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 | 9.1 |
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 |
- To compare to control (Group A) (peginterferon alfa-2a [Peg IFN-a-2a] and ribavirin [RBV] for 48 weeks) the proportion of subjects who achieve sustained viral response (SVR, undetectable HCV RNA 24 weeks after completion of treatment) when given telaprevir in combination with: Peg IFN-a-2a and RBV for 24 weeks followed by 24 weeks of Peg IFN a-2a and RBV given alone (Group B); Peg IFN-a-2a for 24 weeks (Group C); Peg IFN-a-2a and RBV for 12 weeks followed by 12 weeks of Peg IFN-a-2a and RBV given alone (Group D). |
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E.2.2 | Secondary objectives of the trial |
- To compare the proportion of subjects with an end-of-treatment response (ETR) (undetectable HCV RNA at end of treatment) in Groups B, C, and D with the control (Group A). - To compare the proportion of subjects with a continued SVR (undetectable HCV RNA 48 weeks after the end of treatment) in Groups B, C, and D with the proportion of subjects with SVR in the control (Group A). - To assess the safety and tolerability of treatment with telaprevir and Peg-IFN with or without RBV. - To evaluate the nucleotide sequence of the NS3•4A region of HCV isolated from plasma samples during and after completion of study drug dosing. - To evaluate the pharmacokinetics of telaprevir, Peg-IFN-a-2a, 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 to 70 years of age, inclusive. - Genotype 1 (confirmed by standard testing), chronic hepatitis C. Chronic (non-acute) disease status must be confirmed by detectable plasma HCV RNA. - Liver biopsy within 3 years of the date of the Screening Visit. - 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 protocol specified laboratory reference ranges. - Did not achieve SVR with at least 1 adequate prior course of Peg-IFN in combination with RBV (Peg-IFN/RBV) as defined by the protocol. Subjects must have received the last dose of Peg-IFN or RBV at least 12 weeks before the screening visit for this study. - Must agree to use 2 methods of contraception that are highly effective, including one barrier method, during and for 24 weeks after the last dose of study drug (unless the subject is a woman of documented non-child-bearing potential). Female partners of male subjects must use the same precautions. - Female subjects of child-bearing potential must have a negative pregnancy test at all visits (screening and predose 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 21. - Able to read and understand the Informed Consent Form (ICF) and willing to sign the ICF and abide by the study restrictions. - Agree not to participate in other clinical studies for the duration of his/her participation in this trial through antiviral follow-up.
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E.4 | Principal exclusion criteria |
- Any medical contraindications to Peg-IFN or RBV therapy. - Prior response to therapy and failure to achieve SVR which may have been due to treatment non-compliance, in the assessment of the investigator based upon subject’s medical history. - Participation in any clinical trial of a HCV protease inhibitor of any duration. - Participation in any clinical trial of an investigational drug within 90 days before drug administration or participation in more than 2 drug studies in the last 12 months (exclusive of the current study). - History of or current evidence of decompensated liver disease defined as a prior or current history of ascites, hepatic encephalopathy, bleeding esophageal or gastric varices. - Any other cause of significant liver disease in addition to hepatitis C; this may include but is not limited to, hepatitis B, drug or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson’s disease, nonalcoholic steatohepatitis, or primary biliary cirrhosis. - Diagnosed or suspected hepatocellular carcinoma. - Alcohol or drug abuse or excessive use (in the opinion of the investigator, as judged by medical history) in the last 12 months. - Women who are pregnant or breast-feeding. - Male partners of women who are pregnant or breast-feeding. - Hypersensitivity to tartrazine (yellow dye #5).
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary end point: - Undetectable HCV RNA 24 weeks after the completion of treatment
Secondary end points: - Undetectable HCV RNA at end of treatment. - Undetectable HCV RNA 48 weeks after completion of treatment (Groups B, C, and D). - Adverse events and clinical laboratory assessments, including ALT and other liver function tests. - Genotypic and phenotypic analyses of the NS3•4A HCV region. - Pharmacokinetic assessments of telaprevir, Peg-IFN-a-2a, 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 | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
HCV sequencing, gene expression profiling, 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 |
All groups double-blinded to week 24. Group A unblinded after Week 24 if HCV RNA is detectable. |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
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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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End of trial will be last subject visit. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |