Gene Therapy Clinical Trial for the Treatment Of Leber's HereDitary Optic Neuropathy

Launched by WUHAN NEUROPHTH BIOTECHNOLOGY LIMITED COMPANY · May 27, 2021

Keywords

ClinConnect Summary

This clinical trial is investigating a new gene therapy called NR082 to treat Leber's Hereditary Optic Neuropathy (LHON), a genetic condition that causes vision loss. The study aims to find the best dose of the treatment and to ensure it is safe and effective for people with a specific genetic mutation (the ND4 gene mutation). The trial is divided into two parts: the first part will involve adults aged 18 to 75 receiving a single injection of the treatment, while the second part will include younger participants aged 12 to 75, assessing the recommended dose after the first part. Participants must have experienced vision loss related to LHON for more than six months but less than ten years.

To be eligible for the trial, participants need to have a confirmed ND4 gene mutation, and their vision loss must meet specific criteria. This means they should be able to see to a certain degree in at least one eye. If you join the trial, you can expect to receive an injection in your eye and be monitored closely for any side effects or changes in your vision. It's important to note that there are several health conditions and prior treatments that could prevent someone from participating, so potential participants will need to discuss their medical history with the study team. Overall, this trial could be an opportunity to access a new treatment for LHON, and participants will contribute to important research that may help others with this condition in the future.

Gender

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Eligibility criteria

• • Inclusion Criteria Age
• • 1. Age at signing of informed consent form
• • 1. In Part 1, the age of the subjects must be ≥ 18 years old and ≤ 75 years old
• • 2. 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
• • 2. The clinical manifestation caused by LHON is vision loss, with a visual acuity of ≥ 0.5 LogMAR in BCVA in either eye
• • 3. 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)
• • 4. The duration of vision loss in the eye with worse visual acuity lasted \> 6 months and \< 10 years at screening
• • 5. Pupils can be adequately dilated for a comprehensive eye examination and visual acuity test
• • 6. Each eye of the subject must maintain the VA determined by manual visual acuity test (≤ 2.3 LogMAR) as defined in the ocular/vision examination manual (operating manual for optometry and VA examinations) in this study
• • 7. Sign the written informed consent form and willing to comply with the clinical study protocol Sex
• • 8. Male or female
• 1. Male subjects:
• • • A male subject must agree to take contraceptive measures at least 6 months after the treatment visit, see Appendix 5 for details
• 2. Female subjects:
• * A female subject is eligible to participate if she is not pregnant (see Appendix 5), not breastfeeding, and at least one of the following conditions applies:
• • i) Not a woman of childbearing potential (WOCBP) as defined in Appendix 5 or ii) A WOCBP who agrees to follow the contraception guidance in Appendix 5 for at least 6 months after the treatment visit Informed Consent
• • 9. Written informed consent form must be obtained from the subject or his/her parent/legal guardian (if the subject is under 18 years of age) (Part 2) before any study-related procedures are performed (see Section 10.2) If the subject is legally identified as blind (\>1.0 LogMARor decimal acuity meter reading \< 0.1), an impartial witness must be present throughout the informed consent process and discussion process.
• • Exclusion Criteria
• Subjects who meet any of the following criteria will be excluded from the study:
• • 1. Any known allergy and/or hypersensitivity to the study drug or its constituents
• • 2. Contraindication to IVT injection in any eye
• • 3. IVT drug delivery to any eye within 30 days prior to the screening visit
• • 4. History of vitrectomy in either eye
• • 5. Narrow anterior chamber angle in any eye contra-indicating pupillary dilation
• • 6. Presence of disorders or diseases of the eye or adnexa, excluding LHON, which may interfere with visual or ocular assessments, including spectral-domain optical coherence tomography (FD-OCT), during the study
• • 7. 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
• • 8. 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
• • 9. Presence of optic neuropathy from any cause other than LHON
• • 10. 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
• • 11. History of recurrent uveitis (idiopathic or immune-related) or active ocular inflammation
• • 12. 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.
• • 13. Any eye has previously received ocular gene therapy
• • 14. Subjects who refused to stop using idebenone
• • 15. Have undergone ocular surgery of clinical relevance (per investigator's assessment) within 90 days prior to the screening visit
• • 16. Female subjects who are breastfeeding or plan to breastfeed within the first 6 months after the administration of NR082 Injection
• • 17. History of drug or alcohol abuse (including heavy smoking, i.e. \> 20 cigarettes per day or \> 20 pack-years \[equivalent to one pack a day for 20 years or 2 packs a day for 10 years\])
• • 18. Subjects with positive human immunodeficiency virus (HIV), syphilis and HCV antibodies are excluded; subjects who have clinically significant active infection requiring treatment as shown by hepatitis B test (defined as positive hepatitis B core antibody \[HBcAb\] or hepatitis B surface antigen \[HBsAg\], hepatitis B virus deoxyribonucleic acid (HBV-DNA) \>1,000 copies /mL or \>lower limit of quantitative detection with the local laboratory method) will be excluded
• • 19. Unable to tolerate or unable or unwilling to comply with all the protocol requirements
• • 20. Subjects from the study site fail to comply with or do not agree to comply with local and institutional guidelines for suspected 2019 novel coronavirus (COVID-19) infection/testing
• • 21. Any other exclusions determined by the investigator