Hepatitis C virus (HCV) MedDRA version: 12.0 Level: LLT Classification code 10019751 Term: Hepatitis C virus
Conditions
Sponsors
Tibotec Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects who meet all of the following criteria are eligible for this trial: 1. Male or female subject aged between 18 and 70 years, extremes included; 2. Documented chronic hepatitis C infection as evidenced by all of the following: - a liver biopsy demonstrating chronic viral hepatitis within 2 years of screening; - anti-HCV positive; - HCV RNA positive (if only inflammation is present on liver biopsy, HCV RNA presence should be documented for at least 6 months prior to baseline). Note: If no liver biopsy was performed within 2 years prior to screening, this may be done on a separate day during the screening period; 3. Subject with genotype-1 HCV infection (confirmed at screening); 4. Subjects with plasma HCV RNA of > 100,000 IU/mL at screening (as assessed by standard quantitative in vitro nucleic acid amplification assay); Note: Retesting of HCV RNA to reassess eligibility will be allowed only once using an unscheduled visit during the screening period. 5. Subject is not receiving and has never received (Peg)IFN, RBV or any other approved or investigational treatment for chronic HCV infection; Note: prior HCV treatment with herbal products or nutritional elements is allowed but should be stopped at screening. 6. Body weight between 40 and 125 kg; 7. Subject (male with partner of childbearing potential or female of childbearing potential) agrees to use 2 effective methods of contraception (one of the methods needs to be a barrier method, e.g., condom or diaphragm) from screening throughout the duration of study treatment and for 7 months after the last dose of RBV, or is non-heterosexually active, or is vasectomized (male subject) or has a vasectomized partner (female subjects), or is a female (subject or partner of male subject) of non-childbearing potential; 8. Informed consent form signed voluntarily before the first trial-related activity; 9. Subject being able to comply with the protocol requirements. 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. Cirrhosis confirmed by biopsy taken within 2 years prior to enrollment; 2. Decompensated liver disease defined as history or presence of ascites, hepatic encephalopathy, bleeding esophageal, or gastric varices. 3. Any other liver disease of non-HCV etiology. This may include but is not limited to hepatitis A or B, drug- or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson’s disease, non-alcoholic steatohepatitis, or primary biliary cirrhosis. 4. Infection/co-infection with non-genotype 1 HCV; 5. Co-infection with human immunodeficiency virus type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test), or hepatitis B virus infection (hepatitis B surface antigen [HBsAg]); 6. History of invasive malignancy diagnosed or treated within 5 years prior to screening (locally treated non-invasive basal cell skin carcinoma is permitted; cervical carcinoma in situ is allowed if treated prior to screening); 7. Evidence of hepatocellular carcinoma (e.g., alpha-fetoprotein [AFP] > 50 ng/mL); Note: Subjects with AFP levels between 50 and 100 ng/mL can be included if they have a negative ultrasound or other abdominal imaging. 8. Medical conditions which are exclusion criteria for PegIFNa-2a or RBV treatment (please refer to the manufacturer’s prescribing information for details): - Presence or history of psychiatric disorders including but not limited to severe depression, anxiety disorders, psychotic disorders, a history of hospitalization for any psychiatric disorder or a suicidal attempt; Note: Transient and/or situational symptoms such as minor depression, mood disturbances or situational anxiety (e.g., prior to biopsy) would not exclude a subject from the trial. In general, an important consideration is the investigator’s assessment of the clinical risk for the subject to start Pegasys®. - Uncontrolled/unstable cardiac disorders (e.g., congestive heart failure, supraventricular arrhythmias); - Uncontrolled/unstable chronic pulmonary disorders (e.g., chronic obstructive pulmonary disease); - Severe bacterial, viral or fungal infections including acute tuberculosis; - Uncontrolled/unstable thyroid disease (hypo- or hyperthyroidism); - Uncontrolled/unstable diabetes mellitus (e.g., HbA1c = 7%, diabetic retinopathy); - Renal impairment (e.g., serum creatinine > 1.5 x ULN or creatinine clearance 10 x upper limit of laboratory normal range (ULN); - Laboratory evidence of significantly decreased hepatic function or decompensation (i.e., international normalized ratio [INR] > 1.5, or albumin 1.5 x upper limit of laboratory normal range [ULN]); Note: Subjects can be
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is to evaluate the efficacy of 4 different regimens of TMC435 in combination with PegIFNa-2a and RBV (SoC), defined as the proportion of subjects with sustained virologic response at Week 72 (subjects with undetectable HCV RNA [< 10 IU/mL] at the end of treatment and at Week 72), compared to the control group receiving SoC in combination with TMC435-matched placebo.;Secondary Objective: The secondary objectives are the following: - To evaluate and compare the antiviral activity of TMC435 when administered in different regimens versus control (SoC) over the trial period; - To evaluate and compare the safety and tolerability of the TMC435-containing regimens versus SoC over the trial period; - To determine the frequency/kinetics and viral genetics of virologic failures; - To evaluate the pharmacokinetics and the pharmacokinetic/pharmacodynamic relationship for efficacy and safety of TMC435; - To collect Medical Resource Utilization information, and to evaluate Quality of Life (QoL) and the level of fatigue over the trial period.;Primary end point(s): Efficacy of 4 different regimens of TMC435 in combination with peginterferon alfa-2a (PegIFNa-2a) and ribavirin (RBV) versus PegIFNa-2a plus RBV alone in adult treatment-naïve subjects with chronic genotype 1 HCV infection. | — |
Countries
Austria, Belgium, Denmark, France, Germany, Spain
Outcome results
None listed