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

Chronic Hepatitis B Clinical Trial

— CTHBVACADCHB  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02615639
• Other study ID #: SunYatSenIDD
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• First received: November 12, 2015
• Last updated: November 24, 2015
• Start date: November 2015
• Est. completion date: November 2018

Study information

• Verified date: November 2015
• Source: Third Affiliated Hospital, Sun Yat-Sen University
• Contact: Yurong Gu, MD.
• Phone: 18588628204
• Email: guyr163[@]163.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 450
• Est. completion date: November 2018
• Est. primary completion date: November 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Biological:
• HPDC-T cells & Entecavir
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

Drug:
• Entecavir
0.5mg tablet every night by mouth
• HPDC-T cells & IFN-a-2a
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
• IFN-a-2a
IFN-a-2a 180ug subcutaneous injection every week
• HPDC-T cells & Telbivudine
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
• Telbivudine
Telbivudine 600mg tablet every day by mouth

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Third Affiliated Hospital, Sun Yat-Sen University	Shanghai Jiao Tong University School of Medicine

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hepatitis B surface Antigen (HBeAg)seroconversion	to increase Hepatitis B surface antigen (HBsAg) loss rate from 1% up to 11% or more	3 years	No
Secondary	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	Yes
Secondary	Hepatitis B envelope Antigen (HBeAg) seroconversion	to increase HBeAg negative rate by 12 percentage points on the basis of the existing data	3 years	No
Secondary	HBV DNA clearance	to increase the undetectable rate of HBV DNA	3 years	No
Secondary	ALT recovery	to increase the recovery rate of ALT	3 years	No