E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatitis C Virus (HCV) genotype-1 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 | 16.0 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To determine the efficacy of TMC435 plus PegIFNalfa-2a and RBV when administered for 12 weeks in treatment-naïve subjects with chronic genotype 1 HCV infection, as measured by the proportion of subjects with sustained virologic response 12 weeks after planned end of treatment (SVR12).
- To assess the safety and tolerability of TMC435 plus PegIFNalfa-2a and RBV when administered for 12 weeks in treatment-naïve subjects with the chronic genotype 1 HCV infection |
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E.2.2 | Secondary objectives of the trial |
See section 2.1 - Objectives - Major Secondary Objectives, p33 of the Clinical Trial Protocol |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-treatment-naïve (previously untreated) with confirmed chronic Hepatitis C Virus (HCV) infection
- liver biopsy performed within 2 years prior to screening or non-invasive confirmation of the liver disease stage (by transient elastography) performed within 6 months prior to screening
-liver disease stage equivalent to Metavir Score F0-F2 (no fibrosis, or portal fibrosis without or with few septa)
- genotype 1 HCV infection (confirmed at screening)
- Before screening, a woman must be either not of childbearing potential: postmenopausal (> 45 years of age with amenorrhea for at least 12 months or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level > 40 IU/mL); permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral
salpingectomy); or otherwise be incapable of pregnancy OR of childbearing potential and practicing two different highly effective methods of birth control (including at least one barrier method) consistent with local regulations regarding the use of birth control methods for participants participating in clinical studies: e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap
(diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the
vasectomized partner should be the sole partner for that participant); true abstinence (when this is in line with the
preferred and usual lifestyle of the participant) Note: If the childbearing potential changes after start of the study (e.g.,
woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) a woman must begin 2 highly effective methods of birth control, as described above
- A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use two different highly effective methods of birth control (including at least one barrier method). A man who is sexually active with a woman of childbearing potential and has had a vasectomy must agree to use a barrier method of birth control e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. All men must also not donate sperm during the study and for 6 months (or longer if dictated by local regulations) after the last dose of RBV |
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E.4 | Principal exclusion criteria |
- Participants who have been previously exposed to anti-HCV treatment, including any approved or investigational direct-acting antiviral (DAA) therapy
- Participant has chronic liver disease of a non-HCV etiology (including but not limited to hemochromatosis, Wilson’s disease, α1-antitrypsin deficiency, cholangitis, drug- or alcohol-related liver disease, primary biliary cirrhosis)
- Participant is infected with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive) or human immunodeficiency virus (HIV-1 or HIV-2) (HIV-1 or HIV-2 antibody test positive at screening)
- Participant is infected with non-genotype 1 HCV
- Participant has advanced liver disease equivalent to Metavir status F3-F4 (bridging fibrosis or cirrhosis) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The number of participants with sustained virologic response 12
weeks after planned end of treatment (SVR12). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- The number of participants who achieve rapid virologic response
(RVR)
- The number of participants who achieve virologic response at Week 2 (W2VR)
- The number of participants with sustained virologic response 24
weeks after planned end of treatment (SVR24)
- The number of participants with > or = 2 log decrease in hepatitis C virus (HCV) RNA at each time point
- The number of participants with hepatitis C virus (HCV) RNA < 25 IU/mL undetectable at each time point
- The number of participants with viral breakthrough
- The number of participants with viral relapse
- Change from Baseline in the Hepatitis C Treatment Symptom &
Impact Questionnaire (HCV SIQ) symptom and impact scores
- Change from Baseline in The Fatigue Severity Scale (FSS) total
score
- Change from Baseline in The Center for Epidemiologic Studies
Depression Scale (CES-D) score
- Change from Baseline in The Work Productivity and Activity Index
(WPAI) for Hepatitis C missed work time, daily activity impairment, and productivity scores
- Change from Baseline in The EuroQol 5 Dimension (EQ5D) Visual
Analog Scale (VAS) valuation index, and Descriptive System scores
- The number of participants with normalized alanine aminotransferase (ALT) levels
- Change from Screening in liver disease stage assessment
- The number of participants reporting adverse events as a measure of safety and tolerability |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Week 4
- Week 2
- Week 48
- Up to Week 48
- Up to Week 48
- Up to Week 48
- Up to Week 48
- Day 1 and at each study visit up to Week 48
- Day 1 and at each study visit up to Week 48
- Day 1 and at each study visit up to Week 48
- Day 1 and at each study visit up to Week 48
- Day 1 and at each study visit up to Week 48
- Up to Week 48
- Week -6; Week 48
- Up to Week 48 |
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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 | 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 | 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
| 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 | 30 |
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 | No |
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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |