A Booster Dose of Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children

This study has been completed.
Sponsor:
Collaborator:
Bejing Vigoo Biological Co., LTD
Information provided by (Responsible Party):
Fengcai Zhu, Jiangsu Province Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT01734408
First received: November 22, 2012
Last updated: October 21, 2013
Last verified: October 2013
  Purpose

Hand, foot, and mouth disease (HFMD) is a common viral illness in infants and children caused by viruses that belong to the enterovirus genus of the picornavirus family. Although most HFMD cases do not result in serious complications, outbreaks of HFMD caused by enterovirus 71 (EV71) can present with a high rate of neurological complications, including meningoencephalitis, pulmonary complications, and can even cause infant death. HFMD caused by EV71 has become a major emerging infectious disease in Asia and the highly pathogenic potential of EV71 clearly requires the attention of world medical community.

The phase II study of inactivated vaccine (vero cell) against EV71 has completed last month in Jiangsu Province in China. The data from the phase II study suggested that the inactivated EV71 vaccine had a clinically acceptable safety and good immunogenicity for healthy Chinese children and infants. But the antibody titer against EV71 was found decreased significantly at month 8 compared to that at day 56. Considering the similar dynamic trend had also been found in the antibody against poliovirus induced by polio vaccines, and whose immunization schedule contains a booster dose administrated at 1 to 1.5 year after the first 3 doses of fundamental immunity. In order to find a better immunization schedule for children, the investigators decided to perform this booster immunity trial among these children who had received two doses of EV71 vaccines (around one year after the fundamental immunity). The investigators do the recruitment among these children who had participated in the previous phase II trial and received EV71 vaccines, and randomize them in a ratio of 2:1 to receive either a booster dose of EV71 vaccines or placebo.


Condition Intervention Phase
EV71-associated Disease
Biological: alum-adjuvant 160U /0.5ml
Biological: alum-adjuvant 320U /0.5ml
Biological: alum-adjuvant 640U /0.5ml
Biological: adjuvant-free 640U /0.5ml
Biological: 0/0.5ml placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: A Booster Dose of Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children

Resource links provided by NLM:


Further study details as provided by Jiangsu Province Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • Geometric mean titer (GMT) of anti-EV71 antibodies [ Time Frame: 28 days after vaccination ] [ Designated as safety issue: No ]
    GMT of anti-EV71 antibodies in serum 28 days after booster dose injection


Secondary Outcome Measures:
  • Safety of EV71 vaccine in healthy children [ Time Frame: 28 days after vaccination ] [ Designated as safety issue: Yes ]
    Frequency of systemic and local adverse reactions in healthy children following 28 days after the boosting dose of EV71 vaccine

  • Geometric mean fold increase (GMFI) of anti-EV71 antibodies [ Time Frame: 28 days after vaccination ] [ Designated as safety issue: No ]
    GMFI of anti-EV71 antibodies in serum 28 days after vaccination

  • Seroconversion of anti-EV71 antibodies [ Time Frame: 28 days after vaccination ] [ Designated as safety issue: No ]
    Seroconversion of anti-EV71 antibodies in serum 28 days after vaccination


Enrollment: 773
Study Start Date: November 2012
Study Completion Date: February 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: alum-adjuvant 160U /0.5ml EV71 vaccine
A booster dose of alum-adjuvant 160U /0.5ml EV71 vaccine in 160 children whom had received two doses of alum-adjuvant 160U/0.5ml EV71 vaccines one year before.
Biological: alum-adjuvant 160U /0.5ml
inactivated vaccine (vero cell) alum-adjuvant 160U /0.5ml EV71 vaccine
Placebo Comparator: placebo A
A 0/0.5ml placebo in 80 children whom had received two doses of alum-adjuvant 160U/0.5ml EV71 vaccines one year before.
Biological: 0/0.5ml placebo
0/0.5ml placebo
Experimental: alum-adjuvant 320U /0.5ml EV71 vaccine
A booster dose of alum-adjuvant 320U /0.5ml EV71 vaccine in 160 children whom had received two doses of alum-adjuvant 320U/0.5ml EV71 vaccines one year before.
Biological: alum-adjuvant 320U /0.5ml
inactivated vaccine (vero cell) alum-adjuvant 320U /0.5ml EV71 vaccine
Placebo Comparator: placebo B
A 0/0.5ml placebo in 80 children whom had received two doses of alum-adjuvant 320U/0.5ml EV71 vaccines one year before.
Biological: 0/0.5ml placebo
0/0.5ml placebo
Experimental: alum-adjuvant 640U /0.5ml EV71 vaccine
A booster dose of alum-adjuvant 640U /0.5ml EV71 vaccine in 160 children whom had received two doses of alum-adjuvant 640U/0.5ml EV71 vaccines one year before.
Biological: alum-adjuvant 640U /0.5ml
inactivated vaccine (vero cell) alum-adjuvant 640U /0.5ml EV71 vaccine
Placebo Comparator: placebo C
A 0/0.5ml placebo in 80 children whom had received two doses of alum-adjuvant 640U/0.5ml EV71 vaccines one year before.
Biological: 0/0.5ml placebo
0/0.5ml placebo
Experimental: adjuvant-free 640U /0.5ml EV71 vaccine
A booster dose of adjuvant-free 640U /0.5ml EV71 vaccine in 160 children whom had received two doses of adjuvant-free 640U/0.5ml EV71 vaccines one year before.
Biological: adjuvant-free 640U /0.5ml
inactivated vaccine (vero cell) adjuvant-free 640U /0.5ml EV71 vaccine
Placebo Comparator: placebo D
A 0/0.5ml placebo in 80 children whom had received two doses of adjuvant-free 640U/0.5ml EV71 vaccines one year before.
Biological: 0/0.5ml placebo
0/0.5ml placebo

  Eligibility

Ages Eligible for Study:   21 Months to 51 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Had participated in the previous phase II trial and received at least 1 dose of EV71 vaccine.
  • Healthy children as established by medical history and clinical examination
  • The subjects' guardians are able to understand and sign the informed consent
  • Subjects who can and will comply with the requirements of the protocol
  • Subjects with temperature <=37.0°C on axillary setting

Exclusion Criteria:

  • Had participated in the previous phase II trial and received placebo.
  • Subject who has a medical history of EV71-associated disease with specific laboratory evidence
  • <= 37 weeks gestation
  • Subjects with a birth weight <2.5 kg
  • 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 dysgenopathy
  • 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
  • Any acute infections in last 7 days
  • Any prior administration of immunodepressant or corticosteroids in last 6month
  • Any prior administration of blood products in last 3 month
  • Any prior administration of other research medicines in last 1 month
  • Any prior administration of attenuated live vaccine in last 14 days
  • Any prior administration of subunit or inactivated vaccines in last 7 days, such as pneumococcal vaccine
  • Under the anti-TB prevention or therapy
  • Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01734408

Locations
China, Jiangsu
Jiangsu Provincial Center for Diseases Control and Prevention
Nanjing, Jiangsu, China, 210009
Sponsors and Collaborators
Jiangsu Province Centers for Disease Control and Prevention
Bejing Vigoo Biological Co., LTD
  More Information

No publications provided

Responsible Party: Fengcai Zhu, vice director, Jiangsu Province Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT01734408     History of Changes
Other Study ID Numbers: JSVCT005b
Study First Received: November 22, 2012
Last Updated: October 21, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Jiangsu Province Centers for Disease Control and Prevention:
immunogenicity
safety
inactivated EV71 vaccine

Additional relevant MeSH terms:
Aluminum Hydroxide
Aluminum sulfate
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antacids
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014