E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatitis C Virus Infection |
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E.1.1.1 | Medical condition in easily understood language |
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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 | PT |
E.1.2 | Classification code | 10019744 |
E.1.2 | Term | Hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 |
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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 |
The primary objectives of this study are: - To determine the efficacy of sofosbuvir (SOF)+ Ribavirin (RBV) for 16 or 24 weeks as measured by the proportion of subjects with sustained viral response 12 weeks after discontinuation of treatment (SVR12) - To determine the efficacy of SOF+RBV+pegylated interferon alfa 2a (PEG) for 12 weeks as measured by the proportion of subjects with SVR12 - To evaluate the safety and tolerability of all 3 treatment arms as assessed by review of the accumulated safety data |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are: - To determine the proportion of subjects who attain SVR at 4 and 24 weeks after discontinuation of treatment (SVR4 and SVR24) - To evaluate the kinetics of circulating HCV RNA during and after treatment discontinuation - To evaluate the emergence of viral resistance to SOF during and after treatment discontinuation |
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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 |
Optional Pharmacogenomic Substudy All subjects will be eligible to participate in the Pharmacogenomic Substudy. A separate, specific signature will be required to document a subject’s agreement to provide additional samples for optional pharmacogenomic research. From subjects who agree to participate and provide their additional specific consent, one blood sample will be obtained. The specimens collected for optional pharmacogenomic research will be used to identify or validate genetic markers that may increase our knowledge and understanding of the biology of the disease and related diseases and to study the association of genetic markers with disease pathogenesis, progression and/or treatment outcomes, including efficacy, adverse events, and the processes of drug absorption and disposition. These specimens may also be used to develop biomarker or diagnostic assays and establish the performance characteristics of these assays. The collection and analysis of optional future research specimens will facilitate the rational design of new pharmaceutical agents and the development of diagnostic tests, which may allow for individualized drug therapy for patients in the future.
Optional Viral Dynamic Substudy All subjects will be eligible to participate in the Optional Viral Dynamic Substudy. A separate, specific signature will be required to document a subject’s agreement to provide additional samples for optional viral kinetic and immunological testing. In a subset of patients (≥ 20 subjects per treatment arm) visits for will occur between Day 1 and Week 1: subjects will return at 24-, 48-, and 96-hours (specifically Days 2, 3, and 5) following the initial dose of study drugs on Day 1. |
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E.3 | Principal inclusion criteria |
1) Willing and able to provide written informed consent 2) Male or female, aged 18 years or older 3) Chronic HCV infection 4) Willing to undergo liver biopsy, if required 5) Genotype 2 subjects must have cirrhosis of the liver to be eligible 6) Treatment-naïve or prior treatment failure to ≥12 weeks of an interferon-based regimen that was not discontinued prematurely due to an adverse event 7) Infection with HCV genotype 2 or 3 10) A negative serum pregnancy test is required for female subjects (unless surgically sterile or greater than two years post-menopausal). Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception. Lactating females must agree to discontinue nursing before the IMP is administered. |
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E.4 | Principal exclusion criteria |
1) Prior exposure to an direct-acting antiviral targeting the HCV NS5B polymerase 2) Pregnant or nursing female or male with pregnant female partner 3) Chronic liver disease of a non-HCV etiology 4) Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) 5) Significant psychiatric conditions 6) Autoimmune disease 7) Severe chronic pulmonary obstructive disease 8) History of significant cardiac disease including prior myocardial infarction or arrhythmia |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is SVR12 (HCV RNA <LLOQ 12 weeks after discontinuation of therapy).
The primary safety endpoint is any AE leading to permanent discontinuation of study drug(s). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 Weeks after last dose of study drug |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints include the proportion of subjects with HCV RNA < LLOQ at each on-treatment visit and 4 and 24 weeks after discontinuation of active therapy (SVR4 and SVR24); HCV RNA (log10 IU/mL) and change from baseline in HCV RNA (log10 IU/mL); viral breakthrough; and relapse. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During treatment and 4 and 24 weeks after last dose of study drug |
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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 | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Each arm is a treatment regimen being compared to the other 2 arms |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 25 |
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 | 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 |
Australia |
Canada |
New Zealand |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |