E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatitis C Virus genotype-4 (HCV-4) in treatment-naïve or treatment-experienced subjects |
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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 | LLT |
E.1.2 | Classification code | 10019752 |
E.1.2 | Term | Hepatitis C virus (HCV) |
E.1.2 | System Organ Class | 10022891 - Investigations |
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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 is to evaluate the efficacy of TMC435 in combination with PegIFNα-2a/RBV with respect to the proportion of subjects with chronic HCV-4 infection achieving SVR 12 weeks after planned end of treatment (SVR12) in the overall population as well as in the different subpopulations (treatment-naïve, previous relapsers and previous nonresponders). |
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E.2.2 | Secondary objectives of the trial |
See section 2.1, page 31 and 32 of the Protocol |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Genotype 4 Hepatitis C virus (HCV) infection (confirmed at screening)
- Plasma HCV ribonucleic acid (RNA) of > 10,000 IU/mL at screening
- Participants should be either treatmentnaïve or treatment-experienced (non-responder or relapser) with adequate documentation of previous response
- Participants must have voluntarily signed an Informed Consent Form (ICF) indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. To participate in the optional pharmacogenomic component in this study (exploratory host genotyping), participants must have voluntarily signed a separate ICF for this component (where local regulations permit). Refusal to give consent for this component does not exclude a participant from participation in the core study.
- A liver biopsy is required within 3 years prior to screening unless the patient has a contraindication for a liver biopsy. |
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E.4 | Principal exclusion criteria |
- Has an infection/co-infection with non-genotype 4 HCV
- Has a co-infection with Human Immunodeficiency Virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at screening).
- Has any of the following laboratory abnormalities: a. Platelet count < 90,000/mm3 (blacks: < 75 000 cells/mm3); b. Absolute neutrophil count (ANC) < 1500 cells/mm3 (Blacks: < 1000 cells/mm3); c. Hemoglobin < 12 g/dL for women and < 13 g/dL for men; d. Creatinine > 1.5 mg/dL; e. ALT and/or AST > 10 x upper limit of normal (ULN); f. Total serum bilirubin > 1.5 x ULN; g. Alpha-fetoprotein [AFP] > 50 ng/mL; h. Albumin serum concentration < 3.5 g/dL; i. Prothrombin time (PT) expressed as international normalized ratio (INR) > 1.5.
- Uses disallowed concomitant therapy
- Has evidence of hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy of TMC435 with respect to proportion of participants achieving SVR12 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
week 36 or week 60, depending on when the patients can stop treatment |
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E.5.2 | Secondary end point(s) |
- Efficacy of TMC435 with respect to proportion of participants achieving SVR24
- Antiviral activity of TMC435 in combination with PegIFNα-2a/RBV
- on-treatment virologic failure |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- week 48 or week 72, depending on when the patients can stop treatment
- at all timepoints during treatment and follow-up
- Week 4, Week 12, Week 24, Week 36, Week 48
- all visits |
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 |
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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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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 | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |