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A Clinical Trial to Assess the Efficacy and Safety of an Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children Aged 6-35 Months

Primary Purpose

Hand, Foot and Mouth Disease, Herpangina, Other EV71-associated Diseases

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
inactivated vaccine (Vero Cell) against EV71
0/0.5ml placebo
Sponsored by
Jiangsu Province Centers for Disease Control and Prevention
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hand, Foot and Mouth Disease focused on measuring efficacy, safety, inactivated vaccine (Vero Cell) against EV71, EV71-associated diseases

Eligibility Criteria

6 Months - 35 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Only subjects fulfilling all of the following criteria will be eligible for the study:

  • Healthy children aged from 6 to 35 months old
  • General good health as established by medical history and physical examination
  • The subjects' guardians are able to understand and sign the informed consent
  • Had never received the vaccine against EV71
  • The subjects' guardians allow to comply with the requirements of the protocol
  • Available for all visits scheduled in this study
  • Subjects with temperature <=37.0°C on axillary setting

Exclusion Criteria:

Subjects will not be eligible for the study if any of the following criteria is met:

  • Subject who has a medical history of HFMD
  • Subject that has a medical history of any of the following: allergic history, or allergic to any ingredient of vaccine
  • Family history of seizures or progressive neurological disease
  • Family history of congenital or hereditary immunodeficiency
  • Severe malnutrition or hypogenesis
  • Major congenital defects or serious chronic illness, including perinatal brain damage
  • Autoimmune disease
  • Bleeding disorder diagnosed by a doctor or significant bruising or bleeding difficulties with IM injections or blood draws
  • Asplenia, functional asplenia, or splenic excision
  • History of asthma, angioneurotic edema, diabetes or malignant tumour
  • History of thyroidectomy, or thyroid disease in last 12 months
  • Any acute infections 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 other research vaccines or medicines in last 1 month
  • Any prior administration of attenuated live vaccine in last 15 days
  • Any prior administration of subunit or inactivated vaccines in last 7 days
  • Under the anti-TB prevention or therapy
  • Subjects with temperature >37.0°C on axillary setting
  • Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives

Exclusion Criteria for the second dose:

Subjects will not be eligible for the second dose if any of following adverse events happened after the first dose. They can continue other process of the study without the second dose vaccination according to the opinion of the investigator.

  • Had any serious adverse events related to the first dose of inactivated vaccine (vero cell) against EV71 within 7 days
  • Hypersensitivity reactions after vaccination (including urticaria/rashes that occur within 30 minutes after inoculation)
  • Anaphylaxis after vaccination
  • Any confirmed or suspected autoimmune disease or immune deficiency diseases, including human immunodeficiency virus (HIV) infection
  • Any condition that in the opinion of the investigator, or IRB

Sites / Locations

  • Donghai County Center for Disease Control and Prevention
  • Pizhou County-Level City Center for Disease Control and Prevention
  • Baoying County Center for Disease Control and Prevention
  • Chaoyang Distinct Center for Disease Control and Prevention

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

vaccine against EV71

placebo

Arm Description

Inactivated vaccine (Vero Cell) against EV71 of 320U /0.5ml in 5000 children aged 6-35 months on day0, 28

0/0.5ml placebo in 5000 children aged 6-35 months on day0, 28

Outcomes

Primary Outcome Measures

the incidence density of the EV71-associated diseases in the vaccine group and placebo group.
compare the incidence density of the EV71-associated diseases between the vaccine group and placebo group in Chinese children aged 6-35 months.

Secondary Outcome Measures

the frequency of all the adverse events in vaccine group and placebo group.
compare frequency of all the solicited events, unsolicited adverse events and serious adverse events between vaccine group and placebo group.
Seropositive rate of the vaccine group
calculate the seropositive rate of the vaccine group in Chinese children aged 6-35 months at month 8 after first vaccination.
Seroconversion rate of the vaccine group
calculate the seroconversion rate of the vaccine group in Chinese children aged 6-35 months at month 8 after first vaccination.
GMT of the vaccine group
calculate the geometric mean titre (GMT) of the vaccine group in Chinese children aged 6-35 months at month 8 after first vaccination.
Seropositive rate of the vaccine group
calculate the seropositive rate of the vaccine group in Chinese children aged 6-35 months at month 14 after first vaccination.
Seroconversion rate of the vaccine group
calculate the seroconversion rate of the vaccine group in Chinese children aged 6-35 months at month 14 after first vaccination.
GMT of the vaccine group
calculate the geometric mean titre (GMT) of the vaccine group in Chinese children aged 6-35 months at month 14 after first vaccination.
Seropositive rate of the vaccine group and placebo group
compare the seropositive rate of the vaccine group and placebo group in healthy children aged 6-35 months.
Seroconversion rate of the vaccine group and placebo group
compare the Seroconversion rate of the vaccine group and placebo group in healthy children aged 6-35 months.
GMT of the vaccine group and placebo group
compare the geometric mean titre (GMT) of the vaccine group and placebo group in healthy children aged 6-35 months.
GMI of the vaccine group and placebo group
compare the geometric mean fold increase (GMFI) of the vaccine group and placebo group in healthy children aged 6-35 months.

Full Information

First Posted
January 4, 2012
Last Updated
March 27, 2013
Sponsor
Jiangsu Province Centers for Disease Control and Prevention
Collaborators
Bejing Vigoo Biological Co., LTD
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1. Study Identification

Unique Protocol Identification Number
NCT01508247
Brief Title
A Clinical Trial to Assess the Efficacy and Safety of an Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children Aged 6-35 Months
Official Title
A Multiple-center Randomized Double-blind Placebo-controlled Phase 3 Clinical Trial to Assess the Efficacy and Safety of an Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children Aged 6-35 Months
Study Type
Interventional

2. Study Status

Record Verification Date
March 2013
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu Province Centers for Disease Control and Prevention
Collaborators
Bejing Vigoo Biological Co., LTD

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Since its discovery in 1969, enterovirus 71 (EV71) has been recognised as a frequent cause of epidemics of hand-foot-mouth disease (HFMD) associated with severe neurological sequelae in a small proportion of cases. There has been a significant increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997. Recent HFMD epidemics in this region have heen associated with a severe from of brainstem encephalitis associated with pulmonary oedema and high case-fatality rates. The data from the phase 1 and 2 trials suggested that the inactivated EV71 vaccine had a clinically acceptable safety and good immunogenicity for healthy Chinese children and infants. According to the immunogenicity and safety results, the 320U with adjuvant with immunizing schedule of two doses (per 28 day) will be applied in phase 3 clinical trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hand, Foot and Mouth Disease, Herpangina, Other EV71-associated Diseases
Keywords
efficacy, safety, inactivated vaccine (Vero Cell) against EV71, EV71-associated diseases

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
10245 (Actual)

8. Arms, Groups, and Interventions

Arm Title
vaccine against EV71
Arm Type
Experimental
Arm Description
Inactivated vaccine (Vero Cell) against EV71 of 320U /0.5ml in 5000 children aged 6-35 months on day0, 28
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
0/0.5ml placebo in 5000 children aged 6-35 months on day0, 28
Intervention Type
Biological
Intervention Name(s)
inactivated vaccine (Vero Cell) against EV71
Intervention Description
inactivated vaccine (vero cell) against EV71, 320U /0.5ml, two doses, on day0, 28
Intervention Type
Biological
Intervention Name(s)
0/0.5ml placebo
Intervention Description
0/0.5ml placebo, two doses, on day0, 28
Primary Outcome Measure Information:
Title
the incidence density of the EV71-associated diseases in the vaccine group and placebo group.
Description
compare the incidence density of the EV71-associated diseases between the vaccine group and placebo group in Chinese children aged 6-35 months.
Time Frame
begin at day 56 up to 14 months
Secondary Outcome Measure Information:
Title
the frequency of all the adverse events in vaccine group and placebo group.
Description
compare frequency of all the solicited events, unsolicited adverse events and serious adverse events between vaccine group and placebo group.
Time Frame
up to 14 months
Title
Seropositive rate of the vaccine group
Description
calculate the seropositive rate of the vaccine group in Chinese children aged 6-35 months at month 8 after first vaccination.
Time Frame
8 months after first vaccination
Title
Seroconversion rate of the vaccine group
Description
calculate the seroconversion rate of the vaccine group in Chinese children aged 6-35 months at month 8 after first vaccination.
Time Frame
8 months after first vaccination
Title
GMT of the vaccine group
Description
calculate the geometric mean titre (GMT) of the vaccine group in Chinese children aged 6-35 months at month 8 after first vaccination.
Time Frame
8 months after first vaccination
Title
Seropositive rate of the vaccine group
Description
calculate the seropositive rate of the vaccine group in Chinese children aged 6-35 months at month 14 after first vaccination.
Time Frame
14 months after first vaccination
Title
Seroconversion rate of the vaccine group
Description
calculate the seroconversion rate of the vaccine group in Chinese children aged 6-35 months at month 14 after first vaccination.
Time Frame
14 months after first vaccination
Title
GMT of the vaccine group
Description
calculate the geometric mean titre (GMT) of the vaccine group in Chinese children aged 6-35 months at month 14 after first vaccination.
Time Frame
14 months after first vaccination
Title
Seropositive rate of the vaccine group and placebo group
Description
compare the seropositive rate of the vaccine group and placebo group in healthy children aged 6-35 months.
Time Frame
28 days after the second vaccination
Title
Seroconversion rate of the vaccine group and placebo group
Description
compare the Seroconversion rate of the vaccine group and placebo group in healthy children aged 6-35 months.
Time Frame
28 days after the second vaccination
Title
GMT of the vaccine group and placebo group
Description
compare the geometric mean titre (GMT) of the vaccine group and placebo group in healthy children aged 6-35 months.
Time Frame
28 days after the second vaccination
Title
GMI of the vaccine group and placebo group
Description
compare the geometric mean fold increase (GMFI) of the vaccine group and placebo group in healthy children aged 6-35 months.
Time Frame
28 days after the second vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
35 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Only subjects fulfilling all of the following criteria will be eligible for the study: Healthy children aged from 6 to 35 months old General good health as established by medical history and physical examination The subjects' guardians are able to understand and sign the informed consent Had never received the vaccine against EV71 The subjects' guardians allow to comply with the requirements of the protocol Available for all visits scheduled in this study Subjects with temperature <=37.0°C on axillary setting Exclusion Criteria: Subjects will not be eligible for the study if any of the following criteria is met: Subject who has a medical history of HFMD Subject that has a medical history of any of the following: allergic history, or allergic to any ingredient of vaccine Family history of seizures or progressive neurological disease Family history of congenital or hereditary immunodeficiency Severe malnutrition or hypogenesis Major congenital defects or serious chronic illness, including perinatal brain damage Autoimmune disease Bleeding disorder diagnosed by a doctor or significant bruising or bleeding difficulties with IM injections or blood draws Asplenia, functional asplenia, or splenic excision History of asthma, angioneurotic edema, diabetes or malignant tumour History of thyroidectomy, or thyroid disease in last 12 months Any acute infections 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 other research vaccines or medicines in last 1 month Any prior administration of attenuated live vaccine in last 15 days Any prior administration of subunit or inactivated vaccines in last 7 days Under the anti-TB prevention or therapy Subjects with temperature >37.0°C on axillary setting Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives Exclusion Criteria for the second dose: Subjects will not be eligible for the second dose if any of following adverse events happened after the first dose. They can continue other process of the study without the second dose vaccination according to the opinion of the investigator. Had any serious adverse events related to the first dose of inactivated vaccine (vero cell) against EV71 within 7 days Hypersensitivity reactions after vaccination (including urticaria/rashes that occur within 30 minutes after inoculation) Anaphylaxis after vaccination Any confirmed or suspected autoimmune disease or immune deficiency diseases, including human immunodeficiency virus (HIV) infection Any condition that in the opinion of the investigator, or IRB
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Feng-Cai Zhu, Master
Organizational Affiliation
Jiangsu Provincial Center for Diseases Control and Prevention
Official's Role
Principal Investigator
Facility Information:
Facility Name
Donghai County Center for Disease Control and Prevention
City
Lianyungang
State/Province
Jiangsu
Country
China
Facility Name
Pizhou County-Level City Center for Disease Control and Prevention
City
Xuzhou
State/Province
Jiangsu
Country
China
Facility Name
Baoying County Center for Disease Control and Prevention
City
Yangzhou
State/Province
Jiangsu
Country
China
Facility Name
Chaoyang Distinct Center for Disease Control and Prevention
City
Beijing
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
28548626
Citation
Zhu W, Jin P, Li JX, Zhu FC, Liu P. Correlates of protection for inactivated enterovirus 71 vaccine: the analysis of immunological surrogate endpoints. Expert Rev Vaccines. 2017 Sep;16(9):945-949. doi: 10.1080/14760584.2017.1335603. Epub 2017 Jun 12.
Results Reference
derived
PubMed Identifier
28077584
Citation
Wei M, Meng F, Wang S, Li J, Zhang Y, Mao Q, Hu Y, Liu P, Shi N, Tao H, Chu K, Wang Y, Liang Z, Li X, Zhu F. 2-Year Efficacy, Immunogenicity, and Safety of Vigoo Enterovirus 71 Vaccine in Healthy Chinese Children: A Randomized Open-Label Study. J Infect Dis. 2017 Jan 1;215(1):56-63. doi: 10.1093/infdis/jiw502. Epub 2016 Oct 17.
Results Reference
derived
PubMed Identifier
23726161
Citation
Zhu FC, Meng FY, Li JX, Li XL, Mao QY, Tao H, Zhang YT, Yao X, Chu K, Chen QH, Hu YM, Wu X, Liu P, Zhu LY, Gao F, Jin H, Chen YJ, Dong YY, Liang YC, Shi NM, Ge HM, Liu L, Chen SG, Ai X, Zhang ZY, Ji YG, Luo FJ, Chen XQ, Zhang Y, Zhu LW, Liang ZL, Shen XL. Efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in China: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2013 Jun 8;381(9882):2024-32. doi: 10.1016/S0140-6736(13)61049-1. Epub 2013 May 29.
Results Reference
derived

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A Clinical Trial to Assess the Efficacy and Safety of an Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children Aged 6-35 Months

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