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

Chronic Hepatitis B Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01935635
• Other study ID #: 2014ZX10002002-002
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 2015
• Est. completion date: December 2019

Study information

• Verified date: October 2020
• Source: Third Affiliated Hospital, Sun Yat-Sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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):

1. 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):

2. 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.

3. Control groups: antiviral therapy used only (IFN or NAs).

Part3 (36-72W):

4. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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;

Locations

Country	Name	City	State
China	The Third Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	The second people's hospital of yunnan province	Kunming	Yunnan
China	Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai

Sponsors (3)

Lead Sponsor	Collaborator
Third Affiliated Hospital, Sun Yat-Sen University	Ruijin Hospital, Second People's Hospital of Yunnan Province

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HBV makers	HBV DNA loads,HBsAg/HBsAb titer,HBeAg/HBeAb titer	01/01/2014-31/12/2016, total 6 times (3 years)
Secondary	Coagulation tests	PT,PTA,INR	01/01/2014-31/12/2016, total 6 times (3 years)
Secondary	liver function	ALT,AST,Tbil,Alb	01/01/2014-31/12/2016, total 6 times (3 years)
Secondary	alpha-fetal protein	AFP;Biomarkers of hepatocellular carcinoma,one time every 24 weeks	01/01/2014-31/12/2016, total 4 times (3 years)
Secondary	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)
Secondary	Liver biopsy	The examination is performed both before and during experiment.	01/01/2014-31/12/2016, total 2 times (3 years)