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    Summary
    EudraCT Number:2013-001732-21
    Sponsor's Protocol Code Number:MET001
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-02-18
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2013-001732-21
    A.3Full title of the trial
    A randomized, double blind, placebo-controlled phase II study of metformin in myotonic dystrophy type 1 patients
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A phase II study of metformin in myotonic dystrophy type 1 patients
    A.3.2Name or abbreviated title of the trial where available
    Myomet
    A.4.1Sponsor's protocol code numberMET001
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorCentre d'Etude des Cellules Souches (CECS)
    B.1.3.4CountryFrance
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportCECS
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCECS
    B.5.2Functional name of contact pointClinical Trial Information
    B.5.3 Address:
    B.5.3.1Street AddressGenopole Campus 1 - 5 Rue Henri Desbruères
    B.5.3.2Town/ cityEVRY Cedex
    B.5.3.3Post code91030
    B.5.3.4CountryFrance
    B.5.6E-mailclinical_development@genethon.fr
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name metformin 500mg
    D.2.1.1.2Name of the Marketing Authorisation holderMerck
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMETFORMIN
    D.3.9.1CAS number 657-24-9
    D.3.9.4EV Substance CodeSUB08831MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Myotonic dystrophy type 1 (DM1) also known as Steinert disease
    E.1.1.1Medical condition in easily understood language
    myotonic dystrophy, muscular disease
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of metformin on ambulation in patients with myotonic dystrophy type 1.
    E.2.2Secondary objectives of the trial
    To determine the efficacy of metformin on myotonia, insulin resistance, cholesterol and triglycerides, muscle function and strength, quality of life, gastrointestinal function, and cardiac function
    To determine the safety of metformin
    To determine the INSRA and INSRB Messenger Ribonucleic Acid (mRNA) ratio in blood, as well as FAS ATP2A1 and LMNA splice variants
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    A diagnosis of DM1, confirmed by DM1 genetic mutation
    Male or female patients, age ≥18 to ≤ 60 years
    Muscular Impairment Rating Scale (MIRS) score 2 or 3
    Ambulatory, able to perform the 6 Minute Walk Test (6MWT)
    All laboratory parameters must be grade 0 or 1 (as per CTCAE criteria) except for AST, ALT for which a grade 2 will be allowed if stated non clinically significant
    For women of child-bearing potential, i.e. with no history of hysterectomy or tubal ligation, use of one effective method of birth control during the conduct of the study
    Written informed consent
    Patient covered by a national health insurance scheme affiliated with the French healthcare system
    E.4Principal exclusion criteria
    Serious concomitant medical disorder, evidence of renal dysfunction (creatinine clearance < 60 ml/min), blood dyscrasia, hepatic insufficiency, symptomatic pancreatitis, cardiac diseases not controlled, congestive heart failure (NYHA score > 3), cardiac rhythm anomalies (supra-ventricular or ventricular) not controlled or severe conduction abnormalities (AVB I, II or III or HV > 70 ms) without medical device (patients with pacemaker could be included) [echocardiography in the year before the inclusion], congenital heart defect, known history of heart attack, metabolic acidosis, hypertension, significant central nervous system impairment, or neurodegenerative or neuromuscular disease other than DM1
    History of psychiatric conditions including, but not limited to, psychosis, suicidal ideations, or major depression. Patients with mild to moderate depression in the past may be enrolled if, in the Investigator’s opinion, they are suitable for treatment
    Drug or alcohol abuse within 12 months of enrollment
    Other medical condition (besides DM1) that would significantly impact ambulation
    Any history of malignancy except for cases of remission (remission > 12 months) and surgically cured skin cancer or pilomatricoma (benign tumor of the hair follicle that is associated with DM1)
    Vital capacity < 60% or total lung capacity < 60%, hypercapnia (PCO2 ≥ 50 mmHg)
    or other signs of poor respiratory status which is expected to require the initiation of BiPAP within the study period (patients with nocturnal non-invasive ventilation CPAP or BiPAP could be included)
    Use of medications intended for the treatment of DM1 including glucocorticoids, anabolic steroids, testosterone, growth hormone, or insulin-like growth factor I (IGF-I) within 1 year of entry
    Any medical contraindications to metformin
    Known allergy to metformin and/or his excipients
    Symptomatic insulin requiring diabetes or type 2 diabetes requiring oral anti-diabetic agents
    Women who are pregnant or breast-feeding
    Participation in another experimental therapeutic protocol within 6 months prior to baseline and during the study period (participation in natural history study is allowed)
    Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful completion of the study
    Patient unable or unwilling to comply with the protocol requirements
    E.5 End points
    E.5.1Primary end point(s)
    Efficacy: At week 52, change from baseline in distance walked at the 6MWT (6MWT)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Evaluation at week 52
    E.5.2Secondary end point(s)
    Safety: Overall incidence of adverse events and serious adverse events as well as laboratory assessments will be evaluated for each arm and for the study as a whole.
    Efficacy:
    MyoTone test (performed with the hand grip) at W52: improvement ≥ 20% of relaxation phase from baseline
    Muscle MRI at W52: stabilization from baseline of the volume of residual muscle tissue in TA muscle, of the mean T2-relaxation-time of residual muscle tissue, and of the mean fat-to-water ratio in the entire TA muscle
    Insulin resistance, cholesterol and triglycerides will be measured and compared to baseline over time
    Muscle function and strength measured by the grip test (Handgrip) and the Quantitative Muscle Testing (QMT) test at W52: improvement ≥ 5% of the muscle strength from baseline
    Cardiac: 12-lead resting ECG will be analyzed at W52 compared to baseline
    Activity and social participation: Scores of DM1-Activ scale and InQoL questionnaires at baseline and over 52 weeks will be analyzed
    Biomarker Assays: Change of level in blood INSRA and INSRB Messenger Ribonucleic Acid (mRNA), FAS ATP2A1 and LMNA splice variants from screening, W2, W4, W16, and W52
    E.5.2.1Timepoint(s) of evaluation of this end point
    Safety will be evaluated during the whole study.
    Efficacy endpoints will be evaluated at week 52 compared to baseline.
    Biomarkers will be mesured at screening, at Week 2, Week 4, Week 16, and Week 52
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months3
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 40
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2013-08-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-09-06
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-11-17
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