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

Purpose

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.

Condition	Intervention	Phase
Hand, Foot and Mouth Disease Herpangina Other EV71-associated Diseases	Biological: inactivated vaccine (Vero Cell) against EV71 Biological: 0/0.5ml placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Prevention
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

Resource links provided by NLM:

MedlinePlus related topics: Foot Health Mouth Disorders

U.S. FDA Resources

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

Primary Outcome Measures:

the incidence density of the EV71-associated diseases in the vaccine group and placebo group. [ Time Frame: begin at day 56 up to 14 months ] [ Designated as safety issue: No ]
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. [ Time Frame: up to 14 months ] [ Designated as safety issue: Yes ]
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 [ Time Frame: 8 months after first vaccination ] [ Designated as safety issue: No ]
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 [ Time Frame: 8 months after first vaccination ] [ Designated as safety issue: No ]
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 [ Time Frame: 8 months after first vaccination ] [ Designated as safety issue: No ]
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 [ Time Frame: 14 months after first vaccination ] [ Designated as safety issue: No ]
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 [ Time Frame: 14 months after first vaccination ] [ Designated as safety issue: No ]
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 [ Time Frame: 14 months after first vaccination ] [ Designated as safety issue: No ]
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 [ Time Frame: 28 days after the second vaccination ] [ Designated as safety issue: No ]
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 [ Time Frame: 28 days after the second vaccination ] [ Designated as safety issue: No ]
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 [ Time Frame: 28 days after the second vaccination ] [ Designated as safety issue: No ]
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 [ Time Frame: 28 days after the second vaccination ] [ Designated as safety issue: No ]
compare the geometric mean fold increase (GMFI) of the vaccine group and placebo group in healthy children aged 6-35 months.

Enrollment:	10245
Study Start Date:	January 2012
Study Completion Date:	March 2013
Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: vaccine against EV71 Inactivated vaccine (Vero Cell) against EV71 of 320U /0.5ml in 5000 children aged 6-35 months on day0, 28	Biological: inactivated vaccine (Vero Cell) against EV71 inactivated vaccine (vero cell) against EV71, 320U /0.5ml, two doses, on day0, 28
Placebo Comparator: placebo 0/0.5ml placebo in 5000 children aged 6-35 months on day0, 28	Biological: 0/0.5ml placebo 0/0.5ml placebo, two doses, on day0, 28

Eligibility

Ages Eligible for Study:	6 Months to 35 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01508247

Locations

China, Jiangsu
Donghai County Center for Disease Control and Prevention
Lianyungang, Jiangsu, China
Pizhou County-Level City Center for Disease Control and Prevention
Xuzhou, Jiangsu, China
Baoying County Center for Disease Control and Prevention
Yangzhou, Jiangsu, China
China
Chaoyang Distinct Center for Disease Control and Prevention
Beijing, China

Sponsors and Collaborators

Jiangsu Province Centers for Disease Control and Prevention

Bejing Vigoo Biological Co., LTD

Investigators

Principal Investigator:

Feng-Cai Zhu, Master

Jiangsu Provincial Center for Diseases Control and Prevention

More Information

No publications provided

Responsible Party:	Jiangsu Province Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:	NCT01508247 History of Changes
Other Study ID Numbers:	JSVCT010
Study First Received:	January 4, 2012
Last Updated:	March 27, 2013
Health Authority:	China: Food and Drug Administration

Keywords provided by Jiangsu Province Centers for Disease Control and Prevention:

efficacy
safety
inactivated vaccine (Vero Cell) against EV71
EV71-associated diseases

Additional relevant MeSH terms:

Foot-and-Mouth Disease
Hand, Foot and Mouth Disease
Herpangina
Mouth Diseases
Picornaviridae Infections

RNA Virus Infections
Virus Diseases
Coxsackievirus Infections
Enterovirus Infections
Stomatognathic Diseases

ClinicalTrials.gov processed this record on May 16, 2013