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.

Phase 3

Completed

Conditions: Heptitis C infection
10047438
10019654

Registration Number: NL-OMON32876

Lead Sponsor: Janssen-Cilag

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 18

Inclusion Criteria

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.
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.
7. Subjects with cirrhosis should have serum alpha fetoprotein (AFP) less than 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 last dose of RBV.
Note: Hormonal contraceptives may not be reliable when taking telaprevir. Therefore, to be eligible for this trial, subjects should use 2 other effective birth control methods during telaprevir/placebo treatment and for 2 months after the last intake of telaprevir/placebo. As of 2 months after completion of telaprevir/placebo treatment, hormonal contraceptives can again be used as one of the 2 required effective methods of birth control.
Note: The use of birth control methods does not apply if the male partners have been vasectomized minimally 1 month prior to screening or if the female partners have had a bilateral oophorectomy, a total hysterectomy, or tubal ligation, or if they have been post menopausal for at least 2 years.
9. Subject is willing and able to refrain from the concomitant use of any medications, substances, or foods noted under Section 5.3.11, from 14 days prior to the first day of study medication dosing through the end of treatment. <br

Exclusion Criteria

1. Subject is a previous non-responder that is classified as a viral breakthrough case i.e., subject had an 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 a tolerance issue instead of lack of response.
5. Subject has any contraindication to the administration of Peg IFN alfa-2a or RBV.
6. Subject has a pre-existing psychiatric condition that could interfere with the subject*s participation in and completion of the trial.
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:
- 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.
9. Subject has active malignant disease or history of malignant disease within the past 5 years (with the exception of treated basal cell carcinoma).
10. Subject has history of seizure disorders.
11. Subject has history of organ transplant that requires chronic immunosuppression (Note: corneal, skin, and hair grafts are allowed).
12. Subject has a medical condition that requires use of systemic corticosteroids.
13. Diabetic or hypertensive subject with clinically significant ocular exam findings.
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 a 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 the screening visit, that in the investigator*s opinion would compromise the subject*s safety and/or compliance with study procedures.
20. Subject or female partner is pregnant, planning to become pregnant, or breastfeeding.
21. Subject has hypersensitivity to tartrazine (yellow dye #5).
22. Subject has a Grade 3 laboratory abnormality as defined by the grading scale for the severity of AEs in hepatitis C clinical trials (see Section 7.3, Addendum 3), with the exception of Grade 3 elevations in transaminsases (alanine aminotransferase [ALT]; aspartate aminotransferase [AST])
OR
subject has screening laboratory values of the following variables that do not meet the acceptable values defined below:
Laboratory variable Acceptable values
Absolute neutrophil count >= 1,200/mm3
Platelet count >= 90,000/mm3
Hemoglobin >= 12 g/dL for females >= 13 g/dL for males
Uric acid Within normal range
TSH and T4 Within normal range, or adequately controlled thyroid function on treatment
All other hematology and clinical chemistry variables (except transaminases [ALT; AST]) Within normal limits or showing no clinically significant abnormalities in the investigator*s opinion
2