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The Phase IVa of Inactivated Enterovirus 71 Vaccine (Human Diploid Cell, KMB-17)

Primary Purpose

Safety of Inactivated EV71 Vaccine, Immunization of Inactivated EV71 Vaccine

Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
inactivated EV71 vaccine (KMB-17)
Sponsored by
Chinese Academy of Medical Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Safety of Inactivated EV71 Vaccine focused on measuring safety, immune persistence

Eligibility Criteria

6 Months - 71 Months (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy subjects (6-71 months old children) as established by medical history and clinical examination
  • The subjects' legal guardian must be aware of this vaccines
  • The subjects' legal guardian voluntarily participate in the study and signed Informed Consent Form
  • Subjects with temperature ≤ 37.0 ℃
  • The subjects' legal guardian with the ability and objective to comply with the requirements of the protocol
  • Persist for a 24-month visit (and receive blood, stool (or specimens by means of a swab) tests according to program requirements in immunogenicity observation group)
  • report the HFMD cases

Exclusion Criteria:

  • Subject who has a clinical diagnosis history of Hand, Foot and Mouth Disease (HFMD)
  • Allergy or serious side-effects to a vaccine or any ingredient of vaccine
  • Epilepsy, seizures, convulsions, neurological illness
  • Congenital or hereditary immunodeficiency
  • Autoimmune disease
  • Severe malnutrition or dysgenopathy
  • Asthma, thyroidectomy, angioneurotic edema, diabetes or cancer
  • Asplenia, functional asplenia, and any circumstances leading to the asplenia or splenectomy
  • Clinical diagnosis of coagulopathy (such as clotting factor deficiency, coagulation disorders, platelet abnormalities), significant bruising or blood clotting disorder
  • Acute illness or acute exacerbation of chronic disease in last 7 days
  • Any prior administration of immunodepressant or corticosteroids in last 6 months
  • Any prior administration of blood products in last 3 months
  • Any prior administration of live-attenuated vaccine in last 15 days
  • Any prior administration of subunit or inactivated vaccines in last 7 days
  • Fever before vaccination, axillary temperature ﹥37.0 ℃
  • The laboratory test abnormalities before vaccination, including blood tests (hemoglobin, total white blood cells, WBC, platelets), blood biochemistry tests (ALT, total bilirubin, direct bilirubin, Cr, BUN) and urine tests (urine protein, urine sugar, blood cells), etc.
  • Hypertension or hypotension. Systolic blood pressure ﹥140 mmHg and/or diastolic blood pressure ﹥90mmHg; systolic blood pressure ﹤90 mmHg and/or diastolic blood pressure ﹤60 mmHg
  • Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives
  • take part into other vaccine or drug clinical trials in last half year

Sites / Locations

  • Chaoyang of Provincial Center for Diseases Control and Prevention in Beijing

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

3.0 EU in Children

Arm Description

healthy children (6-71 months old) have been injected by inactivated EV71 vaccine (KMB-17) of 3.0 EU (neutralization antibodies titer unit; 100 U in phase III clinical trials, or 320 EU (Elisa assay unit) in phase I and II clinical trials)

Outcomes

Primary Outcome Measures

Incidence of treatment adverse events
The adverse events were observed and recorded within 30 minutes post immunization (p.i.), within 0-7 days post immunization (d.p.i.) and within 8-28 d.p.i after the 1st injection, as well as after the 2nd injection. And the adverse events were also observed and recorded following within 24 months after finishing 2 doses immunization.

Secondary Outcome Measures

The incidence rates of HFMD
All hand, foot and mouth disease (HFMD) cases from the subjects were observed and recorded, including common cases, severe cases, dead cases, the cases caused by enterovirus 71, the severe cases caused by enterovirus 71, the dead cases caused by enterovirus 71. The incidence rates of the subjects from this clinical trial were calculated.
immune response of inactivated EV71 vaccine (KMB-17) in a large crowd
The blood specimens were obtained at 0, 28, 56, 180, 360 and 720 days post the 1st immunization (p.i.). The levels of neutralization antibodies and cytokines were tested at each time point. The seroconversion rate of anti-EV71 antibodies was evaluated in serum of children. And the specific IFN-γ in subjects were tested and evaluated at 0, 180 and 360 d.p.i..

Full Information

First Posted
September 16, 2016
Last Updated
January 18, 2018
Sponsor
Chinese Academy of Medical Sciences
Collaborators
Beijing Chaoyang District Centre for Disease Control and Prevention, Neimenggu Province Centre for Disease Control and Prevention
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1. Study Identification

Unique Protocol Identification Number
NCT02999828
Brief Title
The Phase IVa of Inactivated Enterovirus 71 Vaccine (Human Diploid Cell, KMB-17)
Official Title
The Safety, Immune Persistence and Consistency of Inactivated Enterovirus 71 Vaccine (Human Diploid Cell, KMB-17)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Unknown status
Study Start Date
September 2016 (Actual)
Primary Completion Date
February 2019 (Anticipated)
Study Completion Date
February 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese Academy of Medical Sciences
Collaborators
Beijing Chaoyang District Centre for Disease Control and Prevention, Neimenggu Province Centre for Disease Control and Prevention

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Enterovirus 71 (EV71), a major pathogen causing hand-foot-and-mouth disease (HFMD) worldwide, is a member of the Human Enterovirus species A, family Picornaviridae. Its infection occasionally leads to severe diseases and death, with central nervous system (CNS) damage. Recently, except of inactivated vaccine, several EV71 vaccine candidates have been evaluated in animals but no final results of clinical trials, such as attenuated vaccine, subunit vaccine. A formalin-inactivated EV71 vaccine (Human Diploid cell, KMB-17 Cell) has been finished phase I, II and III clinical trials and licensed by SFDA in China at Dec. 3, 2015. Based on the results of clinical trials, the protective efficacy of inactivated EV71 vaccine is 97% against HFMD caused by EV71. The phase IV clinical trial has been carried out from July 2016. The purpose of phase IV is to evaluated the safety and efficacy of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old).
Detailed Description
Enterovirus 71 (EV71), a major pathogen causing hand-foot-and-mouth disease (HFMD) worldwide, is a member of the Human Enterovirus species A, family Picornaviridae. Its infection occasionally leads to severe diseases and death, with central nervous system (CNS) damage. Recently, except of inactivated vaccine, several EV71 vaccine candidates have been evaluated in animals but no final results of clinical trials, such as attenuated vaccine, subunit vaccine. A formalin-inactivated EV71 vaccine (Human Diploid cell, KMB-17 Cell) has been finished phase I, II and III clinical trials and licensed by SFDA in China at Dec. 3, 2015. Based on the results of clinical trials, the protective efficacy of inactivated EV71 vaccine is 97% against HFMD caused by EV71. The phase IV clinical trial has been carried out from July 2016. The purpose of phase IV is to evaluated the safety and efficacy of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old). There are three parts of phase IV clinical trials have been performed. First, to evaluate the safety of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old). Second, to evaluate the immune persistence of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old). Third, to evaluate the efficacy of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Safety of Inactivated EV71 Vaccine, Immunization of Inactivated EV71 Vaccine
Keywords
safety, immune persistence

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20770 (Actual)

8. Arms, Groups, and Interventions

Arm Title
3.0 EU in Children
Arm Type
Experimental
Arm Description
healthy children (6-71 months old) have been injected by inactivated EV71 vaccine (KMB-17) of 3.0 EU (neutralization antibodies titer unit; 100 U in phase III clinical trials, or 320 EU (Elisa assay unit) in phase I and II clinical trials)
Intervention Type
Biological
Intervention Name(s)
inactivated EV71 vaccine (KMB-17)
Intervention Description
3.0EU of inactivated enterovirus 71 vaccine (KMB-17) on day 0, 28.
Primary Outcome Measure Information:
Title
Incidence of treatment adverse events
Description
The adverse events were observed and recorded within 30 minutes post immunization (p.i.), within 0-7 days post immunization (d.p.i.) and within 8-28 d.p.i after the 1st injection, as well as after the 2nd injection. And the adverse events were also observed and recorded following within 24 months after finishing 2 doses immunization.
Time Frame
Up to 24 months after finishing 2 doses immunization
Secondary Outcome Measure Information:
Title
The incidence rates of HFMD
Description
All hand, foot and mouth disease (HFMD) cases from the subjects were observed and recorded, including common cases, severe cases, dead cases, the cases caused by enterovirus 71, the severe cases caused by enterovirus 71, the dead cases caused by enterovirus 71. The incidence rates of the subjects from this clinical trial were calculated.
Time Frame
Up to 24 months after finishing 2 doses immunization
Title
immune response of inactivated EV71 vaccine (KMB-17) in a large crowd
Description
The blood specimens were obtained at 0, 28, 56, 180, 360 and 720 days post the 1st immunization (p.i.). The levels of neutralization antibodies and cytokines were tested at each time point. The seroconversion rate of anti-EV71 antibodies was evaluated in serum of children. And the specific IFN-γ in subjects were tested and evaluated at 0, 180 and 360 d.p.i..
Time Frame
Up to 24 months after finishing 2 doses immunization
Other Pre-specified Outcome Measures:
Title
The level of anti-EV71 antibodies was evaluated in serum of children
Description
The blood specimens were obtained at 0, 28, 56, 180, 360 and 720 days post the 1st immunization (p.i.). The levels of neutralization antibodies were tested at each time point. The level of anti-EV71 antibodies was evaluated in serum of children.
Time Frame
Up to 24 months after finishing 2 doses immunization

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 subjects (6-71 months old children) as established by medical history and clinical examination The subjects' legal guardian must be aware of this vaccines The subjects' legal guardian voluntarily participate in the study and signed Informed Consent Form Subjects with temperature ≤ 37.0 ℃ The subjects' legal guardian with the ability and objective to comply with the requirements of the protocol Persist for a 24-month visit (and receive blood, stool (or specimens by means of a swab) tests according to program requirements in immunogenicity observation group) report the HFMD cases Exclusion Criteria: Subject who has a clinical diagnosis history of Hand, Foot and Mouth Disease (HFMD) Allergy or serious side-effects to a vaccine or any ingredient of vaccine Epilepsy, seizures, convulsions, neurological illness Congenital or hereditary immunodeficiency Autoimmune disease Severe malnutrition or dysgenopathy Asthma, thyroidectomy, angioneurotic edema, diabetes or cancer Asplenia, functional asplenia, and any circumstances leading to the asplenia or splenectomy Clinical diagnosis of coagulopathy (such as clotting factor deficiency, coagulation disorders, platelet abnormalities), significant bruising or blood clotting disorder Acute illness or acute exacerbation of chronic disease in last 7 days Any prior administration of immunodepressant or corticosteroids in last 6 months Any prior administration of blood products in last 3 months Any prior administration of live-attenuated vaccine in last 15 days Any prior administration of subunit or inactivated vaccines in last 7 days Fever before vaccination, axillary temperature ﹥37.0 ℃ The laboratory test abnormalities before vaccination, including blood tests (hemoglobin, total white blood cells, WBC, platelets), blood biochemistry tests (ALT, total bilirubin, direct bilirubin, Cr, BUN) and urine tests (urine protein, urine sugar, blood cells), etc. Hypertension or hypotension. Systolic blood pressure ﹥140 mmHg and/or diastolic blood pressure ﹥90mmHg; systolic blood pressure ﹤90 mmHg and/or diastolic blood pressure ﹤60 mmHg Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives take part into other vaccine or drug clinical trials in last half year
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nianmin Shi, M.S.
Organizational Affiliation
Chaoyang Provincial Center for Diseases Control and Prevention in Beijing
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Shaohong Yan, M.S.
Organizational Affiliation
Neimenggu Provincial Center for Diseases Control and Prevention
Official's Role
Study Chair
Facility Information:
Facility Name
Chaoyang of Provincial Center for Diseases Control and Prevention in Beijing
City
Beijing
ZIP/Postal Code
100021
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Participants do not agree to share individual data.

Learn more about this trial

The Phase IVa of Inactivated Enterovirus 71 Vaccine (Human Diploid Cell, KMB-17)

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