The Phase IVc of Inactivated Enterovirus 71 Vaccine (Human Diploid Cell)

Study on Immunogenicity of Inactivated Enterovirus 71 (EV71) Vaccine (Human Diploid Cell, KMB-17) in Large-scale Healthy Children in China

Enterovirus 71 (EV71), a major pathogen causing hand-foot-and-mouth disease (HFMD) worldwide, is a member of the Human Enterovirus species A, family Picornaviridae. Its infection occasionally leads to severe diseases and death, with central nervous system (CNS) damage.

Recently, except of inactivated vaccine, several EV71 vaccine candidates have been evaluated in animals but no final results of clinical trials, such as attenuated vaccine, subunit vaccine. A formalin-inactivated EV71 vaccine (Human Diploid cell, KMB-17 Cell) has been finished phase I, II and III clinical trials and licensed by SFDA in China at Dec. 3, 2015. Based on the results of clinical trials, the protective efficacy of inactivated EV71 vaccine is 97% against HFMD caused by EV71. The phase IV clinical trial has been carried out from July 2016. The purpose of phase IVc is to evaluated the immunogenicity of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old) in Hubei Province, China.

Study Overview

• Status: Unknown
• Conditions: Hand, Foot and Mouth Disease (HFMD)
• Intervention / Treatment: Biological: Inactivated EV71 vaccine (human diploid cell, KMB-17)

Detailed Description

There are two parts of phase IVc clinical trials have been performed. First, to evaluate the immunogenicity of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old), within 56-day-post-immunized.

Second, to long-term immunogenicity of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old).

• Study Type: Interventional
• Enrollment (Anticipated): 800
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Hubei Province Center for Diseases Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy subjects (6-71 months old children) as established by medical history and clinical examination
• The subjects' legal guardian must be aware of this vaccines
• The subjects' legal guardian voluntarily participate in the study and signed Informed Consent Form
• Subjects with temperature ≤ 37.0 ℃
• The subjects' legal guardian with the ability and objective to comply with the requirements of the protocol
• Persist for a 14-month visit (and receive blood, stool (or specimens by means of a swab) tests according to program requirements in immunogenicity observation group)

Exclusion Criteria:

• Allergy or serious side-effects to a vaccine or any ingredient of vaccine
• Epilepsy, seizures, convulsions, neurological illness
• Congenital or hereditary immunodeficiency
• Autoimmune disease
• Asthma, thyroidectomy, angioneurotic edema, diabetes or cancer
• Asplenia, functional asplenia, and any circumstances leading to the asplenia or splenectomy
• Clinical diagnosis of coagulopathy (such as clotting factor deficiency, coagulation disorders, platelet abnormalities), significant bruising or blood clotting disorder
• Acute illness or acute exacerbation of chronic disease 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 live-attenuated vaccine in last 15 days
• Any prior administration of subunit or inactivated vaccines in last 7 days
• Fever before vaccination, axillary temperature ﹥37.0 ℃
• The laboratory test abnormalities before vaccination, including blood tests (hemoglobin, total white blood cells, WBC, platelets), blood biochemistry tests (ALT, total bilirubin, direct bilirubin, Cr, BUN) and urine tests (urine protein, urine sugar, blood cells), etc.
• Hypertension or hypotension. Systolic blood pressure ﹥140 mmHg and/ or diastolic blood pressure ﹥90 mmHg; systolic blood pressure ﹤90 mmHg and/or diastolic blood pressure ﹤60 mmHg
• Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives
• take part into other vaccine or drug clinical trials in last half year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vaccine (3.0EU); healthy children (6-71 months old) have been injected by inactivated EV71 vaccine (KMB-17) of 3.0 EU (neutralization antibodies titer unit; 100 U in phase III clinical trials, or 320 EU (Elisa assay unit) in phase I and II clinical trials)	Biological: Inactivated EV71 vaccine (human diploid cell, KMB-17); 3.0 EU of inactivated enterovirus 71 vaccine (KMB-17) on day 0, 28.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the seroconversion rate of anti-EV71 antibodies in serum of children	Bloods were obtained at 0 and 56 days after first vaccination. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated.	at 28 days after finishing 2 doses immunization
Evaluate the antibody titers of anti-EV71 antibodies in serum of children	Bloods were obtained at 0 and 56 days after first vaccination. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated.	at 28 days after finishing 2 doses immunization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate long-term of the seroconversion rate of anti-EV71 antibodies in serum of children	Bloods were obtained at 0, 28 and 56 days after first vaccination, and 180, 360 and 720 days after 2 doses immunization. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated.	Up to 3 years after finishing 2 doses immunization
Evaluate long-term of the antibody titers of anti-EV71 antibodies in serum of children	Bloods were obtained at 0, 28 and 56 days after first vaccination, and 180, 360 and 720 days after 2 doses immunization. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated.	Up to 3 years after finishing 2 doses immunization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment adverse events	The adverse events were observed and recorded within 30 minutes post immunization (p.i.), within 0-1 days post immunization (d.p.i.), within 1-3 d.p.i. and within 3-7 d.p.i. after the 1st injection, as well as after the 2nd injection. And the adverse events were also observed and recorded following within 3 years after finishing 2 doses immunization.	Up to 3 years after finishing 2 doses immunization

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Collaborators: Hubei Provincial Center for Disease Control and Prevention

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2017
• Primary Completion (Anticipated): October 1, 2020
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: June 22, 2017
• First Submitted That Met QC Criteria: August 2, 2017
• First Posted (Actual): August 7, 2017

Study Record Updates

• Last Update Posted (Actual): September 6, 2017
• Last Update Submitted That Met QC Criteria: September 1, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: safety; immunogenicity; Hand, Foot and Mouth Disease (HFMD)
• 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
• Other Study ID Numbers: 2017-003-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No