Phase1/2 with AT132 in patients with X-linked Myotubular Myopathy
Research type
Research Study
Full title
ASPIRO: A Phase 1/2, Randomized, Open-Label, Ascending-Dose, Delayed-Treatment Concurrent Control Clinical Study to Evaluate the Safety and Preliminary Efficacy of AT132, an AAV8-Delivered Gene Therapy in X-Linked Myotubular Myopathy (XLMTM) Patients\n
IRAS ID
223529
Contact name
Francesco Muntoni
Contact email
Sponsor organisation
Audentes Therapeutics Inc.
Eudract number
2017-000876-27
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
017367, IND number; 35481, CPMS ID
Duration of Study in the UK
6 years, 9 months, 24 days
Research summary
X-linked myotubular myopathy (XLMTM) is a rare genetic disease characterised by an impairment in the development, maturation and maintenance of skeletal muscles cells leading to muscle weakness, feeding and speech difficulties and respiratory complications, which can be life-threatening. XLMTM is caused by a mutation in the MTM1 gene, which results in a low level of the active myotubularin and affects predominantly male infants.\n\nCurrently, there is no known treatment for this disease. The disease management is mainly supportive and involves respiratory assistance making patients sensitive to respiratory infections. Suctioning secretions from the throat and airways is constantly required. Regular physical therapy must be provided to improve muscle strength and prevent contractures. The disease has a significant impact on routine life and can be socially isolating for both parents and children. Therefore, there is a significant need for XLMTM treatment, and gene therapy is one therapeutic approach.\n\nThe investigational drug AT132 has been developed to replace the missing or defective endogenous MTM1 gene. AT132 is an inactive virus that has been built to carry the human MTM1 gene. AT132 could potentially produce a new MTM1 protein (myotubularin) in patients’ skeletal muscles and reduce the symptoms of the disease.\n\nThe purpose of this first in human study is to evaluate AT132 safety and its effectiveness in improving care for XLMTM patients. The study is also being done to determine the appropriate amount of AT132 to be given to XLMTM patients.\n\nThe participants will be randomised in the Treated group or Control (delayed-treatment) group. The Treated group will receive one single injection of one of the three AT132 doses in order to determine the optimal dose (dose finding group) of AT132 that patients enrolled in the second phase (Control delayed-treatment group in the first phase) will receive. The Control group will be monitored for at least 9 months before being treated with AT132 and until the most efficient dose has been determined with the Treated group.\n\nThe study could last 5 years for patients enrolled in the Treated group and maximum 7 years for subjects enrolled in the Control delayed-treatment group (subsequent treatment group).\n\nThere will be about 12 subjects participating in this study around the world including approximately 2 from the UK.\n\n
REC name
South Central - Oxford A Research Ethics Committee
REC reference
17/SC/0403
Date of REC Opinion
6 Dec 2017
REC opinion
Further Information Favourable Opinion