NCT05293626

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

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
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 12 (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 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.

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 1.5×109 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

Conditions

• Leber Hereditary Optic Neuropathy (LHON)

Interventions

Type	Name	Description
DRUG	NR082 Injection	The starting dose is 1.5E9 vg, 0.05 mL eye/dose. Dose Escalation: If drug-related dose-limiting toxicity (DLT) events are observed in ≤ 2 of the 6 evaluable subjects using the starting dose within 6 weeks after the dosing of NR082, the dose can be escalated to 4.5E9 vg, 0.05 mL eye/dose (high dose) after approval by SRC. Dose De-escalation： If drug-related dose-limiting toxicity (DLT) events are observed in \> 2 of the 6 evaluable subjects using the starting dose within 6 weeks after the dosing of NR082, the dose can be de-escalated to 0.5E9 vg, 0.05 mL eye/dose (low dose) after 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 3.0E9 vg, 0.05 mL eye/dose (intermediate dose) after the approval by SRC.
DEVICE	Injection needle	19G 1 1/2IN TW filter needle with filter element (BD 305200)，used to NR082 Intraocular injection solution dose preparation; 30G 1/2IN injection needle (BD 305106)，used to NR082 Intraocular injection solution administration; 1 ml screw top syringe (BD 309628),used to NR082 Intraocular injection solution dose preparation and administration.

Timeline

• Start date: 2023-05-22
• Primary completion: 2025-07-01
• Completion: 2029-12-01
• First posted: 2022-03-24
• Last updated: 2024-09-04

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study