Back to resultsImmunogenicity and Safety of Two Different Commercial EV71 Vaccines
Primary Purpose
Hand, Foot and Mouth Disease
Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
EV71 inactived vaccine（Vero cells）
EV71 inactived vaccine（Human diploid cells）
Sponsored by
About this trial
This is an interventional prevention trial for Hand, Foot and Mouth Disease focused on measuring Inactivated Enterovirus Type 71 (EV71) Vaccine, Sequential vaccination, Immunity, Safety
Eligibility Criteria
Inclusion Criteria:
- Healthy volunteer aged 6-35 months;
- Proven legal identity;
- Guardians of the participants should be capable of understanding the written consent form, and such form should be signed before the infant being included into this study.
Exclusion Criteria:
- Prior vaccination with EV71 vaccine;
- History of hand，foot and mouth disease;
- Allergy to gentamicin; history of allergy to any vaccine or vaccine ingredient, or serious adverse reaction(s) to vaccination, such as urticaria,difficulty in breathing, angioneurotic edema, pain, etc;
- Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc;
- Autoimmune diseases or immunodeficiency/immunosuppression;
- Severe neurological disorders (epilepsy, convulsions or convulsions) or psychosis;
- History of thyroidectomy, absence of spleen, functional absence of spleen, and any circumstances leading to absence of spleen or splenectomy;
- Diagnosed coagulation function abnormal (e.g., coagulation factor deficiency, coagulation disorder, or platelet abnormalities) , or obvious bruising or coagulation disorders;
- Any immunosuppressant, cytotoxic medicine, or inhaled corticosteroids (except corticosteroid spray for treatment of allergic rhinitis or corticosteroid treatment on surface for acute non-complicated dermatitis) in the past 6 months;
Receipt of any of the following products:
- Blood product within 3 months prior to study entry;
- Any live attenuated vaccine within 14 days prior to study entry;
- Any subunit vaccine or inactivated vaccine within 7 days prior to study entry;
- Any other study drugs within 30 days prior to study entry;
- Acute disease or acute stage of chronic disease within 7 days prior to study entry;
- Axillary temperature > 37.0℃;
- Any other factor that suggesting the volunteer is unsuitable for this study based on the opinions of investigators.
Sites / Locations
- Rushan City Center for Disease Control and Prevention
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Single vaccine group A
Single vaccine group B
Sequential vaccination group A
Sequential vaccination group B
Arm Description
This group receive two doses injection of EV71 inactived vaccines(Vero cells) on Day 0 and 30, and two times of blood sampling on day of 0 and 60 respectively for EV71 neutralizing antibody detection.The vaccine was manufactured by Sinovac Vaccine Technology Co., Ltd.
This group receive two doses injection of EV71 inactived vaccines(human diploid cells)on Day 0 and 30, two times of blood sampling on day of 0 and 60 respectively for EV71 neutralizing antibody detection.The vaccine was manufactured by Institute of Medical Biology Chinese Academy of Medical Sciences.
One dose injection of EV71 inactived vaccines(Vero cells) on Day 0，following one dose of EV71 vaccine(EV71 inactived vaccines(human diploid cells), and two times of blood sampling on day of 0 and 60 respectively for EV71 neutralizing antibody detection.
One dose injection of EV71 inactived vaccines(human diploid cells)on Day 0，following one does of EV71 vaccine(Sinovac Vaccine Technology Co., Ltd), and two times of blood sampling on day of 0 and 60 respectively for EV71 neutralizing antibody detection.
Outcomes
Primary Outcome Measures
The seroconversion rates (SCR) of the EV71 neutralizing antibody calculated based on the cutoff value of 1:8.
Subjects whose pre-immune EV71 antibody level < 1:8 and post-immune antibody level ≥ 1:8, or those whose pre-immune antibody level ≥ 1:8 and the increase of post-immune EV71 antibody level ≥ 4 folds are considered seroconverted
Secondary Outcome Measures
The incidences of adverse reactions after each does
After each dose, a 30-minute safety observation will be conducted immediately. The body temperature, solicited local and general adverse events (AE) on day 0-7 were reported. Unsolicited adverse events on day 0-30 were also reported. Each AE case will be reviewed by the investigator to determine whether or not it was an adverse reaction (The vaccination-related AE).
The incidence of solicited local and general adverse events after each does
After each dose, a 30-minute safety observation will be conducted immediately. The body temperature, solicited local and general adverse events (AE) on day 0-7 were reported. Each AE case will be reviewed by the investigator to determine whether or not it was an adverse reaction (The vaccination-related AE).
Incidence of serious adverse events (SAEs) during the period of safety monitoring
Serious adverse events (SAEs) will be collected during the period of safety monitoring after each dose.
EV71 neutralizing antibody positive rate of each group after two doses.
Subjects whose post-immune antibody level ≥ 1:8 are considered antibody positive.
The Geometric mean titer (GMT) of the EV71 neutralizing antibody
The GMT 30 days of each group after two doses.
The geometric mean fold increase (GMI) of the EV71 neutralizing antibody
The GMI 30 days of each group after two doses.
Full Information
NCT ID
NCT03873740
First Posted
March 2, 2019
Last Updated
July 26, 2021
Sponsor
Sinovac Biotech Co., Ltd
Collaborators
Shandong Province Centers for Disease Control and Prevention
1. Study Identification
Unique Protocol Identification Number
NCT03873740
Brief Title
Immunogenicity and Safety of Two Different Commercial EV71 Vaccines
Official Title
A Opened，Randomized and Controlled Trial to Evaluate the Immunity and Safety of Sequential Vaccination of Two Different Commercial EV71 Inactived Vaccines in Healthy Infants Aged 6-35 Months
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
November 6, 2018 (Actual)
Primary Completion Date
January 21, 2019 (Actual)
Study Completion Date
January 23, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sinovac Biotech Co., Ltd
Collaborators
Shandong Province Centers for Disease Control and Prevention
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the immunogenicity and safety of sequential vaccination of two EV71 inactived vaccines in healthy infants aged 6-35 months.
Detailed Description
This study is a opened,randomized and controlled phase Ⅳ clinical trial. The purpose of this study is to evaluate the immunogenicity and safety of sequential vaccination of two EV71 inactived vaccines in healthy infants aged 6-35 months. EV71 inactived vaccines(Vero cells）was manufactured by Sinovac Biotech Co., Ltd and EV71 inactived vaccines(Human diploid cells）was manufactured by Institute of Medical Biology Chinese Academy of Medical Sciences.300 infants aged between 6-35 months will be randomly assigned into experimental group in the ratio 1:1:1:1.The experimental group 1 received two doses EV71 inactived vaccines(Vero cells）on day 0 and 30. The experimental group 2 received two doses EV71 inactived vaccines (Human diploid cells）on day 0 and 30. The experimental group 3 received one dose EV71 inactived vaccines (Vero cells）on day 0 and one dose EV71 inactived vaccines (Human diploid cells）on day 30.The experimental group 4 received one dose EV71 inactived vaccines (Human diploid cells）on day 0 and one dose EV71 inactived vaccines (Vero cells）on day 30. To evaluate the immunogenicity of the vaccine, venous blood will be collected for the EV71 neutralizing antibody detection prior to vaccination and 30 days after the 2nd dose vaccination.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hand, Foot and Mouth Disease
Keywords
Inactivated Enterovirus Type 71 (EV71) Vaccine, Sequential vaccination, Immunity, Safety
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
300 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single vaccine group A
Arm Type
Experimental
Arm Description
This group receive two doses injection of EV71 inactived vaccines(Vero cells) on Day 0 and 30, and two times of blood sampling on day of 0 and 60 respectively for EV71 neutralizing antibody detection.The vaccine was manufactured by Sinovac Vaccine Technology Co., Ltd.
Arm Title
Single vaccine group B
Arm Type
Experimental
Arm Description
This group receive two doses injection of EV71 inactived vaccines(human diploid cells)on Day 0 and 30, two times of blood sampling on day of 0 and 60 respectively for EV71 neutralizing antibody detection.The vaccine was manufactured by Institute of Medical Biology Chinese Academy of Medical Sciences.
Arm Title
Sequential vaccination group A
Arm Type
Experimental
Arm Description
One dose injection of EV71 inactived vaccines(Vero cells) on Day 0，following one dose of EV71 vaccine(EV71 inactived vaccines(human diploid cells), and two times of blood sampling on day of 0 and 60 respectively for EV71 neutralizing antibody detection.
Arm Title
Sequential vaccination group B
Arm Type
Experimental
Arm Description
One dose injection of EV71 inactived vaccines(human diploid cells)on Day 0，following one does of EV71 vaccine(Sinovac Vaccine Technology Co., Ltd), and two times of blood sampling on day of 0 and 60 respectively for EV71 neutralizing antibody detection.
Intervention Type
Biological
Intervention Name(s)
EV71 inactived vaccine（Vero cells）
Intervention Description
The EV71 inactived vaccine（Vero cells） was manufactured by Sinovac Biotech Co., Ltd.
Intervention Type
Biological
Intervention Name(s)
EV71 inactived vaccine（Human diploid cells）
Intervention Description
The EV71 inactived vaccine（Human diploid cells） was manufactured by Institute of Medical Biology Chinese Academy of Medical Sciences.
Primary Outcome Measure Information:
Title
The seroconversion rates (SCR) of the EV71 neutralizing antibody calculated based on the cutoff value of 1:8.
Description
Subjects whose pre-immune EV71 antibody level < 1:8 and post-immune antibody level ≥ 1:8, or those whose pre-immune antibody level ≥ 1:8 and the increase of post-immune EV71 antibody level ≥ 4 folds are considered seroconverted
Time Frame
30 days after two doses
Secondary Outcome Measure Information:
Title
The incidences of adverse reactions after each does
Description
After each dose, a 30-minute safety observation will be conducted immediately. The body temperature, solicited local and general adverse events (AE) on day 0-7 were reported. Unsolicited adverse events on day 0-30 were also reported. Each AE case will be reviewed by the investigator to determine whether or not it was an adverse reaction (The vaccination-related AE).
Time Frame
0-30 days after each dose
Title
The incidence of solicited local and general adverse events after each does
Description
After each dose, a 30-minute safety observation will be conducted immediately. The body temperature, solicited local and general adverse events (AE) on day 0-7 were reported. Each AE case will be reviewed by the investigator to determine whether or not it was an adverse reaction (The vaccination-related AE).
Time Frame
0-7 days after each dose
Title
Incidence of serious adverse events (SAEs) during the period of safety monitoring
Description
Serious adverse events (SAEs) will be collected during the period of safety monitoring after each dose.
Time Frame
0-30 days after each dose
Title
EV71 neutralizing antibody positive rate of each group after two doses.
Description
Subjects whose post-immune antibody level ≥ 1:8 are considered antibody positive.
Time Frame
30 days after two doses
Title
The Geometric mean titer (GMT) of the EV71 neutralizing antibody
Description
The GMT 30 days of each group after two doses.
Time Frame
30 days after two doses
Title
The geometric mean fold increase (GMI) of the EV71 neutralizing antibody
Description
The GMI 30 days of each group after two doses.
Time Frame
30 days after two doses
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
35 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy volunteer aged 6-35 months;
Proven legal identity;
Guardians of the participants should be capable of understanding the written consent form, and such form should be signed before the infant being included into this study.
Exclusion Criteria:
Prior vaccination with EV71 vaccine;
History of hand，foot and mouth disease;
Allergy to gentamicin; history of allergy to any vaccine or vaccine ingredient, or serious adverse reaction(s) to vaccination, such as urticaria,difficulty in breathing, angioneurotic edema, pain, etc;
Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc;
Autoimmune diseases or immunodeficiency/immunosuppression;
Severe neurological disorders (epilepsy, convulsions or convulsions) or psychosis;
History of thyroidectomy, absence of spleen, functional absence of spleen, and any circumstances leading to absence of spleen or splenectomy;
Diagnosed coagulation function abnormal (e.g., coagulation factor deficiency, coagulation disorder, or platelet abnormalities) , or obvious bruising or coagulation disorders;
Any immunosuppressant, cytotoxic medicine, or inhaled corticosteroids (except corticosteroid spray for treatment of allergic rhinitis or corticosteroid treatment on surface for acute non-complicated dermatitis) in the past 6 months;
Receipt of any of the following products:
Blood product within 3 months prior to study entry;
Any live attenuated vaccine within 14 days prior to study entry;
Any subunit vaccine or inactivated vaccine within 7 days prior to study entry;
Any other study drugs within 30 days prior to study entry;
Acute disease or acute stage of chronic disease within 7 days prior to study entry;
Axillary temperature > 37.0℃;
Any other factor that suggesting the volunteer is unsuitable for this study based on the opinions of investigators.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AIqiang Xu
Organizational Affiliation
Shandong Provincal Center for Disease Control and Preventione
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rushan City Center for Disease Control and Prevention
City
Rushan
State/Province
Shandong
ZIP/Postal Code
264500
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
32067817
Citation
Xu Q, Cao Q, Yang W, Liu X, Liu H, Tian X, Li J, Fang X, Jia N, Zeng G, Xu A. Interchangeability of two Enterovirus 71 inactivated vaccines in Chinese children: A phase IV, open-label, and randomized controlled trial. Vaccine. 2020 Mar 10;38(12):2671-2677. doi: 10.1016/j.vaccine.2020.02.013. Epub 2020 Feb 14.
Results Reference
derived
Learn more about this trial
Immunogenicity and Safety of Two Different Commercial EV71 Vaccines
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