NCT05820152

Gene Therapy Clinical Trial for the Treatment of Leber's Hereditary Optic Neuropathy Associated With ND1 Mutations

A Phase 1/2, Multi-regional, Single-Arm, Open-Label, Dose-Finding Clinical Trial to Evaluate the Safety, Tolerability and Efficacy of Gene Therapy for Leber's Hereditary Optic Neuropathy (LHON) Associated With ND1 Mutation

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 11 (actual)
• Sponsor: Neurophth Therapeutics Inc · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The objective of this clinical study is to evaluate the safety, tolerability and preliminary efficacy of NFS-02 in the treatment of LHON caused by mitochondrial ND1 gene mutation. This study will enroll subjects aged ≥ 18 years old and ≤ 75 years old to receive a single unilateral intravitreal (IVT) injection of NFS-02 to evaluate its safety, tolerability and preliminary efficacy. The clinical manifestations of all subjects are to be reduced visual acuity caused by LHON associated with ND1 mutation, with laboratory test showing G3460A mutation (a CLIA-certified laboratory) and reduced visual acuity lasted for \> 6 months and \< 10 years.

Detailed 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 1.5×108 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 NFS-02 at the starting dose, the dose can be escalated to 5.0×108 vg, 0.05 mL eye/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 NFS-02 at the 5.0×108 vg, 0.05 mL eye/dose, the dose can be escalated to 1.5×109 vg, 0.05 mL eye/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 NFS-02 at the starting dose, the dose can be de-escalated to 5.0×107 vg, 0.05 mL eye/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.

Conditions

• Leber Hereditary Optic Neuropathy (LHON)

Interventions

Type	Name	Description
DRUG	NFS-02 Injection	The starting dose is 1.5×108 vg, 0.05 mL eye/dose. If drug-related dose-limiting toxicity (DLT) events are observed in \< 2 of the 6 evaluable subjects within 6 weeks after the dosing of NFS-02 at the starting dose, the dose can be escalated to 5.0×108 vg, 0.05 mL eye/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 NFS-02 at the 5.0×108 vg, 0.05 mL eye/dose, the dose can be escalated to 1.5×109 vg, 0.05 mL eye/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 NFS-02 at the starting dose, the dose can be de-escalated to 5.0×107 vg, 0.05 mL eye/dose after the approval by SRC.

Timeline

• Start date: 2023-08-15
• Primary completion: 2024-06-24
• Completion: 2024-06-24
• First posted: 2023-04-19
• Last updated: 2024-09-20

Locations

4 sites across 2 countries: United States, China

Regulatory

• FDA-regulated drug study