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

Hepatitis B, Chronic Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03164889
• Other study ID #: ??2014-2-5033
• Status: Terminated
• Phase: N/A
• Start date: January 2017
• Est. completion date: December 1, 2021

Study information

• Verified date: January 2017
• Source: Beijing 302 Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 80
• Est. completion date: December 1, 2021
• Est. primary completion date: January 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

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.
• Entecavir
Antiviral drug for hepatitis b virus (HBV)

Locations

Country	Name	City	State
China	302 Military Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing 302 Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of HBsAg loss		48 weeks after therapy
Secondary	Rate of HBeAg loss		48 weeks after therapy
Secondary	HBVDNA undetectable rate		48 weeks after therapy