Interferon Alpha 2b Plus Ribavirin for Chronic Hepatitis B

This study has been completed.
Sponsor:
Collaborator:
Schering-Plough
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00275938
First received: January 11, 2006
Last updated: NA
Last verified: January 2006
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis B
Drug: interferon alpha 2b plus ribavirin
Drug: interferon alpha 2b plus placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Pilot Study Of Interferon Alpha 2b Plus Ribavirin In The Treatment Of Patients With Chronic Hepatitis B

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Undetected serum HBV DNA level (i.e. less than 2.5 pg/ml) at the end of the 24-week follow-up period

Secondary Outcome Measures:
  • HBV DNA level at the end of treatment
  • clearance of HBeAg and rate of ALT normalization both at the end of the 32-week treatment period and at the end of the 24-week follow-up

Estimated Enrollment: 120
Study Start Date: October 1998
Estimated Study Completion Date: June 2001
Detailed Description:

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. Conventional IFN alpha monotherapy has a narrow range of efficacy. Lamivudine, is relatively cheaper, better tolerated, and has been shown to be effective in patients with both hepatitis B e antigen (HBeAg)-positive and -negative chronic hepatitis B. However, virologic response to lamivudine is not as durable as that occurred spontaneously or induced by IFN treatment. In addition, prolonged lamivudine treatment is commonly associated with the emergence of drug-resistance HBV mutants accompanied by the development of breakthrough hepatitis. Adefovir is potent and has been approved for the treatment of chronic hepatitis B in several countries, but is nephrotoxic at daily doses higher than 10 mg and is still not available widely. Entecavir, a carbocyclic deoxyguanosine analog, which is active against both lamivudine- and adefovir dipivoxil-resistant HBV, is the most potent anti-HBV agent ever discovered,11 however, its long-term efficacy remains to be evaluated. Pegylated IFN alpha has recently been shown to be superior to conventional IFN alpha and lamivudine, and has also been approved for the treatment of chronic hepatitis B. Overall, satisfactory virologic and serologic responses could be achieved using pegylated IFN alpha alone in around 30-44% 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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00275938

Sponsors and Collaborators
National Taiwan University Hospital
Schering-Plough
Investigators
Principal Investigator: Ming-Yang Lai, Professor National Taiwan University Hospital
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00275938     History of Changes
Other Study ID Numbers: 145R3
Study First Received: January 11, 2006
Last Updated: January 11, 2006
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
hepatitis B virus
e antigen
interferon
ribavirin

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Interferon-alpha
Interferon Alfa-2a
Interferon Alfa-2b
Interferons
Ribavirin
Reaferon
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014