A Phase II, Safety and Efficacy Study of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Infants

NCT01512706 | Completed Phase 2 DMC

• 1 other identifier: EV71-KMB17-II-IMB-CAMS
• Study Type: interventional
• Target: 660
• Locations: 1 country
• Sites: 1

Brief Summary

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 trial was completed, during four months, in Guangxi Province, China. The phase II clinical trial has been carried out, from July 2011. The purpose of phase II is to evaluate the safety and efficacy of the formalin-inactivated EV71 vaccine in Chinese infants (from 6 to 36 months old).

Conditions

The Study Focused on the Safety of Inactivated EV71 Vaccine (Human Diploid Cell) Against Hand, Foot and Mouth Disease in Chinese Children and Infants

Keywords

Human Enterovirus 71 (EV71); Hand, Foot and Mouth Disease; Inactivated Vaccine; Human Diploid cell; Safety; Immunogenicity; Adverse reactions associated with vaccine

Outcome Measures

Primary Outcomes (6)

• Evaluate the safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Infants (from 6 to 11 months old)

  Adverse reactions associated with vaccine were observed in Chinese Infants (from 6 to 11 months old) after the first vaccination.

  within the first 28 days after the first vaccination

• Evaluate the safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Infants (from 12 to 23 months old)

  Adverse reactions associated with vaccine were observed in Chinese Infants (from 12 to 23 months old) after the first vaccination

  within the first 28 days after the first vaccination

• Evaluate the safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese children (from 24 months to 5 years old)

  Adverse reactions associated with vaccine were observed in Chinese children (from 24 months to 5 years old) after the first vaccination

  within the first 28 days after the first vaccination

• Evaluate the safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Infants (from 6 to 11 months old)

  Adverse reactions associated with vaccine were observed in Chinese Infants (from 6 to 11 months old) after the second vaccination

  within the first 56 days after the second vaccination

• Evaluate the safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Infants (from 12 to 23 months old)

  Adverse reactions associated with vaccine were observed in Chinese Infants (from 12 to 23 months old) after the second vaccination

  within the first 56 days after the second vaccination

• Evaluate the safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese children (from 24 months to 5 years old)

  Adverse reactions associated with vaccine were observed in Chinese children (from 24 months to 5 years old) after the second vaccination

  within the first 56 days after the second vaccination

Secondary Outcomes (10)

• Evaluate the seroconversion rate of anti-EV71 antibodies in serum of children and infant, after first vaccination

  at the 28 day after the first vaccination

• Evaluate the seroconversion rate of anti-EV71 antibodies in serum of children and infant, after second vaccination

  at the 28 or 56 days after the second vaccination

• Evaluate the seroconversion rate of antinuclear antibodies in serum of children and infant, after first vaccination

  at the 28 day after the first vaccination

• Evaluate the seroconversion rate of antinuclear antibodies in serum of children and infant, after second vaccination

  at the 28 or 56 days after the second vaccination

• Evaluate the abnormity change of live and kidney function indexes in serum of children and infant, after first vaccination

  at the 28 days after the first vaccination

Study Arms (15)

160Eu/0.5ml in infants (6-11 months old)

EXPERIMENTAL

inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 60 infants aged 6-11 months old on day 0, 28

Biological: 160Eu/0.5ml in infants (6-11 months old)

320Eu/0.5ml in infants (6-11 months old)

EXPERIMENTAL

inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 60 infants aged 6-11 months old on day 0, 28

Biological: 320Eu/0.5ml in infants (6-11 months old)

640Eu/0.5ml in infants (6-11 months old)

EXPERIMENTAL

inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 40 infants aged 6-11 months old on day 0, 28

Biological: 640Eu/0.5ml in infants (6-11 months old)

1280Eu/0.5ml in infants (6-11 months old)

EXPERIMENTAL

inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 40 infants aged 6-11 months old on day 0, 28

Biological: 1280Eu/0.5ml (without adjuvant) in infants (6-11 months old)

0Eu/0.5ml in infants (6-11 months old)

PLACEBO COMPARATOR

0Eu/0.5ml placebo in 80 infants aged 6-11 months old on day 0, 28

Biological: 0Eu/0.5ml in infants (6-11 months old)

160Eu/0.5ml in infants (12-23 months old)

EXPERIMENTAL

inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 30 infants aged 12-23 months old on day 0, 28

Biological: 160Eu/0.5ml in infants (12-23 months old)

320Eu/0.5ml in infants (12-23 months old)

EXPERIMENTAL

inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 30 infants aged 12-23 months old on day 0, 28

Biological: 320Eu/0.5ml in infants (12-23 months old)

640Eu/0.5ml in infants (12-23 months old)

EXPERIMENTAL

inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 40 infants aged 12-23 months old on day 0, 28

Biological: 640Eu/0.5ml in infants (12-23 months old)

1280Eu/0.5ml in infants (12-23 months old)

EXPERIMENTAL

inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 40 infants aged 12-23 months old on day 0, 28

Biological: 1280Eu/0.5ml (without adjuvant) in infants (12-23 months old)

0Eu/0.5ml in infants (12-23 months old)

PLACEBO COMPARATOR

0Eu/0.5ml placebo in 50 infants aged 12-23 months old on day 0, 28

Biological: 0Eu/0.5ml in infants (12-23 months old)

160Eu/0.5ml in children (24 months-5 years old)

EXPERIMENTAL

inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 30 children aged 24 months-5 years months old on day 0, 28

Biological: 160Eu/0.5ml in children (24 months-5 years old)

320Eu/0.5ml in children (24 months-5 years old)

EXPERIMENTAL

inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 30 children aged 24 months-5 years months old on day 0, 28

Biological: 320Eu/0.5ml in children (24 months-5 years old)

640Eu/0.5ml in children (24 months-5 years old)

EXPERIMENTAL

inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 40 children aged 24 months-5 years months old on day 0, 28

Biological: 640Eu/0.5ml in children (24 months-5 years old)

1280Eu/0.5ml in children (24 months-5 years old)

EXPERIMENTAL

inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 40 children aged 24 months-5 years months old on day 0, 28

Biological: 1280Eu/0.5ml (without adjuvant) in children (24 months-5 years old)

0Eu/0.5ml in children (24 months-5 years old)

PLACEBO COMPARATOR

0Eu/0.5ml placebo in 50 children aged 24 months-5 years old on day 0, 28

Biological: 0Eu/0.5ml in children (24 months-5 years old)

Interventions

160Eu/0.5ml in infants (6-11 months old) BIOLOGICAL

inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 60 infants aged 6-11 months old on day 0, 28

160Eu/0.5ml in infants (6-11 months old)

320Eu/0.5ml in infants (6-11 months old) BIOLOGICAL

inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 60 infants aged 6-11 months old on day 0, 28

320Eu/0.5ml in infants (6-11 months old)

640Eu/0.5ml in infants (6-11 months old) BIOLOGICAL

inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 40 infants aged 6-11 months old on day 0, 28

640Eu/0.5ml in infants (6-11 months old)

1280Eu/0.5ml (without adjuvant) in infants (6-11 months old) BIOLOGICAL

inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 40 infants aged 6-11 months old on day 0, 28

1280Eu/0.5ml in infants (6-11 months old)

0Eu/0.5ml in infants (6-11 months old) BIOLOGICAL

0Eu/0.5ml placebo in 80 infants aged 6-11 months old on day 0, 28

0Eu/0.5ml in infants (6-11 months old)

160Eu/0.5ml in infants (12-23 months old) BIOLOGICAL

inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 30 infants aged 12-23 months old on day 0, 28

160Eu/0.5ml in infants (12-23 months old)

320Eu/0.5ml in infants (12-23 months old) BIOLOGICAL

inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 30 infants aged 12-23 months old on day 0, 28

320Eu/0.5ml in infants (12-23 months old)

640Eu/0.5ml in infants (12-23 months old) BIOLOGICAL

inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 40 infants aged 12-23 months old on day 0, 28

640Eu/0.5ml in infants (12-23 months old)

1280Eu/0.5ml (without adjuvant) in infants (12-23 months old) BIOLOGICAL

inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 40 infants aged 12-23 months old on day 0, 28

1280Eu/0.5ml in infants (12-23 months old)

0Eu/0.5ml in infants (12-23 months old) BIOLOGICAL

0Eu/0.5ml placebo in 50 infants aged 12-23 months old on day 0, 28

0Eu/0.5ml in infants (12-23 months old)

160Eu/0.5ml in children (24 months-5 years old) BIOLOGICAL

inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 30 children aged 24 months-5 years months old on day 0, 28

160Eu/0.5ml in children (24 months-5 years old)

320Eu/0.5ml in children (24 months-5 years old) BIOLOGICAL

inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 30 children aged 24 months-5 years months old on day 0, 28

320Eu/0.5ml in children (24 months-5 years old)

640Eu/0.5ml in children (24 months-5 years old) BIOLOGICAL

inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 40 children aged 24 months-5 years months old on day 0, 28

640Eu/0.5ml in children (24 months-5 years old)

1280Eu/0.5ml (without adjuvant) in children (24 months-5 years old) BIOLOGICAL

inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml in 40 children aged 24 months-5 years months old on day 0, 28

1280Eu/0.5ml in children (24 months-5 years old)

0Eu/0.5ml in children (24 months-5 years old) BIOLOGICAL

0Eu/0.5ml placebo in 50 children aged 24 months-5 years old on day 0, 28

0Eu/0.5ml in children (24 months-5 years old)

Eligibility Criteria

• Age: 6 Months - 5 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Healthy subjects (6-35 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

You may not qualify if:

• Subject who has a clinical diagnosis history of Hand, Foot and Mouth Disease (HFMD)
• weeks gestation
• 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

Sponsors & Collaborators

• Institute of Medical Biology, Chinese Academy of Medical Sciences: lead
• Guangxi Center for Disease Control and Prevention: collaborator

Study Sites (1)

Guangxi Provincial Center for Diseases Control and Prevention

Nanning, Guangxi, China

Location

Related Publications (2)

• Zhang Y, Wang L, Liao Y, Liu L, Ma K, Yang E, Wang J, Che Y, Jiang L, Pu J, Guo L, Feng M, Liang Y, Cui W, Yang H, Li Q. Similar protective immunity induced by an inactivated enterovirus 71 (EV71) vaccine in neonatal rhesus macaques and children. Vaccine. 2015 Nov 17;33(46):6290-7. doi: 10.1016/j.vaccine.2015.09.047. Epub 2015 Sep 28.

  PMID: 26419198 DERIVED

• Liu L, Zhang Y, Wang J, Zhao H, Jiang L, Che Y, Shi H, Li R, Mo Z, Huang T, Liang Z, Mao Q, Wang L, Dong C, Liao Y, Guo L, Yang E, Pu J, Yue L, Zhou Z, Li Q. Study of the integrated immune response induced by an inactivated EV71 vaccine. PLoS One. 2013;8(1):e54451. doi: 10.1371/journal.pone.0054451. Epub 2013 Jan 23.

  PMID: 23372725 DERIVED

MeSH Terms

Conditions

Hand, Foot and Mouth Disease

Condition Hierarchy (Ancestors)

Coxsackievirus Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Infections

Study Officials

• Zhaojun Mo, Master

  Guangxi Provincial Center for Diseases Control and Prevention

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2012
• First Posted: January 19, 2012
• Study Start: July 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: February 1, 2012
• Last Updated: October 11, 2023

Record last verified: 2023-10

Locations

CN (1)