Hepatitis C, Hepatitis C, Chronic
Conditions
Keywords
hepatitis C, hepatitis C, chronic
Brief summary
Chronic hepatitis C infection is one of the leading causes of chronic liver disease in the United States. Approximately one-third of patients with hepatitis C infection develop cirrhosis of the liver, which can lead to liver failure or liver cancer. The current treatment for hepatitis C infection in previously untreated patients is successful in only about half of patients. There is no established therapy for non-responders. This is a randomized, double-blinded, multicenter trial to determine the effectiveness of thymosin alpha 1 (thymalfasin) 1.6 mg twice weekly plus PEGinterferon alfa-2a 180 ug/wk compared to placebo plus PEGinterferon alfa-2a in adults with chronic hepatitis C without cirrhosis who are non-responders to previous treatment with interferon or interferon plus ribavirin. The definition of non-response requires a positive HCV RNA test at the end of a course of at least 12 weeks of therapy. Patients will receive treatment for 12 months, and will be followed-up for a further 6 months after the end of therapy.
Interventions
DRUGplacebo + PEGinterferon alfa-2a
DRUGthymalfasin (thymosin alpha 1) + PEGinterferon alfa-2a
Sponsors
SciClone Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed written informed consent. * Age over 18 years old. * Presence of HCV RNA measured by qualitative PCR. * Nonresponder to a previous course of therapy with either IFN alone or IFN plus ribavirin. The patient must have been treated for at least 12 weeks. * Washout period of at least 6 months from previous therapy with IFN alone or IFN plus Ribavirin. * Liver biopsy consistent with chronic hepatitis C within the last 12 months before treatment starts, and at least 6 months after the end of the prior failed therapy. * No clinical or histological evidence of cirrhosis (METAVIR fibrosis score 0 to 3). * Compensated liver disease with prothrombin time prolonged less than 3 seconds over control, serum albumin stable and within normal limits, total bilirubin \< 2 mg/dl, and no history of hepatic encephalopathy, esophageal varices or ascites. * Ultrasound, CT scan, or MRI of the liver within 3 months of entry negative for HCC. * Hematocrit \> 30%, platelet count \> 100 x 109/L, WBC \> 3 x 109/L, and polymorphonuclear white cell count \> 1.5 x 109/L. * Adequate renal function as demonstrated by serum creatinine level \< 2.0 mg/dL. * Normal TSH or adequately controlled thyroid function. * If the patient is a woman, she is using a definitive method of birth control in consultation with her physician, or is surgically sterile or post-menopausal.
Exclusion criteria
* Use of systemic corticosteroids within 6 months of entry. * Current use of any drug known to be hepatotoxic, any drug (other than the study drugs) known to have or suspected of having therapeutic activity in hepatitis C or of any immunosuppressive drug (including corticosteroids). * Any other liver disease including hepatitis B, hepatitis delta, alcoholic liver disease, drug-induced liver injury, primary biliary cirrhosis, sclerosing cholangitis, autoimmune hepatitis, hemochromatosis, alpha 1-antitrypsin deficiency, or Wilson's disease. * Alpha-fetoprotein \> 200 ng/mL. * Current or past diagnosis of cirrhosis. * Evidence of portal hypertension either by Doppler ultrasonography or gastrointestinal endoscopy. * Decompensated liver disease based on a history of hepatic encephalopathy, esophageal varices, or ascites. * HIV infection diagnosed by HIV seropositivity and confirmed by Western blot. * Concomitant or prior history of malignancy other than curatively treated skin cancer or surgically cured in situ carcinoma of the cervix. * Active infectious process other than HCV that is not of a self-limited nature (eg. TB or AIDS). * Rheumatoid arthritis or other autoimmune disease (serum ANA \> 1:160). * Pregnancy as documented by a urine pregnancy test. * Alcohol or intravenous drug abuse within the previous 1 year. * Chronic use of methadone. * Patients who are poor medical risk or who have any non-malignant systemic disease that, in the opinion of the investigator, would make it unlikely that the patient could complete the protocol. * Patients with a history of severe depression that required either hospitalization or electroshock therapy; or depression associated with suicide attempt. * Patients with significant pre-existing cardiac or pulmonary disease. * Any indication that the patient would not comply with the conditions of the study protocol. * Previous treatment with thymosin alpha 1. * Patients with known hypersensitivity to IFNa. * Simultaneous participation in another investigational drug study, or participation in any clinical trial involving investigational drugs with 3 months before study entry. * Family history of intracerebral hemorrhage.
Countries
Puerto Rico, United States
Outcome results
None listed