A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) Plus Entecavir in Treatment-Naive Patients With HBeAg-Positive Chronic Hepatitis B.

A Randomized, Open Label Study of the Effect of Peginterferon Alfa-2a (40KD) (PEGASYS®) Plus Entecavir (Baraclude®) Combination Therapy on Quantitative Changes in HBeAg in Treatment-naive Patients With HBeAg Positive Chronic Hepatitis B

This 3 arm study will assess the efficacy and safety of PEGASYS + entecavir combination therapy in treatment-naive patients with HBeAg positive chronic hepatitis B. Patients will be randomized to receive 1)PEGASYS 180 micrograms s.c./week for 48 weeks, 2)PEGASYS 180 micrograms s.c./week for 48 weeks + entecavir 0.5mg p.o. once daily from week 13 to week 36 or 3) entecavir 0.5mg p.o. once daily for 24 weeks + PEGASYS 180 micrograms s.c./week from week 21 to 68. Treatment will be followed by 24 weeks treatment-free follow up. The anticipated time on study treatment is 3-12 months for groups 1 and 2, and 1-2 years for group 3, and the target sample size is 100-500 individuals.

Study Overview

• Status: Completed
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: peginterferon alfa-2a [Pegasys]; Drug: peginterferon alfa-2a [Pegasys]; Drug: Entecavir; Drug: Entecavir

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100011
  • Hangzhou, China, 310003
  • Shanghai, China, 200021
  • Shanghai, China, 200025
  • Shanghai, China, 200235
  • Xi'an, China, 710038
  • Zhengzhou, China, 450052
• Hong Kong
  • Hong Kong, Hong Kong

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 patients, 18-65 years of age;
• HBsAg positive, HBeAg positive and anti-HBe negative for at least 6 months, anti-HBs negative;
• absence of cirrhosis confirmed by liver biopsy in previous 12 months.

Exclusion Criteria:

• previous treatment for chronic hepatitis B within previous 6 months;
• antiviral, anti-neoplastic or immunomodulatory treatment in previous 6 months;
• co-infection with active hepatitis A, hepatitis C, hepatitis D or HIV;
• history or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2	Drug: peginterferon alfa-2a [Pegasys]; 180 micrograms sc/week for 48 weeks; Drug: peginterferon alfa-2a [Pegasys]; 180 micrograms sc/week from week 21 to week 68; Drug: Entecavir; 0.5mg po daily for 24 weeks; Drug: Entecavir; 0.5mg po daily from week 13 to week 36
Experimental: 3	Drug: peginterferon alfa-2a [Pegasys]; 180 micrograms sc/week for 48 weeks; Drug: peginterferon alfa-2a [Pegasys]; 180 micrograms sc/week from week 21 to week 68; Drug: Entecavir; 0.5mg po daily for 24 weeks; Drug: Entecavir; 0.5mg po daily from week 13 to week 36
Active Comparator: 1	Drug: peginterferon alfa-2a [Pegasys]; 180 micrograms sc/week for 48 weeks; Drug: peginterferon alfa-2a [Pegasys]; 180 micrograms sc/week from week 21 to week 68

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Log change in quantitative HBeAg from baseline to 24 weeks after end of treatment.	Week 72 for Arms 1 and 2. Week 92 for Arm 3.

Secondary Outcome Measures

Outcome Measure	Time Frame
HBeAg seroconversion, HBV-DNA <1000 copies/mL, loss of HBeAg, HBV DNA reduction, ALT normalization, loss of HBsAg seroconversion, reduction of HBsAg 24 weeks after end of treatment.	Week 72 for Arms 1 and 2. Week 92 for Arm 3.
AEs, laboratory parameters.	Throughout study

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Xie Q, Zhou H, Bai X, Wu S, Chen JJ, Sheng J, Xie Y, Chen C, Chan HL, Zhao M. A randomized, open-label clinical study of combined pegylated interferon Alfa-2a (40KD) and entecavir treatment for hepatitis B "e" antigen-positive chronic hepatitis B. Clin Infect Dis. 2014 Dec 15;59(12):1714-23. doi: 10.1093/cid/ciu702. Epub 2014 Sep 4.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: January 30, 2008
• First Submitted That Met QC Criteria: February 11, 2008
• First Posted (Estimate): February 13, 2008

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 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; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Immunologic Factors; Interferon-alpha; Peginterferon alfa-2a; Entecavir
• Other Study ID Numbers: ML20742

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No