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

Phase 1

Completed

• Conditions: Chronic Hepatitis B
• Interventions: Biological: HPDCs-T immune therapy

• Registration Number: NCT01935635
• Lead Sponsor: Third Affiliated Hospital, Sun Yat-Sen University

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

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):

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.

Study Timeline

• Study First Submitted: 2013-09-01
• Study First Submitted QC: 2013-09-04
• Study First Posted: 2013-09-05
• Study Start: 2015-01
• Primary Completion: 2019-12
• Study Completion: 2019-12
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-28
• Last Update Posted: 2020-10-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 400

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HPDCs-T immune therapy combined with IFN	HPDCs-T immune therapy	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
HPDCs-T immune therapy combined with ETV	HPDCs-T immune therapy	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
HPDCs-T immune therapy combined with LdT	HPDCs-T immune therapy	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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
Coagulation tests	01/01/2014-31/12/2016, total 6 times (3 years)	PT,PTA,INR
Liver biopsy	01/01/2014-31/12/2016, total 2 times (3 years)	The examination is performed both before and during experiment.
liver function	01/01/2014-31/12/2016, total 6 times (3 years)	ALT,AST,Tbil,Alb

Trial Locations

Locations (3)

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, China