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A Protected Study of Inactivated EV71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Infants and Children

I

Institute of Medical Biology, Chinese Academy of Medical Sciences

Status and phase

Completed
Phase 3

Conditions

The Efficacy of Inactivated EV71 Vaccine (KMB17) Against HFMD in Chinese Children and Infants

Treatments

Biological: 100U/0.5ml in 6-11 months old infants
Biological: 100U/0.5ml in 24-35 months old children
Biological: 100U/0.5ml in 36-71 months old children
Biological: 100U/0.5ml in 12-23 months old infants

Study type

Interventional

Funder types

Other

Identifiers

NCT01569581
EV71-KMB17-III-IMB-CAMS

Details and patient eligibility

About

Enterovirus 71 (EV71), a major pathogen that is responsible for causing hand-foot-and-mouth disease (HFMD) worldwide, is a member of the Human Enterovirus species A, family Picornaviridae.

Since the late 1990s, a series of large HFMD epidemics caused by EV71 have been reported in the Asia-Pacific region. Notably, there is evidence that the most severe cases from these epidemic outbreaks are associated with neurological disorders with CNS involvement caused by EV71 infection. Because of these EV71 infection-related public health issues, the research and development of EV71 vaccine candidates have been heavily promoted.

Recently, several EV71 vaccine candidates have been evaluated in animals but no final results of clinical trials, including inactivated vaccine, attenuated vaccine, subunit vaccine, DNA vaccine, epitope peptide vaccine, virus-like particles (VLPs).

Basing on the previous studies of elicited protection in mice and rhesus monkeys, a formalin-inactivated EV71 vaccine (Human Diploid cell, KMB-17 Cell) has been licensed by SFDA in China, Dec. 2010. The phase I clinical and phase II trials were completed, in Guangxi Province, China. The results of these clinical trials showed that this vaccine was safe and could induce effective antibodies for the infants. The purpose of phase III is to evaluate the protected and efficacy of the formalin-inactivated EV71 vaccine in Chinese infants and children (from 6 to 71 months old).

Full description

Hand-foot-and-mouth disease (HFMD) is a significant cause of death, usually characterized by vesicular lesions on the skin and oral mucosa and high morbidity rates in children. Additionally, occasional fatal cases have been reported involving brainstem encephalitis and myelitis associated with cardiopulmonary collapse. Pulmonary edema/hemorrhage and respiratory failure are the major causes of death among children less than five years old.

Enterovirus 71 (EV71), a major pathogen that is responsible for causing HFMD worldwide, is a member of the Human Enterovirus species A, family Picornaviridae. Since the late 1990s, a series of large HFMD epidemics caused by EV71 have been reported in the Asia-Pacific region. Notably, there is evidence that the most severe cases from these epidemic outbreaks are associated with neurological disorders with CNS involvement caused by EV71 infection. Because of these EV71 infection-related public health issues, the research and development of EV71 vaccine candidates have been heavily promoted.

Recently, several EV71 vaccine candidates have been evaluated in animals but no final results of clinical trials, including heat-inactivated or formalin-inactivated vaccine, live-attenuated vaccine, recombinant viral protein 1 (VP1) vaccine, VP1 DNA vaccine, VP1 epitope peptide vaccine, EV71 virus-like particles (VLPs) and bacterial or viral vector expressing VP1. Overall, the inactivated whole-virus vaccines seem to be more immunogenic than recombinant VP1 and DNA vaccines.

Basing on the previous studies of elicited protection in mice and rhesus monkeys (Ying Zhang, et al. Pathogenesis study of Enterovirus 71 Infection in Rhesus Monkeys. Lab Invest, 2011, 91:1337-1350; Longding Liu, et al. Neonatal Rhesus Monkey is a Potential Animal Model for Studying Pathogenesis of EV71 Infection. Virology, 2011, 412:91-100; Chenghong Dong, et al. Immunoprotection Elicited by an Enterovirus Type 71 Experimental Inactivated Vaccine in Mice and Rhesus Monkeys. Vaccine, 2011, 29:6269-6275.), a formalin-inactivated EV71 vaccine (Human Diploid cell, KMB-17 Cell) has been licensed by SFDA in China, Dec. 2010. The phase I and phase II clinical trials were completed,in Guangxi Province, China.

The results showed that the formalin-inactivated EV71 vaccine (Human Diploid cell, KMB-17 Cell) was safety in Chinese adults (from 18 to 49 years old), children (from 3 to 11 years old) and infants (from 6 to 35 months old). This vaccine could induce specific cellular and humoral immune responses against EV71.

The phase III clinical trial will been carried out, from April 2012. The purpose of phase III is to evaluate the safety and efficacy of the formalin-inactivated EV71 vaccine in Chinese infants and children(from 6 to 71 months old) to protect them from EV71 infecting.

Enrollment

12,000 patients

Sex

All

Ages

6 to 71 months old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

  • Healthy subjects (6-71 months infants) as established by medical history and clinical examination
  • Full-term (37-42 weeks), weight ≥ 2500 g when it was born
  • 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 2-month visit and receive blood tests according to program requirements

Exclusion criteria

  • Subject who has a clinical diagnosis history of Hand, Foot and Mouth Disease (HFMD)
  • Participated in the phase I or phase II clinical trails of the inactivated EV71 vaccine
  • weight ≤ 2500 g when it was born
  • 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 28 days or 1 months
  • Any prior administration of subunit or inactivated vaccines in last 14 days Under the anti-TB prevention or therapy
  • 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 ﹥140mmHg and/or diastolic blood pressure ﹥90mmHg; systolic blood pressure ﹤90mmHg and/or diastolic blood pressure ﹤60mmHg
  • Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

12,000 participants in 8 patient groups

100U/0.5ml in 6-11 months old infants
Experimental group
Description:
inactivated EV71 vaccine (KMB-17) of 100U/0.5ml (320Eu/0.5ml) in 1750 infants aged 6-11 months old on day 0, 28
Treatment:
Biological: 100U/0.5ml in 6-11 months old infants
100U/0.5ml in 12-23 months old infants
Experimental group
Description:
inactivated EV71 vaccine (KMB-17) of 100U/0.5ml (320Eu/0.5ml) in 1750 infants aged 12-23 months old on day 0, 28
Treatment:
Biological: 100U/0.5ml in 12-23 months old infants
100U/0.5ml in 24-35 months old children
Experimental group
Description:
inactivated EV71 vaccine (KMB-17) of 100U/0.5ml (320Eu/0.5ml) in 1500 children aged 24-35 months old on day 0, 28
Treatment:
Biological: 100U/0.5ml in 24-35 months old children
100U/0.5ml in 36-71 months old children
Experimental group
Description:
inactivated EV71 vaccine (KMB-17) of 100U/0.5ml (320Eu/0.5ml) in 1000 children aged 36-71 months old on day 0, 28
Treatment:
Biological: 100U/0.5ml in 36-71 months old children
0U/0.5ml in infants (6-11 months old)
No Intervention group
Description:
0U/0.5ml (0Eu/0.5ml) placebo in 1750 infants aged 6-11 months old on day 0, 28
0U/0.5ml in infants (12-23 months old)
No Intervention group
Description:
0U/0.5ml (0Eu/0.5ml) placebo in 1750 infants aged 12-23 months old on day 0, 28
0U/0.5ml in children (24-35 months old)
No Intervention group
Description:
0U/0.5ml (0Eu/0.5ml) placebo in 1500 children aged 24-35 months old on day 0, 28
0U/0.5ml in children (36-71 months old)
No Intervention group
Description:
0U/0.5ml (0Eu/0.5ml) placebo in 1000 children aged 36-71 months old on day 0, 28

Trial contacts and locations

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Data sourced from clinicaltrials.gov

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