Tamoxifen in Duchenne Muscular Dystrophy (TAMDMD)

This is an interventional treatment trial for Duchenne Muscular Dystrophy focused on measuring DMD Read More

Inclusion Criteria:

Group A (ambulant patients)

• Documented diagnosis of DMD by mutation analysis in the dystrophin gene or by substantially reduced levels of dystrophin protein (i.e. absent or <5% of normal) on Western blot or immunostaining
• Stable treatment with glucocorticoids >6 months (no significant change in dosage (>0.2mg/kg)) at screening; dosing adaptations according to weight change are allowed
• Male gender
• 6.5 to 12 years of age at time of screening
• weight >20kg
• ambulant patients
• able to walk at least 350 meters in 6 minute walking distance test without assistance at screening
• MFM D1 subdomain of the MFM scale >40% at screening
• Ability to provide informed consent and to comply with study requirements
• Patients harbouring a nonsense mutation treatable with the approved drug ataluren should be under stable ataluren treatment for at least 3 months or in case of nontolerance being off ataluren treatment for at least 3 months before screening

Group B (non-ambulant patients)

• Documented diagnosis of DMD by mutation analysis in the dystrophin gene or by substantially reduced levels of dystrophin protein (i.e. absent or <5% of normal) on Western blot or immunostaining
• Not using glucocorticoids for >6 months
• Male gender
• Non-ambulant patients (walking distance less than 10 meters)
• 10 to 16 years of age at time of screening
• Ability to provide informed consent and to comply with study requirements

Open label extension

- Recent participation and completion of TAMDMD study

Exclusion Criteria:

• Known individual hypersensitivity or allergy to tamoxifen or other ingredients/excipients of IMP
• Female gender
• Use of tamoxifen or testosterone within the last 3 months
• Known or suspected malignancy
• Other chronic disease or clinically relevant limitation of renal, liver or heart function
• Known or suspected non-compliance
• Any injury which may impact functional testing, e.g. upper or lower limb fracture
• Planned or expected spinal fusion surgery during the study period (as judged by the Investigator; i.e. due to rapid progressing scoliosis), previous spinal fusion surgery is allowed if it took place more than 6 months prior to screening.
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders of the participant/parents (as judged by the investigator)
• Concomitant participation in any other interventional trial (and up to 3 months prior to screening)
• Use of CYP2D6 inhibitors or of CYP3A4 inducers (apart from glucocorticoids), platelet aggregation inhibitors and coumarin-type anti-coagulants
• Use of drugs metabolized by CYP2C9, such as phenprocoumon, phenytoin, warfarin, celecoxib, fluvastatin, ginko biloba, St. John's wort and sulfamethoxazol
• Galactosemia (lack of galactose-1-phosphat-uridylyltransferase or UDP-galactose-4-epimerase or galactokinase; Fanconi-Bickel-syndrome); congenital lack of lactase; glucose-galactose malabsorption
• Presence of one or more of the following eye disorders: cataract, retinopathia, optic neuropathy, alteration of the cornea
• Presence of one or more of the following laboratory abnormalities: anaemia, thrombocytopenia, leukopenia, neutropenia or agranulocytosis

Group A:

• Glucocorticoid naïve patients
• Start of glucocorticoid treatment or change in dosage <6 month prior to screening (dosing adaptations according to weight change are allowed)

Group B:

• Glucocorticoid treated patients or patients that stopped glucocorticoid treatment <6 month prior to screening
• Assisted ventilation of any kind necessary