Clinical trial NCT02615639: A Clinical Trial on Hepatitis B Vaccine Activated-Dendritic Cells Combined With Anti-HBV Drugs in CHB
Official title: A Clinical Trial on Hepatitis B Vaccine Activated-Dendritic Cells Combined With Anti-HBV Drugs in Chronic Hepatitis B
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Chronic Hepatitis B
Keywords: HPDC-T cells
CHB
immuno therapy
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Shanghai Jiao Tong University School of Medicine
First posted: 2015-11-26
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hepatitis B surface Antigen （HBeAg）seroconversion
timeFrame: 3 years
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by low-grade fever, Infection and shock.
timeFrame: one and a half year
measure: Hepatitis B envelope Antigen （HBeAg） seroconversion
timeFrame: 3 years
measure: HBV DNA clearance
timeFrame: 3 years
measure: ALT recovery
timeFrame: 3 years
Other outcomes:
Locations:
Study officials:
affiliation: The Third Affiliated Hospital of Sun Yet-sun University
name: Lubiao Chen, MD.&PHD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Luo J, Li J, Chen RL, Nie L, Huang J, Liu ZW, Luo L, Yan XJ. Autologus dendritic cell vaccine for chronic hepatitis B carriers: a pilot, open label, clinical trial in human volunteers. Vaccine. 2010 Mar 16;28(13):2497-504. doi: 10.1016/j.vaccine.2010.01.038. Epub 2010 Jan 29.
citation: Akbar SM, Furukawa S, Horiike N, Abe M, Hiasa Y, Onji M. Safety and immunogenicity of hepatitis B surface antigen-pulsed dendritic cells in patients with chronic hepatitis B. J Viral Hepat. 2011 Jun;18(6):408-14. doi: 10.1111/j.1365-2893.2010.01320.x.