Affiliation:
1. Clinical Research and Education Promotion Division National Center Hospital, National Center of Neurology and Psychiatry Tokyo Japan
2. Department of Child Neurology National Center Hospital, National Center of Neurology and Psychiatry Tokyo Japan
3. Department of Molecular Therapy National Institute of Neuroscience, National Center of Neurology and Psychiatry Tokyo Japan
4. Department of Pediatrics, Graduate School of Medical and Dental Sciences Kagoshima University Kagoshima City Kagoshima Japan
5. Department of Biostatistics and Data Science, Graduate School of Medicine Osaka University Osaka Japan
Abstract
AbstractAimThe purpose of this study is to evaluate the safety and pharmacokinetics of the novel morpholino oligomer NS‐089/NCNP‐02 which can induce exon 44 skipping, in patients with DMD. Additionally, we aimed to identify markers predictive of therapeutic efficacy and determine the optimal dosing for future studies.MethodsThis is an open‐label, dose‐escalation, two‐center phase I/II trial in ambulant patients with DMD, presence of an out‐of‐frame deletion, and a mutation amenable to exon 44 skipping. Part 1 is a stepwise dose‐finding stage (4 weeks) during which NS‐089/NCNP‐02 will be administered intravenously at four dose levels once weekly (1.62, 10, 40, and 80 mg/kg); Part 2 is a 24‐week evaluation period based on the dosages determined during Part 1. The primary (safety) endpoints are the results of physical examinations, vital signs, 12‐lead electrocardiogram and echocardiography tests, and adverse event reporting. Secondary endpoints include expression of dystrophin protein, motor function assessment, exon 44 skipping efficiency, plasma and urinary NS‐089/NCNP‐02 concentrations, and changes in blood creatine kinase levels.DiscussionExon‐skipping therapy using ASOs shows promise in selected patients, and this first‐in‐human study is expected to provide critical information for subsequent clinical development of NS‐089/NCNP‐02.
Funder
Japan Agency for Medical Research and Development
Subject
Pharmacology (medical),Psychiatry and Mental health,Pharmacology,Clinical Psychology