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

October 28, 2020 updated by: Yuehua Huang, Third Affiliated Hospital, Sun Yat-Sen University

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

400

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Shanghai, China, 200000
        • Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine
    • Guangdong
      • Guangzhou, Guangdong, China, 510630
        • The Third Affiliated Hospital of Sun Yat-sen University
    • Yunnan
      • Kunming, Yunnan, China, 650000
        • The Second People's Hospital of Yunnan Province

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / 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:
  • The HBsAg sensitized dendritic cells activated T cells
  • HBsAg Pulse DCs-T
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:
  • The HBsAg sensitized dendritic cells activated T cells
  • HBsAg Pulse DCs-T
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:
  • The HBsAg sensitized dendritic cells activated T cells
  • HBsAg Pulse DCs-T
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HBV makers
Time Frame: 01/01/2014-31/12/2016, total 6 times (3 years)
HBV DNA loads,HBsAg/HBsAb titer,HBeAg/HBeAb titer
01/01/2014-31/12/2016, total 6 times (3 years)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Coagulation tests
Time Frame: 01/01/2014-31/12/2016, total 6 times (3 years)
PT,PTA,INR
01/01/2014-31/12/2016, total 6 times (3 years)
liver function
Time Frame: 01/01/2014-31/12/2016, total 6 times (3 years)
ALT,AST,Tbil,Alb
01/01/2014-31/12/2016, total 6 times (3 years)
alpha-fetal protein
Time Frame: 01/01/2014-31/12/2016, total 4 times (3 years)
AFP;Biomarkers of hepatocellular carcinoma,one time every 24 weeks
01/01/2014-31/12/2016, total 4 times (3 years)
B ultrasound or MRI examination of the liver
Time Frame: 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
01/01/2014-31/12/2016, total 2 times (3 years)
Liver biopsy
Time Frame: 01/01/2014-31/12/2016, total 2 times (3 years)
The examination is performed both before and during experiment.
01/01/2014-31/12/2016, total 2 times (3 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Third Affiliated Hospital, Sun Yat-Sen University

Collaborators

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 record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2015

Primary Completion (ACTUAL)

December 1, 2019

Study Completion (ACTUAL)

December 1, 2019

Study Registration Dates

First Submitted

September 1, 2013

First Submitted That Met QC Criteria

September 4, 2013

First Posted (ESTIMATE)

September 5, 2013

Study Record Updates

Last Update Posted (ACTUAL)

October 30, 2020

Last Update Submitted That Met QC Criteria

October 28, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2014ZX10002002-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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