E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Duchenne Muscular Dystrophy |
Distrofia Muscolare di Duchenne |
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E.1.1.1 | Medical condition in easily understood language |
Ambulant Children with Duchenne Muscular Dystrophy |
Bambini deambulanti affetti da 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 | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10028395 |
E.1.2 | Term | Musculoskeletal and connective tissue disorders |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue 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 establish the histologic effects of Givinostat administered chronically at the selected daily dose |
Stabilire gli effetti istologici di Givinostat somministrato in modo cronico alla dose giornaliera selezionata |
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E.2.2 | Secondary objectives of the trial |
• To establish the effects of Givinostat administered chronically at the selected daily dose on functional parameters, such as the 6-Minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA), and performance of upper limb (PUL) • To establish the safety and tolerability of Givinostat administered chronically at the selected daily dose in children with Duchenne muscular dystrophy (DMD) • To explore the effects of Givinostat administered chronically at the selected daily dose on parameters such as magnetic resonance imaging (MRI), biomarkers, and cytokines |
• Stabilire gli effetti istologici di Givinostat somministrato in modo cronico alla dose giornaliera selezionata sui parametri funzionali, quali i tests: “6-minutes walk test” (6MWT), North Star Ambulatory Assessment (NSAA), e “performance of upper limb” (PUL) • Stabilire la sicurezza e la tollerabilita’ di Givinostat somministrato in modo cronico alla dose giornaliera selezionata in bambini affetti da distrofia muscolare di Duchenne (DMD) • Esplorare gli effetti di Givinostat somministrato in modo cronico alla dose giornaliera selezionata su parametri quali la risonanza magnetica (MRI), i biomarcatori, e le citochine |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male children aged 7 to <11 years with an immunohistochemical and molecular diagnosis of DMD. 3. Able to complete the 2 screening 6MWTs with a minimal distance of at least 250 m each. In addition, the results of these tests must be within ±30 m of each other. 4. On a stable dose of systemic corticosteroids for at least 6 months. 5. At least 6 months worth of data on the 6MWT (this will be the “historical” 6MWT). From the moment of the historical 6MWT assessment(s), the child must not have received any compound that could potentially affect the 6MWT, with the exception of the stable steroid treatment. |
1. Bambini maschi di età tra 7 e <11 anni con una diagnosi di DMD immunoistochimica e molecolare. 2. Bambini in grado di completare i due test di 6MWTs allo screening, con una distanza minima di almeno 250 metri ciascuno. Inoltre, i risultati di questi tests non devono differire tra di loro di ±30 m. 4. Bambini a dosaggio stabile di corticosteroidi sistemici per almeno 6 mesi. 5. Almeno 6 mesi di valore dei dati sul 6MWT (questo sarà lo storico 6MWT). Dal momento dell’effettuazione dello storico 6MWT, il bambino non dovra’ aver assunto alcun composto che possa potenzialmente inficiare il test, ad eccezione del trattamento stabile con steroidi. |
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E.4 | Principal exclusion criteria |
1. Initiation of systemic corticosteroid therapy within 6 months prior to the start of study drug or change in systemic corticosteroid therapy (e.g., initiation, change in type of drug, dose modification not related to body weight change, schedule modification, interruption, discontinuation, or re initiation) within 6 months prior to the start of study drug.
2. Use of any pharmacologic treatment, other than corticosteroids, that might have an effect on muscle strength since the time of the historical 6MWT and in any case within 3 months prior to the start of study treatment (e.g., growth hormone). Vitamin D, calcium, and integrators will be allowed.
3. Surgery that might have an effect on muscle strength or function within 3 months before study entry or planned surgery at any time during the study. |
1. Inizio di una terapia con corticosteroidi entro i 6 mesi precedenti l’assunzione del farmaco in studio o cambiamenti nella terapia con corticosteroidi sistemici (es. Inizio, modifica del tipo di farmaco, modifica del dosaggio non legata a cambiamenti di peso, modifica della posologia, interruzione, o ripresa) nei 6 mesi precedenti l’inizio del farmaco in studio. 2. Uso di qualsiasi agente farmacologico oltre i corticosteroidi, che possa avere un effetto sulla forza muscolare dal momento del valore storico del 6MWT, e in ogni caso nei 3 mesi precedenti l’inizio del farmaco in studio (es. Ormone della crescita). Sono permessi Vitamina D, calcio e integratori 3. Trattamenti chirurgici che possano avere un effetto sulla forza o sulla funzionalità muscolare, effettuati nei 3 mesi precedenti l’inizio dello studio, oppure qualsiasi intervento chirurgico, già pianificato, in qualunque momento durante lo studio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is change in the value of MFA% comparing the histology biopsies before and after 12 months of treatment with Givinostat. |
L’obiettivo primario dello studio è il cambiamento del valore di % MFA (area di fibra muscolare) confrontando le biopsie istologiche prima e dopo i 12 mesi di trattamento con Givinostat. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Change in additional histological endpoints (i.e., cross-sectional area, inflammation, necrosis, fibrosis, and muscle regeneration) after 12 months of treatment with Givinostat at the selected daily dose • Change in muscular function after 12 months of treatment with Givinostat at the selected daily dose based on the 6MWT • Change in muscular function after 12 months of treatment with Givinostat at the selected daily dose based on the NSAA • Change in muscular function after 12 months of treatment with Givinostat at the selected daily dose based the PUL |
• Cambiamento negli obbiettivi istologici aggiuntivi (es. area cross- sectional, infiammazione, necrosi, fibrosi e rigenerazione muscolare) dopo 12 mesi di trattamento con Givinostat alla dose giornaliera selezionata. • Cambiamento nella funzionalità muscolare dopo 12 mesi di trattamento con Givinostat alla dose giornaliera selezionata sulla base del 6MWT • Cambiamento nella funzionalità muscolare dopo 12 mesi di trattamento con Givinostat alla dose giornaliera selezionata sulla base del NSAA • Cambiamento nella funzionalità muscolare dopo 12 mesi di trattamento con Givinostat alla dose giornaliera selezionata sulla base del PUL |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
E.8.7 | Trial 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
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All subjects, regardless of whether they complete the study or terminate early in Part 1 or Part 2 should return to the study center within 4 weeks of the last dose of study drug for the follow-up visit |
tutti i soggetti termineranno lo studio con una visita di follow up effettuata 4 settimana dopo l'ultima somministrazione di farmaco. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | 0 |