Gene Therapy Clinical Trial for the Treatment of Leber's Hereditary Optic Neuropathy Associated With ND4 Mutations

Leber Hereditary Optic Neuropathy (LHON) Clinical Trial

Official title: A Phase 1/2, Single-Arm, Open-Label, Dose-Finding Clinical Trial to Evaluate the Safety and Efficacy of Gene Therapy for Leber's Hereditary Optic Neuropathy (LHON) Associated With ND4 Mutation

Status Active, not recruiting

Clinical Trial Summary

The objective of this clinical study is to evaluate the safety and efficacy of NR082 in the treatment of LHON caused by mitochondrial ND4 gene mutation. This study will enroll subjects aged ≥ 18 years old and ≤ 75 years old to receive a single unilateral intravitreal (IVT) injection of NR082 to evaluate its safety and efficacy. The clinical manifestations of all subjects are to be reduced visual acuity caused by LHON associated with ND4 mutation, with laboratory test showing G11778A mutation (a CLIA-certified laboratory) and reduced visual acuity lasted for > 6 months and < 10 years.

Clinical Trial Description

At the dose-finding stage, the principle is that the Safety Review Committee (SRC) will decide whether to make dose adjustment based on the safety data of the starting dose. The starting dose is 1.5×109 vg, 0.05 mL eye/dose.The safety of the starting dose will be reviewed by the SRC, and dose escalation or de-escalation is by recommendation of the SRC.The safety of the starting dose will first be performed in 6 evaluable subjects.

Criteria for Dose Modification:

Dose Escalation:

If drug-related dose-limiting toxicity (DLT) events are observed in ≤ 2 of the 6 evaluable subjects within 6 weeks after the dosing of NR082 at the starting dose, the dose can be escalated to 4.5×109 vg, 0.05 mL eye/dose (high dose) after the approval by SRC.

Dose De-escalation:

If drug-related dose-limiting toxicity (DLT) events are observed in > 2 of the 6 evaluable subjects within 6 weeks after the dosing of NR082 at the starting dose, the dose can be de-escalated to 0.5×109 vg, 0.05 mL eye/dose (low dose) after the approval by SRC.

If drug-related dose-limiting toxicity (DLT) events are observed in > 2 of the 6 evaluable subjects within 6 weeks after the dosing of NR082 at the high dose, the dose can be de-escalated to 3.0×109vg, 0.05 mL eye/dose (intermediate dose) after the approval by SRC.

Enrollment Sequence:

• The enrollment sequence of any dose group (6 subjects) is that the 2nd subject and the 3rd subject will be enrolled at least 7 days after the enrollment of the 1st subject;

• The 4th, 5th and 6th subjects will be enrolled at least 7 days after the enrollment of the 2nd and the 3rd subjects.

The 7-day interval is to avoid acute safety events to the greatest possible extent ;

Related Conditions & MeSH terms

• Leber Hereditary Optic Neuropathy (LHON)
• Optic Atrophy, Hereditary, Leber
• Optic Nerve Diseases

• NCT number: NCT05293626
• Study type: Interventional
• Source: Neurophth Therapeutics Inc
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: May 22, 2023
• Completion date: December 2029