thymosin plus peg-interferon in non-cirrhotic hepatitis c patients who did not respond to interferon or interferon plus ribavirin

Conditions: Hepatitis C; Hepatitis C, Chronic

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.


Eligibility criteria:
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.

Keywords: hepatitis c hepatitis c, chronic