Tamoxifen in Duchenne Muscular Dystrophy

NCT03354039 | Completed Phase 3 DMC

• 1 other identifier: TAMDMD
• Study Type: interventional
• Target: 93
• Locations: 6 countries
• Sites: 11

Brief Summary

A randomised, double blind, placebo controlled, 48-week clinical trial with a core population (group A) of 79 ambulant 6.5 to 12 years old Duchenne's muscular dystrophy (DMD) patients that are under stable standard treatment of care with glucocorticoids. Furthermore, the investigators plan to include 6-20 non-ambulant patients who do not receive glucocorticoids (as parallel group B), 10 to 16 years old, to obtain efficacy and safety data in a broader DMD population. All patients will receive 20 mg of tamoxifen (TAM) or placebo once daily during 48 weeks. An open label extension (OLE) trial for participants of the TAMDMD main study will be performed. All TAMDMD patients on TAM or placebo are offered to enter this OLE.

Conditions

Duchenne Muscular Dystrophy

Keywords

DMD

Outcome Measures

Primary Outcomes (1)

• Reduction of disease progression

  To test if tamoxifen treatment, compared to placebo, reduces the progression of the disease in 6.5-12 years old ambulant DMD patients (Group A) by at least 50% (using the MFM D1 subscore as primary clinical endpoint).

  Baseline to week 48

Secondary Outcomes (9)

• Muscle function measured by D2 MFM subscore

  Baseline to week 48

• Muscle function measured by D3 MFM subscore

  Baseline to week 48

• Muscle function measured by North Star Ambulatory Assessment

  Baseline to week 48

• Muscle function measured by proximal upper limb function

  Baseline to week 48

• Muscle function measured by 6 minute walking distance in meter

  Baseline to week 48

Other Outcomes (1)

• Patient reported outcome measured by PARS III questionnaire

  Baseline to week 48

Study Arms (2)

Tamoxifen 20 mg once daily

EXPERIMENTAL

DMD patients randomised to verum will receive 20 mg (0.6mg/kg) of TAM daily.

Drug: Tamoxifen

Matching placebo once daily

PLACEBO COMPARATOR

Patients randomised to placebo will be administered matching placebo.

Drug: Matching placebo

Interventions

Tamoxifen DRUG

DMD patients randomised to verum will receive 20 mg (0.6mg/kg) of Tamoxifen daily. Treatment will be given for the total period of 48 weeks.

Tamoxifen 20 mg once daily

Matching placebo DRUG

Patients randomised to placebo will be administered matching placebo. Treatment will be given for the total period of 48 weeks.

Matching placebo once daily

Eligibility Criteria

• Age: 78 Months - 16 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (11)

Hôpitaux Raymond Poincaré

Garches, 92380, France

Location

Hôpital de Hautepierre

Strasbourg, 67098, France

Location

DRK Klinik Berlin Westend

Berlin, 14050, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Radboud umc

Nijmegen, 6525, Netherlands

Location

Hospital Sant Joan de Déu. UB

Esplugues de Llobregat, Barcelona, 08950, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

University Children's Hospital Basel

Basel, 4031, Switzerland

Location

Royal Hospital for Children

Glasgow, G51 4TF, United Kingdom

Location

The Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom

Location

Alder Hey Children's Hospital

Liverpool, L12 2AP, United Kingdom

Location

Related Publications (3)

• Henzi BC, Putananickal N, Schmidt S, Nagy S, Rubino-Nacht D, Schaedelin S, Amthor H, Childs AM, Deconinck N, Horrocks I, Houwen-van Opstal S, Laugel V, Lobato ML, Osorio AN, Schara-Schmidt U, Spinty S, von Moers A, Lawrence F, Hafner P, Dorchies OM, Fischer D. Safety and efficacy of tamoxifen in non-ambulant patients with Duchenne muscular dystrophy: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (TAMDMD Group B). Neuromuscul Disord. 2025 Feb;47:105275. doi: 10.1016/j.nmd.2025.105275. Epub 2025 Jan 16.

  PMID: 39879732 DERIVED

• Henzi BC, Schmidt S, Nagy S, Rubino-Nacht D, Schaedelin S, Putananickal N, Stimpson G; North Star Consortium; Amthor H, Childs AM, Deconinck N, de Groot I, Horrocks I, Houwen-van Opstal S, Laugel V, Lopez Lobato M, Madruga Garrido M, Nascimento Osorio A, Schara-Schmidt U, Spinty S, von Moers A, Lawrence F, Hafner P, Dorchies OM, Fischer D. Safety and efficacy of tamoxifen in boys with Duchenne muscular dystrophy (TAMDMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2023 Oct;22(10):890-899. doi: 10.1016/S1474-4422(23)00285-5.

  PMID: 37739572 DERIVED

• Nagy S, Hafner P, Schmidt S, Rubino-Nacht D, Schadelin S, Bieri O, Fischer D. Tamoxifen in Duchenne muscular dystrophy (TAMDMD): study protocol for a multicenter, randomized, placebo-controlled, double-blind phase 3 trial. Trials. 2019 Nov 21;20(1):637. doi: 10.1186/s13063-019-3740-6.

  PMID: 31752977 DERIVED

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

Tamoxifen

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Dirk Fischer, MD

  University Children's Hospital Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2017
• First Posted: November 27, 2017
• Study Start: June 12, 2018
• Primary Completion: July 25, 2022
• Study Completion: October 18, 2022
• Last Updated: December 20, 2022

Record last verified: 2022-12

Locations

CH (1); NL (1); GB (3); FR (2); DE (2); ES (2)