E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping |
Distrofia muscolare di Duchenne sensibile al salto dell’esone 51 |
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E.1.1.1 | Medical condition in easily understood language |
Duchenne Muscular Dystrophy |
Distrofia muscolare di Duchenne |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10013801 |
E.1.2 | Term | Duchenne muscular dystrophy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of eteplirsen administered once weekly by intravenous (IV) infusion in male Duchenne muscular dystrophy (DMD) patients ages 6 months to 48 months, inclusive |
Valutare la sicurezza e la tollerabilità di eteplirsen somministrato una volta alla settimana mediante infusione endovenosa (e.v.) in pazienti maschi con distrofia muscolare di Duchenne (DMD) da 6 mesi a 48 mesi di età compresi |
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E.2.2 | Secondary objectives of the trial |
To determine the pharmacokinetics (PK) of eteplirsen at the 2-, 10-, 20- and 30-mg/kg dose levels, administered once weekly by IV infusion in male DMD patients ages 6 months to 48 months, inclusive |
• Determinare la farmacocinetica (PK) di eteplirsen a livelli di dose di 2, 10, 20 e 30 mg/kg, somministrato una volta alla settimana mediante infusione e.v. in pazienti maschi con DMD da 6 mesi a 48 mesi di età compresi |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Be a male between 6 months to 48 months of age, inclusive. 2. Have an established clinical diagnosis of DMD with a deletion mutation amenable to exon 51 skipping (e.g., deletions of exons 45-50, 47-50, 48-50, 49-50, 50, 52, 52-63). 3. Have a parent(s) or legal guardian(s) who is able to understand and comply with the study requirements and is willing to provide written informed consent for the patient to participate in the study. |
1.Essere un maschio tra i 6 mesi e i 48 mesi d'età compresi. 2. Avere una diagnosi clinica accertata di DMD con una mutazione per delezione sensibile al salto dell’esone 51 (ad es. delezioni degli esoni 45 50, 47 50, 48 50, 49 50, 50, 52, 52 63). 3. Avere un genitore(i) o tutore(i) legale(i) in grado di comprendere e rispettare i requisiti dello studio e disposto(i) a fornire il consenso informato scritto per la partecipazione del paziente allo studio. |
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E.4 | Principal exclusion criteria |
1. Has received any pharmacologic treatment that might have an effect on muscle strength or function within 12 weeks prior to dosing at Week 1 (e.g., growth hormone, anabolic steroids). 2. Has received previous or current treatment with any experimental treatment. Prior drisapersen therapy is permitted if a patient has not received drisapersen for 6 months prior to the Week 1 dose. 3. Has a clinically significant illness other than DMD, including cardiac, pulmonary, hepatic, renal, hematologic, immunologic, behavioural disease, or malignancy likely to impair the patient's ability to participate in this study. 4. Has a clinically significant laboratory abnormality that is either not expected or is of a greater severity than what is expected in DMD patients. 5. Has any other condition that, in the Investigator's opinion, could interfere with the patient's participation in the study. |
1. Ha ricevuto qualsiasi trattamento farmacologico che potrebbe avere un effetto sulla forza o sulla funzione muscolare nelle 12 settimane precedenti la somministrazione alla Settimana 1 (ad es. ormone della crescita, steroidi anabolizzanti). 2. È stato sottoposto in precedenza o è attualmente sottoposto a un trattamento sperimentale. La precedente terapia con drisapersen è consentita se un paziente non ha ricevuto drisapersen per 6 mesi prima della dose della Settimana 1. 3. È affetto da una malattia clinicamente significativa diversa dalla DMD, incluse malattia cardiaca, polmonare, epatica, renale, ematologica, immunologica, comportamentale, o tumore maligno che potrebbe compromettere la capacità del paziente di partecipare a questo studio. 4. Presenta un'anomalia di laboratorio clinicamente significativa, non prevista o di severità maggiore di quella prevista nei pazienti con DMD. 5. Presenta qualsiasi altra condizione clinica che, a parere dello Sperimentatore, potrebbe interferire con la partecipazione del paziente allo studio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability of eteplirsen as measured by: • Incidence of adverse events (AEs) • Abnormal changes from baseline or clinically significant worsening of clinical safety laboratory abnormalities (hematology, chemistry, coagulation, and urinalysis) • Abnormal changes from baseline or worsening of vital signs • Abnormal changes from baseline or worsening of physical examination findings • Abnormal changes from baseline or clinically significant worsening of ECGs and ECHOs |
L’endpoint primario è costituito dalla sicurezza e tollerabilità di eteplirsen in questa popolazione di studio, misurate da: • Incidenza di AE • Variazioni anomale rispetto al basale o peggioramento clinicamente significativo di anomalie cliniche di laboratorio per la sicurezza (parametri ematologici, parametri chimici, coagulazione e analisi delle urine) • Variazioni anomale rispetto al basale o peggioramento dei parametri vitali • Variazioni anomale rispetto al basale o peggioramento dei risultati dell'esame obiettivo • Variazioni anomale rispetto al basale o peggioramento clinicamente significativo di ECG ed ECHO |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Incidence of AEs: continuous Clinical safety laboratory sample: Screening, Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96 and End-of-Study Follow-up Visit Vital signs: Screening, baseline, on weekly infusion days, Week 96 and End-of-Study Follow-up Visit Physical examination: Screening, baseline, Week 4, 8, 12, 16, 20-48, 60, 72, 84, 96 and End-of-Study Follow-up Visit ECG: Screening, Weeks 8, 12, 24, 48, 60, 72, 84, 96 ECHO: Screening, Weeks 24, 48, 72, 96 |
Incidenza di AE: continuo campione di laboratorio Sicurezza clinica: Screening, settimane 2, 4, 8, 12, 24, 36, 48, 60, 72, 84, 96 e visita di follow-up di fine studio Parametri vitali: Screening, baseline, nei giorni di infusione settimanali, settimane 96 e visita di follow-up di fine studio Esame obiettivo: Screening, baseline, Settimane 4, 8, 12, 16, 20-48, 60, 72, 84, 96 e visita di follow-up di fine studio ECG: Screening, Settimane 8, 12, 24, 48, 60, 72, 84, 96 ECHO: Screening, Settimane 24, 48, 72, 96 |
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E.5.2 | Secondary end point(s) |
PK of eteplirsen by population PK methods, including assessment of the following PK parameters (if evaluable): • Maximum plasma concentration (Cmax) • Time of Cmax (Tmax) • AUC • Apparent volume of distribution at steady state (Vss) • Clearance (CL) • Elimination half-life (t½) • Amount of drug eliminated in urine (Ae%) |
Determinare la PK di eteplirsen mediante metodi di farmacocinetica di popolazione, inclusa la valutazione dei seguenti parametri farmacocinetici (se valutabili): • Concentrazione plasmatica massima (Cmax) • Tempo della Cmax (Tmax) • Area sotto la curva concentrazione/tempo (AUC) • Volume di distribuzione apparente allo steady state (Vss) • Clearance (CL) • Emivita di eliminazione (t½) • Quantità di farmaco eliminata nelle urine (Ae%) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PK plasma and urine sampling: Weeks 2, 6, 8, 10, 24 |
PK plasma e il campionamento delle urine: settimane 2, 6, 8, 10, 24 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Tollerabilità |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial 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
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The trial will be considered to have been completed upon the last visit of the last patient who had their treatment extended to Week 98. |
Lo studio sarà considerato completato al momento dell’ultima visita dell’ultimo paziente il cui trattamento sia stato esteso alla Settimana 98. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |