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 PegIFNa-2a and ribavirin in HCV genotype 1 infected subjects who failed to respond or relapsed following at least 1 course of PegIFNa-2a/b and RBV therapy. - ASPIRE (i.e. Antiviral Stat-C Protease Inhibitor Regimen in Experienced subjects)
- Conditions
- Hepatitis C Virus (HCV)MedDRA version: 12.0Level: LLTClassification code 10019752Term: Hepatitis C virus (HCV)
- Registration Number
- EUCTR2009-010590-20-BE
- Lead Sponsor
- Tibotec Pharmaceuticals
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 455
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 biopsy is available, one will be performed on a separate day during screening. For subjects with cirrhosis diagnosed by prior biopsy (evidence of which should be available in the source documents) and no evidence of hepatocellular carcinoma (confirmed by alpha-fetoprotein [AFP] level < 50 ng/mL and ultrasound at screening), another biopsy is not required.
3. Genotype 1 HCV infection (confirmed at screening);
4. Plasma HCV RNA of > 10,000 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. At least 1 prior documented course of PegIFNa-2a/RBV or PegIFNa-2b/RBV therapy for at least 12 consecutive weeks which has not been discontinued due to intolerability to PegIFNa-2a/b and RBV therapy;
Note: Subjects who were treated with (Peg)IFN monotherapy are not allowed.
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 separate forms of highly effective contraception methods (1 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, vasectomized (male subject) or has a vasectomized partner (female subject), or is a female (subject or partner of male subject) of non-childbearing potential;
8. Informed consent signed voluntarily before the first trial-related activity;
9. 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
Subjects meeting 1 or more of the following criteria cannot be selected:
1. Decompensated liver disease defined as history or presence of ascites, hepatic encephalopathy, esophageal bleeding, or gastric varices.
2. 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 (NASH) or primary biliary cirrhosis;
3. Infection/co-infection with non-genotype 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) or hepatitis B virus infection (hepatitis B surface antigen
[HbsAg]);
5. 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);
6. Evidence of hepatocellular carcinoma (e.g., AFP > 50 ng/mL);
7. Medical conditions that 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 suicide attempt;
- 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., glycated hemoglobin [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).
8. Any active clinically significant disease other than hepatitis C (e.g., chronic pancreatitis) or findings during screening of medical history, 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;
9. Having had an organ transplant (other than cornea or hair transplant or skin graft);
10. Having any of the following laboratory abnormalities:
- AST and/or ALT > 10 x 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]);
- Laboratory abnormalities that are exclusion criteria for PegIFNa-2a or RBV treatment (please refer to the manufacturer’s prescribing information for details):
a. Platelet count < 90,000/mm³;
b. Absolute neutrophil count (ANC) < 1500 cells/mm³;
c. Hemoglobin < 12 g/dL for females and < 13 g/dL for males;
- Any other grade 3 or grade 4 laboratory abnormality according to the World Health
Organization (WHO) Toxicity Grading Scale.
11. History or evidence of current use of alcohol, barbiturates, amphetamines, 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 drug/alcohol misuse must
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method