A Clinical Trial on HB-Vac Activated-DCs Combined With Peg-IFN or NAs in CHB
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: HPDCs-T immune therapy combined with IFN 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
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;
Other Names:
|
| Experimental: HPDCs-T immune therapy combined with ETV 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
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;
Other Names:
|
| Experimental: HPDCs-T immune therapy combined with LdT 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
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;
Other Names:
|
| No Intervention: IFN treatment IFN therapy (Peg-IFN α-2b/2a):one time every 1 week according to the standards for 48 weeks |
|
| No Intervention: ETV treatment 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 Telbivudine(LdT)therapy:600mg per day according guidelines for the treatment of chronic hepatitis B in the Asia Pacific Region |
Outcome Measures
Primary Outcome Measures
- HBV makers [01/01/2014-31/12/2016, total 6 times (3 years)]
HBV DNA loads,HBsAg/HBsAb titer,HBeAg/HBeAb titer
Secondary Outcome Measures
- Coagulation tests [01/01/2014-31/12/2016, total 6 times (3 years)]
PT,PTA,INR
- liver function [01/01/2014-31/12/2016, total 6 times (3 years)]
ALT,AST,Tbil,Alb
- alpha-fetal protein [01/01/2014-31/12/2016, total 4 times (3 years)]
AFP;Biomarkers of hepatocellular carcinoma,one time every 24 weeks
- B ultrasound or MRI examination of the liver [01/01/2014-31/12/2016, total 2 times (3 years)]
The examination is performed both at the end of the pre-experiment and the main experiment
- Liver biopsy [01/01/2014-31/12/2016, total 2 times (3 years)]
The examination is performed both before and during experiment.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Third Affiliated Hospital of Sun Yat-sen University | Guangzhou | Guangdong | China | 510630 |
| 2 | The second people's hospital of yunnan province | Kunming | Yunnan | China | 650000 |
| 3 | Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine | Shanghai | China | 200000 |
Sponsors and Collaborators
- Third Affiliated Hospital, Sun Yat-Sen University
- Ruijin Hospital
- Second People's Hospital of Yunnan Province
Investigators
- Study Director: Yuehua Huang, Doctor, Deparment of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2014ZX10002002-002