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The Phase IVd of Inactivated Enterovirus 71 Vaccine

Primary Purpose

Hand, Foot and Mouth Disease (HFMD)

Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
EV71 and two measles attenuated live vaccine
EV71 and attenuated Japanese encephalitis vaccine
two measles attenuated live vaccine
live attenuated Japanese encephalitis vaccine
EV71 vaccine
Sponsored by
Chinese Academy of Medical Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hand, Foot and Mouth Disease (HFMD) focused on measuring Hand, Foot and Mouth Disease (HFMD), immunogenicity, safety

Eligibility Criteria

8 Months - 9 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 14-month visit (and receive blood, stool (or specimens by means of a swab) tests according to program requirements in immunogenicity observation group)

Exclusion Criteria:

  • Allergy or serious side-effects to a vaccine or any ingredient of vaccine
  • Epilepsy, seizures, convulsions, neurological illness
  • Congenital or hereditary immunodeficiency
  • Autoimmune disease
  • 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 ﹥90 mmHg; 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

  • Guangdong Province Center for Diseases Control and Prevention

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Active Comparator

Active Comparator

Active Comparator

Arm Label

EV71 and two measles attenuated live vaccine

EV71 and attenuated Japanese encephalitis vaccine

two measles attenuated live vaccine

live attenuated Japanese encephalitis vaccine

EV71 vaccine

Arm Description

infants vaccinated with enterovirus type 71 inactivated vaccine (human diploid cell) and two measles attenuated live vaccine at 8 months old, and vaccinated with the second dose of enterovirus type 71 inactivated vaccine (human diploid cell) at 9 months old.

infants vaccinated with enterovirus type 71 inactivated vaccine (human diploid cell) and live attenuated Japanese encephalitis vaccine at 8 months old, and vaccinated with the second dose of enterovirus type 71 inactivated vaccine (human diploid cell) at 9 months old.

infants vaccinated with two measles attenuated live vaccine at 8 months old

infants vaccinated with live attenuated Japanese encephalitis vaccine at 8 months old

infants vaccinated with enterovirus type 71 inactivated vaccine (human diploid cell) at 8 months old, and vaccinated with the second dose of enterovirus type 71 inactivated vaccine (human diploid cell) at 9 months old.

Outcomes

Primary Outcome Measures

Evaluate the seropositive rate of anti-EV71 antibodies in serum of children before first vaccination
Bloods were obtained before first vaccination. The antibody titers were tested in serum of children.
Evaluate the seropositive rate of anti-EBV antibodies in serum of children before first vaccination
Bloods were obtained before first vaccination. The antibody titers were tested in serum of children.
Evaluate the seropositive rate of anti-measles virus antibodies in serum of children before first vaccination
Bloods were obtained before first vaccination. The antibody titers were tested in serum of children.
Evaluate the seropositive rate of anti-Rubella virus antibodies in serum of children before first vaccination
Bloods were obtained before first vaccination. The antibody titers were tested in serum of children.
Evaluate the seroconversion rate of anti-EV71 antibodies in serum of children at 56 days after first vaccination
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children.
Evaluate the seroconversion rate of anti-EBV antibodies in serum of children at 56 days after first vaccination
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children.
Evaluate the seroconversion rate of anti-measles virus antibodies in serum of children at 56 days after first vaccination
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children.
Evaluate the seroconversion rate of anti-Rubella virus antibodies in serum of children at 56 days after first vaccination
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children.

Secondary Outcome Measures

Evaluate the antibody titers of anti-EV71 antibodies in serum of children
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children at 56 days.
Evaluate the antibody titers of anti-EBV antibodies in serum of children
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children at 56 days.
Evaluate the antibody titers of anti-measles virus antibodies in serum of children
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children at 56 days.
Evaluate the antibody titers of anti-Rubella virus antibodies in serum of children
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children at 56 days.
Incidence of treatment adverse events finishing 1st doses immunization
The adverse events were observed and recorded within 30 minutes post immunization (p.i.), within 0-1 days post immunization (d.p.i.), within 1-3 d.p.i. and within 28 d.p.i. after the 1st injection.
Incidence of treatment adverse events finishing 2nd doses immunization
The adverse events were observed and recorded within 30 minutes post immunization (p.i.), within 0-1 days post immunization (d.p.i.), within 1-3 d.p.i. and within 28 d.p.i. after injection.

Full Information

First Posted
September 1, 2017
Last Updated
September 27, 2017
Sponsor
Chinese Academy of Medical Sciences
Collaborators
Guangdong Center for Disease Prevention and Control
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1. Study Identification

Unique Protocol Identification Number
NCT03296410
Brief Title
The Phase IVd of Inactivated Enterovirus 71 Vaccine
Official Title
The Safety and Immunogenicity of Enterovirus Type 71 Inactivated Vaccine (Human Diploid Cell) With Two Measles Attenuated Live Vaccine and Live Attenuated Japanese Encephalitis Vaccine at the Same Time Point in Infants (8-month-old)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Unknown status
Study Start Date
September 14, 2017 (Actual)
Primary Completion Date
September 2, 2019 (Anticipated)
Study Completion Date
September 2, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese Academy of Medical Sciences
Collaborators
Guangdong Center for Disease Prevention and Control

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
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 IVd is to evaluated the immunogenicity and safety of the inactive EV71 vaccine within two measles attenuated live vaccine and live attenuated Japanese encephalitis vaccine at the same time point in large scale population of Chinese children (8 months old) in Guangdong Province, China.
Detailed Description
There are two parts of phase IVd clinical trials have been performed. First, to evaluate the immunogenicity of the inactive EV71 vaccine within two measles attenuated live vaccine and live attenuated Japanese encephalitis vaccine at the same time point in large scale population of Chinese children (8 months old), within 56-day-post-immunized. Second, to safety of the inactive EV71 vaccine within two measles attenuated live vaccine and live attenuated Japanese encephalitis vaccine at the same time point in large scale population of Chinese children (8 months old), within 56-day-post-immunized.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hand, Foot and Mouth Disease (HFMD)
Keywords
Hand, Foot and Mouth Disease (HFMD), immunogenicity, safety

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1220 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
EV71 and two measles attenuated live vaccine
Arm Type
Experimental
Arm Description
infants vaccinated with enterovirus type 71 inactivated vaccine (human diploid cell) and two measles attenuated live vaccine at 8 months old, and vaccinated with the second dose of enterovirus type 71 inactivated vaccine (human diploid cell) at 9 months old.
Arm Title
EV71 and attenuated Japanese encephalitis vaccine
Arm Type
Experimental
Arm Description
infants vaccinated with enterovirus type 71 inactivated vaccine (human diploid cell) and live attenuated Japanese encephalitis vaccine at 8 months old, and vaccinated with the second dose of enterovirus type 71 inactivated vaccine (human diploid cell) at 9 months old.
Arm Title
two measles attenuated live vaccine
Arm Type
Active Comparator
Arm Description
infants vaccinated with two measles attenuated live vaccine at 8 months old
Arm Title
live attenuated Japanese encephalitis vaccine
Arm Type
Active Comparator
Arm Description
infants vaccinated with live attenuated Japanese encephalitis vaccine at 8 months old
Arm Title
EV71 vaccine
Arm Type
Active Comparator
Arm Description
infants vaccinated with enterovirus type 71 inactivated vaccine (human diploid cell) at 8 months old, and vaccinated with the second dose of enterovirus type 71 inactivated vaccine (human diploid cell) at 9 months old.
Intervention Type
Biological
Intervention Name(s)
EV71 and two measles attenuated live vaccine
Intervention Description
infants vaccined with two dose (3.0 EU/dose) of inactivated enterovirus 71 vaccine (KMB-17) at 8 months old and 9 months old (namely interval one month). And meanwhile, they routine vaccined with two measles attenuated live vaccine at 8 months old.
Intervention Type
Biological
Intervention Name(s)
EV71 and attenuated Japanese encephalitis vaccine
Intervention Description
infants vaccined with two dose (3.0 EU/dose) of inactivated enterovirus 71 vaccine (KMB-17) at 8 months old and 9 months old (namely interval one month). And meanwhile, they routine vaccined with attenuated Japanese encephalitis vaccine at 8 months old.
Intervention Type
Biological
Intervention Name(s)
two measles attenuated live vaccine
Intervention Description
infants vaccined with one dose two measles attenuated live vaccine at 8 months old.
Intervention Type
Biological
Intervention Name(s)
live attenuated Japanese encephalitis vaccine
Intervention Description
infants vaccined with one dose attenuated Japanese encephalitis vaccine at 8 months old.
Intervention Type
Biological
Intervention Name(s)
EV71 vaccine
Intervention Description
infants vaccined with two dose (3.0 EU/dose) of inactivated enterovirus 71 vaccine (KMB-17) at 8 months old and 9 months old (namely interval one month).
Primary Outcome Measure Information:
Title
Evaluate the seropositive rate of anti-EV71 antibodies in serum of children before first vaccination
Description
Bloods were obtained before first vaccination. The antibody titers were tested in serum of children.
Time Frame
at 0 day before finishing 1st doses immunization
Title
Evaluate the seropositive rate of anti-EBV antibodies in serum of children before first vaccination
Description
Bloods were obtained before first vaccination. The antibody titers were tested in serum of children.
Time Frame
at 0 day before finishing 1st doses immunization
Title
Evaluate the seropositive rate of anti-measles virus antibodies in serum of children before first vaccination
Description
Bloods were obtained before first vaccination. The antibody titers were tested in serum of children.
Time Frame
at 0 day before finishing 1st doses immunization
Title
Evaluate the seropositive rate of anti-Rubella virus antibodies in serum of children before first vaccination
Description
Bloods were obtained before first vaccination. The antibody titers were tested in serum of children.
Time Frame
at 0 day before finishing 1st doses immunization
Title
Evaluate the seroconversion rate of anti-EV71 antibodies in serum of children at 56 days after first vaccination
Description
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children.
Time Frame
at 56 days after finishing 1st doses immunization
Title
Evaluate the seroconversion rate of anti-EBV antibodies in serum of children at 56 days after first vaccination
Description
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children.
Time Frame
at 56 days after finishing 1st doses immunization
Title
Evaluate the seroconversion rate of anti-measles virus antibodies in serum of children at 56 days after first vaccination
Description
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children.
Time Frame
at 56 days after finishing 1st doses immunization
Title
Evaluate the seroconversion rate of anti-Rubella virus antibodies in serum of children at 56 days after first vaccination
Description
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children.
Time Frame
at 56 days after finishing 1st doses immunization
Secondary Outcome Measure Information:
Title
Evaluate the antibody titers of anti-EV71 antibodies in serum of children
Description
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children at 56 days.
Time Frame
at 56 days after finishing 1st doses immunization
Title
Evaluate the antibody titers of anti-EBV antibodies in serum of children
Description
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children at 56 days.
Time Frame
at 56 days after finishing 1st doses immunization
Title
Evaluate the antibody titers of anti-measles virus antibodies in serum of children
Description
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children at 56 days.
Time Frame
at 56 days after finishing 1st doses immunization
Title
Evaluate the antibody titers of anti-Rubella virus antibodies in serum of children
Description
Bloods were obtained at 56 days after first vaccination. The antibody titers were tested in serum of children at 56 days.
Time Frame
at 56 days after finishing 1st doses immunization
Title
Incidence of treatment adverse events finishing 1st doses immunization
Description
The adverse events were observed and recorded within 30 minutes post immunization (p.i.), within 0-1 days post immunization (d.p.i.), within 1-3 d.p.i. and within 28 d.p.i. after the 1st injection.
Time Frame
within 28 days after finishing 1st doses immunization
Title
Incidence of treatment adverse events finishing 2nd doses immunization
Description
The adverse events were observed and recorded within 30 minutes post immunization (p.i.), within 0-1 days post immunization (d.p.i.), within 1-3 d.p.i. and within 28 d.p.i. after injection.
Time Frame
within 28 days after finishing 2nd doses immunization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Months
Maximum Age & Unit of Time
9 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 14-month visit (and receive blood, stool (or specimens by means of a swab) tests according to program requirements in immunogenicity observation group) Exclusion Criteria: Allergy or serious side-effects to a vaccine or any ingredient of vaccine Epilepsy, seizures, convulsions, neurological illness Congenital or hereditary immunodeficiency Autoimmune disease 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 ﹥90 mmHg; 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
Facility Information:
Facility Name
Guangdong Province Center for Diseases Control and Prevention
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
511430
Country
China

12. IPD Sharing Statement

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The Phase IVd of Inactivated Enterovirus 71 Vaccine

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