A Clinical Trial on Hepatitis B Vaccine Activated-Dendritic Cells Combined With Anti-HBV Drugs in CHB

Phase 1

• Conditions: Chronic Hepatitis B
• Interventions: Biological: HPDC-T cells & Entecavir; Drug: HPDC-T cells & IFN-a-2a; Drug: IFN-a-2a; Drug: HPDC-T cells & Telbivudine; Drug: Telbivudine; Drug: Entecavir

• Registration Number: NCT02615639
• Lead Sponsor: Third Affiliated Hospital, Sun Yat-Sen University

Brief Summary

The anti-virus effects is not satisfying in some of Chronic Hepatitis B（CHB) patients who have been on anti-Hepatitis B Virus (HBV) drugs therapy. Dendritic cell (DC) is critical in Hepatitis B Virus (HBV) specific immunity in the process of producing HBV promoter specific cytotoxic T cells (CTLs) and specific T helper cells (HTLs), however they are defective in CHB patients. Therefore, if it were going to remove HBV completely, it mainly depends if the body itself can produce enough HBV specific cytotoxic T cells (CTLs) and specific T helper cells (HTLs). Our research is to plus Hepatitis B Vaccine Activated-DCs therapy to CHB patients who have been on anti-HBV drugs but with poor effects, supposing to significantly improve anti-HBV efficacy, even to clean HBV from the patients.

Detailed Description

Patients who have been on anti-HBV therapy Complying with the inclusion criteria will be enrolled into our research, Nucleoside analogues (NAs,entecavir） treatment for more than 1 year or interferon（IFN)-a-2a (IFN-a-2a,Pegasys） treatment for more than 24 weeks. The patients will be randomly assigned to experimental group and control group with the ratio of 2:1, one group (control group) will go on receive the anti-HBV drugs treatment solely; another group (experimental group) after enrollment will immediately receive the Hepatitis B Vaccine activated-DCs (HPDC-T cells) for 24 weeks (every 2 weeks once for 24 weeks, 12 times in total), at the same time co-use anti-HBV drugs treatment, as for Pegasys, it will go on to be used for 12 weeks after HPDC-T cells treatment completed.

The technical route of HBV-T cells prepared: First, investigators collect fresh blood of CHB, mononuclear cells were isolated, and induced to HBsAg pulsed DCs in Hepatitis B vaccine (Shenzhen kangtai, Shenzhen, China) and interleukin-4（IL-4)/granulocyte-macrophage colony-stimulating factor(GM-CSF） (Perprotech, New Jersey, USA) (7 days), then co-culture of DCs and Peripheral Blood Mononuclear Cell(PBMCs ）7days, obtain HBV specific T cells, return to the patient finally.

Study Timeline

• Status Verified: 2015-11
• Study Start: 2015-11
• Study First Submitted: 2015-11-12
• Study First Submitted QC: 2015-11-24
• Last Update Submitted: 2015-11-24
• Study First Posted: 2015-11-26
• Last Update Posted: 2015-11-26
• Primary Completion: 2018-11
• Study Completion: 2018-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

• chronic hepatitis B patients, aged 18~65，Chinese
• have been on entecavir（ETV） or telbivudine（LDT） treatment for more than 1 year,and HBV DNA<100 IU/ml（Roche Cobas）;or have been on
• have been on PEG-IFN treatment for more than 24 weeks,and 20 < HBV DNA < 20000 IU/ml（Roche Cobas）.
• HBsAg 100~5000 IU/ml
• HBeAg 10~500 COI

Exclusion Criteria

• Superinfection or co-infection with hepatitis A, C, D, E, cytomegalovirus and HIV, or Epstein-Barr virus;
• other liver diseases such as alcoholic liver disease, drug-induced hepatitis, Wilson disease and autoimmune hepatitis;
• ascites or gastrointestinal bleeding or peptic ulcer or esophageal varix by electronic gastroscope examination;
• liver cirrhosis (including compensated and decompensated cirrhosis) and liver failure;
• severe bacterial or fungal infections;
• a history of diabetes or cardiac disease or hypertension or nephrosis;
• pregnant women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HPDC-T cells & entecavir	HPDC-T cells & Entecavir	HPDC-T cells 1-5×10\^5 intravenous injection, every 2 weeks for 24 weeks , and entecavir(ETV) 0.5mg tablet by mouth, every night.
HPDC-T cells & IFN-a-2a	HPDC-T cells & IFN-a-2a	HPDC-T cells 1-5×10\^5 intravenous injection, every 2 weeks for 24 weeks ,and IFN-a-2a 180ug subcutaneous injection， every week for 9 months.
IFN-a-2a	IFN-a-2a	IFN-a-2a 180ug subcutaneous injection， every week for 9 months.
HPDC-T cells & Telbivudine	HPDC-T cells & Telbivudine	HPDC-T cells 1-5×10\^5 intravenous injection, every 2 weeks for 24 weeks ,and Telbivudine 600mg tablet by mouth, every night.
Telbivudine	Telbivudine	Telbivudine 600mg tablet by mouth, every night.
entecavir	Entecavir	entecavir 0.5mg tablet by mouth, every night.

Primary Outcome Measures

Name	Time	Method
Hepatitis B surface Antigen （HBeAg）seroconversion	3 years	to increase Hepatitis B surface antigen (HBsAg) loss rate from 1% up to 11% or more

Secondary Outcome Measures

Name	Time	Method
HBV DNA clearance	3 years	to increase the undetectable rate of HBV DNA
ALT recovery	3 years	to increase the recovery rate of ALT
Number of participants with treatment-related adverse events as assessed by low-grade fever, Infection and shock.	one and a half year	Safety profiles include side effects of anti-HBV drugs(ETV,LDT and IFN-a), viral resistance of anti-HBV drugs. And side effects of HPDC-T cells infusion,such as low-grade fever, Infection and shock.The difference of side effects rates between anti-HBV drugs monotherapy and anti-HBV drugs plus HPDC-T cells combined therapy will also be analyzed.
Hepatitis B envelope Antigen （HBeAg） seroconversion	3 years	to increase HBeAg negative rate by 12 percentage points on the basis of the existing data