A Phase II, Safety and Efficacy Study of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Infants
Condition: The Study Focused on the Safety of Inactivated EV71 Vaccine (Human Diploid Cell) Against Hand, Foot and Mouth Disease in Chinese Children and Infants
MeSH terms: Foot-and-Mouth Disease; Hand, Foot and Mouth Disease; Mouth Diseases
Study type: Interventional
Phase: Phase 2

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).
    

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 was
      completed, during four months, 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.

      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).
    

Intervention name(s): 160Eu/0.5ml in infants (6-11 months old); 320Eu/0.5ml in infants (6-11 months old); 640Eu/0.5ml in infants (6-11 months old); 1280Eu/0.5ml (without adjuvant) in infants (6-11 months old); 0Eu/0.5ml in infants (6-11 months old); 160Eu/0.5ml in infants (12-23 months old); 320Eu/0.5ml in infants (12-23 months old); 640Eu/0.5ml in infants (12-23 months old); 1280Eu/0.5ml (without adjuvant) in infants (12-23 months old); 0Eu/0.5ml in infants (12-23 months old); 160Eu/0.5ml in children (24 months-5 years old); 320Eu/0.5ml in children (24 months-5 years old); 640Eu/0.5ml in children (24 months-5 years old); 1280Eu/0.5ml (without adjuvant) in children (24 months-5 years old); 0Eu/0.5ml in children (24 months-5 years old)
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 60 infants aged 6-11 months old on day 0, 28; inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 60 infants aged 6-11 months old on day 0, 28; inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 40 infants aged 6-11 months old on day 0, 28; inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 40 infants aged 6-11 months old on day 0, 28; 0Eu/0.5ml placebo in 80 infants aged 6-11 months old on day 0, 28; inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 30 infants aged 12-23 months old on day 0, 28; inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 30 infants aged 12-23 months old on day 0, 28; inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 40 infants aged 12-23 months old on day 0, 28; inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 40 infants aged 12-23 months old on day 0, 28; 0Eu/0.5ml placebo in 50 infants aged 12-23 months old on day 0, 28; inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 30 children aged 24 months-5 years months old on day 0, 28; inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 30 children aged 24 months-5 years months old on day 0, 28; inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 40 children aged 24 months-5 years months old on day 0, 28; inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml in 40 children aged 24 months-5 years months old on day 0, 28; 0Eu/0.5ml placebo in 50 children aged 24 months-5 years 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