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

Not Applicable

Terminated

• Conditions: Hepatitis B, Chronic
• Interventions: Drug: Granulocyte Macrophage-colony Stimulating Factor; Drug: Entecavir

• Registration Number: NCT03164889
• Lead Sponsor: Beijing 302 Hospital

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.

Study Timeline

• Study First Submitted: 2016-11-15
• Status Verified: 2017-01
• Study Start: 2017-01
• Study First Submitted QC: 2017-05-23
• Study First Posted: 2017-05-24
• Primary Completion: 2018-01-01
• Study Completion: 2021-12-01
• Last Update Submitted: 2022-03-09
• Last Update Posted: 2022-03-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 80

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ETV+GM-CSF	Entecavir	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.
ETV+GM-CSF	Granulocyte Macrophage-colony Stimulating Factor	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.
ETV monotherapy	Entecavir	As standard antiviral therapy, Entecavir was given 0.5mg/d, oral.

Primary Outcome Measures

Name	Time	Method
Rate of HBsAg loss	48 weeks after therapy

Secondary Outcome Measures

Name	Time	Method
HBVDNA undetectable rate	48 weeks after therapy
Rate of HBeAg loss	48 weeks after therapy

Trial Locations

Locations (1)

302 Military Hospital; 🇨🇳 Beijing, Beijing, China