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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Biological: HPDC-T cells & Entecavir
* Drug: Entecavir
* Drug: HPDC-T cells & IFN-a-2a
* Drug: IFN-a-2a
* Drug: HPDC-T cells & Telbivudine
* Drug: Telbivudine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HPDC-T cells & entecavir<br>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. | Biological: HPDC-T cells & Entecavir<br>* experimental groups will be given HPDC-T cells & Entecavir. HPDC-T cells will be given for 24weeks on the basis of anti-HBV therapy ,and entecavir 0.5mg tablet every night by mouth<br>* Other names: Hepatitis B Vaccine Activated-DCs & Entecavir;|
| Active Comparator: entecavir<br>entecavir 0.5mg tablet by mouth, every night. | Drug: Entecavir<br>* 0.5mg tablet every night by mouth<br>* Other names: Baraclude;|
| Experimental: HPDC-T cells & IFN-a-2a<br>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. | Drug: HPDC-T cells & IFN-a-2a<br>* experimental groups will be given HPDC-T cells & IFN-a-2a. HPDC-T cells will be given for 24 weeks on the basis of anti-HBV therapy ,and IFN-a-2a 180ug subcutaneous injection every week<br>* Other names: Hepatitis B Vaccine Activated-DCs & Pegasys;|
| Active Comparator: IFN-a-2a<br>IFN-a-2a 180ug subcutaneous injection， every week for 9 months. | Drug: IFN-a-2a<br>* IFN-a-2a 180ug subcutaneous injection every week<br>* Other names: Pegasys;|
| Experimental: HPDC-T cells & Telbivudine<br>HPDC-T cells 1-5×10^5 intravenous injection, every 2 weeks for 24 weeks ,and Telbivudine 600mg tablet by mouth, every night. | Drug: HPDC-T cells & Telbivudine<br>* experimental groups will be given HPDC-T cells & Telbivudine. HPDC-T cells will be given for 24weeks on the basis of anti-HBV therapy ,and Telbivudine 600mg tablet every day by mouth<br>* Other names: Hepatitis B Vaccine Activated-DCs & Telbivudine;|
| Active Comparator: Telbivudine<br>Telbivudine 600mg tablet by mouth, every night. | Drug: Telbivudine<br>* Telbivudine 600mg tablet every day by mouth<br>* Other names: LDT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatitis B surface Antigen （HBeAg）seroconversion | to increase Hepatitis B surface antigen (HBsAg) loss rate from 1% up to 11% or more | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by low-grade fever, Infection and shock. | 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. | one and a half year | 
| Hepatitis B envelope Antigen （HBeAg） seroconversion | to increase HBeAg negative rate by 12 percentage points on the basis of the existing data | 3 years | 
| HBV DNA clearance | to increase the undetectable rate of HBV DNA | 3 years | 
| ALT recovery | to increase the recovery rate of ALT | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPDC-T cells, CHB, immuno therapy