E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Hepatitis C Virus Infection (Genotypes 1 and 4) |
Infezione cronica da Epatite C (genotipo 1 o 4) |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Hepatitis C |
Epatite C cronica |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008912 |
E.1.2 | Term | Chronic hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 |
To assess efficacy, as determined by the proportion of subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12. |
Valutare l’efficacia, determinata dalla proporzione di soggetti con SVR12, definita come HCV RNA < LOQ alla settimana 12 successiva al termine del trattamento. |
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E.2.2 | Secondary objectives of the trial |
• To assess safety, as measured by the frequency of SAEs and discontinuations due to AEs; • To assess the relationship between efficacy endpoints and the rs12979860 single nucleotide polymorphisms (SNP) in the IL28B gene. • To assess the efficacy as determined by: − HCV RNA undetectable at each of the following timepoints: weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [eRVR]; EOT (up to 24 weeks), post-treatment Week 12 or post-treatment Week 24; − HCV RNA < LOQ at each of the following timepoints: weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [VR(4&12)]; EOT (up to 24 weeks), post-treatment Week 24 (SVR24). • To evaluate antiviral activity endpoints for HCV genotype 4 subjects. |
• Valutare la sicurezza, misurata come frequenza di Eventi Avversi Seri e discontinuazioni a causa di Eventi Avversi; • Valutare la relazione tra l’endpoints di efficacia e il polimorfismo del singolo nucleotide (SNP) rs12979860 nel gene IL28B. • Valutare l’efficacia determinata come: - HCV RNA non determinabile ad ognuno dei seguenti momenti dello studio: settimane 1, 2, 4, 6, 8 e 12; ad entrambe le Settimane 4 e 12 [eRVR]; EOT (fino a 24 settimane), alla Settimana 12 o 24 post-trattamento; - HCV RNA < LOQ ad ognuno dei seguenti momenti: settimane 1, 2, 4, 6, 8 and 12; ad entrambe le Settimane 4 e 12 [VR(4&12)]; EOT (fino a 24 settimane), alla Settimana 24 post-trattamento (SVR24). • Valutare gli endpoints di attività antivirale per I soggetti HCV genotipo 4. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Males and females, ≥ 18 years of age; • HCV Genotype 1 or 4 who previously failed treatment with P/R, classified as previous null and partial responders based on previous therapy; • HCV RNA ≥ 10,000 IU/mL; • Seronegative for HIV and HBsAg; • Subjects with compensated cirrhosis are permitted (compensated cirrhotics are capped at approximately 25% of treated population). |
• Maschi e Femmine > 18 anni; • Soggetti che hanno fallito un precedente trattamento con Peginterferone alfa-2a o Peginterferone alfa-2b (pegIFNα) più Ribavirina, classificati come precedente Null e Partial-Responders sulla base della precedente terapia: • HCV RNA > 104 IU/mL (10.000 IU/mL) • Sieronegativo per HIV e HbsAg • Sono consentiti soggetti con cirrosi compensata (limitati a circa il 25% della popolazione trattata). |
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E.4 | Principal exclusion criteria |
• Prior treatment of HCV with HCV direct acting antiviral (DAA); • Evidence of a medical condition contributing to chronic liver disease other than HCV; • Evidence of decompensated liver disease including, but not limited to, a history or presence of ascites, bleeding varices, or hepatic encephalopathy; • Diagnosed or suspected hepatocellular carcinoma or other malignancies; • Uncontrolled diabetes or hypertension; • Total bilirubin ≥ 34 μmol/L (or ≥ 2 mg/dL) unless subject has a documented history of Gilbert's disease; • Confirmed ALT ≥ 5x ULN; • Confirmed Albumin < 3.5 g/dL (35 g/L) • AFP > 100 ng/mL OR ≥ 50 and ≤ 100 ng/mL requires a liver ultrasound and subjects with findings suspicious of HCC are excluded; • ANC < 1.5 x 10 billion cells/L (< 1.2 x 10 billion cells/L for Black/African-Americans); • Confirmed Platelets < 90 x 10 billion cells/L; • Hemoglobin < 12 g/dL for females or < 13 g/dL for males; • Any criteria that would exclude the subject from receiving P/R. |
• Precedente esposizione a qualsiasi HCV DAA; • Evidenza di condizioni mediche che favoriscano malattia epatica cronica diversa dall’ HCV; • Evidenza di malattia epatica scompensata incluso, ma non limitato a, storia o presenza di ascite, varici sanguinanti o encefalopatia epatica; • Diagnosi o sospetto di Carcinoma epatocellulare o altri tumori; • Diabete non controllato o ipertensione; • Bilirubina totale ≥ 34 μmol/L (≥ 2 mg/dL) confermata, a meno che il soggetto abbia una storia documentata di Malattia di Gilbert; • ALT ≥ 5× ULN confermata; • Albumina < 3.5 g/dL (35 g/L) confermata; • Alfa-fetoproteina (AFP) > 100 ng/mL o AFP ≥ 50 e ≤ 100 ng/mL richiede una ecografia epatica e soggetti con risultati che facciano sospettare HCC sono esclusi; • ANC < 1.5 × 109 cellule/L confermato (< 1.2 x 109 cellule/L per soggetti Neri/Afro-Americani); • Piastrine < 90 × 109 cellule/L confermate; • Confermata emoglobina < 12 g/dL (120 g/L) per le donne e < 13 g/dL (130 g/L) per gli uomini; • Qualsiasi altra controindicazione a pegIFNα-2a o RBV, non altrimenti specificata. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Antiviral activity, as determined by the proportion of genotype 1 subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12, for all subjects infected with HCV genotype 1. |
Attività antivirale, determinata dalla proporzione di soggetti con SVR12, definita come HCV RNA < LOQ alla Settimana 12 successiva al termine del trattamento, per tutti i soggetti infetti da HCV genotipo 1. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At 12 weeks post-treatment |
Settimana 12 successiva al trattamento |
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E.5.2 | Secondary end point(s) |
• On-treatment safety, as measured by frequency of SAEs and discontinuations due to AEs through the end of treatment (maximum of 24 weeks) plus 7 days; • Proportion of subjects with SVR12 (HCV RNA < LOQ at post-treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28 gene; • Proportion of subjects with HCV RNA undetectable at each of the following timepoints: weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [eRVR]; EOT (up to 24 weeks), post-treatment Week 12 or posttreatment Week 24; • Proportion of subjects with HCV RNA < LOQ at each of the following timepoints: weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [VR(4&12)]; End of Treatment (EOT) (up to 24 weeks), posttreatment Week 24 (SVR24). • Proportion of patients with SVR12 (HCV RNA < LOQ at post-treatment Week 12) for HCV genotype 4 subjects. |
• Sicurezza durante il trattamento, misurata dalla frequenza di Eventi Avversi Seri (SAEs) e dalle interruzioni dovute ad Eventi Avversi (AEs) fino alla fine del trattamento (al massimo 24 settimane) più 7 giorni; • Proporzione di soggetti con SVR12 (HCV RNA < LOQ alla Settimana 12 successiva al termine del trattamento) da rs12979860 SNP nel gene IL28; • Proporzione di soggetti con HCV RNA indeterminabile ad ognuno dei seguenti timepoints: settimane 1, 2, 4, 6, 8 e 12; ad entrambe le settimane 4 e 12 (eRVR); EOT (fino a 24 settimane), Settimana 12 successiva al trattamento o Settimana 24 successiva al trattamento; • Proporzione di soggetti con HCV RNA < LOQ ad ognuno dei seguenti timepoints: settimane 1, 2, 4, 6, 8 e 12; ad entrambe le Settimane 4 e 12 [VR (4 & 12)]; Fine del Trattamento (EOT) (fino a 24 settimane), Settimana 24 successiva al trattamento (SVR 24); • Proporzione di soggetti con SVR12 (HCV RNA < LOQ alla Settimana 12 successiva al termine del trattamento) per i soggetti con HCV genotipo 4. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Through the end of treatment (maximum of 24 weeks) plus 7 days; • At post-treatment Week 12 • Weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12; EOT (up to 24 weeks), post-treatment Week 12 or post-treatment Week 24; • Weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12; End of Treatment(EOT) (up to 24 weeks), post-treatment Week 24. • Post-treatment Week 12 |
• Fino alla fine del trattamento (massimo 24 settimane) più 7 giorni; • Alla Settimana 12 post-trattamento; • Settimane 1, 2, 4, 6, 8 e 12; ad entrambe le Settimane 4 e 12; EOT (fino a 24 settimane), Settimana 12 o 24 post-trattamento; • Settimane 1, 2, 4, 6, 8 and 12; ad entrambe le Settimane 4 e 12; Fine del Trattamento (EOT) (fino a 24 settimane), Settimana 24 post-trattamento; • Settimana 12 Post-trattamento |
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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 | 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 |
Biomarker Assessments, QoL, Resistance testing |
Biomarker Assessments, QoL, Resistance testing |
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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) | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 |
Argentina |
Canada |
Korea, Republic of |
Mexico |
Russian Federation |
Taiwan |
United States |
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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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The last visit will be considered the date of the last post-treatment
visit. The end of the study will be considered the last subject's last visit
date or when the last data point required for statistical analysis is
received from the last subject, whichever is later. |
La fine dello studio è considerata la LVLS (ultima visita post-trattamento) oppure quando verrà ricevuto l’ultimo dato dell’ultimo soggetto richiesto per l’analisi statistica - a seconda di quale si verifichi più tardi. |
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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 | 19 |
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 | 19 |
E.8.9.2 | In all countries concerned by the trial days | 0 |