E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HAPATITIS C VIRUS IN TREATMENT NAIVE PATIENTS |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019183 |
E.1.2 | Term | 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 demonstrate the superiority of TMC435 versus placebo as part of a treatment regimen including peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV), with respect to the proportion of subjects with sustained virologic response (SVR) 24 weeks after the planned end of treatment (SVR24) |
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E.2.2 | Secondary objectives of the trial |
To demonstrate the superiority of TMC435 versus placebo as part of a treatment regimen including PegIFNα-2a and RBV, with respect to the proportion of subjects with SVR 12 weeks after the planned end of treatment (SVR12). To demonstrate the superiority of TMC435 versus placebo as part of a treatment regimen including PegIFNα-2a and RBV, with respect to the proportion of subjects with SVR at Week 72 (last study-related visit). To compare the antiviral activity of TMC435 versus placebo as part of a treatment regimen including PegIFNα- 2a and RBV at all time points, with focus on Week 4, Week 12, Week 24, Week 36, Week 48, Week 60, and Week 72. To evaluate the incidence of viral breakthrough during the treatment period in the TMC435 and placebo treatment groups. To evaluate the relapse rate after treatment in the TMC435 and placebo treatment groups. To determine the viral NS3/4A sequence in subjects in the TMC435 treatment group with virologic failure. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female subject aged ≥ 18 years; liver biopsy within 3 years prior to the screening visit (or between the screening and baseline visit) with histology consistent with chronic HCV infection; subjects with bridging fibrosis (Metavir score F3) or cirrhosis (Metavir score F4) must have an ultrasound taken within 6 months prior to the screening visit (or between the screening and baseline visit) with no findings suspicious for hepatocellular carcinoma; genotype 1 HCV infection (confirmed at screening); plasma HCV RNA of > 10,000 IU/mL at screening; and no prior treatment with any approved or investigational drug for the treatment of hepatitis C. |
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E.4 | Principal exclusion criteria |
1. Evidence of hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy) 2. Any liver disease of non-HCV etiology. This includes acute hepatitis A, drug- or alcoholrelated liver disease, autoimmune hepatitis, hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HCV liver disease considered clinically significant by the investigator. 3. Infection/co-infection with nongenotype 1 HCV. 4. Co-infection with HIV type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at screening). 5. Co-infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive). 6. Medical conditions which are contraindications for PegIFNα-2a or RBV therapy: a. Major uncontrolled depressive illness; b. Organ transplant (other than cornea or hair transplant or skin graft); c. Severe concurrent medical disease such as severe hypertension, significant coronary heart disease, poorly controlled diabetes, untreated thyroid disease, chronic obstructive pulmonary disease, severe infections (bacterial, viral, fungal, including acute tuberculosis), or hemoglobinopathies (thalassemia major or sickle-cell anemia); d. Autoimmune hepatitis or other autoimmune conditions known to be exacerbated by PegIFN and RBV. 7. Any other clinically significant disease that in the opinion of the investigator would be exacerbated by the known effects of PegIFN and RBV. 8. History of malignancy within 5 years of the screening visit (exceptions: squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator is considered cured with minimal risk of recurrence) |
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E.5 End points |
E.5.1 | Primary end point(s) |
see section 11.2.1 of the protocol (page 72) |
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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 | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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 | 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 | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 | 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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |