Actively Recruiting
A Phase 1/2/3 Multi-center Two-part Clinical Trial to Evaluate the Safety and Efficacy of Gene Therapy for Leber's Hereditary Optic Neuropathy Associated With ND4 Mutation
Led by Wuhan Neurophth Biotechnology Limited Company · Updated on 2022-11-14
102
Participants Needed
1
Research Sites
208 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are investigating the safety and effectiveness of a gene therapy called NR082 for treating Leber's Hereditary Optic Neuropathy (LHON) caused by a mitochondrial ND4 gene mutation. The study includes two parts: Part 1 is a Phase 1/2 dose-finding study involving adults aged 18 to 75 years to determine a safe and effective dose. Part 2 is a Phase 3 study with a safety run-in phase and a randomized, double-blind, sham-injection controlled trial involving participants aged 12 to 75 years. All participants have vision loss related to LHON with a specific genetic mutation and have had reduced visual acuity for more than 6 months but less than 10 years. In Part 1, participants receive a single intravitreal injection of NR082 at varying doses, starting with 1.5 × 10^9 viral genomes (vg) in 0.05 mL per eye. The Safety Review Committee (SRC) reviews safety data to decide on dose adjustments. Part 2 starts with a safety run-in phase where six subjects, including at least one minor aged 12 to under 18, receive a higher dose of 4.5 × 10^9 vg in 0.05 mL per eye. After at least 6 weeks of monitoring and SRC approval, the study continues with a randomized, double-blind phase comparing NR082 injections to sham injections in one eye. Participants will be monitored through various visits over time to assess safety and vision outcomes. Safety and tolerability are tracked at multiple timepoints up to 12 weeks in Part 1, and up to 52 weeks in Part 2. Researchers will evaluate visual acuity improvements, immune responses, and quality of life changes. Eye examinations, genetic testing, and comprehensive safety assessments will be conducted throughout the study. The total study duration includes initial dose-finding, safety monitoring, and long-term follow-up to understand the effects of NR082 treatment.
CONDITIONS
Brief Title
Gene Therapy Clinical Trial for the Treatment Of Leber's HereDitary Optic Neuropathy
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 to 75 years for Part 1; 12 to 75 years for Part 2
- Diagnosed with vision loss caused by LHON with visual acuity of at least 0.5 LogMAR in either eye
- Confirmed G11778A mutation in the ND4 gene without other primary LHON mutations (ND1 or ND6)
- Vision loss duration in the worse eye more than 6 months and less than 10 years
- Pupils can be dilated adequately for eye exams and vision tests
- Each eye must have visual acuity of 2.3 LogMAR or better
- Able and willing to sign informed consent and follow the study protocol
- Male subjects must agree to use contraception for at least 6 months after treatment
- Female subjects must not be pregnant or breastfeeding and agree to contraception if applicable
- For minors, consent must be obtained from parent or legal guardian
You will not qualify if you...
- Known allergy or hypersensitivity to NR082 or its components
- Contraindications to intravitreal injection in any eye
- Intravitreal drug delivery in any eye within 30 days before screening
- History of vitrectomy in either eye
- Narrow anterior chamber angle preventing pupil dilation
- Eye diseases other than LHON that interfere with vision assessments
- Known mutations causing optic nerve or retina diseases other than LHON
- Systemic or ocular diseases causing vision loss besides LHON
- Optic neuropathy from causes other than LHON
- Illness or treatments affecting visual function or participant safety
- History of recurrent or active eye inflammation
- Participation in another clinical trial with investigational product within 90 days (exceptions apply)
- Prior ocular gene therapy in any eye
- Refusal to stop using idebenone
- Recent relevant ocular surgery within 90 days
- Females breastfeeding or planning to breastfeed within 6 months after treatment
- History of drug or alcohol abuse, including heavy smoking
- Positive tests for HIV, syphilis, or active hepatitis requiring treatment
- Unable or unwilling to comply with study protocol
- Non-compliance with local COVID-19 guidelines
- Other exclusions as determined by the investigator
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 12 weeks
Participants receive a single intravitreal injection of NR082 at varying doses to evaluate safety and determine the recommended dose for the next study phase.
Visits at Weeks 2, 6, and 12
Duration - 6 weeks
Participants receive a single intravitreal injection at the recommended high dose and are monitored for safety before the randomized study begins.
Visits during the 6-week monitoring period
Duration - 52 weeks
Participants are randomly assigned to receive either the NR082 injection or a sham injection and are followed to assess safety and efficacy.
Visits at Weeks 2, 6, 12, 26, 40, and 52
Trial Site Locations
Total: 1 location
1
Beijing Tongren Hospital, Capital Medical University
Beijing, China
Actively Recruiting
Research Team
X
Xiaoning Guo, PHD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
QUADRUPLE
Allocation
RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
Frequently Asked Questions
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