Ensayo en fase III, aleatorizado, doble ciego, controlado con placebo, de dos regímenes de telaprevir (con y sin comienzo retrasado) combinado con interferón pegilado alfa 2a (Pegasys®) y ribavirina (Copegus®) en sujetos con infección de hepatitis C crónica genotipo 1, que fracasaron tratamiento previo con interferón pegilado y ribavirina.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

Phase 1

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

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-08-25
• Study Completion: 2010-07-16
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 0

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 values at start of treatment (all subjects), at 12 weeks after start of treatment (all subjects), 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.
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- asectomized 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

Exclusion Criteria

Subjects meeting one or more of the following criteria cannot be selected:
1. Subject is a previous non-responder that is classified as a viral breakthrough case i.e., subject had an undetectable HCV RNA level (by bDNA, RT-PCR, or TMA-based assay) 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, including but not limited to any of the following:
- hypersensitivity to Peg-IFN alfa-2a, RBV, or any of their components;
- hemoglobinopathies (including thalassemia major, sickle-cell disease);
- 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 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 the 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 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
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 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

Study & Design

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