An Efficacy Trial in Inactivated Enterovirus Type 71 (EV71) Vaccine

A Multicentered, Double - Blind, Randomized, and Placebo - Controlled Clinical Trial With Inactivated Enterovirus Type 71 (EV71) Vaccines

The purpose of this study is to evaluate the efficacy, immunogenicity and safety of EV71 Vaccines in preventing Hand, Foot and Mouth disease caused by EV71 in a total 10,000 healthy infants volunteers aged from 6 to 35months old.

Study Overview

• Status: Completed
• Conditions: Hand, Foot and Mouth Disease
• Intervention / Treatment: Biological: 0/0.5ml placebo; Biological: 400U /0.5ml EV71 vaccine

Detailed Description

The phase II study of inactivated vaccine (vero cell) against EV71 has completed on Dec 2011 in China. The data from the phase I and II study suggested that the inactivated EV71 vaccine had a clinically acceptable safety and good immunogenicity for healthy Chinese infants. In order to evaluate the efficacy of the vaccine against Hand, Foot and Mouth disease caused by EV71, and to further explore the safety profile of this vaccine in expending infant population, a phase III clinical trial is planed to conduct.

• Study Type: Interventional
• Enrollment (Actual): 10077
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Lianyungang, Jiangsu, China
      • Ganyu
    • Taizhou, Jiangsu, China
      • Taixing
    • Yancheng, Jiangsu, China
      • Sheyang CDC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 2 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy males and females, aged from 6 months to 11 years old Health is determined by medical history, physical examination, laboratory examination and clinical judgment of the investigator
• Provided legal identification for the sake of recruitment
• Subjects and/or parent(s)/legal guardian(s) are able to understand and sign informed consents

Exclusion Criteria:

• History of Hand-foot-mouth Disease
• Subject that has allergic history of vaccine, or allergic to any ingredient of vaccine
• Serious adverse reactions to vaccines such as anaphylaxis, hives, respiratory difficulty, angioedema, or abdominal pain
• Congenital malformations or developmental disorders, genetic defects, or severe malnutrition
• Epilepsy, seizures or convulsions history, or family history of mental illness
• Autoimmune disease or immunodeficiency, or parents, brothers and sisters have autoimmune diseases or immunodeficiency
• History of asthma, angioedema, diabetes or malignancy
• History of thyroidectomy or thyroid disease that required medication within the past 12 months
• Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws
• Asplenia, functional asplenia or any condition resulting in the absence or removal the spleen
• Acute illness or acute exacerbation of chronic disease within the past 7 days
• Any history of immunosuppressive medications or cytotoxic medications or inhaled corticosteroids within the past six months (with the exception of corticosteroid nasal spray for allergic rhinitis or topical corticosteroids for an acute uncomplicated dermatitis)
• History of any blood products within 3 months
• Administration of any live attenuated vaccine within 14 days
• Administration of subunit or inactivated vaccines ,e.g., pneumococcal vaccine, or allergy treatment within 7 days
• Axillary temperature > 37.0 centigrade before vaccination
• Abnormal laboratory parameters before vaccination
• Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 400U /0.5ml in infants; inactivated vaccine(vero cell) against EV71 of 400U /0.5ml in 5000 infants aged 6-35 months old on day0,28	Biological: 400U /0.5ml EV71 vaccine; inactivated vaccine (vero cell) against EV71 of 400U /0.5ml, two doses, 28 days interval; Other Names: EV71 vaccine
PLACEBO_COMPARATOR: 0/0.5ml placebo in infants; 0/0.5ml placebo in 5000 infants aged 6-35 months old on day0,28	Biological: 0/0.5ml placebo; 0/0.5ml placebo, two doses, 28 days interval; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence rate of Hand, Foot and Mouth disease caused by EV71 within one year observation period after the second vaccination	to evaluate the efficacy of EV71 vacccine against HFMD caused by EV71	From 28 days after the second vaccination to one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The GMT of anti-EV71 antibodies in serum after second vaccination	to evaluate the GMT of anti-EV71 antibodies in serum 28 days after second vaccination	28 days after first vaccination
The GMT of anti-EV71 antibodies in serum 7 and 13 months after second vaccination	to evaluate the immune persistence of anti-EV71 antibodies in serum	7 and 13 months after second vaccination
Frequency of systemic and local adverse reactions after the first vaccination	Frequency of systemic and local adverse reactions in healthy infants following first doses of EV71 vaccine	28 days after the first vaccination
Frequency of systemic and local adverse reactions after the second vaccination	Frequency of systemic and local adverse reactions in healthy infants following second doses of EV71 vaccine	28 days after the second vaccination

Collaborators and Investigators

• Sponsor: Sinovac Biotech Co., Ltd
• Investigators: Principal Investigator: Hua Wang, BS, Jiangsu Center for Diseases Control and Prevention

Publications and helpful links

General Publications

• Zhu F, Xu W, Xia J, Liang Z, Liu Y, Zhang X, Tan X, Wang L, Mao Q, Wu J, Hu Y, Ji T, Song L, Liang Q, Zhang B, Gao Q, Li J, Wang S, Hu Y, Gu S, Zhang J, Yao G, Gu J, Wang X, Zhou Y, Chen C, Zhang M, Cao M, Wang J, Wang H, Wang N. Efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in China. N Engl J Med. 2014 Feb 27;370(9):818-28. doi: 10.1056/NEJMoa1304923.
• Chong P, Hsieh SY, Liu CC, Chou AH, Chang JY, Wu SC, Liu SJ, Chow YH, Su IJ, Klein M. Production of EV71 vaccine candidates. Hum Vaccin Immunother. 2012 Dec 1;8(12):1775-83. doi: 10.4161/hv.21739. Epub 2012 Sep 19.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (ACTUAL): March 1, 2013
• Study Completion (ACTUAL): March 1, 2013

Study Registration Dates

• First Submitted: January 2, 2012
• First Submitted That Met QC Criteria: January 6, 2012
• First Posted (ESTIMATE): January 11, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): November 28, 2013
• Last Update Submitted That Met QC Criteria: November 27, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: efficacy; HFMD; EV71 vaccine; EV71 associated disease
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Stomatognathic Diseases; Enterovirus Infections; Picornaviridae Infections; Coxsackievirus Infections; Mouth Diseases; Foot-and-Mouth Disease; Hand, Foot and Mouth Disease; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: PRO-EV71-3001