Combination or Sequential Therapy of Peginterferon Alfa-2a and Entecavir for Patients With Chronic Hepatitis B

August 14, 2015 updated by: Beijing 302 Hospital

Combination or Sequential Therapy of Peginterferon Alfa-2a and Entecavir for Hepatitis B e Antigen-positive Patients With Chronic Hepatitis B

Currently, seven medications are approved for the treatment of hepatitis B: two formulations of interferon and five nucleons(t)ide analogues. The current treatment strategy of chronic hepatitis B is now standard: initial selection of entecavir, tenofovir, or peginterferon alfa-2a (peg-IFNα-2a). Interferon is administered for a finite duration while nucleotide analogues are usually administered for many years. But among hepatitis B e antigen （HBeAg） positive patients with high serum hepatitis B virus DNA levels, the rates of virological response are poor. And antiviral drug resistance is a major limiting factor to the success of nucleotide analogue treatment. Therefore, combination therapy using peginterferon with an oral agent with a high genetic barrier to resistance might be superior to standard current monotherapy. However, the addition of lamivudine to peg-IFNα-2a therapy led to a greater decrease in serum HBV DNA levels during treatment but did not increase the rate of HBeAg sero¬conversion. Entecavir is a nucleoside analogue superior to lamivudine and adefovir in achieving higher virological response, histological improvement and normalisation of ALT. Moreover, Entecavir has a high genetic barrier with a very low incidence of drug resistance. This study is aimed to investigate the efficacy of combination or sequential therapy using peg-IFNα-2a and entecavir in HBeAg-positive chronic hepatitis B(CHB) patients.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

105

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China, 100039
        • Recruiting
        • Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital
        • Contact:
          • Sa Lv, MD
          • Phone Number: 2015.12 86-10-63879735
          • Email: lvsa@sina.com

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

16 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age≥16 years
  2. HBsAg positive for more than 6 months, and HBeAg detection is positive for two times in 6 months before enrollment
  3. Serum HBVDNA >2×10^4IU/ml
  4. 80U/L < serum ALT < 400U/L, and TBIL < 34 umol/L
  5. Serum ALT < 80U/L, but hepatic inflammation scores ≥ G2 or hepatic fibrosis stage ≥ S3

Exclusion Criteria:

  1. Co-infected with HCV, HDV or HIV, or autoimmune liver diseases combined
  2. Hepatic decompensation
  3. received antiviral therapy or immunosuppressant drugs before 6 months prior to enrollment
  4. Blood routine examination: WBC <3×10^9/L，neutrophile granulocyte < 1.5×10^9/L，PLT <80×10^9/L
  5. Renal function: creatinine >1.5 times of upper normal limit
  6. Alcoholism or a history of addiction and abuse
  7. Combined with hepatocarcinoma

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 Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Peg-IFNα-2a monotherapy
Participants will receive 180ug peg-IFNα-2a therapy for 72 weeks, and then followed to 96 weeks.
Drug: Peg-IFNα-2a
180ug peg-IFNα-2a, subcutaneous injection per week
Other Names:
  • peginterferon alfa-2a
Experimental: Sequential therapy
Participants will receive entecavir monotherapy for 12 weeks, and 180ug peg-IFNα-2a therapy is added for the following 12 weeks. After that, entecavir will be stopped and 180ug peg-IFNα-2a monotherapy for the following 48 weeks. All participants will followed to 96 weeks.
Drug: Peg-IFNα-2a
180ug peg-IFNα-2a, subcutaneous injection per week
Other Names:
  • peginterferon alfa-2a
Drug: Entecavir
0.5mg,oral administration every day
Other Names:
  • Baraclude
Experimental: Combination therapy
Participants will receive 180ug peg-IFNα-2a combined with entecavir therapy for 72 weeks, and then followed to 96 weeks.
Drug: Peg-IFNα-2a
180ug peg-IFNα-2a, subcutaneous injection per week
Other Names:
  • peginterferon alfa-2a
Drug: Entecavir
0.5mg,oral administration every day
Other Names:
  • Baraclude

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
the rates of HBeAg seroconversion
Time Frame: at week 72
at week 72

Secondary Outcome Measures

Outcome Measure
Time Frame
normalisation of ALT
Time Frame: at week 2、4、12、24、36、48、60、72、84、96
at week 2、4、12、24、36、48、60、72、84、96
liver histological improvement
Time Frame: at baseline and at week 72
at baseline and at week 72
The rates of HBsAg negative
Time Frame: at week12、24、36、48、60、72、84、96
at week12、24、36、48、60、72、84、96
the rate of virological response
Time Frame: at week 4、12、24、36、48、60、72、84、96
at week 4、12、24、36、48、60、72、84、96
the rate of HBeAg negative
Time Frame: at week 12、24、36、48、60、72、84、96
at week 12、24、36、48、60、72、84、96

Collaborators and Investigators

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

Sponsor

Beijing 302 Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

July 1, 2011

Primary Completion (Anticipated)

July 1, 2016

Study Completion (Anticipated)

July 1, 2016

Study Registration Dates

First Submitted

May 30, 2013

First Submitted That Met QC Criteria

July 21, 2013

First Posted (Estimate)

July 24, 2013

Study Record Updates

Last Update Posted (Estimate)

August 17, 2015

Last Update Submitted That Met QC Criteria

August 14, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011030D

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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