject as the worst value observed from baseline to year 5

   Time frame: From nadir to 5 years post-treatment

4. Responder Analyses - Clinically Relevant Recovery From Nadir at 5 Years

   Proportion of patients with clinically relevant recovery (CRR) from nadir that was defined as patient with a CRR in at least one eye - Patient with at least one eye which was on chart at nadir, and which had an improvement of at least -0.2 LogMAR from nadir, or which was off-chart at nadir but became on-chart

   Time frame: From nadir to 5 years post-treatment

5. Responder Analyses- Clinically Relevant Benefit at 5 Years

   Proportion of patients who had clinically relevant stabilization (CRS), defined as eyes with LogMAR BCVA \< 1 at baseline and at 5 years post-treatment or had a clinically relevant recovery (CRR) from nadir. The best response observed in either eye was considered.

   Time frame: From baseline nadir to 5 years post-treatment

6. Quality of Life Questionnaire: VFQ-25 - Composite Score

   Change from baseline to 5 years follow up in the Visual Function Questionnaire (VFQ-25) composite score. The VFQ-25 is a patient-reported outcome instrument assessing vision-related quality of life and consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs plus an additional single-item general health rating question. Each item was converted to a 0-100 scale for scoring, where 100 represents the best possible score on the measure and 0 represents the worst. Items within each subscale were averaged to create 12 subscale scores (11 subscales related to vision + 1 subscale related to general health). The vision-related subscale scores (excluding the general health rating question) were then averaged to calculate the composite score.

   Time frame: From baseline to 5 years post-treatment

Baseline characteristics

2 further baseline measures are reported on the registry.

Publications

• Carelli V, Newman NJ, Yu-Wai-Man P, Biousse V, Moster ML, Subramanian PS, Vignal-Clermont C, Wang AG, Donahue SP, Leroy BP, Sergott RC, Klopstock T, Sadun AA, Rebolleda Fernandez G, Chwalisz BK, Banik R, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA; the LHON Study Group. Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G>A MT-ND4 Mutation. Ophthalmol Ther. 2023 Feb;12(1):401-429. doi: 10.1007/s40123-022-00611-x. Epub 2022 Nov 30. PubMed 36449262 ↗

Related links

• GenSight Biologics website ↗

Study documents

• Study protocol ↗ · Dec 23, 2019
• Statistical analysis plan ↗ · Oct 10, 2024

PDFs hosted by the registry, ClinicalTrials.gov.