Overview

Interferon Alpha 2b Plus Ribavirin for Chronic Hepatitis B

Status:
Completed
Trial end date:
2001-06-01
Target enrollment:
0
Participant gender:
All
Summary
Hepatitis B virus (HBV) causes a wide spectrum of liver diseases, such as fulminant or acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The number of individuals infected with this virus has been estimated to be as high as 350 million. Thus, in addition to global hepatitis B vaccination, effective treatment of chronic hepatitis B is also needed. Currently, there are no effective antiviral treatments to cure HBV infection in patients with chronic hepatitis B. Five drugs have been approved for the treatment of chronic hepatitis B at present: conventional interferon (IFN) alpha, lamivudine, adefovir dipivoxil, pegylated IFN alpha and recently entecavir. Overall, satisfactory virologic and serologic responses could be achieved using pegylated IFN alpha alone in around 20-44% of these patients. Nevertheless, better treatment options are still needed for the remaining >50% non-responders. Although the best treatment choice for chronic hepatitis B is not clarified yet, certain therapeutic concepts could be derived from the experience of treating patients with chronic hepatitis C. A major advancement in treating hepatitis C virus (HCV) infection has been the development of combination therapy with IFN and ribavirin. IFN monotherapy is limited by poor sustained virologic responses, even when higher doses of IFN are used. IFN plus ribavirin combination therapy, in contrast, results in much improved treatment outcomes. In our previous study and others, sustained remission rate after cessation of therapy were significantly higher in patients receiving combination therapy than those receiving IFN alone. Therefore, combination therapy with IFN and ribavirin has been recommended as the standard treatment regimen for chronic hepatitis C. Furthermore, we have used ribavirin and IFN combination for the treatment of dual chronic hepatitis B and C, and the results also revealed that the efficacy of clearing HCV RNA was not affected by the presence of HBV infection. Interestingly, after a little more than 2-year post-treatment follow-up, we found that a significant portion (21%) of the responsive patients also cleared HBsAg. These findings imply that this combination regimen might be also effective for the control of chronic hepatitis B. We thus conducted a randomized, multi-center, placebo-controlled study in patients with HBeAg-positive chronic hepatitis B.
Phase:
Phase 2/Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Taiwan University Hospital
Collaborator:
Schering-Plough
Treatments:
Interferon alpha-2
Interferon-alpha
Interferons
Ribavirin
Criteria
Inclusion Criteria:

- Adult male or female, 18 to 60 years of age chronic hepatitis B patients Patient must
have documented positive serum HBsAg for a minimum of 6 months prior to entry into
study.

Patients must show evidence of HBV replication and hepatitis documented by Positive serum
HBV-DNA within 3 months prior to entry (HBV-DNA > 2.5 pg/ml) Positive serum HBeAg within 3
months prior to entry. Documented presence of abnormal alanine aminotransferase (ALT) twice
within 3 months prior to entry (2 to 10 fold above the upper normal level) Liver biopsy
finding shows chronic hepatitis without liver cirrhosis

Compensated liver disease with the following minimum hematological and serum biochemical
criteria:

- Hemoglobin values of ≥ 12 gm/dL for both sexes

- WBC ≥ 3,000/mm3

- Neutrophil count ≥ 1,500/ mm3

- Platelets ≥ 100,000/ mm3

- Total bilirubin ≤ 2 mg/dL

- Albumin ≥ 3.5 g/dL

- Uric acid within normal ranges

- Serum creatinine ≤ 123.76 mmol/L (≤1.4 mg/dL)

- Fasting blood sugar ≤ 6.38 mmol/L (≤115 mg/dL) for non-diabetic patients

- Hemoglobin ≤ 8.5% for diabetic patients (whether on medication and/or controlled with
diet) Thyroid Stimulating Hormone (TSH), T3 & T4 within normal limits Negative serum
antibody to hepatitis C Negative antibody to human immunodeficiency virus (anti-HIV)
ELISA method If the patient has a history of diabetes or hypertension, a baseline
ocular examination will be required.

Alfa-fetoprotein within normal range Written informed consent



Exclusion Criteria:

- Patients older than 60 years of age

Any cause for the liver disease based on patient history or biopsy (where applicable) other
than chronic hepatitis B, including but not limited to:

Co-infection with HCV and/or HIV Hemochromatosis (iron despistion > 2 + in liver
parenchyma) Alpha-1 antitrypsin deficiency Wilson's disease Renal or liver transplant
patients Autoimmune hepatitis Alcoholic liver disease Obesity related liver disease Drug
related liver disease Evidence of decompensated liver disease such as history or presence
of ascites, bleeding varices, hepatic encephalopathy.

Any known pre-existing medical condition that could interfere with the patient's
participation in and completion of the treatment such as:

Pre-existing psychiatric condition, especially severe epression, or a history of severe
psychiatric disorder CNS trauma or active seizure disorders requiring medication. Patients
with any history of cardiovascular dysfunction. Patients with any hemoglobinopathy
including but not limited to thalassemia major and minor Poorly controlled diabetes
mellitus Chronic pulmonary disease Immunologically mediated disease Clinical gout Sexually
active females of childbearing potential must be practicing adequate contraception,
Sexually active males must be practicing acceptable methods of contraception (vasectomy,
condom + spermicide, monogamous relationship with a female partner who practices an
acceptable method of contraception) during the treatment period and for 6 months after
discontinuation of therapy.

Female patients must not breast feed during the treatment period. Patients must agree to
limit the drinking of alcohol during the course or the treatment.

Patients receiving Chinese herbal medication during the past 3 months prior to study entry.

Patient who did not respond to previous interferon therapy or who relapsed after a previous
course of Interferon therapy.

Patients who have been enrolled in any clinical trial for the treatment of chronic
hepatitis B.