NCT01014845

Brief Summary

The primary purpose of this study is to determine whether the preventive hepatitis E are effective in the prevention of hepatitis E occurring at least 30 days after the administration of the third dose of vaccine. The secondary purpose of this study is to to evaluate the safety and immunogenicity and immunopersistence of the study vaccine. The initial study is planed to be ended on month 19 and the results were analysed and used for registration purpose. The extended study will be continued to assess the long-term efficacy, immunogenicity and safety.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
112,604

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Aug 2007

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2007

Completed
2.3 years until next milestone

First Submitted

Initial submission to the registry

November 13, 2009

Completed
4 days until next milestone

First Posted

Study publicly available on registry

November 17, 2009

Completed
7.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2017

Completed
Last Updated

July 13, 2020

Status Verified

July 1, 2020

Enrollment Period

10.2 years

First QC Date

November 13, 2009

Last Update Submit

July 9, 2020

Conditions

Hepatitis E

Keywords

hepatitis Evaccineefficacy

Outcome Measures

Primary Outcomes (1)

  • Rate of confirmed hepatitis E cases

    One year since one month post the third injection

Secondary Outcomes (2)

  • IgG anti-HEV seroconversion rate

    On one month post the third injection

  • Persistency of IgG anti-HEV

    One year

Study Arms (2)

Hepatitis E vaccine

EXPERIMENTAL

Hepatitis E vaccine, containing 30mcg of HEV239 recombinant antigen adsorbed to alum adjuvant suspended in 0.5ml phosphate buffer, was given at 0, 1, 6m for three doses.

Biological: hepatitis E vaccine

HBV vaccine

PLACEBO COMPARATOR

Hepatitis B vaccine, containing 5mcg of HBsAg recombinant antigen adsorbed to alum adjuvant suspended in 0.5ml phosphate buffer, was given at 0, 1, 6m for three doses.

Biological: Hepatitis B vaccine

Interventions

hepatitis E vaccineBIOLOGICAL

Intramuscularly given at 0, 1, 6m for three doses.

Also known as: Hecolin
Hepatitis E vaccine
Hepatitis B vaccineBIOLOGICAL

Intramuscularly given at 0, 1, 6m for three doses.

HBV vaccine

Eligibility Criteria

Age16 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Healthy people aged from 16 years to 65 years old at the time of the first vaccination, normal intelligence and agree to sign the informed consent form.
  • Subjects will reside in the study region in the next 19 months.
  • Free of history of hepatitis B or hepatitis E.
  • Can comply with the request of study.
  • Axillary temperature is below 37 degree centigrade.

You may not qualify if:

  • For dose 1:
  • Having other vaccine or immunoglobulin within two weeks;
  • Having allergic history to vaccine and medicine
  • Eclampsia, epilepsy, encephalopathy and history of mental disease or family;
  • Thrombocytopenia or other disturbance of blood coagulation which would lead to muscle injection taboo;
  • Fixed or suspected deficiency of immunologic function, containing immunosuppressant treatment(radiation therapy, chemical treatment, steroid hormone, antimetabolites, cytotoxic drugs), genetic defect(e.g. fabism), HIV or other factors;
  • congenital malformation, eccyliosis or severe chronic disease(e.g. Down Syndrome, diabetes, sickle cell anemia or mental disease);
  • fixed or suspected other disease including fever, active infection, liver and kidney disease, angiocardiopathy, malignancy, acute and chronic disease;
  • joining other clinical study undergoing;
  • women pregnant or in lactation.
  • For dose 2 or 3:
  • Severe allergy for dose 1 or 2;
  • Severe adverse reaction associated with last vaccination;

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Dongtai Center for Disease Control and Prevention

Dongtai, Jiangsu, 224200, China

Location

Related Publications (15)

  • Zhang J, Liu CB, Li RC, Li YM, Zheng YJ, Li YP, Luo D, Pan BB, Nong Y, Ge SX, Xiong JH, Shih JW, Ng MH, Xia NS. Randomized-controlled phase II clinical trial of a bacterially expressed recombinant hepatitis E vaccine. Vaccine. 2009 Mar 13;27(12):1869-74. doi: 10.1016/j.vaccine.2008.12.061. Epub 2009 Jan 23.

    PMID: 19168109BACKGROUND

  • Li S, Tang X, Seetharaman J, Yang C, Gu Y, Zhang J, Du H, Shih JW, Hew CL, Sivaraman J, Xia N. Dimerization of hepatitis E virus capsid protein E2s domain is essential for virus-host interaction. PLoS Pathog. 2009 Aug;5(8):e1000537. doi: 10.1371/journal.ppat.1000537. Epub 2009 Aug 7.

    PMID: 19662165BACKGROUND

  • He S, Miao J, Zheng Z, Wu T, Xie M, Tang M, Zhang J, Ng MH, Xia N. Putative receptor-binding sites of hepatitis E virus. J Gen Virol. 2008 Jan;89(Pt 1):245-249. doi: 10.1099/vir.0.83308-0.

    PMID: 18089748BACKGROUND

  • Li SW, Zhang J, Li YM, Ou SH, Huang GY, He ZQ, Ge SX, Xian YL, Pang SQ, Ng MH, Xia NS. A bacterially expressed particulate hepatitis E vaccine: antigenicity, immunogenicity and protectivity on primates. Vaccine. 2005 Apr 22;23(22):2893-901. doi: 10.1016/j.vaccine.2004.11.064.

    PMID: 15780738BACKGROUND

  • Zhang J, Gu Y, Ge SX, Li SW, He ZQ, Huang GY, Zhuang H, Ng MH, Xia NS. Analysis of hepatitis E virus neutralization sites using monoclonal antibodies directed against a virus capsid protein. Vaccine. 2005 Apr 22;23(22):2881-92. doi: 10.1016/j.vaccine.2004.11.065.

    PMID: 15780737BACKGROUND

  • Li SW, Zhang J, He ZQ, Gu Y, Liu RS, Lin J, Chen YX, Ng MH, Xia NS. Mutational analysis of essential interactions involved in the assembly of hepatitis E virus capsid. J Biol Chem. 2005 Feb 4;280(5):3400-6. doi: 10.1074/jbc.M410361200. Epub 2004 Nov 22.

    PMID: 15557331BACKGROUND

  • Zhu FC, Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ, Wang H, Yang CL, Jiang HM, Cai JP, Wang YJ, Ai X, Hu YM, Tang Q, Yao X, Yan Q, Xian YL, Wu T, Li YM, Miao J, Ng MH, Shih JW, Xia NS. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet. 2010 Sep 11;376(9744):895-902. doi: 10.1016/S0140-6736(10)61030-6. Epub 2010 Aug 20.

    PMID: 20728932RESULT

  • Wu T, Huang SJ, Zhu FC, Zhang XF, Ai X, Yan Q, Wang ZZ, Yang CL, Jiang HM, Liu XH, Guo M, Du HL, Ng MH, Zhang J, Xia NS. Immunogenicity and safety of hepatitis E vaccine in healthy hepatitis B surface antigen positive adults. Hum Vaccin Immunother. 2013 Nov;9(11):2474-9. doi: 10.4161/hv.25814. Epub 2013 Jul 25.

    PMID: 23887167RESULT

  • Wu T, Zhu FC, Huang SJ, Zhang XF, Wang ZZ, Zhang J, Xia NS. Safety of the hepatitis E vaccine for pregnant women: a preliminary analysis. Hepatology. 2012 Jun;55(6):2038. doi: 10.1002/hep.25522. No abstract available.

    PMID: 22161542RESULT

  • Zhu FC, Huang SJ, Wu T, Zhang XF, Wang ZZ, Ai X, Yan Q, Yang CL, Cai JP, Jiang HM, Wang YJ, Ng MH, Zhang J, Xia NS. Epidemiology of zoonotic hepatitis E: a community-based surveillance study in a rural population in China. PLoS One. 2014 Jan 31;9(1):e87154. doi: 10.1371/journal.pone.0087154. eCollection 2014.

    PMID: 24498033RESULT

  • Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ, Yao X, Liang ZL, Wu T, Li JX, Yan Q, Yang CL, Jiang HM, Huang HJ, Xian YL, Shih JW, Ng MH, Li YM, Wang JZ, Zhu FC, Xia NS. Protection against hepatitis E virus infection by naturally acquired and vaccine-induced immunity. Clin Microbiol Infect. 2014 Jun;20(6):O397-405. doi: 10.1111/1469-0691.12419. Epub 2013 Nov 18.

    PMID: 24118636RESULT

  • Huang S, Zhang X, Su Y, Zhuang C, Tang Z, Huang X, Chen Q, Zhu K, Hu X, Ying D, Liu X, Jiang H, Zang X, Wang Z, Yang C, Liu D, Wang Y, Tang Q, Shen W, Cao H, Pan H, Ge S, Huang Y, Wu T, Zheng Z, Zhu F, Zhang J, Xia N. Long-term efficacy of a recombinant hepatitis E vaccine in adults: 10-year results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024 Mar 2;403(10429):813-823. doi: 10.1016/S0140-6736(23)02234-1. Epub 2024 Feb 19.

    PMID: 38387470DERIVED

  • Kmush BL, Yu H, Huang S, Zhang X, Wu T, Nelson KE, Labrique AB. Long-term Antibody Persistence After Hepatitis E Virus Infection and Vaccination in Dongtai, China. Open Forum Infect Dis. 2019 Mar 28;6(4):ofz144. doi: 10.1093/ofid/ofz144. eCollection 2019 Apr.

    PMID: 31024978DERIVED

  • Chen S, Zhou Z, Wei FX, Huang SJ, Tan Z, Fang Y, Zhu FC, Wu T, Zhang J, Xia NS. Modeling the long-term antibody response of a hepatitis E vaccine. Vaccine. 2015 Aug 7;33(33):4124-9. doi: 10.1016/j.vaccine.2015.06.050. Epub 2015 Jun 28.

    PMID: 26126668DERIVED

  • Zhang J, Zhang XF, Huang SJ, Wu T, Hu YM, Wang ZZ, Wang H, Jiang HM, Wang YJ, Yan Q, Guo M, Liu XH, Li JX, Yang CL, Tang Q, Jiang RJ, Pan HR, Li YM, Shih JW, Ng MH, Zhu FC, Xia NS. Long-term efficacy of a hepatitis E vaccine. N Engl J Med. 2015 Mar 5;372(10):914-22. doi: 10.1056/NEJMoa1406011.

    PMID: 25738667DERIVED

MeSH Terms

Conditions

Hepatitis E

Interventions

hecolinHepatitis B Vaccines

Condition Hierarchy (Ancestors)

Hepatitis, Viral, HumanVirus DiseasesInfectionsRNA Virus InfectionsHepatitisLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

Viral Hepatitis VaccinesViral VaccinesVaccinesBiological ProductsComplex Mixtures

Study Officials

  • Jun Zhang, M.D.

    National Institute of Diagnostics and Vaccine Development in infectious disease, Xiamen University

    STUDY DIRECTOR

  • Feng-Cai Zhu, M.D.

    Jiangsu Provincial Center for Disease Control and Prevention, China

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
professor

Study Record Dates

First Submitted

November 13, 2009

First Posted

November 17, 2009

Study Start

August 1, 2007

Primary Completion

October 1, 2017

Study Completion

October 1, 2017

Last Updated

July 13, 2020

Record last verified: 2020-07

Locations

CN(1)