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

NCT00597259 | Unknown Phase 4

• 2 other identifiers: 200710028MNo other ID
• Study Type: interventional
• Target: 294
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Hepatitis B

Keywords

hepatitis B, entecavir, pegylated interferon alfa-2a

Outcome Measures

Primary Outcomes (1)

• HBeAg seroconversion

  at the end of 24 weeks post-treatment follow-up

Secondary Outcomes (1)

• Serum ALT normalization, HBeAg loss, serum HBV DNA disappearance, HBsAg disappearance, histologic change, entecavir resistance

  At the end of treatment and 24 weeks after end of treatment

Study Arms (2)

A

EXPERIMENTAL

Drug: Pegasys plus Entecavir

B

ACTIVE COMPARATOR

Entecavir Alone

Drug: Entecavir

Interventions

Pegasys plus Entecavir DRUG

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

A

Entecavir DRUG

ETV 0.5 mg daily monotherapy for 144 weeks

B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Negative serum antibody to hepatitis C (anti-HCV)
• Negative antibody to human immunodeficiency virus (anti-HIV)
• 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.)
• Subject must be willing to give written informed consent and be able to adhere to dose and visit schedules
• Subjects presenting with any of the following will not be included in the study:
• Women who are pregnant or nursing
• Prior treatment for hepatitis with any interferon, NA or other investigational agents
• Prior treatment for hepatitis with immunomodulatory drug within previous 2 years
• Suspected hypersensitivity to interferon
• Have evidence of cirrhosis
• History of severe psychiatric disease, especially depression
• Concurrent malignancies (including hepatocellular carcinoma)
• 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)
• Prolonged exposure to known hepatotoxins such as alcohol or drugs
• History of thyroid disease poorly controlled on prescribed medication

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

National Taiwan University Hospital Department of Internal medicine

Taipei, 100, Taiwan

RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Interventions

peginterferon alfa-2a; entecavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Pei-Jer Chen, M.D., Ph.D.

  National Taiwan University Hospital Department of Internal Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pei-Jer Chen, M.D., Ph.D.

CONTACT

886-2-23123456; peijerchen@ntu.edu.tw

Chun-Jen Liu, M.D., Ph.D.

CONTACT

886-2-23123456; cjliu@ntu.edu.tw

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 9, 2008
• First Posted: January 18, 2008
• Study Start: January 1, 2008
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: June 29, 2010

Record last verified: 2010-06

Locations

TW (1)