A Safety Study of Inactivated EV71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Adults, Children and Infants
Condition: Hand, Foot and Mouth Disease
MeSH terms: Foot-and-Mouth Disease; Hand, Foot and Mouth Disease; Mouth Diseases
Study type: Interventional
Phase: Phase 1

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 has been carried out, during four months, in
      Guangxi Province, China. The purpose of this study is to evaluate the safety, tolerability
      and immunogenicity of the formalin-inactivated EV71 vaccine in Chinese adults (from 18 to 49
      years old), children (from 3 to 11 years old) and infants (from 6 to 35 months old).
    

Detailed 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,
      doi:10.1038/labinest.2011.82; 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, doi:
      10.1016/j.vaccine.2011.06.044.), 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 has
      been carried out, during four months, in Guangxi Province, China. The purpose of this study
      is to evaluate the safety, tolerability and immunogenicity of the formalin-inactivated EV71
      vaccine in Chinese adults (from 18 to 49 years old), children (from 3 to 11 years old) and
      infants (from 6 to 35 months old).
    

Intervention name(s): 160Eu/0.5ml in adults; 320Eu/0.5ml in adults; 640Eu/0.5ml in adults; 1280Eu/0.5ml (without adjuvant) in 12 adults; 0Eu/0.5ml in adults; 160Eu/0.5ml in children; 320Eu/0.5ml in children; 640Eu/0.5ml in children; 1280Eu/0.5ml (without adjuvant) in children; 0Eu/0.5ml in children; 160Eu/0.5ml in infants; 320Eu/0.5ml in infants; 640Eu/0.5ml in infants; 1280Eu/0.5ml (without adjuvant) in infants; 0Eu/0.5ml in infants
Intervention type(s): Biological; Biological; Biological; Biological; Biological; Biological; Biological; Biological; Biological; Biological; Biological; Biological; Biological; Biological; Biological
Intervention description(s): inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 12 adults aged 18-49 years old on day 0, 14.; inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 12 adults aged 18-49 years old on day 0, 14.; inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 12 adults aged 18-49 years old on day 0, 14.; inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 12 adults aged 18-49 years old on day 0, 14.; 0Eu/0.5ml placebo in 24 adults aged 18-49 years old on day 0, 14.; inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 12 children aged 3-11 years old on day 0, 14.; inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 12 children aged 3-11 years old on day 0, 14.; inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 12 children aged 3-11 years old on day 0, 14.; inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 12 children aged 3-11 years old on day 0, 14.; 0Eu/0.5ml placebo in 24 children aged 3-11 years old on day 0, 14.; inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 24 infants aged 6-35 months old on day 0, 28.; inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 24 infants aged 6-35 months old on day 0, 28.; inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 24 infants aged 6-35 months old on day 0, 28.; inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 24 infants aged 6-35 months old on day 0, 28.; 0Eu/0.5ml placebo in 48 infants aged 6-35 months old on day 0, 28.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: Human Enterovirus 71 (EV71); Hand, Foot and Mouth Disease; Inactivated Vaccine; Human Diploid cell; Safety; Immunogenicity; Adverse reactions associated with vaccine