A Clinical Trial on HB-Vac Activated-DCs Combined With Peg-IFN or NAs in CHB

Study Overview
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Brief Summary
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The purpose of this study is to investigate whether HB-Vac Activated-DCs Combined With Peg-IFN or NAs has more efficacy than Peg-IFN or NAs alone in the treatment of chronic hepatitis B patients

Detailed Description
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The 450 patients meeting the entry criteria are divided into 6 groups, the clinical trial procedure is divided into 3 parts, according to the following steps: Part1 (0-12W): The research objects will be grouped according to the principle of a multicenter, randomized, open, parallel controlled clinical trial, 300 cases of cell therapy groups (100 cases with PEG-IFN treatment, LdT treatment for 100 cases, ETV treatment for 100 cases), 150 cases of control groups (PEG-IFN therapy in 50 cases, LdT therapy for 50 cases, ETV treatment for 50 cases). Part2 (12-36W): Cell therapy groups: enter the HBsAg sensitized dendritic cells activated T cells (HBsAg Pulse DCs-T, HPDCs-T) immune therapy combined with interferon (IFN) or nucleoside analogues treatment (NAs), infusion of HPDC-T every 2 weeks for 1 time, total 12 times. Control groups: antiviral therapy used only (IFN or NAs). Part3 (36-72W): The observation stage: discontinuation of interferon in the treatment of 48 weeks; NAs cases will continue on treatment with NAs. HPDCs-T produced procedure: The first step: 1-7 days Monocytes will be isolated from peripheral blood of patients. The monocytes obtained will be then incubated in fresh serum-free AIM-V medium (Gibco) containing 800U/ml of GM-CSF and 400U/ml of IL-4 (Peprotech) for 5 days. After 5 days of culture in vitro, The DCs induced will be cultured with a commercially available hepatitis B vaccine containing 10 ug of HBsAg (GSK) for 2 days. The second step: 8-14 days The hepatitis B vaccine sensitized DCs (HPDCs) (from the first step) will be sub-cultured with patient's own PBMCs for 7 days: HBsAg can be efficiently presented to PBMCs by DCs, with producing HBV specific CTLs and HTLs (HPDCs-T). The third step: 15 days The PBMCs (the second step) containing enough HPDCs-T will be transfused back into the patient.

Official Title
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A Clinical Trial on Hepatitis B Vaccine Activated-DCs Combined With Peg-interferon or Nucleotide Analogs in Chronic Hepatitis B

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Biological: HPDCs-T immune therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: serum hepatitis B surface antigen(HBsAg) positive for at least 6 months; HBV DNA loads≥ 104IU/ml(Roche Cobas); Containing the IFN treatment: 2ULN ≤ ALT ≤ 10ULN and TBil ≤ 2ULN; Containing the ETV/LdT treatment: 2ULN ≤ ALT and TBil ≤ 5ULN; All patients have not received antiviral treatment or immunotherapy for the last 6 months. 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; 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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No

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: HPDCs-T immune therapy combined with IFN<br>HPDCs-T immune therapy:one time every 2 weeks during 12 weeks to 36 weeks, about 2*105-1*106 cells per time,total 12 times; IFN therapy (Peg-IFN α-2b/2a):one time every 1 week according to the standards for 48 weeks | Biological: HPDCs-T immune therapy<br>* HPDCs-T immune therapy:one time every 2 weeks during 12 weeks to 36 weeks, IV (in the vein), about 2*105-1*106 cells per time,total 12 times;<br>* Other names: HBsAg Pulse DCs-T;|
| Experimental: HPDCs-T immune therapy combined with ETV<br>HPDCs-T immune therapy:one time every 2 weeks during 12 weeks to 36 weeks, about 2*105-1*106 cells per time,total 12 times; Entecavir(ETV)therapy:0.5mg per day according guidelines for the treatment of chronic hepatitis B in the Asia Pacific Region | Biological: HPDCs-T immune therapy<br>* HPDCs-T immune therapy:one time every 2 weeks during 12 weeks to 36 weeks, IV (in the vein), about 2*105-1*106 cells per time,total 12 times;<br>* Other names: HBsAg Pulse DCs-T;|
| Experimental: HPDCs-T immune therapy combined with LdT<br>HPDCs-T immune therapy:one time every 2 weeks during 12 weeks to 36 weeks, about 2*105-1*106 cells per time,total 12 times; Telbivudine(LdT)therapy:600mg per day according guidelines for the treatment of chronic hepatitis B in the Asia Pacific Region | Biological: HPDCs-T immune therapy<br>* HPDCs-T immune therapy:one time every 2 weeks during 12 weeks to 36 weeks, IV (in the vein), about 2*105-1*106 cells per time,total 12 times;<br>* Other names: HBsAg Pulse DCs-T;|
| No Intervention: IFN treatment<br>IFN therapy (Peg-IFN α-2b/2a):one time every 1 week according to the standards for 48 weeks | |
| No Intervention: ETV treatment<br>Entecavir(ETV)therapy:0.5mg per day according guidelines for the treatment of chronic hepatitis B in the Asia Pacific Region | |
| No Intervention: LdT treatment<br>Telbivudine(LdT)therapy:600mg per day according guidelines for the treatment of chronic hepatitis B in the Asia Pacific Region | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBV makers | HBV DNA loads,HBsAg/HBsAb titer,HBeAg/HBeAb titer | 01/01/2014-31/12/2016, total 6 times (3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coagulation tests | PT,PTA,INR | 01/01/2014-31/12/2016, total 6 times (3 years) | 
| liver function | ALT,AST,Tbil,Alb | 01/01/2014-31/12/2016, total 6 times (3 years) | 
| alpha-fetal protein | AFP;Biomarkers of hepatocellular carcinoma,one time every 24 weeks | 01/01/2014-31/12/2016, total 4 times (3 years) | 
| B ultrasound or MRI examination of the liver | The examination is performed both at the end of the pre-experiment and the main experiment | 01/01/2014-31/12/2016, total 2 times (3 years) | 
| Liver biopsy | The examination is performed both before and during experiment. | 01/01/2014-31/12/2016, total 2 times (3 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CHB, Antiviral, Dentritic cells, Immune Therapy