Clinical trial NCT00040027: Thymosin Plus PEG-Interferon in Non-Cirrhotic Hepatitis C Patients Who Did Not Respond to Interferon or Interferon Plus Ribavirin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C
Hepatitis C, Chronic
Keywords: hepatitis C
hepatitis C, chronic
Lead sponsor: SciClone Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2002-07-04
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of Alabama - Knollwood Physician's Group Bldg.
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Berkeley
country: United States
facility: Gastroenterology Associates of East Bay Medical Group
state: California
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: Veterans Administration Medical Center GI Section (111B)
state: California
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami Center for Liver Diseases
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Savannah
country: United States
facility: Center for Digestive and Liver Health
state: Georgia
city: Meridian
country: United States
facility: Idaho Gastroenterology Associates
state: Idaho
city: Chicago
country: United States
facility: University of Chicago Hospital & Clinic
state: Illinois
city: Louisville
country: United States
facility: Hepatitis C Treatment Centers, Inc.
state: Kentucky
city: Louisville
country: United States
facility: Liver Research Center - University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Louisiana State University Healthcare Network
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Chevy Chase
country: United States
facility: Chevy Chase Clinical Research
state: Maryland
city: Boston
country: United States
facility: New England Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Jackson
country: United States
facility: Mississippi Gastrointestinal Associates
state: Mississippi
city: Kansas City
country: United States
facility: VAMC
state: Missouri
city: SainT Louis
country: United States
facility: Saint Louis University Hospital
state: Missouri
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Bronx VA Medical Center
state: New York
city: New York
country: United States
facility: NY VAMC
state: New York
city: New York
country: United States
facility: NYU Hospitals Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Center for Liver Diseases
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati - College of Medicine
state: Ohio
city: Cleveland
country: United States
facility: Metro Health Medical Center, GI Division
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Roger Williams Medical Center
state: Rhode Island
city: Memphis
country: United States
facility: GI Center MidSouth
state: Tennessee
city: Memphis
country: United States
facility: University of Tennessee Gastroenterology
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor, VAMC
state: Texas
city: Fairfax
country: United States
facility: Metropolitan Research
state: Virginia
city: Richmond
country: United States
facility: McGuire Research Institute
state: Virginia
city: Milwaukee
country: United States
facility: Wisconsin Center for Advanced Research
state: Wisconsin
city: Ponce
country: Puerto Rico
facility: Ponce School of Medicine
city: Santurce
country: Puerto Rico
facility: Fundacion de Investigacion de Diego
Study officials:
References: