The Treatment With HBIG+GM-CSF+HBV Vaccine for Chronic Hepatitis B Patients With HBeAg Seroconversion

NCT01878565 | Unknown Phase 1 DMC

• 2 other identifiers: Beijing302-009yes
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The host immunity has been generally recognized as the main factors to determine the outcome of chronic hepatitis B virus (HBV) infection; however, previous studies have shown that HBV-specific T cell and B cell function are exhausted in chronic hepatitis B (CHB) patients. Recently, It is suggested that hepatitis B surface antigen (HBsAg) may play a key role in the immune tolerance or immune exhaustion. Anti-HBV immune responses are partially recovered when patients achieved hepatitis B e antigen (HBeAg) seroconversion during antiviral therapy, and can be nearly recovered during HBsAg seroconversion. However, it is still difficult to achieve the ideal terminal, HBsAg seroconversion. For this reason, immunotherapy would be helpful to enhance the anti-HBV immunity and acquire higher HBsAg seroconversion. Here, the investigators propose a hypothesis that hepatitis B immune globin (HBIG)+granulocyte-macrophage colony-stimulating factor (GM-CSF)+HBV vaccine can enhance anti-HBV immune responses and improve HBsAg seroconversion in CHB patients who has achieved HBeAg seroconversion using nucleoside analogues treatment.

Conditions

Chronic Hepatitis B

Keywords

HBIg; GM-CSF; HBV vaccine; immune regulatory therapy

Outcome Measures

Primary Outcomes (1)

• the rate of hepatitis B surface antigen (HBsAg) seroconversion

  At week 48

Secondary Outcomes (6)

• The rates of serum hepatitis B surface antigen (HBsAg) negative

  At Baseline and at week 4, 12, 24, 36 and 48

• the decreased levels of serum hepatitis B surface antigen (HBsAg)

  At Baseline and at week 4, 12, 24, 36 and 48

• Number of participants with adverse events as a measure of safety and tolerability

  at baseline and up to week 48 week

• The frequency of hepatitis B virus (HBV)-specific T cells

  At baseline and at week 4, 12, 24, 36 and 48

• The frequency of hepatitis B virus (HBV)-specific B cells

  At baseline and at week 4, 12, 24, 36 and 48

Other Outcomes (2)

• plasma hepatitis B virus (HBV) DNA load

  At Entry and at Weeks 24 and 48

• Hepatitis B virus (HBV) serum markers (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb)

  At baseline and at week 24 and 48

Study Arms (2)

Drug treatment

EXPERIMENTAL

Drug: Given four times in week 0, 4, 12 and 24. At each time of treatment, the patients will be hospitalized and treated with 800 unit of HBIG intramuscularly at day 0, 1, 2, 3 and 4, then were treated with 75 μg of GM-CSF subcutaneously at day 2, 3, 4, 5 and 6, and finally were injected 20μg of HBV vaccine subcutaneously at day 6.

Drug: Drug

GM-CSF control

OTHER

GM-CSF was given four times as control in week 0, 4, 12 and 24. At each time of treatment, the patients will be hospitalized and treated with GM-CSF intramuscularly or subcutaneously at day 2, 3, 4, 5, 6.

Drug: GM-CSF control

Interventions

Drug DRUG

Given four times in week 0, 4, 12 and 24. At each time of treatment, the patients will be hospitalized and treated with 800 unit of HBIG intramuscularly at day 0, 1, 2, 3 and 4, then were treated with 75 μg of GM-CSF subcutaneously at day 2, 3, 4, 5 and 6, and finally were injected 20 μg of HBV vaccine subcutaneously at day 6.

Also known as: treatment group

Drug treatment

GM-CSF control DRUG

Given four times in week 0, 4, 12 and 24. At each time of treatment, the patients will be hospitalized and treated with saline placebo intramuscularly or subcutaneously at day 2, 3, 4, 5, 6.

Also known as: drug control

GM-CSF control

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• chronic hepatitis B patients with HBeAg seroconversion (eAg negative and eab positive)
• age 18-50, male or female
• HBsAg positive for at least 6 months, quantitative HBsAg \<1000 IU/ml (Abbott Diagnostic, Wiesbaden, Germany)
• HBeAg positive CHB patients who have received NAs (lamivudine, adefovir dipivoxil, entecavir, alone or in combination) treatment and achieved HBeAg seroconversion (HBeAg-, HBeAb+), HBV DNA\<40 IU/ml and ALT normalization and maintained for at least 6 months.
• Urine pregnancy test is negative in gestational age female subjects before enrollment, who can take effective contraceptive measures and agree to contraception during treatment and follow-up period.
• Enrolled subjects should understand and sign the informed consent and comply with the requirement of the research before study.
• Enrolled subjects should agree not to participate in other studies, and not to accept other immunomodulatory therapy during the study. Other treatments such as corticosteroids should be informed timely

You may not qualify if:

• Be allergic to HBIG, GM-CSF and HBV vaccine.
• Coinfected with other virus. Any positive for anti-hepatitis A virus (HAV), anti-hepatitis C virus (HCV), anti-hepatitis D virus (HDV), anti-hepatitis E virus (HEV) and anti-HIV.
• Advanced cirrhosis or Child-Pugh 7 scores or above.
• Autoimmune thrombocytopenic purpura, coronary heart disease, cerebrovascular disease, hypertension, diabetes mellitus, high myopia, history of epilepsy.
• Other causes of liver disease, such as autoimmune liver disease, alcoholic liver disease, nonalcoholic liver disease, drug-induced liver disease and other unknown causes of chronic liver diseases.
• Associated with other serious organic disease, mental illness, including any uncontrolled urinary, respiratory, circulation, nervous, digestive, endocrine, spirit, immune system diseases and tumor.
• Suspected liver cancer or alpha feto protein (AFP) \> 100ng/ml.
• Neutrophil count \< 2.5×109/L, or hemoglobin \< 100g/L, or platelet \< 80×109/L.
• Pregnant or lactating women.
• Allergic constitution, allergy history for blood products, known allergy to experimental drugs.
• Alcohol or drug addiction, drug use history evidence within one year before enrolled in the study.
• Received immunosuppressive or other immune modulators (including thymosin) or systemic cytotoxic drug 6 months before enrolled in the study.
• Incompliance during antiviral therapy.
• Enrolled in other clinical trials at present, and possible to be against the treatment and observation index.
• Unable or unwilling to provide informed consent or fails to comply with the requirements of the study.

Sponsors & Collaborators

• Beijing 302 Hospital: lead

Study Sites (1)

Beijing 302 Hospital

Beijing, 100039, China

RECRUITING

Related Publications (4)

• Xu DZ, Wang XY, Shen XL, Gong GZ, Ren H, Guo LM, Sun AM, Xu M, Li LJ, Guo XH, Zhen Z, Wang HF, Gong HY, Xu C, Jiang N, Pan C, Gong ZJ, Zhang JM, Shang J, Xu J, Xie Q, Wu TF, Huang WX, Li YG, Xu J, Yuan ZH, Wang B, Zhao K, Wen YM; YIC Efficacy Trial Study Team. Results of a phase III clinical trial with an HBsAg-HBIG immunogenic complex therapeutic vaccine for chronic hepatitis B patients: experiences and findings. J Hepatol. 2013 Sep;59(3):450-6. doi: 10.1016/j.jhep.2013.05.003. Epub 2013 May 11.

  PMID: 23669281 BACKGROUND

• Shouval D. Focus: quantitative HBsAg measurement as a new surrogate marker for assessment of hepatic fibrosis in HBeAg+ chronic hepatitis B. J Hepatol. 2013 Jun;58(6):1063-4. doi: 10.1016/j.jhep.2013.03.002. Epub 2013 Mar 14. No abstract available.

  PMID: 23499728 BACKGROUND

• Seto WK, Wong DK, Fung J, Huang FY, Lai CL, Yuen MF. Reduction of hepatitis B surface antigen levels and hepatitis B surface antigen seroclearance in chronic hepatitis B patients receiving 10 years of nucleoside analogue therapy. Hepatology. 2013 Sep;58(3):923-31. doi: 10.1002/hep.26376. Epub 2013 Jul 24.

  PMID: 23468172 BACKGROUND

• Tseng TC, Liu CJ, Yang HC, Su TH, Wang CC, Chen CL, Hsu CA, Kuo SF, Liu CH, Chen PJ, Chen DS, Kao JH. Serum hepatitis B surface antigen levels help predict disease progression in patients with low hepatitis B virus loads. Hepatology. 2013 Feb;57(2):441-50. doi: 10.1002/hep.26041. Epub 2012 Dec 6.

  PMID: 22941922 BACKGROUND

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Pharmaceutical Preparations; Drug and Narcotic Control

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Legislation, Drug; Legislation as Topic; Social Control, Formal; Health Care Economics and Organizations; Pharmacy Administration; Organization and Administration; Health Services Administration

Study Officials

• Fu-Sheng Wang, M.D.

  Research Center for Biotherapy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fu-Sheng Wang, M.D.

CONTACT

86-10-63879735; fswang302@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Center for Biotherapy

Study Record Dates

• First Submitted: June 12, 2013
• First Posted: June 17, 2013
• Study Start: June 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: July 1, 2015
• Last Updated: July 24, 2013

Record last verified: 2013-07

Locations

CN (1)