E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10008912 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019744 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10021881 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10019805 |
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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 objective of this study is to compare the efficacy of boceprevir in combination with peginterferon alfa-2a (PEG2a) plus ribavirin (PEG2a/R) to the same PEG2a/R regimen without boceprevir for 48 weeks in adult subjects with chronic hepatitis C (CHC) genotype 1 with demonstrated interferon responsiveness who failed prior treatment with peginterferon/ribavirin. |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives: The secondary objectives of this study are: To evaluate the safety of boceprevir when used in combination with PEG2a/R. To define predictors of sustained virologic response (SVR), such as epidemiologic factors, disease characteristics, and on-treatment response. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects with CHC (genotype 1) who failed to achieve SVR on prior adequate treatment with any peginterferon alfa and ribavirin but demonstrated interferon responsiveness (a decrease in HCV-RNA viral load ≥2 log10 by TW 12 or undetectable HCV-RNA at End of Treatment [EOT]) will be selected for the study. Inclusion Criteria for Interferon-Responsive CHC Patients Who Have Failed Treatment: 1. For inclusion in the study, subjects must have a qualifying regimen defined as PEG2a/R or PEG2b/R for a minimum of 12 weeks. If a subject has received more than one such regimen, the most recent regimen is considered the qualifying regimen. Note: Maintenance therapy, following failure of qualifying therapy, with any interferon alfa is acceptable; however, the subject must have discontinued the maintenance therapy at least 1 month prior to the Screening Visit. 2. During the qualifying regimen, subjects must have either: a. A documented undetectable HCV-RNA within 30 days of EOT and a subsequent detectable HCVRNA during follow-up OR b. A documented decline in HCV-RNA by ≥2 log10 by TW 12. Note: For subjects who did not participate in Schering-Plough Research Institute (SPRI) protocols, qualifying virology reports and documentation of qualifying previous treatment regimen must be completely deidentified and faxed to the sponsor`s project physician for confirmation that the documentation meets protocol-specified criteria. 3. Subject must have previously documented CHC genotype 1 infection. Subjects with other or mixed genotypes are not eligible. The HCV-RNA result obtained from the central laboratory at the Screening Visit must confirm genotype 1 infection and be ≥10,000 IU/mL. 4. Subject must have a liver biopsy with histology consistent with CHC and no other etiology. Copies of the pathology report and slides are required for the subject to be included in the study. The study site must be able to access the pathology report and histology slides prior to subject randomization. Two unstained slides are preferred; however, one slide stained with hematoxylin plus eosin (H & E) plus one slide stained with Massons trichrome will be accepted (slides should be reviewed by the investigator to confirm adequacy). The central pathologists reading will be used for analysis purposes. a. If no cirrhosis is present: The liver biopsy must be within 3 years of the Screening Visit. b. If cirrhosis is present: Any historic liver biopsy demonstrating cirrhosis will be accepted regardless of length of time since biopsy. |
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E.4 | Principal exclusion criteria |
1.Subjects known to be coinfected with the human immunodeficiency virus (HIV) or hepatitis B virus (hepatitis B surface antigen [HBsAg] positive) and/or demonstrating signs and symptoms consistent with co-infection. 2. Subjects who required discontinuation of previous interferon or ribavirin regimen for an adverse event considered by the investigator to be possibly or probably related to ribavirin and/or interferon. 3. Treatment with ribavirin within 90 days and any interferon alfa within 1 month of Screening. 4. Treatment for hepatitis C with any investigational medication. Prior treatment with herbal remedies with known hepatotoxicity is exclusionary. All herbal remedies used for hepatitis C treatment other than silymarin (milk thistle) must be discontinued before Day 1. 5. Treatment with any investigational drug within 30 days of the randomization visit in this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the achievement of SVR, defined as undetectable plasma HCV-RNA at FW 24. If a subject is missing FW 24 data and has undetectable HCV-RNA at FW 12, the subject will be considered a sustained virologic responder. Subjects will be declared treatment failures in one of the following ways: Subjects in any treatment arm with detectable HCV-RNA at Follow-up Week (FW) 24. Subjects in any treatment arm with detectable HCV-RNA at TW 12. Subjects in any treatment arm who are missing their HCV-RNA at FW 24 with detectable or missing HCV-RNA at FW 12. |
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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 | No |
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 | 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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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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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 | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |