Switch or Sequential Combination Therapy of Peginterferon in Hepatitis B Patients With Longterm Entecavir Therapy

October 27, 2015 updated by: Wen-hong Zhang, Huashan Hospital

Efficacy of Switch or Sequential Combination Therapy of Pegylated Interferon Alfa-2a in Chronic Hepatitis B Patients With Low HBsAg and HBeAg Titers After Long-term Entecavir Therapy: A Multicenter, Prospective Cohort Study

This is a multicenter, prospective cohort study to evaluate the efficacy and safety of sequential combination or switch therapy of pegylated interferon alfa-2a in chronic hepatitis B patients with low HBsAg and HBeAg titers after long-term entecavir therapy, and compared to those who continued on ETV therapy.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Chronic hepatitis B (CHB) infection remains a global health treat. The ideal end point of therapy is HBsAg loss or HBsAg seroconversion, indicating a complete remission of CHB. In patients with HBeAg-positive CHB, sustained HBeAg seroconversion is also a desirable end point. Current therapies include pegylated interferon (PegIFN) finite and nucleos(t)ide analogues (NUCs) longterm therapy. However, only 30-40% of patients may achieve HBeAg seroconversion on PegIFN monotherapy, whereas 15-20% of patients on entecavir (ETV). Recently, accumulating evidence had shown that optimization of switching or combining PegIFN in patients on long-term ETV therapy may increase rate of HBeAg seroconversion and even lead to the complete eradication of HBV. However, these two regimens has not been tested adequately in patients with low HBsAg/HBeAg titers on long-term ETV therapy.

This is a multicenter, prospective cohort study to evaluate the efficacy and safety of sequential combination or switch therapy of pegylated interferon alfa-2a in chronic hepatitis B patients with low HBsAg and HBeAg titers after long-term entecavir therapy, and compared to those who continued on ETV therapy.

Study Type

Observational

Enrollment (Anticipated)

294

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
    • Anhui
      • Hefei, Anhui, China
        • The first affiliated hospital, anhui medical university
      • Hefei, Anhui, China
        • The second affiliated hospital, anhui medical university
    • Beijing
      • Beijing, Beijing, China
        • Beijing Ditan Hospital
    • Fujian
      • Fuzhou, Fujian, China
        • Fuzhou Municipal Infectious Disease Hospital
    • Guangdong
      • Guangzhou, Guangdong, China
        • Zhongshan No.2 People's Hospital, Zhongshan, Guangdong
      • Shenzhen, Guangdong, China
        • The Third People's Hospital of Shenzhen
    • Hebei
      • Shijiazhuang, Hebei, China
        • The Third Hospital of Hebei Medical University
    • Jiangsu
      • Suzhou, Jiangsu, China
        • Fifth People's Hospital of Suzhou
      • Xuzhou, Jiangsu, China
        • The Affiliated Hospital of Xuzhou Medical College
    • Liaoning
      • Shenyang, Liaoning, China
        • Shenyang Municipal Infectious Disease Hospital
    • Shandong
      • Jinan, Shandong, China
        • Shandong Provincial Hospital of Shandong University
    • Shanxi
      • Xi'an, Shanxi, China
        • The First Affiliated Hospital Medical School of Xi'an Jiaotong University
    • Sichuan
      • Luzhou, Sichuan, China, 646000
        • The Affiliated Hospital of Luzhou Medical College
      • Sichuan, Sichuan, China
        • Sichuan Provincial People's Hospital
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • The First Affiliated Hospital, College of Medicine, Zhejiang University
      • Ningbo, Zhejiang, China, 315040
        • The Second Hospital of Yinzhou of Ningbo
      • Rui'an, Zhejiang, China
        • Rui'an People's Hospital

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 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Chronic Hepatitis B Patients with Low HBsAg and HBeAg Titers after Long-term Entecavir Therapy

Description

Inclusion Criteria:

  • Male and female patients > 18 and ≤ 60 years of age;
  • Positive HBsAg for more than 6 months;
  • Patients receiving previous ETV therapy ≥2 years;
  • Patients who have achieved undetectable HBV DNA, HBsAg <1500IU/mL and HBeAg <200S/CO prior to switch or S-C therapy;
  • ALT<=10*ULN and TB<2*ULN;
  • Patients who have been assigned to treatment with PegIFN (S-C or switch) or continuous ETV after previous ETV therapy

Exclusion Criteria:

  • Evidence of decompensated cirrhosis or hepatocellular carcinoma;
  • Serological evidence of co-infection with HCV, HDV or HIV;
  • Pregnant or breast-feeding women;
  • Patients with diseases that might contraindicate to PegIFN therapy including severe psychiatric diseases, immunological diseases, severe retinopathy, thyroid dysfunction, leukocytopenia, thrombopenia, etc
  • Patients receiving concomitant therapy with telbivudine;
  • A history of drug or alcohol abuse;
  • Other conditions that investigates consider not suitable for participate

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Switch group
Patients who have been assigned to pegylated interferon alfa-2a.
Drug: Pegylated interferon alfa-2a
ETV 0.5mg oral daily plus PegIFN alfa-2a 180ug subcutaneous injection weekly for 8 weeks and followed by PegIFN alfa-2a 180ug subcutaneous injection weekly for 40 weeks
Other Names:
  • PegIFN alpha-2a
Sequential combination group (S-C group)
Patients who have been assigned to pegylated interferon alfa-2a plus entecavir.
Drug: Pegylated interferon alfa-2a plus Entecavir
ETV 0.5mg oral daily plus PegIFN alfa-2a 180ug subcutaneous injection weekly for 48 weeks
Other Names:
  • ETV
  • PegIFN alpha-2a
ETV group
Patients who have been assigned to entecavir monotherapy.
Drug: Entecavir
ETV 0.5mg oral daily for 48 weeks
Other Names:
  • ETV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of HBeAg seroconversion
Time Frame: week 72 (24 weeks after 48 weeks of treatment)
Loss of HBeAg and detection of anti-HBe antibodies
week 72 (24 weeks after 48 weeks of treatment)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of HBsAg loss
Time Frame: week 72 (24 weeks after 48 weeks of treatment)
HBsAg loss with or without detection of anti-HBs antibodies
week 72 (24 weeks after 48 weeks of treatment)
Rate of HBV DNA <20IU/mL
Time Frame: week 72 (24 weeks after 48 weeks of treatment)
week 72 (24 weeks after 48 weeks of treatment)
Rate of HBsAg seroconversion
Time Frame: week 72 (24 weeks after 48 weeks of treatment)
week 72 (24 weeks after 48 weeks of treatment)
Percentage of patients reaching a ≥ 1log10 decline of quantitative HBsAg
Time Frame: week 72 (24 weeks after 48 weeks of treatment)
week 72 (24 weeks after 48 weeks of treatment)
Decline of quantitative HBsAg from baseline
Time Frame: week 72 (24 weeks after 48 weeks of treatment
week 72 (24 weeks after 48 weeks of treatment

Collaborators and Investigators

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

Sponsor

Huashan Hospital

Investigators

  • Principal Investigator: Wenhong Zhang, MD, PhD, Huashan Hospital

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

October 1, 2015

Primary Completion (Anticipated)

October 1, 2017

Study Completion (Anticipated)

October 1, 2017

Study Registration Dates

First Submitted

October 25, 2015

First Submitted That Met QC Criteria

October 27, 2015

First Posted (Estimate)

October 28, 2015

Study Record Updates

Last Update Posted (Estimate)

October 28, 2015

Last Update Submitted That Met QC Criteria

October 27, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 81271833

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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