Clinical trial NCT01935635: A Clinical Trial on HB-Vac Activated-DCs Combined With Peg-IFN or NAs in CHB
Official title: A Clinical Trial on Hepatitis B Vaccine Activated-DCs Combined With Peg-interferon or Nucleotide Analogs in Chronic Hepatitis B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Hepatitis B
Keywords: CHB
Antiviral
Dentritic cells
Immune Therapy
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Ruijin Hospital
name: Second People's Hospital of Yunnan Province
First posted: 2013-09-05
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: HBV makers
timeFrame: 01/01/2014-31/12/2016, total 6 times (3 years)
Secondary outcomes:
measure: Coagulation tests
timeFrame: 01/01/2014-31/12/2016, total 6 times (3 years)
measure: liver function
timeFrame: 01/01/2014-31/12/2016, total 6 times (3 years)
measure: alpha-fetal protein
timeFrame: 01/01/2014-31/12/2016, total 4 times (3 years)
measure: B ultrasound or MRI examination of the liver
timeFrame: 01/01/2014-31/12/2016, total 2 times (3 years)
measure: Liver biopsy
timeFrame: 01/01/2014-31/12/2016, total 2 times (3 years)
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Kunming
country: China
facility: The second people's hospital of yunnan province
state: Yunnan
city: Shanghai
country: China
facility: Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine
Study officials:
affiliation: Deparment of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University
name: Yuehua Huang, Doctor
role: STUDY_DIRECTOR
References: