Study

This is a double-blind, international trial with sites in Belgium, France, Germany, Netherlands, Spain, Switzerland and the UK. Neither the patients/parents nor the physicians and study nurses will know which treatment will be applied.

The medication (tamoxifen) and the placebo (medication without active ingredient) will look the same. Group allocation (verum/placebo) will be done at randomly 1:1.

Scroll down for more.

Course of study

Screening

Signing the informed consent
Patient history, physical exam
Check inclusion/exclusion criteria
ECG, vital signs
Blood withdrawal
Muscle strength/function (physiotherapeutical evaluation)
Ophthalmological examination

Visit 1 / Day 0

Physical exam
ECG, vital signs
Blood withdrawal
Muscle strength/function (physiotherapeutical evaluation)
MRT
Ophthalmological examination
X-ray hand and DEXA (in selected sites only)
Questionnaire
Dispensing study drug

Telephone Call / Week 6

A few questions will be asked by phone

Visit 2 / Week 12

Physical exam
ECG, vital signs
Blood withdrawal
Muscle strength/function (physiotherapeutical evaluation)
Collection study drug
Dispensing study drug

Visit 3 / Week 24

Physical exam
ECG, vital signs
Blood withdrawal
Muscle strength/function (physiotherapeutical evaluation)
MRT
Ophthalmological examination
Questionnaire
Collection study drug
Dispensing study drug

Visit 4 / Week 36

Physical exam
ECG, vital signs
Blood withdrawal
Muscle strength/function (physiotherapeutical evaluation)
Collection study drug
Dispensing study drug

Visit 5 / Week 48

Physical exam
ECG, vital signs
Blood withdrawal
Muscle strength/function (physiotherapeutical evaluation)
MRT
Ophthalmological examination
X-ray hand and DEXA (in selected sites only)
Questionnaire
Collection study drug

Visit 6 / Week 60

Physical examination
ECG, vital signs
Blood withdrawal

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 steroids >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 >15kg
ambulant patients
able to walk at least 350 meters in 6 minute walking distance test without assistance
MFM D1 subdomain of the MFM scale >40% at screening
Ability to provide informed consent and to comply with study requirements

Group B (non-amblulant 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

Exclusion criteria

The exclusion criteria are as follows:

Known individual hypersensitivity or allergy to tamoxifen
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
Presence of one or more of the following eye disorders: cataract, retinopathia, optic
neuropathy, alteration of the corneasurgery 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 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
Presence of one or the following disorders: Galactosemia (lack of galactose-1-phosphat-uridylyltransferase or UDP-galactose-4-
epimerase or galactokinase; Fanconi-Bickel-syndrome) or congenital lack of lactase or
glucose-galactose malabsorption
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

Quantitative muscle MRI

The magnetic resonance tomography (MRT) is a method often used in research and does not have a significant risk if the safety regulations are observed. Damaging effect is unknown according to current knowledge. As there is a strong magnetic field in the MR tomographer, no magnetic objects must be brought near the device. Therefore, patients with metal implants or pacemaker cannot be examined. Other magnetic objects as watches, credit cards or belt buckles have to be put down before the examination.

Children who suffer from claustrophobia may experience this examination as stressful. However, as only the legs are examined the head of the child will be outside the analysis tube during the whole examination. Also the knocking sound during the examination can be unpleasant but does not represent a health risk. The examination lasts approximately 20 minutes in total. No contrast agent will be given and the examination is performed without anesthesia.

Open Extension Label

Open Label Extension Visit 1 / Week 48

Physical examination
Vital signs, ECG
Blood draw
Ophthalmological examination
DEXA scan and x-ray bone age determination (selected sites)
Physiotherapeutical evaluation
MRI
Questionnaires
Check inclusion/exclusion criteria
Dispense study medication

Telephone Call / Week 54

A few questions will be asked by phone

Open Label Extension Visit 2 / Week 60

Physical examination
Vital signs, ECG
Blood draw
Physiotherapeutical evaluation
Collection of study medication
Dispense of study medication

Open Label Extension Visit 3 / Week 72

Physical examination
Vital signs, ECG
Blood draw
Ophthalmological examination
Physiotherapeutical evaluation
MRI
Questionnaires

Open Label Extension Visit 4 / Week 84

Physical examination
Vital signs, ECG
Blood draw
Physiotherapeutical evaluation
Collection of study medication
Dispense of study medication

Open Label Extension Visit 5 / Week 96

Physical examination
Vital signs, ECG
Blood draw
Ophthalmological examination
DEXA scan and x-ray bone age determination (selected sites)
Physiotherapeutical evaluation
MRI
Questionnaires
Collection of study medication