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

March 8, 2017 updated by: Merck Sharp & Dohme LLC

An Open-Label, Randomized, Comparative Study With PegIntron vs. Adefovir in the Treatment of Chronic Hepatitis B (CHB) e Antigen Positive Patients in Taiwan

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: PegIntron
PegIntron, 1.5 micrograms/kg weekly, for up to 24 weeks followed by a 48-week observation phase
Powder for injection in vials ( 100, and 120 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for up to 24 weeks
Other Names:
  • SCH 54031, Peg-Intron
ACTIVE_COMPARATOR: Adefovir
Adefovir, 10 mg daily, for up to 48 weeks followed by a 24-week observation phase
10 mg adefovir dipivoxil (equivalent to 5.4.5 mg adefovir) tablets, oral, dose of 1 tablet per day for up to 48 weeks
Other Names:
  • Hepsera

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With a Combined Response Consisting of All Three Responses - (a) Serological Response, (b) Virological Response, and (c) Biochemical Response
Time Frame: 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.
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]

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (ACTUAL)

February 1, 2009

Study Completion (ACTUAL)

February 1, 2009

Study Registration Dates

First Submitted

August 31, 2006

First Submitted That Met QC Criteria

August 31, 2006

First Posted (ESTIMATE)

September 4, 2006

Study Record Updates

Last Update Posted (ACTUAL)

April 6, 2017

Last Update Submitted That Met QC Criteria

March 8, 2017

Last Verified

March 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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