Back to resultsClinical Trial of Enterovirus 71（EV71） Inactivated Vaccine in Children Aged 36-71 Months
Primary Purpose
Hand, Foot and Mouth Disease
Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
36-71 months old children-experimental EV71 vaccine.
36-71 months old children-control EV71 vaccine.
6-35 months old children-experimental EV71 vaccine.
Sponsored by
About this trial
This is an interventional prevention trial for Hand, Foot and Mouth Disease
Eligibility Criteria
Inclusion Criteria:
- Healthy volunteers ≥ 2 years old;
- Proven legal identity;
- Participants or guardians of the participants should be capable of understanding the written consent form, and such form should be signed prior to enrolment.
Exclusion Criteria:
- Prior vaccination with EV71 vaccine;
- History of hand, foot and mouth disease;
- History of allergy to any vaccine or vaccine ingredient, asthma, serious adverse reactions to vaccination, such as urticaria, dyspnea, angioneurotic edema, abdominal pain, etc;
- Congenital malformation, developmental disorders, genetic defects, or severe malnutrition;
- Autoimmune disease or immunodeficiency/immunosuppressive;
- Severe/uncontrollable nervous system disease (epilepsy, seizures or convulsions) or mental illness;
- History of thyroidectomy, no spleen and functional spleen;
- Diagnosed coagulation function abnormal (e.g., coagulation factor deficiency, coagulation disorder, or platelet abnormalities) , or obvious bruising or coagulation disorders;
Receipt of any of the following products:
- 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) within 6 month prior to study entry
- Blood products within 2 months prior to study entry
- Any other investigational products (drug or vaccine）within 30 days 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;
- Acute disease or acute stage of chronic disease within 7 days prior to study entry;
- Axillary temperature > 37.0 °C;
- Any other factor that suggesting the volunteer is unsuitable for this study based on the opinions of investigators.
Sites / Locations
- Yun County Center for Disease Control and Prevention
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
Experimental group
Vaccine-controlled group
Age-controlled group
Arm Description
36-71 months old children-experimental EV71 vaccine.
36-71 months old children-control EV71 vaccine.
6-35 months old children-experimental EV71 vaccine.
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 antibody titer < 1:8 and post-immune antibody titer ≥ 1:8, or those whose pre-immune antibody titer ≥ 1:8 and the increase of post-immune antibody level ≥ 4 folds are considered seroconverted.
The Geometric mean titer (GMT) of the EV71 neutralizing antibody in the susceptible population
The susceptible population refer to the subjects whose pre-immune antibody titer <1:8
Secondary Outcome Measures
The overall incidence of adverse reactions
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. The solicited local symptoms include pain, induration, redness, swelling, rash, and pruritus. The solicited general adverse symptoms include allergy, fatigue, irritability, inappetence, vomiting, diarrhea, and fever. Unsolicited adverse events on day 0-30 were also reported, which include the unsolicited symptoms happened within 0-7 days, and any symptoms happened within the 8-28 days. Each AE case will be reviewed by the investigator to determine whether it was an adverse reaction (The vaccination-related AE). The incidence of adverse reactions=Number of subjects who have adverse reactions of any symptoms/number of all the subjects whose safety information are collected.
The incidence of the serious adverse events (SAE)
After each dose, the serious adverse events in the safety observation period will be reported. The SAE incidence=Number of subjects who have SAE of any symptoms/Number of subjects whose safety information are collected.
The seroconversion rates (SCR) of the EV71 neutralizing antibody calculated based on the cutoff value of 1:16, 1:32, and 1:64 respectively
Subjects whose pre-immune antibody titer <1:16(1:32/1:64) and post-immune antibody titer ≥1:16(1:32/1:64), or those whose pre-immune antibody titer ≥ 1:16(1:32/1:64) and the increase of post-immune antibody level ≥ 4 folds are considered seroconverted.
The Geometric mean titer (GMT) of the EV71 neutralizing antibody
The GMT 30 days after two doses.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03909074
Brief Title
Clinical Trial of Enterovirus 71（EV71） Inactivated Vaccine in Children Aged 36-71 Months
Official Title
A Phase III Clinical Trial With Randomized, Double-blinded, Controlled Design as Well as Bridging Design to Evaluate the Safety and Immunogenicity of EV71 Vaccine in Children Aged 36-71 Months
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
March 10, 2019 (Actual)
Primary Completion Date
June 17, 2019 (Actual)
Study Completion Date
November 13, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sinovac Biotech Co., Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the non-inferiority of experimental EV71 vaccine compared to the control EV71 vaccine in children aged 36-71 months, to evaluate the non-inferiority of EV71 vaccine used in children aged 36-71 months compared to 6-35 months. The experimental vaccine was manufactured by Sinovac Biotech Co., Ltd, and the control vaccine was manufactured by Institute of Medical Biology Chinese Academy of Medical Sciences.
Detailed Description
This study is a randomized, double-blind, single-center, controlled phase III clinical trial in children aged 36-71 months, and bridging trial between agegroup of 6-35 and 36-71 months. The purpose of this study is to evaluate the immunogenicity and safety of the experimental EV71 vaccine in children aged 36-71 months. The primary objective of this study is to evaluate the non-inferiority of experimental EV71 vaccine compared to the control EV71 vaccine in children aged 36-71 months, and the non-inferiority of EV71 vaccine used in children aged 36-71 months compared to 6-35 months. The secondary objective is to evaluate the safety of the experimental vaccine used in children aged 36-71 months. The experimental vaccine is manufactured by Sinovac Biotech Co., Ltd, and the control vaccine is manufactured by Institute of Medical Biology Chinese Academy of Medical Sciences. 600 children aged 36-71 months will be randomly assigned in to receive the experimental vaccine or control vaccine, and 300 children aged 6-35 months will receive the experimental vaccine.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hand, Foot and Mouth Disease
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
900 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Experimental group
Arm Type
Experimental
Arm Description
36-71 months old children-experimental EV71 vaccine.
Arm Title
Vaccine-controlled group
Arm Type
Active Comparator
Arm Description
36-71 months old children-control EV71 vaccine.
Arm Title
Age-controlled group
Arm Type
Active Comparator
Arm Description
6-35 months old children-experimental EV71 vaccine.
Intervention Type
Biological
Intervention Name(s)
36-71 months old children-experimental EV71 vaccine.
Intervention Description
Two doses experimental EV71 vaccine at the 0, 30 days vaccination schedule.
Intervention Type
Biological
Intervention Name(s)
36-71 months old children-control EV71 vaccine.
Intervention Description
Two doses control EV71 vaccine at the 0, 30 days vaccination schedule.
Intervention Type
Biological
Intervention Name(s)
6-35 months old children-experimental EV71 vaccine.
Intervention Description
Two doses experimental EV71 vaccine at the 0, 30 days vaccination schedule.
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 antibody titer < 1:8 and post-immune antibody titer ≥ 1:8, or those whose pre-immune antibody titer ≥ 1:8 and the increase of post-immune antibody level ≥ 4 folds are considered seroconverted.
Time Frame
30 days after two doses
Title
The Geometric mean titer (GMT) of the EV71 neutralizing antibody in the susceptible population
Description
The susceptible population refer to the subjects whose pre-immune antibody titer <1:8
Time Frame
30 days after two doses
Secondary Outcome Measure Information:
Title
The overall incidence of adverse reactions
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. The solicited local symptoms include pain, induration, redness, swelling, rash, and pruritus. The solicited general adverse symptoms include allergy, fatigue, irritability, inappetence, vomiting, diarrhea, and fever. Unsolicited adverse events on day 0-30 were also reported, which include the unsolicited symptoms happened within 0-7 days, and any symptoms happened within the 8-28 days. Each AE case will be reviewed by the investigator to determine whether it was an adverse reaction (The vaccination-related AE). The incidence of adverse reactions=Number of subjects who have adverse reactions of any symptoms/number of all the subjects whose safety information are collected.
Time Frame
0-30 days after each dose
Title
The incidence of the serious adverse events (SAE)
Description
After each dose, the serious adverse events in the safety observation period will be reported. The SAE incidence=Number of subjects who have SAE of any symptoms/Number of subjects whose safety information are collected.
Time Frame
0-30 days after each dose
Title
The seroconversion rates (SCR) of the EV71 neutralizing antibody calculated based on the cutoff value of 1:16, 1:32, and 1:64 respectively
Description
Subjects whose pre-immune antibody titer <1:16(1:32/1:64) and post-immune antibody titer ≥1:16(1:32/1:64), or those whose pre-immune antibody titer ≥ 1:16(1:32/1:64) and the increase of post-immune antibody level ≥ 4 folds are considered seroconverted.
Time Frame
30 days after two doses
Title
The Geometric mean titer (GMT) of the EV71 neutralizing antibody
Description
The GMT 30 days 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
71 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy volunteers ≥ 2 years old;
Proven legal identity;
Participants or guardians of the participants should be capable of understanding the written consent form, and such form should be signed prior to enrolment.
Exclusion Criteria:
Prior vaccination with EV71 vaccine;
History of hand, foot and mouth disease;
History of allergy to any vaccine or vaccine ingredient, asthma, serious adverse reactions to vaccination, such as urticaria, dyspnea, angioneurotic edema, abdominal pain, etc;
Congenital malformation, developmental disorders, genetic defects, or severe malnutrition;
Autoimmune disease or immunodeficiency/immunosuppressive;
Severe/uncontrollable nervous system disease (epilepsy, seizures or convulsions) or mental illness;
History of thyroidectomy, no spleen and functional spleen;
Diagnosed coagulation function abnormal (e.g., coagulation factor deficiency, coagulation disorder, or platelet abnormalities) , or obvious bruising or coagulation disorders;
Receipt of any of the following products:
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) within 6 month prior to study entry
Blood products within 2 months prior to study entry
Any other investigational products (drug or vaccine）within 30 days 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;
Acute disease or acute stage of chronic disease within 7 days prior to study entry;
Axillary temperature > 37.0 °C;
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
Lifen Zhang, Master
Organizational Affiliation
Yunnan Center for Disease Control and Prevention
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yun County Center for Disease Control and Prevention
City
Lincang
State/Province
Yunnan
ZIP/Postal Code
675800
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
33269798
Citation
Zhang L, Gao F, Zeng G, Yang H, Zhu T, Yang S, Meng X, Mao Q, Liu X. Immunogenicity and Safety of Inactivated Enterovirus 71 Vaccine in Children Aged 36-71 Months: A Double-Blind, Randomized, Controlled, Non-inferiority Phase III Trial. J Pediatric Infect Dis Soc. 2021 Apr 30;10(4):440-447. doi: 10.1093/jpids/piaa129.
Results Reference
derived
Learn more about this trial
Clinical Trial of Enterovirus 71（EV71） Inactivated Vaccine in Children Aged 36-71 Months
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