Multicenter, Open-Label, Early Access Program of Telaprevir in Combination With Peginterferon Alfa and Ribavirin in Genotype 1 Chronic Hepatitis C Subjects With Severe Fibrosis and Compensated Cirrhosis

Study Objective

The objectives of this early access program are to provide telaprevir for subjects with genotype 1 chronic hepatitis C with severe fibrosis and compensated cirrhosis who reside in countries in which telaprevir is not yet commercially available and who are not eligible for enrollment into an ongoing clinical study of telaprevir, and to collect additional safety and tolerability data on telaprevir treatment in combination with Peg-IFN-alfa and RBV.

Participation conditions

Inclusion criteria

• Be a man or woman, between 18 and 70 years of age, inclusive.
• Have evidence of HCV infection genotype 1 (molecular assay).
• Have a quantifiable plasma HCV RNA.
• Have documentation of liver fibrosis assessed by liver biopsy or non-invasive test (eg, fibrotest, fibroscan) showing severe fibrosis (Metavir F3 or Ishak 3-4) or cirrhosis (Metavir F4 or Ishak 5-6). For subjects with Metavir F3 or Ishak 3-4, the liver biopsy or non-invasive test should have been performed within the past 18 months.
• Have compensated liver disease (Child-Pugh Grade A clinical classification).
• Have access to the Hepatitis C treatments Peg-IFN-alfa/RBV.
• If a women of childbearing potential, must have a negative serum -human chorionic gonadotropin (-hCG) or urine pregnancy test documented at the screening visit and a negative serum or urine pregnancy test before the first dose of study drug to ensure that they are not pregnant at the time of starting treatment.
• If heterosexually active, a female subject of childbearing potential and a nonvasectomized male subject who has a female partner of childbearing potential must agree to use 2 effective contraceptives from screening onwards until 4 months (female subject) or 7 months (male subject) after RBV therapy has ended.
Note: Hormonal contraceptives may be continued but may not be reliable during telaprevir dosing and for 2 months following cessation of telaprevir. Therefore, to be eligible for this early access program, subjects should agree to use 2 effective non-hormonal methods of contraception during telaprevir combination therapy and for 2 months after the last intake of telaprevir.
• Sign the informed consent document indicating that they understand the purpose of and procedures required for the early access program and are willing to participate in the early access program.
• Sign the informed consent form for pharmacogenomic research in order to participate in the optional pharmacogenomic component of this early access program (where local regulations permit). Refusal to give consent for this component does not exclude a subject from participation in the early access program.

Exclusion criteria

• Is eligible for enrollment into an ongoing clinical study of telaprevir.
• Is infected or coinfected with HCV of another genotype than genotype 1.
• Has a contraindication to the administration of Peg-IFN-alfa or RBV, or medical history or laboratory values that preclude treatment with Peg-IFN-alfa or RBV according to the respective local prescribing information.
• Has a history of having received investigational HCV protease or polymerase inhibitors at any previous time.
• Has signs or symptoms of HCC. Serum alpha-fetoprotein (AFP) level and ultrasonography should be available at screening for all subjects to screen for HCC (both tests should have been done a maximum of 4 months before the screening visit).
• Has a 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 the upper limit of the laboratory normal range, unless isolated or in subjects with Gilbert’s Syndrome
• Has a coinfection with active hepatitis B or HIV.
• Has any of the following laboratory abnormalities (assessed at local laboratory) as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS).
- Absolute neutrophil count (ANC) <1,500 cells/mm3
- Platelet count <90,000 cells/mm3
- Hemoglobin concentration <12 g/dL in females or <13 g/dL in males
- Calculated creatinine clearance <50 mL/min
- Potassium <3.5 mmol/L
• Has inadequately controlled thyroid function, as judged by the investigator based on the thyroid stimulating hormone (TSH) results 10. Has baseline increased risk for anemia (eg, thalassemia, sickle cell anemia, spherocytosis, history of gastrointestinal bleeding) or for whom anemia would be medically problematic.
• Has congenital QT prolongation or family history of congenital QT prolongation or sudden death.
• Has a history of severe psychiatric disease, including psychosis and/or depression, characterized by a suicide attempt, hospitalization for psychiatric disease, or a period of disability as a result of psychiatric disease.
• Has a history of immunologically mediated disease (eg, inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis [defined as affecting >10% of the body, where the palm of one hand equals 1%, or if the hands and feet are affected], rheumatoid arthritis requiring more than intermittent nonsteroidal anti-inflammatory medications for management).
• Has clinical evidence of chronic pulmonary disease associated with functional impairment.
• Has a history of uncontrolled severe seizure disorders.
• Has a history or other evidence of a clinically relevant ophthalmologic disorder due to diabetes mellitus or hypertension or history or other evidence of severe retinopathy (eg, cytomegalovirus, macular degeneration).
• Has a history of major organ transplantation with an existing functional graft with the exception of corneal transplants and skin grafts.
• Is currently enrolled in an investigational drug study or has participated in such a study within 30 days before Day 1.
• Is a woman who is pregnant or breast-feeding.
• Any condition (including, but not limited to, alcohol and drug use), which, in the opinion of the investigator, could compromise the subject’s safety or adherence to the early access program.

Centre Hospitalier de Luxembourg