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Clinical Trial of Recombinant Hepatitis E Vaccine

Primary Purpose

Hepatitis E

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
hepatitis E vaccine
Hepatitis B vaccine
Sponsored by
Xiamen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hepatitis E focused on measuring hepatitis E, vaccine, efficacy

Eligibility Criteria

16 Years - 65 Years (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

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;
  • New occurrence of symptoms meet dose 1 exclusion criteria after the first dose.

Sites / Locations

  • Dongtai Center for Disease Control and Prevention

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Hepatitis E vaccine

HBV vaccine

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Rate of confirmed hepatitis E cases

Secondary Outcome Measures

IgG anti-HEV seroconversion rate
Persistency of IgG anti-HEV

Full Information

First Posted
November 13, 2009
Last Updated
July 9, 2020
Sponsor
Xiamen University
Collaborators
Xiamen Innovax Biotech Co., Ltd, Beijing Wantai Biological Pharmacy Enterprise Co., Ltd., National Institute of Diagnostics and Vaccine Development in infectious disease, Jiangsu Provincial Center for Disease Control and Prevention
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1. Study Identification

Unique Protocol Identification Number
NCT01014845
Brief Title
Clinical Trial of Recombinant Hepatitis E Vaccine
Official Title
A Phase 3, Randomized, Double-blind, Placebo (Hepatitis B Vaccine) Controlled Clinical Trial of Recombinant (E. Coli) Hepatitis E Vaccine
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
October 2017 (Actual)
Study Completion Date
October 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Xiamen University
Collaborators
Xiamen Innovax Biotech Co., Ltd, Beijing Wantai Biological Pharmacy Enterprise Co., Ltd., National Institute of Diagnostics and Vaccine Development in infectious disease, Jiangsu Provincial Center for Disease Control and Prevention

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
Participants were randomly allocated into two groups, one received Hepatitis E vaccine and the other received hepatitis B vaccine. The study was carried out with two stages. In the first stage (phase 3a), 2 645 subjects was enrolled and actively monitored for solicited adverse events for 1 month after each injection. Serum samples from all the subjects were collected on day 0, 7m, 13m, 19m and timely after then to evaluate the immunogenicity and immuno-persistency. In the second stage (phase 3b), another 109 959 subjects was enrolled and monitored for solicited adverse events for 1 month after each injection. Serum samples from 9764 subjects among the phase 3b participants were collected on day 0, 7m, 19m and timely after then to evaluate the immunogenicity and immuno-persistency. Serious adverse events during the trial were followed up. Suspected hepatitis cases were identified through an established active hepatitis surveillance system. The sentinels of the system comprised all the healthcare facilities in the field. Suspected hepatitis was defined as when patients presented with systemic symptoms such as fatigue and/or loss of appetite for more than 3 days with alanine aminotransferase (ALT) exceeding 2.5 fold upper limit of normal range (ULN). Paired sera were obtained from these patients at the time of presentation and 2-6 weeks later. Sera were tested for the HEV antibodies and HEV-RNA.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis E
Keywords
hepatitis E, vaccine, efficacy

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
112604 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hepatitis E vaccine
Arm Type
Experimental
Arm Description
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.
Arm Title
HBV vaccine
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
hepatitis E vaccine
Other Intervention Name(s)
Hecolin
Intervention Description
Intramuscularly given at 0, 1, 6m for three doses.
Intervention Type
Biological
Intervention Name(s)
Hepatitis B vaccine
Intervention Description
Intramuscularly given at 0, 1, 6m for three doses.
Primary Outcome Measure Information:
Title
Rate of confirmed hepatitis E cases
Time Frame
One year since one month post the third injection
Secondary Outcome Measure Information:
Title
IgG anti-HEV seroconversion rate
Time Frame
On one month post the third injection
Title
Persistency of IgG anti-HEV
Time Frame
One year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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; New occurrence of symptoms meet dose 1 exclusion criteria after the first dose.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jun Zhang, M.D.
Organizational Affiliation
National Institute of Diagnostics and Vaccine Development in infectious disease, Xiamen University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Feng-Cai Zhu, M.D.
Organizational Affiliation
Jiangsu Provincial Center for Disease Control and Prevention, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dongtai Center for Disease Control and Prevention
City
Dongtai
State/Province
Jiangsu
ZIP/Postal Code
224200
Country
China

12. IPD Sharing Statement

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Clinical Trial of Recombinant Hepatitis E Vaccine

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