Clinical trial NCT01399853: A Phase II Clinical Trial for Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children and Infants
Official title: A Phase II Clinical Trial for Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children and Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Immunogenicity
Safety
Keywords: immunogenicity
safety
inactivated EV71 vaccine
Lead sponsor: Jiangsu Province Centers for Disease Control and Prevention
Sponsor class: NETWORK
Collaborators: name: Bejing Vigoo Biological Co., LTD
First posted: 2011-07-22
Enrollment: 1200
Sex: ALL
Minimum age (years): 6
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: 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.

The phase I study of inactivated vaccine (vero cell) against EV71 has completed last month in Jiangsu Province in China. The data from the phase I study suggested that the inactivated EV71 vaccine had a clinically acceptable safety and good immunogenicity for healthy Chinese children and infants. In order to provide more evidence for the immunogenicity of the vaccine, to further explore the probable immunizing dose and the safety profile of this vaccine, a phase II clinical trial is planed to conduct.


Eligibility criteria: Inclusion Criteria:

For children group (aged from 12-36 months):

* Healthy children aged from 12 to 36 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 \<=37.0°C on axillary setting

For infants group (aged from 6-11 months):

* Healthy infants aged from 6 to 11 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 \<=37.0°C on axillary setting

Exclusion Criteria:

For children group (aged from 12-36 months):

* 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 1 month
* Any prior administration of attenuated live vaccine in last 28 days
* Any prior administration of subunit or 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 infants group (aged from 6-11 months):

* 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 1 month
* Any prior administration of attenuated live vaccine in last 28 days
* Any prior administration of subunit or 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

Exclusion Criteria for the second dose:

* Had any Grade 3 or Grade 4 adverse reaction within 7 days after first dose
* Any situation meet the exclusion criteria stated in the exclusion criteria for first dose
* Had any SAE related to first dose during the following-up of first dose
* Any condition that in the opinion of the investigator, or IRB

Primary outcomes:
measure: The GMT of anti-EV71 antibodies in serum after first vaccination
timeFrame: 28 days after first vaccination
measure: The GMT of anti-EV71 antibodies in serum after second vaccination
timeFrame: 28 days after second vaccination
measure: Frequency of systemic and local adverse reactions after the first vaccination
timeFrame: 28 days after the first vaccination
measure: Frequency of systemic and local adverse reactions after the second vaccination
timeFrame: 28 days after the second vaccination
Secondary outcomes:
measure: The seroconversion rate of anti-EV71 antibodies in serum after first vaccination
timeFrame: 28 days after first vaccination
measure: The seroconversion rate of anti-EV71 antibodies in serum after second vaccination
timeFrame: 28 days after second vaccination
measure: Frequency of adverse events and any SAE after the first vaccination
timeFrame: 28 days after the first vaccination
measure: Frequency of adverse events and any SAE after the second vaccination
timeFrame: 28 days after the second vaccination
measure: The clinical abnormality of hematological examination, blood biochemical test and urinalysis after first vaccination in children
timeFrame: 3 days after first vaccination
measure: The clinical abnormality of hematological examination, blood biochemical test and urinalysis after second vaccination in children
timeFrame: 3 days after second vaccination
measure: The persistence of immunogenicity of the EV71vaccine after two doses in children and infants
timeFrame: 6 months after blood collection at day 56
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Jiangsu Provincial Center for Diseases Control and Prevention
state: Jiangsu
Study officials:
References:
citation: Zhu FC, Liang ZL, Li XL, Ge HM, Meng FY, Mao QY, Zhang YT, Hu YM, Zhang ZY, Li JX, Gao F, Chen QH, Zhu QY, Chu K, Wu X, Yao X, Guo HJ, Chen XQ, Liu P, Dong YY, Li FX, Shen XL, Wang JZ. Immunogenicity and safety of an enterovirus 71 vaccine in healthy Chinese children and infants: a randomised, double-blind, placebo-controlled phase 2 clinical trial. Lancet. 2013 Mar 23;381(9871):1037-45. doi: 10.1016/S0140-6736(12)61764-4.