A Phase 3, Multicenter, Randomized, Double-Masked, Sham-Controlled Clinical Trial for Leber's Hereditary Optic Neuropathy (LHON) Associated With ND4 Mutation

NCT07406854 | Active Not Recruiting Phase 3

• 1 other identifier: NFS-01-201
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief 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 ≥ 12 years old and ≤ 75 years old to receive a single bilateral intravitreal (IVT) injection of NR082 to evaluate 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 and reduced visual acuity lasted for \>6 months and \<10 years.

Conditions

Leber Hereditary Optic Neuropathy (LHON)

Outcome Measures

Primary Outcomes (1)

• Efficacy of NR082 in study eye

  Proportion of ≥ 0.3 LogMAR from baseline in BCVA in the study eye in the NR082 treatment and the sham-injection at Week 52 after treatment

  52 weeks

Secondary Outcomes (3)

• Efficacy of NR082 in study eye and non-study eye

  52 weeks

• Mean change from baseline in visual field, contrast sensitivity

  52 weeks

• Safety and tolerability of NR082

  52 weeks

Study Arms (2)

Experimental: NR082 injection

EXPERIMENTAL

4.5E9 viral genomes (vg) , 0.05 mL eye/dose , bilaterally

Genetic: rAAV2-ND4

Sham Comparator: sham-injection

SHAM COMPARATOR

Sham intravitreal injection （bilateral）will be performed by applying pressure to the eye at the location of a typical intravitreal injection procedure using the blunt end of a syringe without a needle.

Other: Sham (No Treatment)

Interventions

Sham (No Treatment) OTHER

sham-injection

Sham Comparator: sham-injection

rAAV2-ND4 GENETIC

a single bilateral intravitreal (IVT) injection of NR082

Experimental: NR082 injection

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age at the time of signing the informed consent form: the age of the subjects must be ≥ 12 years old and ≤ 75 years old
• The clinical manifestation of all subjects is reduced visual acuity caused by LHON associated with ND4 mutation, while the reduced visual acuity lasted for \> 6 months and \< 10 years
• The clinical manifestation caused by LHON is vision loss, with a visual acuity of ≥ 0.5 LogMAR and ≤1.68 in BCVA in both eye The genotype test result is that there is G11778A mutation in ND4 gene, and there are no other primary LHON-associated mutations in the mitochondrial DNA (mtDNA) (ND1\[G3460A\] or ND6\[T14484C\]) (confirmed by a CLIA-certified international laboratory) Pupils can be adequately dilated for a comprehensive eye examination and visual acuity test

You may not qualify if:

• Any known allergy and/or hypersensitivity to the study drug or its constituents Contraindication to IVT injection in any eye
• IVT drug delivery to any eye within 30 days prior to the screening visit History of vitrectomy in either eye
• Narrow anterior chamber angle in any eye contra-indicating pupillary dilation
• Presence of disorders or diseases of the eye or adnexa, excluding LHON, which may interfere with visual or ocular assessments, including optical coherence tomography during the study
• Presence of known/documented mutations, other than the LHON-related mutation, which are known to cause pathology of the optic nerve, retina or afferent visual system
• Presence of systemic or ocular/vision diseases, disorders or pathologies, other than LHON, known to cause or be associated with vision loss, or whose associated treatment(s) or therapy(ies) is/are known to cause or be associated with vision loss
• Presence of optic neuropathy from any cause other than LHON
• Presence of illness or disease that, in the opinion of the investigator, include symptoms and/or the associated treatments that can alter visual function, for instance cancers or pathology of the CNS, including multiple sclerosis (diagnosis of multiple sclerosis must be based on the 2010 Revisions to the McDonald Criteria) (Polman et al., 2011), and/or diseases or conditions that affect the safety of subjects participating in the study
• History of recurrent uveitis (idiopathic or immune-related) or active ocular inflammation
• Participated in another clinical study and receive IP within 90 days prior to the screening visit
• a) Exceptions: Subjects who have completed the clinical study of idebenone as IP within 90 days prior to the screening visit, and has completely discontinued idebenone at least 7 days prior to dosing are still eligible to participate in the study.
• Any eye has previously received ocular gene therapy
• Subjects who refused to stop using idebenone
• Have undergone ocular surgery of clinical relevance (per investigator's assessment) within 90 days prior to the screening visit
• Female subjects who are breastfeeding or plan to breastfeed within the first 6 months after the administration of NR082 Injection

Sponsors & Collaborators

• Wuhan Neurophth Biotechnology Limited Company: lead

Study Sites (1)

Beijing Tongren Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Location

MeSH Terms

Conditions

Optic Atrophy, Hereditary, Leber

Interventions

salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Optic Atrophies, Hereditary; Optic Atrophy; Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Eye Diseases, Hereditary; Eye Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, Randomized, Double-Masked, Sham-Controlled

Study Record Dates

• First Submitted: February 4, 2026
• First Posted: February 12, 2026
• Study Start: September 19, 2024
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): May 30, 2030
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)