| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Hepatitis C infection |
| Infezione Cronica da Virus dell¿Epatite C |
|
| E.1.1.1 | Medical condition in easily understood language |
| Hepatitis C Infection |
| Infezione da Virus dell¿Epatite C |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10008912 |
| E.1.2 | Term | Chronic hepatitis C |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
¿ In Part 2, the primary objectives are to evaluate the safety and efficacy (percentage of treatment-na¿ve subjects achieving SVR24) of OBV, PTV, RTV and DSV with or without RBV in HCV GT1-infected subjects and OBV, PTV, RTV with RBV in GT4-infected pediatric subjects with or without compensated cirrhosis.
¿ In Part 3, the primary and secondary objectives are to assess the durability of response for subjects who achieved SVR, to assess the persistence of specific HCV amino acid variants associated with drug resistance in subjects who experienced virologic failure, and to assess the impact of OBV, PTV, RTV with or without DSV coadministered with or without RBV on growth and development. |
¿ Parte 2, l¿obiettivo principale ¿ di valutare la sicurezza e l¿efficacia (percentuale di soggetti na¿ve al trattamento che ottengono SVR24) di OBV, PTV, RTV e DSV con o senza RBV in soggetti con infezione da HCV di genotipo 1 e OBV, PTV, RTV con RBV in soggetti pediatrici con infezione da HCV di genotipo 4 con o senza cirrosi compensata.
¿ Parte 3, gli obiettivi primari e secondari sono di valutare la durata della risposta per i soggetti che hanno ottenuto SVR, valutare la persistenza di specifiche varianti degli aminoacidi dell¿HCV che si associano alla resistenza farmacologica in soggetti che manifestano fallimento virologico, e valutare l¿impatto di OBV, PTV, RTV con o senza DSV e con o senza RBV su crescita e sviluppo. |
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| E.2.2 | Secondary objectives of the trial |
¿ Part 2 (Safety and Efficacy): To evaluate the percentage of treatmentna¿ve subjects with SVR12 and the percentage of treatment-na¿ve subjects with ALT normalization by the end of treatment.
¿ Part 3 (Long-term Follow-up): To assess the long term impact of OBV PTV, RTV with or without DSV coadministered with or without RBV on growth and development. |
¿ Parte 2 (Sicurezza ed Efficacia): Valutare la percentuale di soggetti na¿ve al trattamento con SVR12 e la percentuale di soggetti na¿ve al trattamento con normalizzazione dei valori di ALT alla fine del trattamento.
¿ Parte 3 (Follow-Up a Lungo Termine): Valutare l¿impatto a lungo termine di OBV, PTV, RTV con o senza DSV e con o senza RBV su crescita e sviluppo. |
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenetics
Version: Am.1
Date: 23/07/2015
Title: See main protocol.
Objectives: The Pharmacogenetic Sub-Study procedure is described in the M14-748 Protocol. DNA samples from the Pharmacogenetic Sub-study may be sequenced and data analyzed for genetic factors contributing to the disease or to the subject's response to OBV, PTV, DSV in terms of pharmacokinetics, efficacy, tolerability, and safety. Such genetic factors may include genes for drug metabolizing enzymes, drug transport proteins, genes within the target pathway, genes believed to be related to the disease or to drug response. Some genes currently insufficiently characterized or unknown may be understood to be important at the time of analysis. The samples may be analyzed as part of a multi-study assessment of genetic factors involved in the response to OBV, PTV, DSV, drugs of this class, or the disease state. The samples may also be used for the development of diagnostic tests related to OBV, PTV, DSV, drugs of this class, or the disease state.
|
Farmacogenetica
Versione: Am.1
Data: 23/07/2015
Titolo: Si veda il protocollo principale.
Obiettivi: The Pharmacogenetic Sub-Study procedure is described in the M14-748 Protocol. DNA samples from the Pharmacogenetic Sub-study may be sequenced and data analyzed for genetic factors contributing to the disease or to the subject's response to OBV, PTV, DSV in terms of pharmacokinetics, efficacy, tolerability, and safety. Such genetic factors may include genes for drug metabolizing enzymes, drug transport proteins, genes within the target pathway, genes believed to be related to the disease or to drug response. Some genes currently insufficiently characterized or unknown may be understood to be important at the time of analysis. The samples may be analyzed as part of a multi-study assessment of genetic factors involved in the response to OBV, PTV, DSV, drugs of this class, or the disease state. The samples may also be used for the development of diagnostic tests related to OBV, PTV, DSV, drugs of this class, or the disease state.
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|
| E.3 | Principal inclusion criteria |
1. Positive anti-HCV Ab and HCV RNA greater than or equal to 1000 IU/mL at the time of screening.
2. HCV genotype 1 or 4 for enrollment into Part 2.
3. Parent or legal guardian with the willingness and ability to provide written informed consent and participant willing and able to give assent, as appropriate for age and country. |
1. Infezione da HCV confermata da positività agli anticorpi anti-HCV e da livelli HCV RNA = 1.000 UI/mL al momento dello screening.
2. Genotipo 1 o 4 per l’arruolamento nella Parte 2.
3. Genitori o tutori disponibili e in grado di rilasciare il proprio consenso informato scritto e soggetti disponibili ed in grado di rilasciare il proprio assenso, secondo quanto appropriato in base all’età e alla nazione di appartenenza. |
|
| E.4 | Principal exclusion criteria |
1. Women who are pregnant or breastfeeding.
2. Use of known strong inducers and inhibitors (e.g., gemfibrozil) of cytochrome P450 2C8 (CYP2C8) in participants receiving dasabuvir, or strong or moderate inducers of CYP3A, within 2 weeks or 10 half lives, whichever is longer, of the respective medication/supplement prior to study drug administration.
3. Positive test result for Hepatitis B surface antigen (HbsAg) or anti-HIV antibody (HIV Ab) test.
4. Current enrollment in another interventional clinical study, previous enrollment in this study, prior or current use of any investigational or commercially available anti-HCV agents other than IFNs or RBV or receipt of any investigational product within 6 weeks prior to study drug administration. |
1. Soggetti di sesso femminile in stato di gravidanza o che stanno allattando.
2. Uso di noti induttori o inibitori potenti (es., gemfibrozil) del citocromo P450 2C8 (CYP2C8) nei soggetti che ricevono dasabuvir, oppure di induttori potenti o moderati del CYP3A, per un periodo di 2 settimane o per un periodo pari a 10 emivite del medicinale/supplemento in questione, a seconda di quale sia più lungo, (quale dei due periodi sia più lungo) prima della somministrazione del medicinale sperimentale.
3. Positività all’antigene di superficie per l’epatite l’Epatite B (HbsAg) o conferma di positività all’anticorpo anti-HIV (test HIV ab).
4. Attuale arruolamento in un’altra sperimentazione clinica interventistica, arruolamento pregresso nell’ambito di questa stessa sperimentazione, uso pregresso o attuale di qualsiasi agente anti-HCV commercializzato o sperimentale diverso da Interferoni IFN in qualsiasi combinazione o RBV, oppure trattamento con qualsiasi prodotto sperimentale nelle 6 settimane precedenti la somministrazione del medicinale sperimentale. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
¿ Part 2: The primary endpoint is the percentage of treatment-naïve subjects with SVR24
¿ Part 3: The primary endpoints of the Long-term Follow-up study are the percentage of subjects who relapse and the percentage of subjects who have new HCV infection at any time up to the last follow-up in this study out of subjects who achieved SVR in the previous study and enroll in this study. |
• Parte 2: L’endpoint primario è rappresentato dalla percentuale di soggetti naïve rispetto al trattamento che ottengono SVR24;
• Parte 3: Gli endpoint primari della sperimentazione di Follow-Up a Lungo Termine sono rappresentati dalla percentuale di soggetti con recidiva e dalla percentuale di soggetti con nuova infezione da HCV a qualsiasi tempistica fino all’ultimo follow-up nell’ambito di questa sperimentazione fra i soggetti che hanno ottenuto SVR nella sperimentazione precedente e sono stati arruolati in questa sperimentazione. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
An interim analysis on all the study data from Parts 1, 2 and 3 will occur after approximately 30 subjects enrolled in the = 12 to 17 years age group in Part 2 complete PT Week 24 or prematurely discontinue from the study. An interim analysis on all the study data from Parts 1, 2 and 3 will occur after approximately 100 treatment-naïve subjects enrolled in Part 2 complete PT Week 24 or prematurely discontinue from the study.
The same interim analysis will be repeated or updated once all subjects enrolled into Part 2 complete PT Week 24 or prematurely discontinue from the study. |
| Sarà realizzata un’analisi ad interim su tutti i dati della sperimentazione generati dalle Parti 1, 2 e 3 dopo che circa 30 soggetti arruolati nel gruppo di età compresa fra = 12 e 17 anni, nella Parte 2, abbiano completato la Settimana 24 del Periodo Post-Trattamento o si siano ritirati in maniera anticipata dalla sperimentazione. Un’analisi ad interim su tutti i dati della sperimentazione delle Parti 1, 2 e 3 sarà eseguita dopo che circa 100 soggetti naïve rispetto al trattamento arruolati nella Parte 2 abbiano completato la Settimana 24 del Periodo Post-Trattamento o si siano ritirati in maniera anticipata dalla sperimentazione. La stessa analisi ad interim sarà ripetuta oppure aggiornata una volta che tutti i soggetti arruolati nella Parte 2 abbiano completato la Settimana 24 del Perio |
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| E.5.2 | Secondary end point(s) |
¿ Part 2: The percentage of treatment-na¿ve subjects who achieve SVR12; and the percentage of treatment-na¿ve subjects with ALT .normalization during treatment, defined as ALT = ULN at the final treatment visit for subjects with ALT > ULN at baseline
¿ Resistance: For subjects with virologic failure and HCV RNA > 1000 IU/mL, the variants at each amino acid position (by population, deep, and/or clonal nucleotide sequencing) at available post baseline time points compared to baseline and prototypic reference standard sequences will be summarized by DAA target genes and accompanying
listings will be provided. Growth and Development: The following growth and development endpoints will be calculated through Post-Treatment Week 24 in Part 1 and Part 2, and in Part 3 for later visits. Growth rate at each post baseline visit (defined as change in height over change in age from the previous visit); Height z score; Waist circumference; Tanner staging. |
¿ Parte 2: La percentuale di soggetti na¿ve al trattamento che ottengono SVR12; e la percentuale di soggetti na¿ve al trattamento che ottengono la normalizzazione dei livelli di ALT in corso di trattamento, definita come ALT = ULN alla visita finale del Periodo di Trattamento per i soggetti con ALT > ULN al baseline.
¿ Resistenza: Nei soggetti con fallimento virologico e livelli HCV RNA > 1.000 UI/mL, le varianti presso ciascuna posizione di aminoacidi (mediante sequenziamento di popolazione, profondo e/o clonale dei nucleotidi) alle tempistiche post basali disponibili e confrontate rispetto al baseline e al sequenziamento prototipico standard di riferimento saranno riassunti per geni target dei DAA e saranno presentati i rispettivi listati. Crescita e Sviluppo: Saranno calcolati i seguenti endpoint relativi a crescita e sviluppo fino alla Settimana 24 del Periodo Post-Trattamento nell¿ambito della Parte 1 e Parte 2, e per le visite dell¿ultimo periodo della Parte 3. Tasso di crescita a ciascuna visita post-basale (definito come la variazione dell¿altezza rispetto alla variazione di et¿ rispetto alla visita precedente); Punteggio Z per l¿altezza; Circonferenza della vita; Stadio secondo Tanner. |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
An interim analysis on all the study data from Parts 1, 2 and 3 will occur after approximately 30 subjects enrolled in the = 12 to 17 years age group in Part 2 complete PT Week 24 or prematurely discontinue from the study. An interim analysis on all the study data from Parts 1, 2 and 3 will occur after approximately 100 treatment-na¿ve subjects enrolled in Part 2 complete PT Week 24 or prematurely discontinue from the study.
The same interim analysis will be repeated or updated once all subjects enrolled into Part 2 complete PT Week 24 or prematurely discontinue from the study. |
| Sar¿ realizzata un¿analisi ad interim su tutti i dati della sperimentazione generati dalle Parti 1, 2 e 3 dopo che circa 30 soggetti arruolati nel gruppo di et¿ compresa fra = 12 e 17 anni, nella Parte 2, abbiano completato la Settimana 24 del Periodo Post-Trattamento o si siano ritirati in maniera anticipata dalla sperimentazione. Un¿analisi ad interim su tutti i dati della sperimentazione delle Parti 1, 2 e 3 sar¿ eseguita dopo che circa 100 soggetti na¿ve rispetto al trattamento arruolati nella Parte 2 abbiano completato la Settimana 24 del Periodo Post-Trattamento o si siano ritirati in maniera anticipata dalla sperimentazione. La stessa analisi ad interim sar¿ ripetuta oppure aggiornata una volta che tutti i soggetti arruolati nella Parte 2 abbiano completato la Settimana 24 del Perio |
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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 | No |
| E.6.7 | Pharmacodynamic | No |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
Part 2: Safety & Efficacy;
Part 3: Dose Response |
Parte 2: Sicurezza ed Efficacia
Parte 3: Dose-Risposta |
|
| 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 | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| 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.8.2.4 | 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 | 26 |
| 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 | Information not present in EudraCT |
| 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 |
| Canada |
| Puerto Rico |
| United States |
| Belgium |
| Germany |
| Italy |
| Spain |
| Switzerland |
| United Kingdom |
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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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 7 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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