Thymosin Plus PEG-Interferon in Hepatitis C Patients With Cirrhosis Who Did Not Respond to Interferon or Interferon Plus Ribavirin
Thymosin Plus PEG-Interferon in Hepatitis C Patients With Cirrhosis 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 with early
 cirrhosis or progression to 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 3 months (12 weeks).

 -  Washout period of at least 6 months from previous therapy with IFN alone or IFN plus
 Ribavirin.

 -  Liver biopsy consistent with cirrhosis or progression to cirrhosis (METAVIR fibrosis
 score 3 to 4) due to chronic hepatitis C within the last 12 months before treatment
 starts, and at least 6 months after the end of the prior failed therapy.

 -  Cirrhosis classified as Child-Pugh "A" (no more than 6 points).

 -  Compensated liver disease with prothrombin time prolonged less than 3 seconds over
 control, total bilirubin < 2 mg/dl, and no history of hepatic encephalopathy, bleeding
 varices or a history of detection of stigmata of recent bleeding on existing varices
 or ascites.

 -  Ultrasound, CT scan, or MRI of the liver within 3 months of entry negative for HCC.

 -  Hematocrit > 30%, platelet count > 75,000, WBC > 2,500, and absolute neutrophil cell
 count > 1,500.

 -  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.

 -  Evidence of drug-induced liver injury.

 -  Current use of any drug known to have or suspected of having therapeutic activity in
 hepatitis C, or any immunosuppressive drug (including corticosteroids).

 -  Evidence of any other liver disease including hepatitis B, hepatitis delta, alcoholic
 liver disease, primary biliary cirrhosis, sclerosing cholangitis, autoimmune
 hepatitis, hemochromatosis, alpha 1-antitrypsin deficiency, or Wilson's disease.

 -  Alpha-fetoprotein > 200 ng/mL.

 -  Child-Pugh "B" or "C" cirrhosis (score of 7 or more points), either currently or at
 any occasion in the past.

 -  Decompensated liver disease based on a history of hepatic encephalopathy, bleeding
 varices or a history of detection of stigmata of recent bleeding on existing 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.

 -  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.

 -  Recipients of transplants.

 -  Patients with uncontrolled seizure disorder.

 -  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 IFN a.

 -  Simultaneous participation in another investigational drug study, or participation in
 any clinical trial involving investigational drugs within 3 months of study entry.

 -  Family history of intracerebral hemorrhage.