Clinical trial NCT03164889: Clinical and Basic Research of ETV Plus GM-CSF in Chronic Hepatitis B Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Hepatitis B, Chronic
Keywords: Chronic hepatitis B, antiviral treatment
Lead sponsor: Beijing 302 Hospital
Sponsor class: OTHER
First posted: 2017-05-24
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: 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.

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

Primary outcomes:
measure: Rate of HBsAg loss
timeFrame: 48 weeks after therapy
Secondary outcomes:
measure: Rate of HBeAg loss
timeFrame: 48 weeks after therapy
measure: HBVDNA undetectable rate
timeFrame: 48 weeks after therapy
Other outcomes:
Locations:
city: Beijing
country: China
facility: 302 Military Hospital
state: Beijing
Study officials:
affiliation: 302 Military Hospital, Beijing, China
name: Ping Zhao, Director
role: STUDY_DIRECTOR
References: