The Phase IVd of Inactivated Enterovirus 71 Vaccine

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Unknown; Phase 4

Conditions: Hand, Foot and Mouth Disease (HFMD)

Treatments: Biological: EV71 and two measles attenuated live vaccine; Biological: two measles attenuated live vaccine; Biological: EV71 vaccine; Biological: EV71 and attenuated Japanese encephalitis vaccine; Biological: live attenuated Japanese encephalitis vaccine

Study type: Interventional

Funder types: Other

Identifiers

NCT03296410

20170710

Details and patient eligibility

About

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 IVd is to evaluated the immunogenicity and safety of the inactive EV71 vaccine within two measles attenuated live vaccine and live attenuated Japanese encephalitis vaccine at the same time point in large scale population of Chinese children (8 months old) in Guangdong Province, China.

Full description

There are two parts of phase IVd clinical trials have been performed. First, to evaluate the immunogenicity of the inactive EV71 vaccine within two measles attenuated live vaccine and live attenuated Japanese encephalitis vaccine at the same time point in large scale population of Chinese children (8 months old), within 56-day-post-immunized.

Second, to safety of the inactive EV71 vaccine within two measles attenuated live vaccine and live attenuated Japanese encephalitis vaccine at the same time point in large scale population of Chinese children (8 months old), within 56-day-post-immunized.

Enrollment: 1,220 estimated patients

Sex: All

Ages: 8 to 9 months old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,220 participants in 5 patient groups

EV71 and two measles attenuated live vaccine

Experimental group

Description:

infants vaccinated with enterovirus type 71 inactivated vaccine (human diploid cell) and two measles attenuated live vaccine at 8 months old, and vaccinated with the second dose of enterovirus type 71 inactivated vaccine (human diploid cell) at 9 months old.

Treatment:

Biological: EV71 and two measles attenuated live vaccine

EV71 and attenuated Japanese encephalitis vaccine

Experimental group

Description:

infants vaccinated with enterovirus type 71 inactivated vaccine (human diploid cell) and live attenuated Japanese encephalitis vaccine at 8 months old, and vaccinated with the second dose of enterovirus type 71 inactivated vaccine (human diploid cell) at 9 months old.

Treatment:

Biological: EV71 and attenuated Japanese encephalitis vaccine

two measles attenuated live vaccine

Active Comparator group

Description:

infants vaccinated with two measles attenuated live vaccine at 8 months old

Treatment:

Biological: two measles attenuated live vaccine

live attenuated Japanese encephalitis vaccine

Active Comparator group

Description:

infants vaccinated with live attenuated Japanese encephalitis vaccine at 8 months old

Treatment:

Biological: live attenuated Japanese encephalitis vaccine

EV71 vaccine

Active Comparator group

Description:

infants vaccinated with enterovirus type 71 inactivated vaccine (human diploid cell) at 8 months old, and vaccinated with the second dose of enterovirus type 71 inactivated vaccine (human diploid cell) at 9 months old.

Treatment:

Biological: EV71 vaccine