E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
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 | 10019751 |
E.1.2 | Term | Hepatitis C virus |
E.1.2 | System Organ Class | 10022891 - Investigations |
|
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 |
|
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). |
|
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. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subject aged 18 years or above.
2. Subject must have a liver biopsy within 3 years prior to the screening visit (or between the
screening and baseline visit) with histology consistent with chronic HCV infection:
a. If only inflammation is present, there should be laboratory evidence of chronic hepatitis
C infection, i.e., presence of anti-HCV antibody or HCV RNA for at least 6 months
prior to Day 1;
b. If cirrhosis (Metavir score F4) has been demonstrated on a previous liver biopsy, the
3-year time window does not apply and there is no need for a new biopsy.
c. A biopsy is not required for subjects with bleeding disorders.
3. 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.
4. Genotype 1 HCV infection (confirmed at screening).
5. Plasma HCV RNA of > 10,000 IU/mL at screening.
6. Subjects must have received (Peg)IFN-based therapy for at least 24 weeks with documented
undetectable HCV RNA at the last measurement on treatment, and a subsequent detectable
HCV RNA level within 1 year after the last medication intake. |
|
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. Previous discontinuation of (Peg-)IFN or RBV for an adverse event that in the opinion of the investigator would likely be treatment limiting during re-exposure to PegIFNα-2a or RBV. 7. Known allergy or hypersensitivity to TMC435, PegIFNα-2a, RBV, or any of the other components of the formulation. 8. 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. 9. Any other clinically significant disease that in the opinion of the investigator would be exacerbated by the known effects of PegIFN and RBV. 10. 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). 11. Subject with any of the following laboratory abnormalities: a. Platelet count < 90,000/mm3; b. Absolute neutrophil count < 1500 cells/mm3 (blacks: < 1200 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 laboratory normal range (ULN); f. Total serum bilirubin > 1.5 x ULN; |
|
E.5 End points |
E.5.1 | Primary end point(s) |
See section 11.2.1 of the Protocol (pages 73 and 74) |
|
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 | 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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | 48 |
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 |
|
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
| |
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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |