Thymosin Plus PEG-Interferon in Non-Cirrhotic Hepatitis C Patients Who Did Not Respond to Interferon or Interferon Plus Ribavirin
Thymosin Plus PEG-Interferon in Non-Cirrhotic Hepatitis C Patients Who Did Not Respond to Interferon or Interferon Plus Ribavirin
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.
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.