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

Sun Yat-sen University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Chronic Hepatitis B

Treatments: Biological: HPDCs-T immune therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT01935635

2014ZX10002002-002

Details and patient eligibility

About

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

Full 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.

Enrollment: 400 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 6 patient groups

HPDCs-T immune therapy combined with IFN

Experimental group

Description:

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

Treatment:

Biological: HPDCs-T immune therapy

HPDCs-T immune therapy combined with ETV

Experimental group

Description:

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

Treatment:

Biological: HPDCs-T immune therapy

HPDCs-T immune therapy combined with LdT

Experimental group

Description:

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

Treatment:

Biological: HPDCs-T immune therapy

IFN treatment

No Intervention group

Description:

IFN therapy (Peg-IFN α-2b/2a):one time every 1 week according to the standards for 48 weeks

ETV treatment

No Intervention group

Description:

Entecavir(ETV)therapy:0.5mg per day according guidelines for the treatment of chronic hepatitis B in the Asia Pacific Region

LdT treatment

No Intervention group

Description:

Telbivudine(LdT)therapy:600mg per day according guidelines for the treatment of chronic hepatitis B in the Asia Pacific Region