DMD CLINICAL THERAPIES I: P.119Tamoxifen in Duchenne muscular dystrophy: rationale and protocol for a multicentre, randomised, double-blind, placebo-controlled, phase 3 safety and efficacy 48-week trial

Abstract

Most current research on therapeutics of Duchenne muscular dystrophy (DMD) focuses on correcting the gene defect. However, as there are more than 250 mutations in the human dystrophin gene, this approach will treat only a small percentage of patients and will be expensive. Using the mouse DMD model it could be shown that tamoxifen (TAM), given orally for periods of 2 or 15 months, results in almost full recovery of force and structure of muscles. TAM is one of the most efficacious drugs ever investigated in an animal model of DMD. Our aim is to investigate whether TAM treatment, compared to placebo, reduces the disease progression in DMD patients. We are setting up an international (France, Germany, Greece, Spain, Switzerland, United Kingdom, The Netherlands, Turkey) randomised double blind placebo controlled 48-week clinical trial with a core population (group A) of 79 ambulant 6.5 to 12 years old DMD patients that are on a stable standard treatment with glucocorticoids. Parallel we will include 16-20 non-ambulant patients age 10 to 16 years who do not receive glucocorticoids (group B) to obtain efficacy and safety data in a broader DMD population. All patients will receive 20 mg of TAM or placebo once daily over 48 weeks. The primary outcome for group A is the motor function measure (MFM) D1. In group B the MFM D2 is the primary endpoint, allowing extrapolation of MFM D2 data from the group A population. In addition, to investigate whether longterm TAM treatment can slow muscle degeneration, quantitative thigh muscle magnetic resonance imaging will be performed. The study aims to describe an efficacy and safety profile for tamoxifen in the treatment of DMD patients. The purpose of this study is to evaluate if TAM shows positive effects on muscle function and muscle force in comparison to placebo in DMD-patients. Recruitment is expected to start in June 2018.