A randomized, double-blind, placebo-controlled, Phase III trial of 2 regimens of telaprevir (with and without delayed start) combined with pegylated interferon alfa-2a (Pegasys®) and ribavirin (Copegus®) in subjects with chronic genotype 1 hepatitis C infection who failed prior pegylated interferon plus ribavirin treatment. - REALIZE

• Conditions: Chronic genotype 1 Hepatitis C infection; MedDRA version: 9.1Level: LLTClassification code 10008912Term: Chronic hepatitis C

• Registration Number: EUCTR2008-000533-22-AT
• Lead Sponsor: Tibotec BVBA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-07-23
• Last Update Posted: 10 July 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 650

Inclusion Criteria

Subjects who meet all of the following criteria are eligible for this trial:
1. Subject is male or female, 18 to 70 years of age, inclusive.
2. Subject has chronic hepatitis C infection genotype 1 with HCV RNA level = 1000 IU/mL. Genotype must be confirmed during screening. Chronic infection status must be confirmed by diagnosis of HCV > 6 months before the screening period.
3. Subject failed at least 1 prior course of Peg-IFN/RBV therapy, defined as:
- Subject had an undetectable HCV RNA level (by branched-chain DNA [bDNA], reverse transcription-polymerase chain reaction [RT-PCR], or transcription mediated amplification [TMA]-based assay) at the end (6 weeks or less after the last dose of medication) of a prior course of at least 42 weeks of Peg-IFN/RBV therapy but did not achieve SVR (viral relapser); or
- Subject never had an undetectable HCV RNA level (by bDNA, RT-PCR, or TMA-based assay) during or at the end of a prior course of at least 12 weeks of Peg-IFN/RBV therapy (null-responder and partial responder).
Subject must have received 80% or more of the intended dose of Peg-IFN/RBV.
The following information related to the virologic response to the last course of Peg-IFN/RBV therapy (that qualifies as an adequate course as defined above) must be available in the medical records of the subject:
- start and end date of the previous treatment course;
- HCV RNA results at start of treatment (all subjects), at 12 weeks after start of treatment (null and partial responders), at end of treatment (all subjects), and during follow-up (relapsers);
Note: the following time window is allowed for the Week 12 assessment time point: Week 11 to Week 16
- HCV RNA assay used and limit of detection.
4. Subject must have received the last dose of Peg-IFN or RBV at least 12 weeks before the screening visit.
5. Subject is judged to be in good health (besides HCV infection) in the opinion of the investigator, on the basis of medical history and physical examination (including vital signs and screening electrocardiogram [ECG]), with any chronic medical conditions under stable medical control.
6. Subject must have had a liver biopsy within 18 months prior to the screening visit and the biopsy report should be available, or he/she should agree to have a biopsy performed within the screening period.
Note: If a biopsy more than 18 months prior to screening has already demonstrated histological cirrhosis (Metavir F4; Ishak score = 5), the biopsy does not need to be repeated if the biopsy report can be provided.
Note: If a biopsy was performed > 18 months but = 21 months prior to screening, the biopsy does not need to be repeated if information supportive of the absence of progression of fibrosis since the time of the previous biopsy is provided by the investigator (e.g., recent fibrotest/fiboscan consistent with previous results) and if the biopsy report can be provided.
7. Subjects with cirrhosis should have serum alpha-fetoprotein (AFP) = 50 ng/mL and normal abdominal ultrasound. If AFP > 50 ng/mL or ultrasound abnormal, subjects must have a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan to exclude hepatocellular carcinoma.
8. If heterosexually active, a female subject of childbearing potential and a non-vasectomized male subject who has a female partner of childbearing potential must agree to the use of 2 effective methods of contraception from screening onwards until 6 months (female subject) or 7 months (male subject) after the la

Exclusion Criteria

Subjects meeting one or more of following criteria cannot be selected:
1. Subject is a previous non-responder that is classified as a viral breakthrough case i.e., subject had undetectable HCV RNA level during prior course of Peg-IFN/RBV therapy but regained detectable HCV RNA before therapy ended.
2. Subject is infected with HCV genotype 1 exhibiting more than one subtype.
3. Subject has HCV genotype 1 and exhibits co-infection with any other genotype.
4. Subject discontinued prior course(s) of Peg-IFN/RBV therapy due to tolerance issue instead of lack of response.
5. Subject has any contraindication to administration of Peg-IFN alfa-2a or RBV, including but not limited to any of following:
- hypersensitivity to Peg-IFN alfa-2a, RBV, or any of their components;
- hemoglobinopathies;
- history or clinical evidence of significant or unstable cardiac disease and/or clinically significant ECG abnormalities;
- abnormal thyroid function that cannot be controlled effectively by medication;
- poorly controlled diabetes mellitus as evidenced by hemoglobin A1c (HbA1c) = 8.5% at screening;
- creatinine clearance = 50 mL/min at screening;
- antinuclear antibody (ANA) titer = 1:640 at screening, evidence of
autoimmune-mediated disease and/or evidence of autoimmune hepatitis.
6. Subject has a pre-existing psychiatric condition that could interfere with subject’s participation in and completion of the trial, including but not limited to:
- severe depression or hospitalization for depression;
- schizophrenia, bipolar illness, severe anxiety, or personality disorder;
- a period of disability or impairment due to a psychiatric disease within the past 5 years.
7. Subject has history of decompensated liver disease: history of ascites, hepatic
encephalopathy, or bleeding esophageal varices, and/or any of the following screening laboratory results:
- International Normalized Ratio (INR) of = 1.5;
- Serum albumin < 3.3 g/dL;
- Serum total bilirubin > 1.8 times ULN, unless isolated and for subjects with Gilbert’s Syndrome.
8. Subject shows evidence of significant liver disease in addition to hepatitis C, which may include but is not limited to, drug or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson’s disease, Nonalcoholic Steatohepatitis (NASH), or primary biliary cirrhosis.
9. Subject has active malignant disease or history of malignant disease within past 5 years
10. Subject has history of seizure disorders.
11. Subject has history of organ transplant that requires chronic immunosuppression
12. Subject has a medical condition that requires use of systemic corticosteroids
13. Diabetic or hypertensive subject with clinically significant ocular exam findings, e.g., retinopathy, cotton wool spots, and optic nerve disorder.
14. Subject has history or other clinical evidence of chronic pulmonary disease associated with functional impairment.
15. Subject has hemophilia.
16. Subject has evidence of serious or severe bacterial or fungal infection(s), including active tuberculosis.
17. Subject has human immunodeficiency virus (HIV) or hepatitis B virus (HBV) co-infection.
18. Subject has history of acute or chronic pancreatitis.
19. Suspicion exists of alcohol, barbiturate, amphetamine recreational or narcotic drug use, current or within 2 years prior to screening visit, that in investigator’s opinion would compromise the subject’s safety and/or compliance with study procedures.
20. Subject or female partner is pregnant, planning to beco

Study & Design

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