E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Nonsense mutation dystrophinopathy |
Distrofinopatie da mutazione non-senso |
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E.1.1.1 | Medical condition in easily understood language |
Duchenne and Becker muscular dystrophy (muscle diseases that weaken the musculoskeletal system) |
Distrofia muscolare di Duchenne e di Becker (malattia muscolare che indebolisce il sistema muscolo-scheletrico) |
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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 | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059117 |
E.1.2 | Term | Becker's muscular dystrophy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
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 assess the long-term safety and tolerability of 10, 10, 20 mg/kg ataluren in patients with nmDBMD who had prior exposure to ataluren in a PTC-sponsored clinical trial |
L'obiettivo primario del presente studio consiste nel valutare la sicurezza e la tollerabilità di 10, 10, 20 mg/kg di Ataluren in pazienti affetti da nmDBMD precedentemente esposti ad Ataluren in uno studio clinico sponsorizzato da PTC. |
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E.2.2 | Secondary objectives of the trial |
Ambulatory patients (able to run/walk 10 meters in ≤30 seconds) - To determine the effect of ataluren on ambulation and other aspects of physical function - Nonambulatory patients (unable to run/walk 10 meters in ≤30 seconds) - To assess the effect of ataluren on activities of daily living, upper limb function, and pulmonary function - All patients – To assess patient and/or parent/caregiver reports of changes in disease status: -Retrospectively during and after participation in previous studies (Studies 007 and 007e) -Prospectively during the current study |
- pazienti deambulanti all'inizio dello studio (in grado di correre/camminare per 10 metri in ≤30 secondi): determinare l'effetto di ataluren sulla deambulazione e su i suoi aspetti funzionali.
- nei pazienti non deambulanti (non in grado di correre/camminare per 10 metri in ≤30 secondi):valutare l'effetto di ataluren sulle attività della vita quotidiana, funzione degli arti inferuiorie funzioni polmonari.
- tutti i pazienti: valutare cambiamenti della patologia riferiti dai pazienti, genitori o assistenti-
Restrospettivamente durante e dopo la partecipazione ai precedenti studi e prospettivamente duarante questo studio |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial. 2. History of exposure to ataluren in a prior PTC study in nmDBMD. Note: Subjects who have participated in a prior or ongoing PTC study with ataluren in nmDBMD at a trial site in the US or Canada, but reside outside of the US and Canada, may be eligible for this study (with the approval of the PTC Therapeutics Medical Monitor). 3. Male sex. 4. Confirmed screening laboratory values within the central laboratory ranges specified in the protocol. 5. In patients who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during ataluren administration and the 6-week follow-up period. 6. Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions |
1. Documento/i relativi al consenso/assenso informato debitamente firmato/i e datato/i, attestante che il soggetto (e/o il genitore/tutore legale) è stato informato di tutti gli aspetti inerenti allo studio clinico;
2.Storia di esposizione ad Ataluren in uno studio preliminare sulla nmDBMD sponsorizzato da PTC;
3.Sesso maschile;
4.Valori di screening di laboratorio confermati entro i limiti del laboratorio centrale di cui alla tabella 2.
5.Nei pazienti sessualmente attivi è richiesta la volontà di astenersi da rapporti sessuali o di impiegare un metodo contraccettivo di barriera o medico durante la somministrazione di Ataluren e il periodo di follow-up di 6 settimane;
6.Sono richieste, inoltre, la volontà e la capacità di osservare le visite programmate, il piano di somministrazione del farmaco, i trattamenti dello studio, gli esami di laboratorio e le restrizioni dello studio. |
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E.4 | Principal exclusion criteria |
1. Exposure to another investigational drug within 1 month prior to start of study treatment. 2. Eligibility for another ataluren clinical trial that is actively enrolling study participants. 3. Known hypersensitivity to any of the ingredients or excipients of ataluren. 4. Ongoing use of the following medications: a. Coumarin based anticoagulants (eg, warfarin), phenytoin, tolbutamide, or paclitaxel. b. Systemic aminoglycoside therapy. 5. Ongoing uncontrolled medical/surgical condition, ECG findings, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the patient or make it unlikely that follow-up would be completed |
1.Esposizione a un altro farmaco sperimentale entro 1 mese precedente all'inizio del trattamento in studio.
2.Idoneità ad un altro studio clinico su Ataluren per cui si è in procinto di essere attivamente arruolati.
3.Nota ipersensibilità ad uno qualsiasi degli ingredienti o eccipienti di Ataluren (LitesseUltraTM [polidestrosio raffinato], polietilenglicole 3350, Lutrol micro F127 [poloxamer 407], mannitolo 25C, crospovidone XL10, idrossietilcellulosa, vaniglia, Cab O Sil M5P [silice colloidale], stearato di magnesio).
4.Uso in corso dei seguenti farmaci:
a.Farmaci a base di anticoagulanti cumarinici (ad esempio, warfarin), fenitoina, tolbutamide o paclitaxel.
b.Terapia sistemica con antibiotici aminoglicosidici
5.Disturbo in corso non controllato da un medico/chirurgico, esiti di ECG o anomalie di laboratorio che, a giudizio dello sperimentatore, possano influire negativamente sulla sicurezza del paziente o rendano improbabile il completamento del periodo di follow-up. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety profile characterized by type, frequency, severity, timing, and relationship to ataluren of any adverse events or laboratory abnormalities. |
Profilo di sicurezza caraterizzato dal tipo, frequenza, severità, tempistica e relazione di ataluren con eventi avversi o anomalie di laboratorio |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
every 12 weeks |
ogni 12 settimane |
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E.5.2 | Secondary end point(s) |
• In ambulatory patients, change from baseline in 6MWD as measured by the 6-minute walk test (6MWT) •In ambulatory patients, change from baseline in physical function as measured by the North Star Ambulatory Assessment (NSAA) • In ambulatory patients, change from baseline in timed function tests (time to stand from supine and time to run/walk 10 meters) • In nonambulatory patients, change from baseline in pulmonary function as measured by spirometry • In nonambulatory patients, change from baseline in patient and parent/caregiver-reported activities of daily living, as measured by the Egen Klassifikation (EK) scale •In all patients, changes in patient and/or parent/caregiver reports of disease status as measured by a standardized survey administered by site personnel |
- pazienti ambulanti:
+ variazione dal basale del test di camminata valutato con il test di camminata di 6 minuti (6MWD);
+ la variazione dal basale nelle prove di funzionalità con misurazione dei tempi (il tempo intercorrente tra lo stare in piedi e lo sdraiarsi supini e il tempo impiegato per correre/camminare su una distanza di 10 metri) e la Valutazione ambulatoriale North Star.
- pazienti non ambulanti:
+ variazione dal basale della funzionalità polmonare, misurata mediante spirometria;
+ variazione dal basale nelle attività della vita quotidiana riferite dal soggetto stesso e dai genitori/prestatore di cure, secondo la scala Egen Klassifikation (EK).
- tutti i pazienti: variazioni nello stato della malattia riferite dal paziente stesso e/o dai genitori/prestatore di cure, misurate mediante un sondaggio standardizzato somministrato dal personale del centro |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6MWT: Screening Visit, Week 24, Week 48 NSAA: Screening, Week 48 Timed function test: Screening, Week 48 Spirometry: Screening, Week 24, Week 48 EK Scale: Screening Visit, Week 48 Disease status survey: Screening, Week 12, Week 24, Week 36 and Week 48 |
6MWT: screening, settimana 24 e 48;
NSAA: screnning e settimana 48;
Prove di funzionalità con misura dei tempi: screening, settimana 48;
Spirometria: Screening e settimana 48;
Scala EK: screening, settimana 48;
stato della malattia: screening, settimana 12, 24 , 36 e 48; |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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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 | 21 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 21 |
E.8.9.2 | In all countries concerned by the trial days | 0 |