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.

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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.

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Scroll down for more.

 

Course of study

Screening

  1. Signing the informed consent

  2. Patient history, physical exam

  3. Check inclusion/exclusion criteria

  4. ECG, vital signs

  5. Blood withdrawal

  6. Muscle strength/function (physiotherapeutical evaluation)

  7. Ophthalmological examination

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Visit 1 / Day 0

  1. Physical exam

  2. ECG, vital signs

  3. Blood withdrawal

  4. Muscle  strength/function (physiotherapeutical evaluation)

  5. MRT

  6. Ophthalmological examination

  7. X-ray hand and DEXA (in selected sites only)

  8. Questionnaire

  9. Dispensing study drug

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Telephone Call / Week 6

  • A few questions will be asked by phone

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Visit 2 / Week 12

  1. Physical exam

  2. ECG, vital signs

  3. Blood withdrawal

  4. Muscle strength/function (physiotherapeutical evaluation)

  5. Collection study drug

  6. Dispensing study drug

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Visit 3 / Week 24

  1. Physical exam

  2. ECG, vital signs

  3. Blood withdrawal

  4. Muscle strength/function (physiotherapeutical evaluation)

  5. MRT

  6. Ophthalmological examination

  7. Questionnaire

  8. Collection study drug

  9. Dispensing study drug

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Visit 4 / Week 36

  1. Physical exam

  2. ECG, vital signs

  3. Blood withdrawal

  4. Muscle strength/function (physiotherapeutical evaluation)

  5. Collection study drug

  6. Dispensing study drug

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Visit 5 / Week 48

  1. Physical exam

  2. ECG, vital signs

  3. Blood withdrawal

  4. Muscle strength/function (physiotherapeutical evaluation)

  5. MRT

  6. Ophthalmological examination

  7. X-ray hand and DEXA (in selected sites only)

  8. Questionnaire

  9. Collection study drug

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Visit 6 / Week 60

  1. Physical examination

  2. ECG, vital signs

  3. 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

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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

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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)

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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

  1. Physical examination

  2. Vital signs, ECG

  3. Blood draw

  4. Ophthalmological examination

  5. DEXA scan and x-ray bone age determination (selected sites)

  6. Physiotherapeutical evaluation

  7. MRI

  8. Questionnaires

  9. Check inclusion/exclusion criteria

  10. Dispense study medication

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Telephone Call / Week 54

  • A few questions will be asked by phone

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Open Label Extension Visit 2 / Week 60

  1. Physical examination

  2. Vital signs, ECG

  3. Blood draw

  4. Physiotherapeutical evaluation

  5. Collection of study medication

  6. Dispense of study medication

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Open Label Extension Visit 3 / Week 72

  1. Physical examination

  2. Vital signs, ECG

  3. Blood draw

  4. Ophthalmological examination

  5. Physiotherapeutical evaluation

  6. MRI

  7. Questionnaires

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Open Label Extension Visit 4 / Week 84

  1. Physical examination

  2. Vital signs, ECG

  3. Blood draw

  4. Physiotherapeutical evaluation

  5. Collection of study medication

  6. Dispense of study medication

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Open Label Extension Visit 5 / Week 96

  1. Physical examination

  2. Vital signs, ECG

  3. Blood draw

  4. Ophthalmological examination

  5. DEXA scan and x-ray bone age determination (selected sites)

  6. Physiotherapeutical evaluation

  7. MRI

  8. Questionnaires

  9. Collection of study medication