TAMDMD - Tamoxifen in Duchenne Muscular Dystrophy
Research type
Research Study
Full title
Tamoxifen in case of Duchenne muscular dystrophy - TAMDMD\nA multi-centre, randomised, double-blind, placebo-controlled phase 3 study examining safety and effectiveness for 48 weeks
IRAS ID
246306
Contact name
Dirk Fischer
Contact email
Sponsor organisation
University of Basel Childrens Hospital
Eudract number
2017-004554-42
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
SNCTP000002387, SNCTP
Duration of Study in the UK
2 years, 6 months, 1 days
Research summary
Research Summary
Duchenne muscular dystrophy (DMD) is a rare disease that affects about 1\nin 3500 to 1 in 6000 boys. Patients suffer from progressive muscle wasting,\nrespiratory and cardiac impairments and premature death. DMD is the\nmost frequent hereditary muscular dystrophy. Currently, only symptomatic\ntreatment with glucocorticoids is available. The European Medical agency (EMA) and the US Federal drug agency (FDA) recognize the unmet medical need in DMD.\nMost current research on therapeutics of DMD focusses on correcting the\ngene defect. However, as there are more than 250 mutations in the\nTAMDMD human dystrophin gene, this approach will treat only a small percentage of\npatients and will be expensive, i.e. 100.000 – 250.000€ per patient per\nyear as compared to tamoxifen (TAM) (about 300€).\nUsing the mouse DMD model, our partners in Geneva, (Dorchies et al. 2013), have shown that TAM, given orally for periods of 2 or 15 months at doses as low as 0.3mg/kg/day, resulted in almost full recovery of force and structure of muscles. TAM is likely the most efficacious compounds ever investigated in an animal model of DMD. TAM is a drug used since 1980 to treat breast cancer and hormonal disorders in pre-pubertal boys. There is a broad clinical evidence and reliable data suggesting a very good safety\nprofile. Our aim is to investigate whether TAM treatment, compared to placebo, reduces the disease progression in DMD patients
Summary of Results
This trial did not meet its pre-specified primary endpoint. While the degree of disease progression was less in the tamoxifen group than in the placebo group against all endpoints, the differences were not found to be either clinically or statistically significant. Unfortunately, these results advise currently against the pursuit of tamoxifen as a treatment for DMD.
Group B: No difference between tamoxifen group and placebo was reported for the primary efficacy endpoint in non-ambulant patients. Although tamoxifen was safe and well tolerate, we cannot recommend the use of tamoxifen in daily clinical practice as a treatment option for Duchenne muscular dystrophy due to the lack of sufficient clinical evidence up to date.
OLE: We did not observe a sustained and timing treatment effect in ambulant patients with DMD treated with tamoxifen. Consistent with the results of the RCT phase of ambulant and non-ambulant patients, the OLE phase did not demonstrate that Tamoxifen slows disease progression. Unfortunately, it can not be assumed that Tamoxifen treatment can stop peripheral skeletal muscle in DMD.REC name
Wales REC 3
REC reference
18/WA/0336
Date of REC Opinion
29 Jan 2019
REC opinion
Further Information Favourable Opinion