A blinded, randomized, placebo-controlled trial in genotype 1 hepatitis C-infected subjects to evaluate the efficacy, safety, tolerability and pharmacokinetics of repeated doses of TMC435350, with or without peginterferon alpha-2a and ribavirin.

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 16

Inclusion Criteria

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. ICF signed voluntarily before the first trial related activity;
4. Able to comply with the protocol requirements and having good accessible veins;
5. HCV plasma viral load * 10,000 IU/mL at screening (as assessed by the Taqman assay);
6. 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.

Exclusion Criteria

1. Evidence of Child Pugh B or C liver disease or Metavir score 4 at screening with a history or evidence of decompensated cirrhosis 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 or protease inhibitor 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 PegIFN*-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 < 80,000/mm3;
- White blood cell (WBC) count < 2,000 cells/mm3;
- Any other lab toxicity found to be clinically significant by the Investigator.
8. Subjects coinfected with HIV-1 or HIV-2, or hepatitis A or B virus infection (confirmed by hepatitis A antibody immunoglobulin [IgM], or hepatitis B surface antigen [HBsAg]) at screening;
9. Subjects with a pathologically prolonged QTc value (> 500 ms) at screening, or any active clinically significant disease (e.g., tuberculosis, cardiac dysfunction), or medical history or physical examination findings during screening that, in the Investigator*s opinion, would compromise the outcome of the trial;
10. Subjects having uncontrolled/unstable diabetes, epilepsy, a manifest psychiatric disease;
11. Non-stable methadone use or subjects having any other unstable disease;
12. Subjects enrolled in another clinical trial within 90 days prior to screening;

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary efficacy parameter is the viral load drop at the end of the 4-week<br /><br>treatment regimen.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary parameters include:<br /><br>- the proportion of subjects with viral load below the limit of quantification<br /><br>and limit of detection respectively.<br /><br>- Also the proportion of subjects per treatment regimen with viral breakthrough<br /><br>will be assessed.<br /><br>- The results of the viral genotype will be evaluated by the Sponsor<br /><br>Virologist. Relevant changes<br /><br>in the viral sequence, detected by the viral genome sequencing will be<br /><br>tabulated and described. </p><br>

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