A Phase IIb, randomized, double-blind, placebo-controlled trial to investigate the efficacy, tolerability, safety and pharmacokinetics of TMC435 as part of a treatment regimen including peginterferon alfa-2a and ribavirin in treatment-naïve genotype 1 hepatitis C-infected subjects. - PILLAR

• Conditions: Hepatitis C virus (HCV); MedDRA version: 12.0Level: LLTClassification code 10019751Term: Hepatitis C virus

• Registration Number: EUCTR2008-007147-13-DE
• Lead Sponsor: Tibotec Pharmaceuticals

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-03-13
• Last Update Posted: 26 June 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 400

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

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
< 50 mL/min);
- Anti-nuclear antibody (ANA) titer = 1:320;
- Autoimmune disease (e.g., Graves’ disease);
- Hemoglobinopathies (e.g., thalassemia major or sickle-cell anemia).
Note: Subjects with thalassemia minor can be included if their hemoglobin level is
normal at screening.
9. Any active clinically significant disease other than hepatitis C (e.g., chronic pancreatitis) or findings during screening of medical history or physical examination, laboratory testing or ECG recordings that, in the investigator’s opinion, would compromise the subject’s safety or the outcome of the trial;
10. Subject with organ transplant (other than cornea or hair transplant or skin graft);
11. Subject with any of the following laboratory abnormalities:
- AST and/or ALT > 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 < 30 g/L, or bilirubin
> 1.5 x upper limit of laboratory normal range [ULN]);
Note: Subjects can be

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified