About this trial
The objective of this clinical study is to select the optimal dose and evaluate the safety and efficacy of NR082 in treatment of LHON caused by mitochondrial ND4 gene mutation. Part 1 (Phase 1/2) is a safety dose-finding study, which will enroll subjects aged ≥ 18 years old and ≤ 75 years old to receive a single unilateral intravitreal (IVT) injection of NR082 to observe its safety and efficacy. In Part 2 (Phase 3) of the clinical study, the dose recommended after the end of Part 1 is used to further verify the safety and efficacy of the study drug. Part 2 of the study is divided into the safety run-in phase and the randomized, double-blind and control study. Subjects aged ≥ 12 years and ≤ 75 years will be enrolled in the Part 2. The run-in phase will enroll 6 evaluable subjects. After monitoring for at least 6 weeks, if no new safety signals are observed, the clinical trial will enter the randomized, double-blind and control study phase upon approval by the Safety Review Committee(SRC). The clinical manifestation of all subjects is reduced visual acuity caused by LHON associated with ND4 mutation, and central laboratory test showed G11778A mutation (a CLIA-certified laboratory), while the reduced visual acuity lasted for \> 6 months and \< 10 years.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age at signing of informed consent form
In Part 1, the age of the subjects must be ≥ 18 years old and ≤ 75 years old
In Part 2, the age of the subjects must be ≥ 12 years old and ≤ 75 years old, and the 6 evaluable subjects must be monitored for at least 6 weeks during the safety run-in phase. If SRC believes that there is no safety issue, the randomized double-blind control study will be initiated Subject Type and Disease Characteristics
The clinical manifestation caused by LHON is vision loss, with a visual acuity of ≥ 0.5 LogMAR in BCVA in either eye
Disqualifiers
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
Trial design
Sequential
Treatments tested in this trial
NR082 injection
DrugIntravitreal injection(IVT)
Sham Injection
DeviceSham Intravitreal Injection
Treatment groups
Trial outcomes
Primary outcomes
Safety and tolerability of NR082 at different doses
Incidence rates of AEs, SAEs and DLTs within 12 weeks after injection of NR082 at different doses
Safety after NR082 treatment among subjects 12 ≤ aged ≤ 75 years
Incidence rates of AEs and SAEs within 6 weeks after NR082 treatment
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
Secondary outcomes
The efficacy and safety following intravitreal injection of NR082 at different doses
Improvent and mean change from baseline in BCVA; Change from baseline in visual field, contrast sensitivity and visual evoked potential
Further assess the efficacy and safety following intravitreal injection of NR082 at different doses
Descriptions of safety evaluation at Weeks 26, 40 and 52
Immunogenicity and vector shedding/biodistribution
Assessment of cell immunity, humoral immunity, vector DNA shedding in tears (both eyes) and biodistribution in whole blood
The change in quality of life from baseline
Change from baseline in VFQ-25 and SF-36
Sponsors and contacts
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