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

NCT ID: NCT01935635

Last Updated: 2020-10-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-31

Study Completion Date

2019-12-31

Brief Summary

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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

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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.

Conditions

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Chronic Hepatitis B

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

HPDCs-T immune therapy

Intervention Type BIOLOGICAL

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;

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

Group Type EXPERIMENTAL

HPDCs-T immune therapy

Intervention Type BIOLOGICAL

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;

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

Group Type EXPERIMENTAL

HPDCs-T immune therapy

Intervention Type BIOLOGICAL

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;

IFN treatment

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

Group Type NO_INTERVENTION

No interventions assigned to this group

ETV treatment

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

Group Type NO_INTERVENTION

No interventions assigned to this group

LdT treatment

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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;

Intervention Type BIOLOGICAL

Other Intervention Names

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The HBsAg sensitized dendritic cells activated T cells HBsAg Pulse DCs-T

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ruijin Hospital

OTHER

Sponsor Role collaborator

Second People's Hospital of Yunnan Province

OTHER

Sponsor Role collaborator

Third Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role lead

Responsible Party

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Yuehua Huang

director of liver disease laboratory

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yuehua Huang, Doctor

Role: STUDY_DIRECTOR

Deparment of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University

Locations

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The Third Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status

The second people's hospital of yunnan province

Kunming, Yunnan, China

Site Status

Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine

Shanghai, , China

Site Status

Countries

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China

References

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Gu Y, Gu L, Chen L, Li J, Liao C, Bi Y, Huang Z, Cai W, Wei J, Huang Y. Immunotherapy Using HBV Vaccine Pulsed DCs and Induced T-Cells Combined Antiviral Drugs in Treatment Naive CHB Patients-A Multi-Centre Phase II Study. J Viral Hepat. 2025 Feb;32(2):e14045. doi: 10.1111/jvh.14045.

Reference Type DERIVED
PMID: 39815989 (View on PubMed)

Other Identifiers

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2014ZX10002002-002

Identifier Type: -

Identifier Source: org_study_id