Tamoxifen in Duchenne Muscular Dystrophy

• Register: ClinicalTrials.gov
• Last refreshed on: 9 January 2023
• Main ID: NCT03354039
• Date of registration: 10/10/2017
• Prospective Registration: Yes
• Primary sponsor: University Hospital, Basel, Switzerland
• Public title: Tamoxifen in Duchenne Muscular Dystrophy TAMDMD
• Scientific title: Tamoxifen in Duchenne Muscular Dystrophy: A Multicenter, Randomised, Double-blind, Placebo-controlled, Phase 3 Safety and Efficacy 48-week Trial
• Date of first enrolment: June 12, 2018
• Target sample size: 93
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03354039
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

France, Germany, Netherlands, Spain, Switzerland, United Kingdom

Contacts

• Name: Dirk Fischer, MD
• Affiliation: University Children's Hospital Basel

Key inclusion & exclusion criteria

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



Age minimum: 78 Months
Age maximum: 16 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Duchenne Muscular Dystrophy

Intervention(s)

Drug: Tamoxifen

Drug: Matching placebo

Primary Outcome(s)

Reduction of disease progression [Time Frame: Baseline to week 48]

Secondary Outcome(s)

Muscle force measured by quantitative muscle testing (using Myogrip) [Time Frame: Baseline to week 48]

Muscle function measured by 6 minute walking distance in meter [Time Frame: Baseline to week 48]

Muscle function measured by North Star Ambulatory Assessment [Time Frame: Baseline to week 48]

Muscle function measured by time to rise from lying on the floor / supine up in seconds [Time Frame: Baseline to week 48]

Muscle function measured by D3 MFM subscore [Time Frame: Baseline to week 48]

Muscle function measured by D2 MFM subscore [Time Frame: Baseline to week 48]

Muscle function measured by 10 meter walking time in seconds [Time Frame: Baseline to week 48]

Muscle function measured by proximal upper limb function [Time Frame: Baseline to week 48]

Muscle Degeneration measured by MRI [Time Frame: Baseline to week 48]

Secondary ID(s)

TAMDMD

Source(s) of Monetary Support

Please refer to primary and secondary sponsors