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    Summary
    EudraCT Number:2019-003758-97
    Sponsor's Protocol Code Number:MEX-NM-303
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-11-20
    Trial 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 number2019-003758-97
    A.3Full title of the trial
    Open-label Extension Study to Evaluate the Long-term Safety and Efficacy of Mexiletine in Paediatric Patients with Myotonic Disorders Who Have Completed MEX-NM-301 and MEX-NM-302 Studies
    Étude de prolongation ouverte visant à évaluer l’innocuité et l’efficacité à long terme de la mexilétine chez des patients pédiatriques présentant des troubles myotoniques et ayant terminé les études MEX-NM-301 et MEX-NM-302
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Evaluate the Long-term Safety and Efficacy of Mexiletine in Paediatric Patients with Myotonic Disorders
    Étude visant à évaluer l’innocuité et l’efficacité de la mexilétine à long terme chez des patients pédiatriques présentant des troubles myotoniques et ayant terminé les études MEX-NM-301 et MEX-NM-302
    A.4.1Sponsor's protocol code numberMEX-NM-303
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/155/2017
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorLupin Europe GmbH
    B.1.3.4CountryGermany
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportLupin Atlantis Holdings SA
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationLupin Healthcare (UK) Ltd.
    B.5.2Functional name of contact pointSenior Regulatory Affairs Manager
    B.5.3 Address:
    B.5.3.1Street AddressThe Urban Building, 2nd Floor, 3-9 Albert street
    B.5.3.2Town/ citySlough
    B.5.3.3Post codeSL1 2BE
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+441565751378
    B.5.5Fax number+441565751379
    B.5.6E-mailEU-RA@lupin.com
    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 Namuscla
    D.2.1.1.2Name of the Marketing Authorisation holderLupin Europe GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/14/1353 (EMA/OD/074/14)
    D.3 Description of the IMP
    D.3.1Product nameMexiletine 167 mg
    D.3.4Pharmaceutical form Capsule, hard
    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 INNMexiletine hydrochloride (HCl)
    D.3.9.1CAS number 5370-01-4
    D.3.9.3Other descriptive nameMEXILETINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB03281MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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.IMP: 2
    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 No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/14/1353 (EMA/OD/074/14)
    D.3 Description of the IMP
    D.3.1Product nameMexiletine 83 mg
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation Yes
    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 INNMexiletine hydrochloride (HCl)
    D.3.9.1CAS number 5370-01-4
    D.3.9.3Other descriptive nameMEXILETINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB03281MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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.IMP: 3
    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 No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/14/1353 (EMA/OD/074/14)
    D.3 Description of the IMP
    D.3.1Product nameMexiletine 62 mg
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation Yes
    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 INNMexiletine hydrochloride (HCl)
    D.3.9.1CAS number 5370-01-4
    D.3.9.3Other descriptive nameMEXILETINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB03281MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Myotonic disorders: Nondystrophic myotonias (NDM) or myotonic dystrophies (DM, type 1 or type 2); ICD-10 code G71.1
    Myotonies non dystrophiques (NDM) ou dystrophies myotoniques (DM, type 1 ou 2)
    E.1.1.1Medical condition in easily understood language
    Myotonic disorders
    Troubles myotoniques
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10028658
    E.1.2Term Myotonic disorders
    E.1.2System Organ Class 100000004852
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The aim of this study is to obtain additional information regarding the long-term safety and efficacy of mexiletine for the symptomatic treatment of myotonia in paediatric subjects who have completed the initial paediatric studies. The co-primary objectives are: 1) to assess the long-term safety and tolerability of mexiletine in paediatric patients (aged 0 to < 18 years) with myotonic disorders; 2) to evaluate long-term effectiveness of oral dosing with mexiletine.
    L’objectif de cette étude est de recueillir des informations complémentaires sur l’innocuité et l’efficacité à long terme de la mexilétine pour le traitement symptomatique de la myotonie chez des sujets pédiatriques qui ont terminé les études pédiatriques initiales. Les objectifs principaux sont : 1) Evaluer l’innocuité et la tolérance à long terme de la mexilétine chez les patients pédiatriques (âgés de 0 à moins de 18 ans) qui présentent des troubles myotoniques ; 2) Evaluer l’efficacité à long terme de doses orales de mexilétine.
    E.2.2Secondary objectives of the trial
    6 to < 18 years are: 1) to evaluate the efficacy of mexiletine; 2) to evaluate efficacy and tolerability of mexiletine as measured by Clinical Global Impression (CGI) scale indices; 3) to determine changes in health-related quality-of-life.

    6 months to < 6 years are: 1) to determine the changes in health-related quality-of-life; 2) to determine severity score of stiffness, pain, weakness and tiredness; 3) to determine global impression of efficacy (CGI-Efficacy index); 4) to evaluate the assessment of pain by the investigator using the FLACC (face, legs, activity, crying, and consolability) scale; 5) to determine the global impression of tolerability (CGI-Tolerability index); and 6) to evaluate daily dose of mexiletine, dose changes.

    < 6 months are: 1) to determine the global impression of efficacy (CGI-Efficacy index) and 2) to determine the number of apnoeic episodes throughout the study in newborns with severe neonatal episodic laryngospasm (SNEL).
    6 ans à < 18 ans : 1) Evaluer l’efficacité de la mexilétine ; 2) Evaluer l’efficacité et la tolérance de la mexilétine telles que mesurées par les indices sur l’échelle des impressions cliniques globales (CGI) et 3) Déterminer les modifications de la qualité de vie liée à la santé.

    6 mois à < 6 ans : 1) Déterminer les modifications de l’évaluation de la qualité de vie liée à la santé ; 2) Déterminer le score de gravité des raideurs, des douleurs, de la faiblesse et de la fatigue ; 3) Déterminer l’impression globale en termes d’efficacité (indice CGI-efficacité) ; 4) Evaluer la douleur (échelle FLACC) ; 5) Déterminer l’impression globale en termes de tolérance (indice CGI-tolérance) et 6) Evaluer la dose journalière de mexilétine et les changements de dose.

    < 6 mois : 1) Déterminer l’impression globale en termes d’efficacité et 2) Déterminer le nombre d’épisodes d’apnée tout au long de l’étude chez les nouveau-nés présentant un laryngospasme néonatal épisodique sévère.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Patients previously enrolled in parent study PIP study 4 (MEX-NM-301) or PIP Study 5 (MEX-NM-302);
    2. Able and willing to provide assent to study participation and a parent or legal guardian willing to sign written informed consent prior to study entry.
    1. Patients précédemment inclus dans l’étude parente PIP 4 (MEX-NM-301) ou PIP 5 (MEX-NM-302) et qui l’ont terminée ;
    2. Patients en mesure et désireux de fournir leur accord pour une participation à l’étude, et parent ou tuteur légal disposé à signer le formulaire de consentement éclairé avant l’inclusion dans l’étude.
    E.4Principal exclusion criteria
    1. Clinically significant laboratory abnormality, ECG or other clinical findings on physical examination indicative of a clinically significant exclusionary disease as determined by the investigator;
    2. Any contra-indication to mexiletine as listed in the Namuscla Summary of Product Characteristics (SmPC):
    2.a. Hypersensitivity to the active substance, or to any of the excipients;
    2.b. Hypersensitivity to any local anaesthetic;
    2.c. Ventricular tachyarrhythmia;
    2.d. Complete heart block (i.e., third-degree atrioventricular block) or any heart block susceptible to evolve to complete heart block (first-degree atrioventricular block with markedly prolonged PR interval (≥ 200 ms) and/or wide QRS complex (≥ 120 ms), second-degree atrioventricular block, bundle branch block, bifascicular and trifascicular block);
    2.e. QT interval > 450ms;
    2.f. Myocardial infarction (acute or past), or abnormal Q-waves;
    2.g. Symptomatic coronary artery disease;
    2.h. Heart failure with ejection fraction <50%;
    2.i. Atrial tachyarrhythmia, fibrillation or flutter;
    2.j. Sinus node dysfunction (including sinus rate < 50 bpm);
    2.k. Co-administration with medicinal products inducing torsades de pointes;
    2.l. Co-administration with medicinal products with narrow therapeutic index;
    3. Co- administration with antiarrhythmics;
    4. Any other neurological or psychiatric condition that might affect the assessment of the study measurements;
    5. Any concurrent illness, or medications which could affect the muscle function;
    6. Seizure disorder, diabetes mellitus requiring treatment by insulin;
    7. Pregnant or breastfeeding;
    8. Concurrent participation in any other clinical trial.
    1. Anomalie cliniquement significative des examens biologiques, ECG ou autres résultats cliniques des examens physiques indiquant une maladie d’exclusion cliniquement significative, ainsi que déterminé par l’investigateur ;
    2. Contre-indication à la mexilétine (telle que décrite dans le résumé des caractéristiques du produit (RCP) de Namuscla) :
    2.a. Hypersensibilité au principe actif ou à l’un des excipients,
    2.b. Hypersensibilité à un anesthésique local,
    2.c. Tachyarythmie ventriculaire,
    2.d. Bloc cardiaque complet (c.-à-d. bloc auriculo-ventriculaire du 3e degré) ou bloc cardiaque susceptible d’évoluer vers un bloc cardiaque complet (bloc auriculo-ventriculaire du premier degré avec intervalle PR sensiblement prolongé (≥ 200 ms) et/ou complexe QRS large (≥ 120 ms), bloc auriculo-ventriculaire du second degré, bloc de branche, bloc bifasciculaire et trifasciculaire),
    2.e. Intervalle QT > 450 ms,
    2.f. Infarctus du myocarde (aigu ou antérieur) ou anomalies des ondes Q,
    2.g. Coronaropathie symptomatique,
    2.h. Insuffisance cardiaque à fraction d’éjection < 50 %,
    2.i. Tachyarythmie, fibrillation ou flutter auriculaire,
    2.j. Dysfonction du noeud sinusal (notamment une fréquence sinusale < 50 bpm),
    2.k. Co-administration avec des médicaments induisant des torsades de pointes,
    2.l. Co-administration avec des médicaments présentant un indice thérapeutique étroit ;
    3. Co-administration avec des anti-arythmiques ;
    4. Autre maladie neurologique ou psychiatrique pouvant affecter l’évaluation des mesures de l’étude ;
    5. Toute maladie concomitante, ou médicaments pouvant avoir un impact sur la fonction musculaire ;
    6. Trouble épileptique ou diabète sucré nécessitant une insulinothérapie ;
    7. Patientes enceintes ou qui allaitent ;
    8. Participation concomitante à un autre essai clinique.
    E.5 End points
    E.5.1Primary end point(s)
    Patients aged 0 (new-borns) to 18 years: 1) Number and frequency of adverse events (AEs)/serious adverse events (SAEs); 2) Incidence of adverse events of special interest (AESI) and 3) Changes in electrocardiogram (ECG) assessments from baseline.

    Children and adolescents aged 6 years to < 18 years: 4) Mean change in Visual Analogue Scale (VAS) or Faces score for muscle stiffness (myotonia severity) and 5) Score of handgrip myotonia as quantitatively measured using a commercially available grip dynamometer and computerized capture system in standardized conditions.

    Children aged 6 months to < 6 years: 6) Changes in health-related quality-of-life as measured by the PedsQL Quality of Life and Neuromuscular modules by the subject and/or parent or proxies.

    New-borns and infants aged 0 to <6 months: 7) Clinical Global Impression of efficacy (CGI-Efficacy index), evaluated by the investigator and 8) Number of apnoeic episodes, to be determined in the hospital setting by polysomnography only in newborns with severe neonatal episodic laryngospasm (SNEL).
    Les critères d’évaluation de la sécurité principaux pour tous les patients sont : 1) Nombre et fréquence des événements indésirables (EI) / événements indésirables graves (EIG) ; 2) Incidence des événements indésirables d’intérêt particulier (EIIP) et 3) Modifications des évaluations ECG par rapport aux valeurs de référence.

    Pour les patients âgés de 6 ans à moins de 18 ans, les critères d’évaluation de l’efficacité principaux sont : 4) Variation moyenne du score sur l’échelle visuelle analogique (EVA) ou du score d’expressions faciales pour la raideur musculaire (sévérité de la myotonie) et 5) Score de la myotonie de préhension selon la mesure quantitative à l’aide d’un dynamomètre de force de préhension disponible dans le commerce et d’un système de recueil informatisé dans des conditions normalisées.

    Pour les patients âgés de 6 mois à moins de 6 ans, les critères d’évaluation de l’efficacité principaux sont : 6) Modifications de la qualité de vie liée à la santé telles que mesurées par les PedsQL Quality of Life and Neuromuscular modules par le sujet et/ou un parent ou une personne ayant procuration.

    Pour les nouveau-nés et nourrissons âgés de moins de 6 mois, les critères d’évaluation de l’efficacité principaux sont : 7) Impression clinique globale en termes d’efficacité (indice CGI-efficacité), évaluée par l’investigateur et 8) Nombre d’épisodes d’apnée, à déterminer au sein de l’établissement hospitalier au moyen d’une polysomnographie uniquement chez les nouveau-nés souffrant d’un laryngospasme néonatal épisodique sévère (SNEL).
    E.5.1.1Timepoint(s) of evaluation of this end point
    1) Throughout the study while on treatment with Namuscla;
    2) Throughout the study while on treatment with Namuscla;
    3) Every 3 months (at each study visit: V1 to V9);
    4) Every 3 months (at each study visit: V1 to V9);
    5) Every 6 months (V1, V3, V5, V7 and V9);
    6) Every 6 months (V1, V3, V5, V7 and V9);
    7) Every 3 months (at each study visit: V1 to V9);
    8) Every 6 months (V1, V3, V5, V7 and V9).
    1) Tout au long de l'étude ;
    2) Tout au long de l'étude ;
    3) Tous les 3 mois (à chaque visite: V1 à V9) ;
    4) Tous les 3 mois (à chaque visite: V1 à V9) ;
    5) Tous les 6 mois (V1, V3, V5, V7 et V9) ;
    6) Tous les 6 mois (V1, V3, V5, V7 et V9) ;
    7) Tous les 3 mois (à chaque visite: V1 à V9) ;
    8) Tous les 6 mois (V1, V3, V5, V7 et V9).
    E.5.2Secondary end point(s)
    Patients aged 0 (new-borns) to 18 years: 1) Changes in vital signs and 2) Changes in clinical laboratory values.

    Children and adolescents aged 6 years to < 18 years: 3) Mean change in VAS (8 to < 18 years) or Faces (6 to < 8 years) score for severity of muscle stiffness (if not a primary endpoint) pain, weakness and fatigue; 4) Clinical myotonia assessment: mean change in time to open the eyes after forced eye closure as measured on a stopwatch (when eyelid myotonia present); clinical improvement in flexor myotonia (right hand flexor muscles); and mean change in time to perform Timed-up and go (TUG) test; 5) Mean change in health-related quality-of-life as measured by the Paediatric Quality of Life (PedsQL) score; 6) Clinical Global Impression (CGI) scores (efficacy and tolerability) evaluated by the patient, a parent or proxy and by the investigator and 7) Mean change in Myotonia Behaviour Scale (MBS) scores.

    Children aged 6 months to < 6 years: 8) Mean change in Faces (4 to < 6 years only) score for severity of muscle stiffness, pain, weakness and fatigue; 9) Clinical Global Impression (CGI) scores (efficacy and tolerability) evaluated by the patient, a parent or proxy and by the investigator and 10) Assessment of pain by the investigator using the FLACC scale.

    New-borns and infants aged 0 to <6 months: 11) Clinical Global Impression (CGI) scores (tolerability) evaluated by the patient, a parent or proxy and by the investigator and 12) Assessment of pain by the investigator using the premature infant pain profile (PIPP) scale.
    Les critères d’évaluation de la sécurité secondaires pour tous les patients sont : 1) Les modifications des signes vitaux et 2) Les variations des valeurs biologiques cliniques.

    Pour les patients âgés de 6 ans à moins de 18 ans, les critères d’évaluation de l’efficacité secondaires sont : 3) Variation moyenne du score sur l’échelle visuelle analogique (de 8 ans à moins de 18 ans) ou du score d’expressions faciales (de 4 ans à moins de 8 ans) pour la gravité des raideurs musculaires (s’il ne s’agit pas d’un critère principal), de la faiblesse et de la fatigue musculaires ; 4) Évaluation clinique de la myotonie : variation du délai d’ouverture de l’oeil après fermeture forcée, tel que mesuré à l’aide d’un chronomètre (en cas de présence d’une myotonie palpébrale), amélioration clinique de la myotonie des muscles fléchisseurs (muscles fléchisseurs de la main droite) et variation moyenne du temps mis pour réaliser le test chronométré du lever de chaise de Mathias (TUG) ; 5) Variation moyenne de la qualité de vie liée à la santé telles que mesurées par le score Paediatric Quality of Life (PedsQL) ; 6) Scores sur l’échelle des impressions cliniques globales (CGI) (efficacité et tolérance) évalués par le patient, un parent ou une personne ayant procuration et par l’investigateur et 7) Variation moyenne des scores sur l’échelle du comportement dans la myotonie (MBS).

    Pour les patients âgés de 6 mois à moins de 6 ans, les critères d’évaluation de l’efficacité secondaires sont : 8) Variation moyenne du score d’expressions faciales (de 4 ans à moins de 6 ans) pour la gravité des raideurs, des douleurs, de la faiblesse et de la fatigue musculaires ; 9) Scores sur l’échelle des impressions cliniques globales (CGI) (efficacité et tolérance) évalués par le patient, un parent ou une personne ayant procuration et par l’investigateur et 10) Évaluation de la douleur par l’investigateur à l’aide de l’échelle FLACC.

    Pour les nouveau-nés et nourrissons âgés de moins de 6 mois, les critères d’évaluation de l’efficacité secondaires sont : 11) Scores sur l’échelle des impressions cliniques globales (CGI) (tolérance) évalués par un parent ou une personne ayant procuration et par l’investigateur et 12) Évaluation de la douleur par l’investigateur à l’aide de l’échelle du profil de douleur de l’enfant prématuré (PIPP).
    E.5.2.1Timepoint(s) of evaluation of this end point
    1) Every 3 months (at each study visit: V1 to V9);
    2) Every 3 months (at each study visit: V1 to V9);
    3) Every 3 months (at each study visit: V1 to V9);
    4) Every 6 months (V1, V3, V5, V7 and V9);
    5) Every 6 months (V1, V3, V5, V7 and V9);
    6) Every 6 months (V1, V3, V5, V7 and V9);
    7) Every 6 months (V1, V3, V5, V7 and V9);
    8) Every 3 months (at each study visit: V1 to V9);
    9) Every 3 months (at each study visit: V1 to V9);
    10) Every 6 months (V1, V3, V5, V7 and V9);
    11) Every 3 months (at each study visit: V1 to V9);
    12) Every 6 months (V1, V3, V5, V7 and V9).
    1) Tous les 3 mois (à chaque visite: V1 à V9) ;
    2) Tous les 3 mois (à chaque visite: V1 à V9) ;
    3) Tous les 3 mois (à chaque visite: V1 à V9) ;
    4) Tous les 6 mois (V1, V3, V5, V7 et V9) ;
    5) Tous les 6 mois (V1, V3, V5, V7 et V9) ;
    6) Tous les 6 mois (V1, V3, V5, V7 et V9) ;
    7) Tous les 6 mois (V1, V3, V5, V7 et V9) ;
    8) Tous les 3 mois (à chaque visite: V1 à V9) ;
    9) Tous les 3 mois (à chaque visite: V1 à V9) ;
    10) Tous les 6 mois (V1, V3, V5, V7 et V9) ;
    11) Tous les 3 mois (à chaque visite: V1 à V9) ;
    12) Tous les 6 mois (V1, V3, V5, V7 et V9).
    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) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Paediatric investigation plan
    Plan d'investigation pédiatrique
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Information not present in EudraCT
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Information not present in EudraCT
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    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 Yes
    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, or earlier in case of early discontinuation. Criteria for treatment discontinuation are: 1) An adverse event, which in the opinion of the Investigator and/or Sponsor, necessitates discontinuation of treatment; and/or 2) The patient becomes pregnant during the study period.
    Dernière visite de la dernière personne participant à l’essai.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 12
    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) Yes
    F.1.1.3.1Number of subjects for this age range: 3
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 3
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 3
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 3
    F.1.2Adults (18-64 years) No
    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 No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Paediatric population
    Population pédiatrique
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state12
    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)
    After 24 months of treatment, no study specific visits and data collection are required and patients will be treated and followed up as per investigator site’s protocol. The Sponsor will ensure to supply study drug if it is not commercially available in the country.
    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 Decision2020-05-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-05-07
    P. End of Trial
    P.End of Trial StatusOngoing
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