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Follistatin Gene Transfer to Patients With Becker Muscular Dystrophy and Sporadic Inclusion Body Myositis

key information

study id #: NCT01519349

condition: Becker Muscular Dystrophy, Sporadic Inclusion Body Myositis

status: completed


The investigators are performing a gene therapy clinical trial in Becker muscular dystrophy (BMD) and sporadic inclusion body myositis (sIBM) patients. Both of these conditions have an important common feature: loss of ability to walk because of weakness of the thigh muscles. The investigators plan to do a gene therapy trial to deliver a gene to muscle called follistatin (FS344) that can build muscle size and strength. If successful, the investigators can increase the size of the thigh muscle and potentially prolong a patient’s ability to walk. The gene will be carried into the muscle by a virus called adeno-associated virus (AAV). This virus occurs naturally in muscle and does not cause any human disease, setting the stage for its safe use in a clinical trial. Presently there is no treatment that can reverse Becker muscular dystrophy or sporadic inclusion body myositis. Only supportive care is currently possible. In this study, subjects with either of these diseases will have shots of the follistatin gene injected directly into thigh muscle on one (first cohort) or both legs (2nd and 3rd cohort). One hundred and eighty days following the gene delivery, the muscle will undergo biopsy to look closely at the muscle to see if the muscle fibers are bigger. Between the time of the gene transfer and the muscle biopsy, patients will be carefully monitored for any side effects of the treatment. This will include an MRI of the thigh muscle before treatment and at day 180 following treatment. Blood and urine tests, as well as physical examination will be done on the subjects during the screening visit and on days 0, 1, 2, 7, 14, 30, 60, 90, and 180 to make sure that there are no side effects from the gene injections. Sutures will be removed 2 weeks post-biopsy. Additional blood samples will be collected at 9, 12, 18, and 24 months. Patients will be seen at the end of 1st and 2nd years for a physical exam, assessment of muscle strength and appropriate blood tests.

intervention: rAAV1.CMV.huFollistatin344

mechanism of action: Gene therapy to introduce a version of dystrophin

results: https://clinicaltrials.gov/ct2/show/results/NCT01519349

last updated: November 22, 2018

study details

start date: January 2012

estimated completion: October 2017

phase of development: Phase 1

size / enrollment: 15

primary outcomes:

  • Safety [ Time Frame: 2 years ]
    Safety trial based on development of unacceptable toxicity defined as the occurrence of any Grade III or higher treatment-related toxicities.

secondary outcomes:

  • Muscle Function and Strength Testing [ Time Frame: 2 years ]
    -Muscle function and strength:
    -MRI of quadriceps muscles (bilateral)
    -Muscle biopsies on quadriceps muscles (a muscle biopsy on one leg at baseline screening visit - except for cohort 1 - and the post gene transfer biopsy on the opposite leg at day 180)
    -Thigh circumference measurement at baseline and post-gene transfer follow up visits up to day 180 (prior to second biopsy)

inclusion criteria:

• Eligible Sexes:

• All subjects [sIBM and BMD must be ambulatory and have identifiable atrophy of the quadriceps muscle with muscle weakness >=2 standard deviations below predicted using quantitative muscle testing (maximum voluntary isometric strength testing), and difficulty getting out of chairs, climbing stairs, and getting up from the floor.
• sIBM patients include males and post-menopause females of any ethnic or racial group. Diagnosis of sIBM is based on previously published criteria that include distribution of weakness (knee extensor weakness, finger flexor weakness) and histological presence of inflammation and vacuolar myopathy. Patients with inflammation, vacuolar changes and intracellular amyloid deposits or 15/18nm filaments fulfill criteria irrespective of clinical features.
• BMD patients include adult males (>18yo) of any ethnic or racial group with proven mutation of dystrophin gene and continued ambulation after age 15 years old.
• Ability to cooperate for muscle testing
• Deficit in muscle strength greater than 2 standard deviation below age expectations
• Willingness of sexually active subjects with reproductive capacity (only male population) to practice reliable method of contraception until two negative sperm samples are obtained post gene transfer

exclusion criteria:
• Active viral infection
• History or evidence of active infection with hepatitis C, hepatitis A or B, or HIV
• Patients with any other cause of muscle weakness based on medical history and screening physical exam including: myopathy (other dystrophies, polymyositis, and dermatomyositis), neuropathy (from any cause), myasthenia gravis, and weakness related to degenerative joint disease of the spine.
• Ongoing immunosuppressive therapy or immunosuppressive therapy within 3 months of starting the trial (e.g. corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab)
• Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer. Patients taking any of the following drugs will be excluded: drugs for treatment of myopathy or neuropathy or agents used to treat diabetes mellitus
• Knee or ankle contractures preventing proper muscle strength testing
• Patients with AAV1 neutralizing antibody titers >= 1:1600 as determined by ELISA immunoassay
• Patients with history of angina and patients with past history of myocardial infarction in the past 6 months

study contacts

sponsor: Nationwide Children's Hospital

investigators: Jerry R Mendell, M.D.

trial center locations: United States