Clinical and Basic Research of ETV Plus GM-CSF in Chronic Hepatitis B Patients

March 9, 2022 updated by: Beijing 302 Hospital

Clinical and Basic Research of Relationship Between Hepatitis B Virus Quasi-Species Evolution and Function of Natural Killer Cells With Antiviral Therapy Response in Chronic Hepatitis B Patients

Previous studies indicated that Granulocyte Macrophage-colony Stimulating Factor (GM-CSF) could improve survival rate in patients with acute liver failure and obtain higher HBsAg seroconversion rate when in combination with peg-interferon for chronic hepatitis B (CHB) patients. In this study, investigators will study the clinical effect of entecavir (ETV) plus GM-CSF in patients with CHB compared to ETV monotherapy.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Antiviral treatment plays critical role in treatment of chronic HBV infection. Entecavir, an nucleos(t)ide analogs (NA) targeting the viral polymerase, is widely used in China as the first line drug in antiviral treatment for CHB patients. The sustained suppression of serum HBV DNA to undetectable level has been proven to be associated with the prevention of progression of liver disease and inhibition of the development of hepatocellular carcinoma. According to data published, a rate about 70% HBVDNA undetectable could be reached after 1 year therapy. However, the rate of HBsAg loss is very low about 0% to 1%. Granulocyte-macrophage colony-stimulating factor(GM-CSF) is an important cytokine for the generation and propagation of antigen-presenting cells and for priming a cellular immune response. It increases the production of macrophage precursors and, in turn,enhances the T-helper cell (Th cell)-mediated cytotoxicity and regulates the tumoricidal cytokines. Previous studies indicated that when combined with IFN in patients with chronic HBV infection, it increased the therapeutic efficacy of the latter. Recent studies showed that GM-CSF benefit patients with acute liver failure. In this study, entecavir (ETV) plus GM-CSF would be used in patients with CHB compared to ETV monotherapy. Primary objective of the study is to see if there is significant improvement in HBsAg loss, rates of HBeAg loss and HBV undetectable are also to be observed. Function of NK cell from the patients enrolled will be measured during the therapy.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Not Applicable

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
      • Beijing, Beijing, China, 100039
        • 302 Military 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 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • HBsAg positive for more than 6 months
  • HBeAg positive
  • ALT≥80U/L or inflammation score ≥2 of histological examination

Exclusion Criteria:

  • History of drug allergy to GM-CSF
  • coinfection with HCV, HIV, HAV, HEV
  • liver cirrhosis or CHILD score >7
  • diagnosis of hepatocellular carcinoma or AFP>100ng/ml
  • Allergic thrombocytopenic purpura

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ETV+GM-CSF
Entecavir (ETV) plus Granulocyte Macrophage-colony Stimulating Factor (GM-CSF). ETV was given 0.5mg/d, oral; GM-CSF was given 100ug, the 3th, 4th, 5th day at week1, 4, 12, 24, 48, subcutaneous injection.
Drug: Granulocyte Macrophage-colony Stimulating Factor
The intervention drug was used as an immunomodulator in order to improve rates of HBsAg loss and HBeAg loss.
Other Names:
  • GM-CSF
Drug: Entecavir
Antiviral drug for hepatitis b virus (HBV)
Other Names:
  • ETV
Active Comparator: ETV monotherapy
As standard antiviral therapy, Entecavir was given 0.5mg/d, oral.
Drug: Entecavir
Antiviral drug for hepatitis b virus (HBV)
Other Names:
  • ETV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Rate of HBsAg loss
Time Frame: 48 weeks after therapy
48 weeks after therapy

Secondary Outcome Measures

Outcome Measure
Time Frame
Rate of HBeAg loss
Time Frame: 48 weeks after therapy
48 weeks after therapy
HBVDNA undetectable rate
Time Frame: 48 weeks after therapy
48 weeks after therapy

Collaborators and Investigators

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

Sponsor

Beijing 302 Hospital

Investigators

  • Study Director: Ping Zhao, Director, 302 Military Hospital, Beijing, China

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 (Actual)

January 1, 2017

Primary Completion (Actual)

January 1, 2018

Study Completion (Actual)

December 1, 2021

Study Registration Dates

First Submitted

November 15, 2016

First Submitted That Met QC Criteria

May 23, 2017

First Posted (Actual)

May 24, 2017

Study Record Updates

Last Update Posted (Actual)

March 24, 2022

Last Update Submitted That Met QC Criteria

March 9, 2022

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 首发2014-2-5033

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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