PegIntron Versus Adefovir in the Treatment of Chronic Hepatitis B (CHB) e Antigen Positive Patients in Taiwan (P04498/MK-4031-278)

Phase 3

Completed

• Conditions: Hepatitis B, Chronic (CHB)
• Interventions: Biological: Pegylated interferon alfa-2b (PegIntron); Drug: Adefovir dipivoxil (adefovir)

• Registration Number: NCT00371761
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

This is an open label, randomized, comparative, multi-center study. Subjects will be screened within 2 weeks prior to study entry to establish eligibility. Subjects who meet all the selection criteria will be randomly assigned 1:1 to (1) once-a-week, subcutaneous Pegylated interferon alfa-2b (PegIntron) (1.5 mcg/kg body weight) or (2) oral adefovir 10 mg daily. The treatment phase will be 24 weeks for PegIntron and 48 weeks for adefovir. All subjects completing the assigned treatment phase will be followed up for an additional 48 weeks for PegIntron and 24 weeks for adefovir as observation phase. The primary objective is to establish the efficacy profile of PegIntron. Secondary objectives are to compare the efficacy profile of PegIntron with that of adefovir, compare efficacy of PegIntron in lamivudine-naïve and lamivudine-experienced subjects, and to establish the safety profile of PegIntron in treating patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2006-08-31
• Study First Submitted QC: 2006-08-31
• Study Start: 2006-09
• Study First Posted: 2006-09-04
• Primary Completion: 2009-02
• Study Completion: 2009-02
• Results First Submitted: 2010-07-15
• Results First Submitted QC: 2010-11-18
• Results First Posted: 2010-12-15
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-08
• Last Update Posted: 2017-04-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

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

• Documented positive serum hepatitis B surface antigen (HBsAg) for a minimum of 6 months prior to randomization.

• Hepatitis B virus (HBV) replication and hepatitis documented by:

  • Serum HBV DNA (Hepatitis B Virus Deoxyribonucleic acid) >= 10^5 copies/mL within 3 months prior to entry
  • Positive serum hepatitis B e antigen (HBeAg) within 3 months prior to entry
  • Documented presence of ALT (Alanine Aminotransferase) twice (1 month apart) 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, document acceptable if no anti-HBV treatment within 1 year prior to randomization
  • Naïve or exposed to lamivudine (3 months treatment-free interval prior to randomization)
  • Adequate renal function (creatinine within normal upper limit).

• Compensated liver disease with certain minimum hematological and serum biochemical criteria.

• Thyroid stimulating hormone (TSH) and free T4 within normal ranges.

• Negative antibody to hepatitis C and hepatitis D.

• Negative antibody to human immunodeficiency virus.

• Negative evidence for hepatocellular carcinoma by alfa-fetoprotein and ultrasound within 1 month prior to randomization.

Exclusion Criteria

• Women who are pregnant or nursing.
• Prior treatment for hepatitis with any interferon or adefovir, or other investigational anti-virus agents.
• Prior treatment for hepatitis with immunomodulatory drug within 2 years prior to randomization.
• Suspected hypersensitivity to interferon or adefovir.
• Liver cirrhosis.
• History of severe psychiatric disease, especially depression.
• Concurrent malignancies (including hepatocellular carcinoma).
• Unstable or significant cardiovascular diseases.
• Prolonged exposure to known hepatotoxins.
• History of thyroid disease poorly controlled on prescribed medication.
• Poorly controlled diabetes mellitus.
• Have suspected or confirmed significant hepatic disease from an etiology other than HBV.
• Severe renal disease or myeloid dysfunction.
• History of organ transplantation other than cornea and hair transplant.
• Any medical condition requiring chronic systemic administration of steroids.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PegIntron	Pegylated interferon alfa-2b (PegIntron)	PegIntron, 1.5 micrograms/kg weekly, for up to 24 weeks followed by a 48-week observation phase
Adefovir	Adefovir dipivoxil (adefovir)	Adefovir, 10 mg daily, for up to 48 weeks followed by a 24-week observation phase

Primary Outcome Measures

Name	Time	Method
Number of Participants With a Combined Response Consisting of All Three Responses - (a) Serological Response, (b) Virological Response, and (c) Biochemical Response	At Week 72 [for Pegylated interferon alfa-2b (PegIntron), at 48 weeks post PegIntron treatment for up to 24 weeks; for Adefovir, at 24 weeks post adefovir treatment for up to 48 weeks]	1. Serological response is defined as Loss of HBeAg (Hepatitis B e antigen) and Appearance of anti-HBe (Hepatitis B e antibodies); participant is HBeAg negative and anti-HBe positive.; 2. Virological response was defined as having \< 10\^5 copies/mL of serum HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid) by real-time PCR (Polymerase Chain Reaction).; 3. Biochemical response was defined as acheiving normal levels of ALT (Alanine Aminotransferase) level in Units/L.