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

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

Status

Terminated

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03164889

Enrollment

Registered

2017-05-24

Start date

2017-01-31

Completion date

2021-12-01

Last updated

2022-03-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hepatitis B, Chronic

Keywords

Chronic hepatitis B, antiviral treatment

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.

Interventions

DRUGGranulocyte Macrophage-colony Stimulating Factor

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

DRUGEntecavir

Antiviral drug for hepatitis b virus (HBV)

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
Rate of HBsAg loss	48 weeks after therapy

Secondary

Measure	Time frame
Rate of HBeAg loss	48 weeks after therapy
HBVDNA undetectable rate	48 weeks after therapy

Countries

China

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026