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Background <p>This study aimed to assess the safety and efficacy of a rAAV2 carrying normal <i>ND4</i> (rAAV2-<i>ND4</i>) (NR082) in individuals with visual loss due to LHON carrying the m.11778G&gt;A mutation. Additionally, it aimed to determine a safe dose of NR082 for intravitreal injection.</p> Methods <p>This was a single-arm, open-label, dose-finding clinical trial. A total of 12 participants with the m.11778G&gt;A mitochondrial DNA mutation and vision loss exceeding 6 months in both eyes were enrolled in this trial. The participants received NR082 by unilateral intravitreal injections. 6 participants received 1.5 × 10<sup>9</sup> vg, 0.05 mL (Group I), and 6 participants received 4.5 × 10<sup>9</sup> vg, 0.05 mL (Group II) and were followed for 52 weeks and underwent safety assessments, with visual structure and function examinations.</p> Results <p>No serious ocular or systemic adverse events or dose-limiting toxicity were reported. Adverse events possibly related to treatment included uveitis, subconjunctival haemorrhage, vitreous opacity and keratic precipitates. In Group I, the mean baseline best-corrected visual acuity (BCVA) in injected eyes improved from 1.86 ± 0.36 LogMAR at baseline to 1.59 ± 0.10 LogMAR in week 52 post intravitreal rAAV2-<i>ND4</i>. In Group II, baseline BCVA was 2.15 ± 0.23 LogMAR, improving to 1.92 ± 0.32 LogMAR in week 52. Two eyes in Group I and four eyes in Group II showed significant improvement (at least 0.3 LogMAR BCVA improvement) after 52 weeks.</p> Conclusion <p>This Phase 1/2 trial demonstrated no serious safety concerns among the 12 participants. And dose of 4.5 × 10<sup>9</sup> vg, 0.05 mL was to be used in future Phase 3 study.</p>

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Efficacy and safety of intravitreal rAAV2-ND4 therapy for Leber’s hereditary optic neuropathy

  • 期刊论文

  • 发表日期：

    2025年9月30日

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  • Libin Jiang,
  • Sitong Guo,
  • Bin Li,
  • Su Xiao,
  • Fei Wang,
  • Wenbin Wei

摘要

Background

This study aimed to assess the safety and efficacy of a rAAV2 carrying normal ND4 (rAAV2-ND4) (NR082) in individuals with visual loss due to LHON carrying the m.11778G>A mutation. Additionally, it aimed to determine a safe dose of NR082 for intravitreal injection.

Methods

This was a single-arm, open-label, dose-finding clinical trial. A total of 12 participants with the m.11778G>A mitochondrial DNA mutation and vision loss exceeding 6 months in both eyes were enrolled in this trial. The participants received NR082 by unilateral intravitreal injections. 6 participants received 1.5 × 109 vg, 0.05 mL (Group I), and 6 participants received 4.5 × 109 vg, 0.05 mL (Group II) and were followed for 52 weeks and underwent safety assessments, with visual structure and function examinations.

Results

No serious ocular or systemic adverse events or dose-limiting toxicity were reported. Adverse events possibly related to treatment included uveitis, subconjunctival haemorrhage, vitreous opacity and keratic precipitates. In Group I, the mean baseline best-corrected visual acuity (BCVA) in injected eyes improved from 1.86 ± 0.36 LogMAR at baseline to 1.59 ± 0.10 LogMAR in week 52 post intravitreal rAAV2-ND4. In Group II, baseline BCVA was 2.15 ± 0.23 LogMAR, improving to 1.92 ± 0.32 LogMAR in week 52. Two eyes in Group I and four eyes in Group II showed significant improvement (at least 0.3 LogMAR BCVA improvement) after 52 weeks.

Conclusion

This Phase 1/2 trial demonstrated no serious safety concerns among the 12 participants. And dose of 4.5 × 109 vg, 0.05 mL was to be used in future Phase 3 study.