A Study to Evaluate Efficacy and Safety of Peginterferon Alfa-2a (Pegasys) and Adeforvir Dipivoxil (ADV) in Participants With Lamivudine-Resistant Hepatitis B e Antigen (HBeAg)-Positive Chronic Hepatitis B

A Randomized, Open-label Study Evaluating the Efficacy and Safety of Peginterferon Alfa-2a (40KD) (PEGASYS®) or Adefovir Dipivoxil (ADV) in Patients With Lamivudine-resistant HBeAg Positive Chronic Hepatitis B

This study will evaluate the efficacy and safety of peginterferon alfa-2a or ADV, in participants with lamivudine-resistant HBeAg-positive chronic hepatitis B. Participants will be randomized to receive either peginterferon alfa-2a for 48 weeks in combination with oral lamivudine for the first 12 weeks, or ADV for 72 weeks in combination with oral lamivudine for the first 12 weeks. The anticipated time on study treatment is 72 weeks, and the target sample size is 255 individuals.

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: Adefovir dipivoxil; Drug: Lamivudine; Drug: Peginterferon alfa-2a

• Study Type: Interventional
• Enrollment (Actual): 255
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
  • Beijing, China, 100050
  • Beijing, China, 100054
  • Chongqing, China, 400038
  • Guangzhou, China, 510515
  • Hangzhou, China, 310003
  • Jinan, China, 250021
  • Shanghai, China, 200025
  • Shanghai, China, 200040
  • Shanghai, China, 201508
• Hong Kong
  • Hong Kong, Hong Kong
  • Hong Kong, Hong Kong, 852

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult participants 18-65 years of age
• Hepatitis B surface antigen (HBsAg)-positive, HBeAg-positive, and anti-HBs-negative for greater than or equal to (>=) 6 months
• Receiving lamivudine currently, and for >=6 months
• hepatitis B virus (HBV)-deoxyribonucleic acid (DNA) decreased >=2 log during lamivudine treatment on >=1 occasion
• Absence of cirrhosis confirmed by liver biopsy in previous 6 months

Exclusion Criteria:

• Other drugs with activity against HBV within the prior 6 months, except lamivudine
• Antiviral, anti-neoplastic, or immunomodulatory therapy less than or equal to (<=) 6 months before study - Active infection with hepatitis A, C, or D virus, or human immunodeficiency virus
• Decompensated liver disease
• Medical condition associated with another chronic liver disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ADV + Lamivudine; Participants will receive ADV and lamivudine tablets at a dose of 10 mg orally QD for first 12 weeks followed by ADV for 60 weeks.	Drug: Adefovir dipivoxil; ADV will be administered orally at a dose of 10 mg QD for 72 weeks.; Drug: Lamivudine; Lamivudine tablets will be administered orally at a dose of 10 mg QD for 12 weeks.
Experimental: Peginterferon alfa-2a + Lamivudine; Participants will receive peginterferon alfa-2a injection at a dose of 180 micrograms (mcg) once weekly (QW) and 100 milligrams (mg) lamivudine tablets orally once daily (QD) for first 12 weeks followed by peginterferon alfa-2a for 36 weeks.	Drug: Lamivudine; Lamivudine tablets will be administered orally at a dose of 10 mg QD for 12 weeks.; Drug: Peginterferon alfa-2a; Peginterferon alfa-2a injection will be administered at a dose of 180 mcg QW for 48 weeks.; Other Names: Pegasys

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
HBeAg seroconversion (defined as loss of HBeAg and presence of anti-HBe) at Week 72	Week 72

Secondary Outcome Measures

Outcome Measure	Time Frame
Loss of HBeAg	Week 48, and 72
Reduction in hepatitis B virus deoxyribonucleic acid (HBV DNA)	Week 48, and 72
Alanine transaminase (ALT) normalization	Week 48, and 72
Hepatitis B surface antigen (HBsAg) seroconversion	Week 48, and 72

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: November 4, 2015
• First Submitted That Met QC Criteria: November 4, 2015
• First Posted (Estimate): November 5, 2015

Study Record Updates

• Last Update Posted (Estimate): February 2, 2016
• Last Update Submitted That Met QC Criteria: February 1, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Peginterferon alfa-2a; Lamivudine; Adefovir; Adefovir dipivoxil
• Other Study ID Numbers: ML18376