Clinical trial NCT02999828: The Phase IVa of Inactivated Enterovirus 71 Vaccine (Human Diploid Cell, KMB-17)
Official title: The Safety, Immune Persistence and Consistency of Inactivated Enterovirus 71 Vaccine (Human Diploid Cell, KMB-17)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Safety of Inactivated EV71 Vaccine
Immunization of Inactivated EV71 Vaccine
Keywords: safety
immune persistence
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
Collaborators: name: Beijing Chaoyang District Centre for Disease Control and Prevention
name: Neimenggu Province Centre for Disease Control and Prevention
First posted: 2016-12-21
Enrollment: 20770
Sex: ALL
Minimum age (years): 6
Maximum age (years): 71
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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 IV is to evaluated the safety and efficacy of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old).

Detailed description: 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 IV is to evaluated the safety and efficacy of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old).

There are three parts of phase IV clinical trials have been performed. First, to evaluate the safety of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old).

Second, to evaluate the immune persistence of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old).

Third, to evaluate the efficacy of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old).

Eligibility criteria: 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 24-month visit (and receive blood, stool (or specimens by means of a swab) tests according to program requirements in immunogenicity observation group)
* report the HFMD cases

Exclusion Criteria:

* Subject who has a clinical diagnosis history of Hand, Foot and Mouth Disease (HFMD)
* Allergy or serious side-effects to a vaccine or any ingredient of vaccine
* Epilepsy, seizures, convulsions, neurological illness
* Congenital or hereditary immunodeficiency
* Autoimmune disease
* Severe malnutrition or dysgenopathy
* 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 ﹥90mmHg; 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

Primary outcomes:
measure: Incidence of treatment adverse events
timeFrame: Up to 24 months after finishing 2 doses immunization
Secondary outcomes:
measure: The incidence rates of HFMD
timeFrame: Up to 24 months after finishing 2 doses immunization
measure: immune response of inactivated EV71 vaccine (KMB-17) in a large crowd
timeFrame: Up to 24 months after finishing 2 doses immunization
Other outcomes:
measure: The level of anti-EV71 antibodies was evaluated in serum of children
timeFrame: Up to 24 months after finishing 2 doses immunization
Locations:
city: Beijing
country: China
facility: Chaoyang of Provincial Center for Diseases Control and Prevention in Beijing
Study officials:
affiliation: Chaoyang Provincial Center for Diseases Control and Prevention in Beijing
name: Nianmin Shi, M.S.
role: PRINCIPAL_INVESTIGATOR
affiliation: Neimenggu Provincial Center for Diseases Control and Prevention
name: Shaohong Yan, M.S.
role: STUDY_CHAIR
References: