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Pegasys Plus Entecavir Versus Entecavir Alone for Hepatitis Be Antigen-Positive Chronic Hepatitis B

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00597259
Recruitment Status : Unknown
Verified June 2010 by National Taiwan University Hospital.
Recruitment status was:  Recruiting
First Posted : January 18, 2008
Last Update Posted : June 29, 2010
Bristol-Myers Squibb
Information provided by:
National Taiwan University Hospital

Brief Summary:

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 or human immunodeficiency virus (HIV) infection. A major advancement in treating hepatitis C or HIV infection has been the development of combination therapy. Whether the combination therapy using Peg-IFN alfa-2a plus ETV can achieve a long-term beneficial effect against ETV alone is not clarified. A prior single-arm pilot study suggested that similar combination therapy may be beneficial in patients with chronic hepatitis B. In this proposal, we thus hypothesize that the efficacy by using combination therapy with pegylated IFN alfa-2a plus ETV is superior to that by using ETV alone in that Peg-IFN may restore host immunity against HBV and prolonged ETV can maximize viral suppression.

The objective of this clinical trial is to evaluate the efficacy of the combination of Peg-IFN alfa-2a at a dose of 180 mcg administered subcutaneously per week and ETV 0.5 mg daily for 24 weeks followed by ETV 0.5 mg daily monotherapy for an additional 120 weeks versus ETV 0.5 mg daily monotherapy for 144 weeks in patients with HBeAg-positive chronic hepatitis B. It will be an open-label, randomized, comparative, multi-center clinical trial. The recruited patients will be equally randomized into two treatment groups. Treatment-free follow-up period will be 48 weeks in both groups of patients. All subjects will be assessed for loss of HBeAg, presence of anti-HBe, loss of HBsAg, presence of anti-HBs, suppression of HBV DNA, and normalization of serum ALT at the end of treatment and end of follow-up. Genotypic and virologic resistance to ETV will also be assessed at baseline and at end of years 1, 2 and 3. The primary efficacy will be HBeAg seroconversion.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: Pegasys plus Entecavir Drug: Entecavir Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 294 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pegasys Plus Entecavir Versus Entecavir Alone for Hepatitis Be Antigen-Positive Chronic Hepatitis B
Study Start Date : January 2008
Estimated Primary Completion Date : February 2014
Estimated Study Completion Date : February 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: A Drug: Pegasys plus Entecavir
Pegasys 180 mcg in 0.5 mL solution administered sc once weekly for 24 weeks plus entecavir (0.5mg mg/capsule) 0.5 mg administered po daily for 24 weeks

Active Comparator: B
Entecavir Alone
Drug: Entecavir
ETV 0.5 mg daily monotherapy for 144 weeks

Primary Outcome Measures :
  1. HBeAg seroconversion [ Time Frame: at the end of 24 weeks post-treatment follow-up ]

Secondary Outcome Measures :
  1. Serum ALT normalization, HBeAg loss, serum HBV DNA disappearance, HBsAg disappearance, histologic change, entecavir resistance [ Time Frame: At the end of treatment and 24 weeks after end of treatment ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

Subjects meeting all of the following criteria will be considered for entering the study:

  1. Adult male or female, 18 to 70 years of age

    • 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 >100,000 copies/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 folds above the upper normal level)
      • Liver biopsy finding shows evidence of chronic hepatitis without liver cirrhosis
      • Naïve to lamivudine
  2. Compensated liver disease with the following minimum hematological and serum biochemical criteria:

    • Hemoglobin values of ≥ 12 gm/dL for both genders
    • WBC ≥ 3,000/mm3
    • Neutrophil count ≥ 1,500/ mm3
    • Platelets ≥ 100,000/ mm3
    • PT prolong < 3 sec, INR < 1.2
    • 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)
    • Hemoglobin A1C ≤ 8.5% for diabetic patients (whether on medication and/or controlled with diet)
  3. Thyroid stimulating hormone (TSH), within normal ranges (subjects requiring medication to maintain TSH levels in the normal range are eligible if all other inclusion/exclusion criteria are met)
  4. Negative serum antibody to hepatitis C (anti-HCV)
  5. Negative antibody to human immunodeficiency virus (anti-HIV)
  6. Alfa-fetoprotein within normal range (obtained within the previous year, or if elevated and <100 ng/ml, then a negative ultrasound for hepatocellular carcinoma within prior 3 months is required.)
  7. Subject must be willing to give written informed consent and be able to adhere to dose and visit schedules

Exclusion criteria:

Subjects presenting with any of the following will not be included in the study:

  1. Women who are pregnant or nursing
  2. Prior treatment for hepatitis with any interferon, NA or other investigational agents
  3. Prior treatment for hepatitis with immunomodulatory drug within previous 2 years
  4. Suspected hypersensitivity to interferon
  5. Have evidence of cirrhosis
  6. History of severe psychiatric disease, especially depression
  7. Concurrent malignancies (including hepatocellular carcinoma)
  8. Unstable or significant cardiovascular diseases (e.g., angina, congestive heart failure, recent myocardial infarction, severe hypertension or significant arrhythmia; subjects with ECG showing clinically significant abnormalities)
  9. Prolonged exposure to known hepatotoxins such as alcohol or drugs
  10. History of thyroid disease poorly controlled on prescribed medication
  11. Poorly controlled diabetes mellitus
  12. Have suspected or confirmed significant hepatic disease from an etiology other than HBV (e.g., alcohol, autoimmune disease etc.)
  13. Patients co-infected with hepatitis C and /or HIV
  14. Severe renal disease or myeloid dysfunction
  15. History of organ transplantation other than cornea and hair transplant
  16. Any medical condition requiring, or likely to require during the course of the study, chronic systemic administration of steroids
  17. Any other condition which in the opinion of the investigator would make the subject unsuitable for enrollment, or could interfere with the subject participating in and completing the protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00597259

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Contact: Pei-Jer Chen, M.D., Ph.D. 886-2-23123456 ext 7072
Contact: Chun-Jen Liu, M.D., Ph.D. 886-2-23123456 ext 6644

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National Taiwan University Hospital Department of Internal medicine Recruiting
Taipei, Taiwan, 100
Contact: Pei-Jer Chen, M.D., Ph.D.    886-2-23123456 ext 7072   
Principal Investigator: Pei-Jer Chen, M.D., Ph.D.         
Sponsors and Collaborators
National Taiwan University Hospital
Bristol-Myers Squibb
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Principal Investigator: Pei-Jer Chen, M.D., Ph.D. National Taiwan University Hospital Department of Internal Medicine
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Responsible Party: Pei-Jer Chen, National Taiwan University Hospital Identifier: NCT00597259    
Other Study ID Numbers: 200710028M
No other ID
First Posted: January 18, 2008    Key Record Dates
Last Update Posted: June 29, 2010
Last Verified: June 2010
Keywords provided by National Taiwan University Hospital:
hepatitis B, entecavir, pegylated interferon alfa-2a
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents