Clinical Trial: A Phase II, Safety and Efficacy Study of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Infants
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Phase II Clinical Trial for Inactivated Enterovirus Type 71 Vaccine (Human Diploid Cell, KMB-17 Cell) in Chinese Infants
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).
Detailed Summary:
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 Mode
Sponsor: Chinese Academy of Medical Sciences
Current Primary Outcome:
- Evaluate the safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Infants (from 6 to 11 months old) [ Time Frame: within the first 28 days after the first vaccination ]Adverse reactions associated with vaccine were observed in Chinese Infants (from 6 to 11 months old) 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) [ Time Frame: within the first 28 days after the first vaccination ]Adverse reactions associated with vaccine were observed in Chinese Infants (from 12 to 23 months old) 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) [ Time Frame: within the first 28 days after the first vaccination ]Adverse reactions associated with vaccine were observed in Chinese children (from 24 months to 5 years old) 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) [ Time Frame: within the first 56 days after the second vaccination ]Adverse reactions associated with vaccine were observed in Chinese Infants (from 6 to 11 months old) 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) [ Time Frame: within the first 56 days after the second vaccination&
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Evaluate the seroconversion rate of anti-EV71 antibodies in serum of children and infant, after first vaccination [ Time Frame: at the 28 day after the first vaccination ]The seroconversion rate of anti-EV71 antibodies was evaluated in serum of children and infant, 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 [ Time Frame: at the 28 or 56 days after the second vaccination ]The seroconversion rate of anti-EV71 antibodies was evaluated in serum of children and infant, 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 [ Time Frame: at the 28 day after the first vaccination ]The seroconversion rate of antinuclear antibodies was evaluated in serum of children and infant, at the 28 day after the first vaccination
- Evaluate the seroconversion rate of antinuclear antibodies in serum of children and infant, after second vaccination [ Time Frame: at the 28 or 56 days after the second vaccination ]The seroconversion rate of antinuclear antibodies was evaluated in serum of children and infant, 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 [ Time Frame: at the 28 days after the first vaccination ]The abnormity change of live and kidney function indexes were evaluated in serum of children and infant, at the 28 days after the first vaccination
- Evaluate the abnormity change of live and kidney function indexes in serum of children and infant, after second vaccination [ Time Frame: at the 28 or 56 days after the second vaccination ]The abnormity change of live and kidney function indexes were evaluated in serum of children and infant, the 28 or 56 days after the second vaccination
- Evaluate the abnormity change of body temperature of children and infant, after first vaccination [ Time Frame: within the first 28 days after the first vaccination ]The abnormity change of body temperature of children and infant were evaluated, at the 28 days after the first vaccination
- Evaluate the abnormity change of body temperature of children and infant, after second vaccination [ Time Frame: within the first 56 days after the second vaccination ]The abnormity change of body temperature of children and infant were evaluated, within the first 56 days after the second vaccination
- Evaluate the vaccine-induced cellular immune responses in children and infant after first vaccination [ Time Frame: at the 28 day after the first vaccination ]The vaccine-induced cellular immune responses were evaluated in serum of children and infant, at the 28 day after the first vaccination
- Evaluate the vaccine-induced cellular immune responses in children and infant after second vaccination [ Time Frame: at the 28 or 56 days after the second vaccination ]The vaccine-induced cellular immune responses were evaluated in serum of children and infant, at the 28 or 56 days after the second vaccination
Original Secondary Outcome: Same as current
Information By: Chinese Academy of Medical Sciences
Dates:
Date Received: January 15, 2012
Date Started: July 2011
Date Completion:
Last Updated: April 26, 2012
Last Verified: June 2011
- Evaluate the seroconversion rate of anti-EV71 antibodies in serum of children and infant, after first vaccination [ Time Frame: at the 28 day after the first vaccination ]
