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

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
105

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Sa Lv, MD
  • Phone Number: 2014.12 86-10-63879735
  • Email: lvsa@sina.com

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
the rates of HBeAg seroconversion
Time Frame: at week 72
at week 72

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2011

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2016

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 30, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 21, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 24, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 17, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 14, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2011030D

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