E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatitis C virus (HCV) infection |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019744 |
E.1.2 | Term | Hepatitis C |
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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 |
Primary objective: - To assess the proportion of subjects in each group with undetectable plasma HCV RNA, 24 weeks after the completion of the assigned study drug regimen. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives: - To assess the proportion of subjects in each group with undetectable plasma HCV RNA, 12 weeks after the completion of the assigned study drug regimen. - To assess the proportion of subjects who received VX-950 (Groups B, C, and D) with undetectable plasma HCV RNA at the completion of the assigned study drug regimen. - To assess the safety of 12 weeks of dosing of VX-950 and peginterferon alfa-2a (Peg-IFN), with and without ribavirin (RBV). - To examine the nucleotide sequence of the NS3·4A region of hepatitis C virus (HCV) isolated from plasma samples during and after completion of study drug dosing. - To examine the pharmacokinetics of VX-950, Peg-IFN and RBV. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female subjects, 18-65 years of age, inclusive. - Genotype 1 (confirmed by standard testing), chronic hepatitis C, confirmed by detectable plasma HCV RNA. - Judged to be in good health on the basis of medical history and physical examination (including vital signs and ECG), with any chronic medical conditions under stable medical control. - Both Screening Visit 1 and Screening Visit 2 laboratory values must be within protocl-specified laboratory reference ranges. - Must agree to use 2 methods of contraception that are highly effective, one barrier method (condom or diaphragm with spermicidal jelly) with a second method such as oral contraceptives, hormonal implant, injectable contraceptive, an intrauterine device or surgical sterilization (i.e. vasectomy or female surgical sterilization) during and for 24 weeks after the last dose of study medication (unless the subject is a woman of documented non-child-bearing potential). Female subjects and female partners of male subjects must use the same precautions. Male subjects must not father a child while on study, and for 24 weeks after the last dose of the study medications. - Female subjects must have a negative pregnancy test at all visits (screening and pre-dose Day 1) before the first dose of study drugs. - Willing to refrain from the concomitant use of any medications, substances or foods noted in Section 12.8 of the protocol. - Willing to initiate SOC (Peg-IFN and RBV) off-study at the conclusion of study drug dosing, if subjects have detectable virus or relapse. |
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E.4 | Principal exclusion criteria |
- Received any approved or investigational drug or drug regimen for the treatment of hepatitis C. - Any medical contraindications to Peg-IFN or RBV therapy. - Decompensated liver disease as shown by screening laboratory results. - Any other cause of significant liver disease in addition to hepatitis C. - Diagnosed or suspected hepatocellular carcinoma. - Histologic evidence of hepatic cirrhosis on any liver biopsy. Most recent liver biopsy must be within 2 years before Study Day 1. - Alcohol abuse or excessive use (in the opinion of the investigator, as judged by medical history) in the last 12 months. - Hypersensitivity to tartrazine (yellow dye #5). - Men whose female partners are pregnant. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary end point: - Proportion of subjects in each group with undetectable plasma HCV RNA, 24 weeks after the completion of the assigned study drug regimen.
Secondary end points: - Proportion of subjects in each group with undetectable plasma HCV RNA, 12 weeks after the completion of the assigned study drug regimen. - To assess the proportion of subjects who received VX-950 (Groups B, C, and D) with undetectable plasma HCV RNA at the completion of the assigned study drug regimen. - Adverse events and clinical laboratory assessments, including alanine aminotransferase (ALT) and other liver function tests. - Genotypic and phenotypic analyses of the NS3·4A HCV region. - Pharmacokinetic assessments of VX-950, Peg-IFN, and RBV. |
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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 | 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 |
HCV sequencing, gene expression profiling, and plasma proteomics |
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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) | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Groups A,B&C: Partially double-blinded to week10. Group D: Unblinded. See Section 9.1.1 of protocol |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 12 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 completion of the study shall be defined as the time of hardlock of the clinical database (including all on study and antiviral follow up data) |
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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 | |
E.8.9.1 | In the Member State concerned months | 20 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 20 |