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A Clinical Trial for Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children and Infants

Phase 1
Completed
Conditions
Hand, Foot, and Mouth Disease
Enterovirus Infections
Interventions
Biological: 160U /0.5ml
Biological: 320U /0.5ml
Biological: 640U /0.5ml
Biological: 0/0.5ml placebo
Registration Number
NCT01313715
Lead Sponsor
Jiangsu Province Centers for Disease Control and Prevention
Brief Summary

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.

Recently, an inactivated vaccine(vero cell) against EV71 has been licensed by SFDA in China, this clinical trial phase Ib is armed to evaluate safety in Chinese healthy children (from 13 to 60 months old) and infants (from 6 to 12 months old) and also provide the evidences for the EV71 vaccine immunogenicity and the probable immunizing dose.

Detailed Description

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 development of vaccine against EV71 is active and ongoing in Asian countries now. Several studies have examined the effectiveness of inactivated viral vaccines against EV71 in animal model. A wide range of experimental EV71 vaccine approaches have been studied including heat-inactivated or formaldehyde-inactivated virion, EV71 virus-like particles (VLP) , VP1 recombinant protein ,VP1 DNA vaccine , VP1 peptide-based vaccine targeting the neutralizing domain, bacterial or viral vector expressing VP1, and a Vero cell-adapted live attenuated virus. Furthermore, neutralizing antibodies against EV71 have been suggested as one of the most important factors in prevention of the severe EV71 infection.

Recently, an inactivated vaccine(vero cell) against EV71 has been licensed by SFDA in China, this clinical trial phase Ib is armed to evaluate safety in Chinese healthy children and infants and also provide the evidences for the EV71 vaccine immunogenicity and the probable immunizing dose.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
360
Inclusion Criteria
  • Healthy subjects aged from 13 to 60 months old as established by medical history and clinical examination
  • The subjects' guardians are able to understand and sign the informed consent
  • Had never received the vaccine against EV71
  • Subjects who can and will comply with the requirements of the protocol
  • Subjects with temperature <37.1°C on axillary setting
Exclusion Criteria
  • Subject who has a medical history of HFMD
  • <= 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 1month
  • Any prior administration of attenuated live vaccine in last 28 days
  • Any prior administration of inactivated vaccines in last 14 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

For the subjects aged from 6-12 months:

Inclusion Criteria:

  • Healthy subjects aged from 6 to 12 months old as established by medical history and clinical examination
  • The subjects' guardians are able to understand and sign the informed consent
  • Had never received the vaccine against EV71
  • Subjects who can and will comply with the requirements of the protocol
  • Subjects with temperature <37.1°C on axillary setting

Exclusion Criteria:

  • Subject who has a medical history of HFMD
  • <= 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 1month
  • Any prior administration of attenuated live vaccine in last 28 days
  • Any prior administration of inactivated vaccines in last 14 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
160U /0.5ml in children160U /0.5mlinactivated vaccine(vero cell) against EV71 of 160U /0.5ml in 45 children aged 13-60 months old on day0,28
320U /0.5ml in children320U /0.5mlinactivated vaccine(vero cell) against EV71 of 320U /0.5ml in 45 children aged 13-60 months old on day0,28
640U /0.5ml in children640U /0.5mlinactivated vaccine(vero cell) against EV71 of 640U /0.5ml in 45 children aged 13-60 months old on day0,28
160U /0.5ml in infants160U /0.5mlinactivated vaccine(vero cell) against EV71 of 160U /0.5ml in 45 infants aged 6-12 months old on day0,28
320U /0.5ml in infants320U /0.5mlinactivated vaccine(vero cell) against EV71 of 320U /0.5ml in 45 infants aged 6-12 months old on day0,28
640U /0.5ml in infants640U /0.5mlinactivated vaccine(vero cell) against EV71 of 640U /0.5ml in 45 infants aged 6-12 months old on day0,28
0/0.5ml placebo in children0/0.5ml placebo0/0.5ml placebo in 45 children aged 13-60 months old on day0,28
0/0.5ml placebo in infants0/0.5ml placebo0/0.5ml placebo in 45 infants aged 6-12 months old on day0,28
Primary Outcome Measures
NameTimeMethod
Number of participants with adverse events after first vaccination28 days after the first vaccination

To evaluate the adverse events of EV71 vaccine in healthy children and infants after first vaccination

Number of participants with adverse events after second vaccination28 days after the second vaccination

To evaluate the adverse events of EV71 vaccine in healthy children and infants after second vaccination

Secondary Outcome Measures
NameTimeMethod
The seroconversion rate of anti-EV71 antibodies in serum after first vaccination28 days after the first vaccination

To evaluate the seroconversion rate of anti-EV71 antibodies in serum 28 days after first vaccination

The seroconversion rate of anti-EV71 antibodies in serum after second vaccination28 days after second vaccination

To evaluate the seroconversion rate of anti-EV71 antibodies in serum 28 days after second vaccination

The abnormity change of liver and kidney function indexes in serum after first vaccination in children3 days after first vaccination

To evaluate the abnormity change of liver and kidney function indexes in serum 3 days after first vaccination in children

The abnormity change of liver and kidney function indexes in serum after second vaccination in children3 days after second vaccination

To evaluate the abnormity change of liver and kidney function indexes in serum 3 days after second vaccination in children

Trial Locations

Locations (1)

Donghai Center for Diseases Control and Prevention

🇨🇳

Lianyungang, Jiangsu, China

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