Hepatitis C virus (HCV) MedDRA version: 9.1 Level: LLT Classification code 10019751 Term: Hepatitis C virus
Conditions
Sponsors
Tibotec Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be eligible for this trial: 1. Aged between 18 and 70 years, extremes included; 2. Documented chronic (diagnosis of hepatitis C > 6 months before the screening period) genotype 1a or 1b HCV infection (as assessed by line probe assay); treatment-naïve subjects or prior non-responding subjects/relapsers to previous treatment regimens (IFN/RBV or pegylated IFN/RBV), who did not discontinue anti-HVC therapy due to AEs; genotype 1 HCV patients with hemophilia or with stable methadone use may be enrolled; (subtyping in genotype 1a and 1b patients will also be done); 3. Patients with either no cirrhosis or up to Child Pugh A (compensated cirrhosis) liver disease 4. ICF signed voluntarily before the first trial related activity; 5. Able to comply with the protocol requirements and having good accessible veins; 6. HCV plasma viral load of = 10,000 IU/mL at screening (as assessed by the Taqman assay); 7. Bodyweight as defined by a Quetelet Index (Body Mass Index [BMI], weight in kg divided by the square of height in meters) between 18 and 32 kg/m², extremes included. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects meeting one or more of the following criteria cannot be selected: 1. Evidence of Child Pugh B or C liver disease at screening; evidence of decompensated liver disease defined as prior or current history of ascites, hepatic encephalopathy, bleeding esophageal or gastric varices. Any other cause of significant liver disease in addition to hepatitis C; this may include but is not limited to hepatitis B, drug- or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson’s disease, non-alcoholic steatohepatitis, or primary biliary cirrhosis. Subjects with diagnosed or suspected hepatocellular carcinoma; 2. Subjects receiving or having received polymerase inhibitor, protease inhibitor or SoC (Copegus® and Pegasys®) treatment for HCV during the 6 months before screening; 3. Male subjects with female partners of childbearing potential not agreeing to use a reliable birth control method for 90 days after the last dosing of TMC435350 in the trial or as prescribed in the leaflet of the medication as administered in the SoC treatment period (when taking PegIFNa-2a in combination with RBV, all subjects must use effective birth control methods during treatment and for 7 months afterwards); 4. Female, except if postmenopausal for over 2 years, or posthysterectomy, or post-tubal ligation (without reversal operation); 5. History or evidence of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use, which in the Investigator’s opinion would compromise the subject’s safety and/or compliance with the trial procedures (period of non-drug/alcoholic misuse must at least be 1 month before the first administration of study medication). 6. A positive urine drug test at screening. Urine will be tested to check the current use of amphetamines, cocaine, and opioids (with the exclusion of methadone). 7. Subjects with at least one of the following laboratory abnormalities as defined by the Division of Microbiology and Infectious Diseases (DMID) Adult Toxicity Table at screening: - Bilirubin = 1.5x upper limit of laboratory normal range (ULN); - Platelet count 480 ms) at screening (see Section 8.5, Addendum 5) 10. Subjects with any cardiac disease at screening, or any active clinically significant disease (e.g., cardiac dysfunction, cardio(myo)pathy, cardiac insufficiency), or medical history or physical examination findings during screening that, in the Investigator’s opinion, would compromise the outcome of the trial; 11. Subjects having uncontrolled/unstable diabetes, epilepsy, a manifest psychiatric disease; 12. Non-stable methadone (or equivalent drug) use or subjects having any other unstable disease; 13. Subjects enrolled in another clinical trial within 90 days prior to screening. 14. Subjects having a grade 4 increase in transaminases (ALT/AST) at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of this trial are the following: - to determine the dose dependency of the antiviral effect of TMC435350 during 1 week of monotherapy in treatment-naïve HCV-infected subjects; - to determine the dose dependency of the antiviral effect of TMC435350 during combined tritherapy with PegIFNa-2a and RBV in treatment-naïve HCV-infected subjects.;Secondary Objective: - to determine the safety, tolerability and pharmacokinetic profile of TMC435350 during 1 week of monotherapy, and during combined tritherapy with PegIFNa-2a and RBV, in treatment-naïve HCV-infected subjects; - to determine the 4-week efficacy and safety of 3 selected doses of TMC435350 given in combination with PegIFNa-2a and RBV in treatment-experienced (prior non-responders to IFN-based therapy/relapsers, who did not discontinue anti-HCV therapy due to AEs) HCV-infected subjects; - to follow-up rapid virologic response (RVR) in subjects at Week 4 until Week 24 (after 20 weeks of SoC treatment) or Week 48 (after 44 weeks of SoC treatment), to determine the end of treatment (EOT) response and the incidence of sustained virologic response (SVR) defined as undetectability of HCV RNA at 24 weeks after EOT;Primary end point(s): Determine the dose dependency of antiviral effect of TMC435350 in treatment-naïve subjects during one week of monotherapy and during combined tritherapy with PegIFNa-2a and RBV. | — |
Countries
Belgium, France, Germany, Netherlands, United Kingdom
Outcome results
None listed