Duchenne muscular dystrophy MedDRA version: 20.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
University of Basel Children's Hospital, Division of Neuropediatrics
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 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 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 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 Are the trial subjects under 18? yes Number of subjects for this age range: 100 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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-Bickelsyndrome); 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To test if tamoxifen treatment, compared to placebo, reduces the progression of the disease in 6.5-12 years old ambulant DMD patients by at least 50% (using the MFM D1 subscore as primary clinical endpoint in group A patients). To test if tamoxifen treatment, compared to placebo, reduces the progression of the disease in 10-16 years old non-ambulant DMD patients not treated with glucocorticoids (using the MFM D2 subscore as primary endpoint.) initiation compared to delayed start of tamoxifen treatment reduces the progression of the disease and to evaluate long-term efficacy and safety. Therefore, disease progression during the OLE phase will be compared between both OLE treatment arms. ;Secondary Objective: Secondary clinical outcomes to assess muscle function: 1. MFM total score, the D2, and D3 MFM subscores, North Star Ambulatory Assessment, proximal upper limb function from baseline to week 48 under TAM treatment compared to placebo. 2. Timed function tests (6 minute walking distance in meter, 10 meter walking time in seconds, time to rise from lying on the floor / supine up in seconds,) from baseline to week 48 under TAM treatment compared to placebo. Secondary clinical outcomes to assess muscle force: 3. Quantitative muscle testing (using Grip force) from baseline to week 48 under TAM treatment compared to placebo. Secondary surrogate marker to assess muscle degeneration: 4. Quantitative muscle MRI including muscle fat fraction (MFF) and T2 times of thigh muscles visualised by MRI from baseline to week 48 under TAM treatment compared to placebo. ;Primary end point(s): Group A: The primary efficacy outcome will be the change of motor function under TAM treatment compared to placebo. This will be assessed by the motor function measure (MFM) D1 subscore (standing and transfers) in ambulant patients. For the MFM D1 subscore several exercises that will be scored have to be done by the patients such as: - to sit up on a mat (without support of | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary clinical outcomes to assess muscle function: - MFM total score, the D2, and D3 MFM subscores, North Star Ambulatory Assessment from baseline to week 48 under tamoxifen treatment compared to placebo. - Timed function tests (6 minute walking distance in meter, 10 meter walking time in seconds, time to rise from lying on the floor / supine up in seconds,) from baseline to week 48 under tamoxifen treatment compared to placebo. Secondary clinical outcomes to assess muscle force: - Quantitative muscle testing (using Grip force) from baseline to week 48 under tamoxifen treatment compared to placebo. Secondary surrogate marker to assess muscle degeneration: - Quantitative muscle MRI including muscle fat fraction (MFF) and T2 times of thigh muscles visualised by MRI from baseline to week 48 under tamoxifen treatment compared to placebo. ;Timepoint(s) of evaluation of this end point: MRI: Baseline, week 24, week 48, week 72, week 96 Timed Function test, MFM: Screening, Baseline, week 12, week 24, week 36, week 48, week 60, week 72, week 84, week 96 | — |
Countries
Belgium, France, Germany, Netherlands, Spain, Switzerland, United Kingdom
Contacts
Public ContactDr. Josef Reisinger
multi-service-monitoring
Outcome results
None listed