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

NCT ID: NCT03164889

Last Updated: 2022-03-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2021-12-01

Brief Summary

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.

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.

Conditions

Hepatitis B, Chronic

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Granulocyte Macrophage-colony Stimulating Factor

Intervention Type: DRUG

The intervention drug was used as an immunomodulator in order to improve rates of HBsAg loss and HBeAg loss.

Entecavir

Intervention Type: DRUG

Antiviral drug for hepatitis b virus (HBV)

ETV monotherapy

As standard antiviral therapy, Entecavir was given 0.5mg/d, oral.

Group Type: ACTIVE_COMPARATOR

Entecavir

Intervention Type: DRUG

Antiviral drug for hepatitis b virus (HBV)

Interventions

Granulocyte Macrophage-colony Stimulating Factor

The intervention drug was used as an immunomodulator in order to improve rates of HBsAg loss and HBeAg loss.

Intervention Type: DRUG

Entecavir

Antiviral drug for hepatitis b virus (HBV)

Intervention Type: DRUG

Other Intervention Names

GM-CSF; ETV

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing 302 Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ping Zhao, Director

Role: STUDY_DIRECTOR

302 Military Hospital, Beijing, China

Locations

302 Military Hospital

Beijing, Beijing Municipality, China

Countries

China

Other Identifiers

首发2014-2-5033

Identifier Type: -

Identifier Source: org_study_id