The study examines boys suffering from Duchenne muscular dystrophy. We are carrying out this study to examine the effect and tolerance of Tamoxifen in this disease.

• Register: EUCTR
• Last refreshed on: 23 October 2023
• Main ID: EUCTR2017-004554-42-ES
• Date of registration: 17/09/2018
• Prospective Registration: Yes
• Primary sponsor: University of Basel Children's Hospital, Division of Neuropediatrics
• Public title: The study examines boys suffering from Duchenne muscular dystrophy. We are carrying out this study to examine the effect and tolerance of Tamoxifen in this disease.
• Scientific title: Tamoxifen in Duchenne muscular dystrophy - TAMDMD A multicentre, randomised, double-blind, placebo-controlled, phase 3 safety and efficacy 48-week trial
• Date of first enrolment: 22/01/2019
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004554-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Dr. Josef Reisinger
• Affiliation: multi-service-monitoring

• Name: Dr. Josef Reisinger
• Affiliation: multi-service-monitoring

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 >15kg
-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

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
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:
-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 surgery is allowed if it took place more than 6 month 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, platelet aggregation inhibitors and coumarin-type anti-coagulants.

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 steroid treatment <6 month prior to screening
-Assisted ventilation of any kind necessary


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

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

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Trade Name: TAMOX
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Tamoxifen
CAS Number: 54965-24-1
Other descriptive name: TAMOXIFEN CITRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Screening, Baseline, week 12, week 24, week 36, week 48

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.)

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 upper limbs),
-to stand up from sitting on a mat,
-to sit down on the chair from standing,
-to walk forward 10 steps on both heels,
-to walk forward 10 steps on a straight line,
-to run 10 m,
-and to hop 10 times on one foot,

Group B: The primary efficacy outcome in this group will be the motor function from baseline to week 48 under TAM treatment compared to placebo. This will be assessed by the motor function measure (MFM) D2 subscore in non-ambulant patients allowing a partial extrapolation and comparison of MFM D2 values between group A and group B. Note that the MFM D1 subscore in non-ambulant patients is usually 0%; therefore the MFM D1 subscore is not suitable for this population.
For the MFM D2 subscore several exercises that will be scored have to be done by the patients such as:
-from supine on a mat to raise the head and maintain the raised position
-from supine on a mat to raise one hand and move it to the opposite shoulder
-from seated on the chair to raise the head from fully flexed position and maintain the raised position
-from seated on the chair to place the two forearms and/or the hands on the table at the same time without moving the trunk.

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.

Secondary Outcome(s)

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
Timed Function test, MFM: Screening, Baseline, week 12, week 24, week 36, week 48

Secondary ID(s)

NCT03354039

2017-004554-42-DE

TAMDMD

Source(s) of Monetary Support

Scientific and Technological Research Council of Turkey (TÜBITAK)

Swiss National Science Foundation (SNSF)

Duchenne Parent Project Netherlands

French National Research Agency (ANF)

Association Monegasque contre les myopathies

Duchenne UK

Ethics review

Status: Approved
Approval date: 15/01/2019
Contact: