Chronic hepatitis C infection MedDRA version: 12.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C
Conditions
Interventions
Trade Name: Pegasys 180mcg/135mcg
Product Name: Pegasys
Pharmaceutical Form: Injection*
INN or Proposed INN: PEGINTERFERON ALFA 2A
CAS Number: 198153-51-4
Concentration unit: µg microgram(s)
Concentr
Sponsors
Dept. of Infectious diseases / virology University of Gothenburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Written informed consent • Male and female patients >/=18 years of age • Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test • Serum HCV-RNA >/=15 IU/mL. • HCV genotype 1 infection confirmed within the past 2 years preceding the initiation of test drug dosing. • Compensated liver disease (Child-Pugh Grade A clinical classification) • Patients with cirrhosis or transition to cirrhosis must have an abdominal ultrasound, CT scan, or MRI scan without evidence of hepatocellular carcinoma and a serum AFP =100 ng/mL within 2 months of randomization • Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug • All fertile males and females receiving ribavirin must be using effective contraception during treatment and during 4 months for female patients / 7 months for male patients after end of treatment • Subject must weigh between 45 and 105 kg at screening 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
Exclusion criteria
Exclusion criteria: • Women with ongoing pregnancy or breast feeding • IFN/ peg-interferon with or without ribavirin therapy at any previous time • Therapy with any systemic anti-viral, anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) *6 months prior to the first dose of study drug • Any investigational drug 2 mg/dl (>124 µmol/L) or creatinine clearance =50 ml/minute at screening • Severe psychiatric disease, especially depression, as judged by the treating physician. • History of a severe seizure disorder or current anticonvulsant use • History of immunologically mediated disease, severe chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, malignancy, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study • Thyroid dysfunction not adequately controlled (TSH and T4 levels out of normal range) • Evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration) or clinically relevant ophthalmological disorder due to diabetes mellitus or hypertension • Evidence of drug abuse (including excessive alcohol consumption) in accordance with local therapeutic traditions. • Inability or unwillingness to provide informed consent or abide by the requirements of the study • Male partners of women who are pregnant • Hemoglobin <12 g/dL in women or <13 g/dL in men at screening. • Any patient with an increased baseline risk for anemia (e.g. thalassemia major, spherocytosis, history of GI bleeding, etc) or for whom anemia would be medically problematic coagulopathy. • Patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4 g/dL (as may be seen with ribavirin therapy) would not be well-tolerated
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of (A) 2 weeks of high dose of ribavirin (“loading”, =26 mg/kg/day for 14 days followed by =13 mg/kg/day) vs. (B) 4 weeks of ribavirin dosing before initiation of PEG-interferon dosing (“priming”, =13 mg/kg/day) followed by concentration targeted (= 2.5 mg/L (10.25 µmol/L) 28 days after initiation of ribavirin therapy) dosing of ribavirin in combination with peginterferon alpha-2a in interferon naïve patients with chronic hepatitis C (CHC) virus genotype 1 infection as compared to (C) standard-of-care dosing of ribavirin (=13 mg/kg/day without monitoring of ribavirin concentrations) in combination with peginterferon alpha-2a as evaluated by the early viral kinetic response and SVR measured by effect on the initial decline of HCV-RNA (during the first days after initiating peginterferon and ribavirin therapy) and second phase decline (day 7 to week 12 of therapy). ;Secondary Objective: To prospectively evaluate: •efficacy of 2 week loading or 4 week priming as evaluated by the proportion of patients achieving VRVR, RVR, cEVR, and pEVR •predictive value of monitoring of viral load at day 0, 3, 7 and 28 •association between the trough concentrations of ribavirin and the therapeutic efficacy •association between plasma IP-10 and the therapeutic efficacy. •effect of IL-28B ploymorfism on the viral kinetic response. •effect of baseline vitamin D concentrations on the viral kinetic response. •effect of baseline IP-10 concentrations on the viral kinetic response. •association between liver histology and the therapeutic efficacy. •association between liver stiffness as evaluated by the FibroScan and the therapeutic efficacy. •association between liver fibrosis as evaluated by the GUCI and APRI indexes as well as hyaluronic acid, and the therapeutic efficacy. •association between BMI and age and the therapeutic efficacy.;Primary end point(s): The early virological response as measures by the decline in HCV-RNA during the first 12 wee | — |
Countries
Denmark, Finland
Outcome results
None listed