The Study Focused on the Safety of Inactivated EV71 Vaccine (Human Diploid Cell) Against Hand, Foot and Mouth Disease in Chinese Children and InfantsPhase 2NCT01512706
A Phase II, Safety and Efficacy Study of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Infants
A Phase 2 study testing 160Eu/0.5ml in infants (6-11 months old), 320Eu/0.5ml in infants (6-11 months old) and 640Eu/0.5ml in infants (6-11 months old) in people with The Study Focused on the Safety of Inactivated EV71 Vaccine (Human Diploid Cell) Against Hand, Foot and Mouth Disease in Chinese Children and Infants, run by Institute of Medical Biology, Chinese Academy of Medical Sciences at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months to 5 yearsHealthy volunteers can take part
- Conditions the study is for
- The Study Focused on the Safety of Inactivated EV71 Vaccine (Human Diploid Cell) Against Hand, Foot and Mouth Disease in Chinese Children and Infants
- What is being tested?
- 160Eu/0.5ml in infants (6-11 months old), 320Eu/0.5ml in infants (6-11 months old) and 640Eu/0.5ml in infants (6-11 months old)
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 660 participants
- Where
- 1 siteChina
- Study dates
- Jul 2011to Feb 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 5 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Who cannot join
- Subject who has a clinical diagnosis history of Hand, Foot and Mouth Disease (HFMD)
- 37 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
Show all 20Show fewer
- 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 locations and contacts
1 site in 1 country.
China1 site
Guangxi Provincial Center for Diseases Control and Prevention
Nanning, Guangxi
About this study
Official title: A Phase II Clinical Trial for Inactivated Enterovirus Type 71 Vaccine (Human Diploid Cell, KMB-17 Cell) in Chinese Infants
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.
Read more
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).
Read the 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).
- Being tested
- 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)
- Keywords
- Human Enterovirus 71 (EV71), Hand, Foot and Mouth Disease, Inactivated Vaccine, Human Diploid cell, Safety, Immunogenicity, Adverse reactions associated with vaccine
- Medical subject headings
- Hand, Foot and Mouth Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Biological: 0Eu/0.5ml in children (24 months-5 years old) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
The seroconversion rate of anti-EV71 antibodies was evaluated in serum of children and infant, at the 28 day after the first vaccination
Measured: 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
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
Measured: 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
The seroconversion rate of antinuclear antibodies was evaluated in serum of children and infant, at the 28 day after the first vaccination
Measured: at the 28 day after the first vaccination
Evaluate the seroconversion rate of antinuclear antibodies in serum of children and infant, after 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
Measured: 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
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
Measured: 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
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
Measured: at the 28 or 56 days after the second vaccination
Evaluate the abnormity change of body temperature of children and infant, after first vaccination
The abnormity change of body temperature of children and infant were evaluated, at the 28 days after the first vaccination
Measured: within the first 28 days after the first vaccination
Evaluate the abnormity change of body temperature of children and infant, after second vaccination
The abnormity change of body temperature of children and infant were evaluated, within the first 56 days after the second vaccination
Measured: within the first 56 days after the second vaccination
Evaluate the vaccine-induced cellular immune responses in children and infant after first vaccination
The vaccine-induced cellular immune responses were evaluated in serum of children and infant, at the 28 day after the first vaccination
Measured: at the 28 day after the first vaccination
Evaluate the vaccine-induced cellular immune responses in children and infant after 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
Measured: at the 28 or 56 days after the second vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2012 (estimated)
- Study startJul 2011
- Primary completionJan 2012
- Study completionFeb 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for The Study Focused on the Safety of Inactivated EV71 Vaccine (Human Diploid Cell) Against Hand, Foot and Mouth Disease in Chinese Children and InfantsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 660 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Medical Biology, Chinese Academy of Medical Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Guangxi Center for Disease Control and Prevention
- Responsible party
- Sponsor
- Investigators
- Zhaojun Mo, Master, Principal investigator, Guangxi Provincial Center for Diseases Control and Prevention
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01512706
- Sponsor's protocol ID
- EV71-KMB17-II-IMB-CAMS
- Status last verified
- Oct 2023
- First submitted
- 15 Jan 2012
- Last updated
- 11 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 26419198Liu 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.
PubMed 23372725
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Trial for Inactivated Enterovirus Type 71 Vaccine (Human Diploid Cell, KMB-17 Cell) in Chinese Infants
- ClinicalTrials.gov ID
- NCT01512706
- Acronym / sponsor ID
- EV71-KMB17-II-IMB-CAMS
- Keywords
- Human Enterovirus 71 (EV71), Hand, Foot and Mouth Disease, Inactivated Vaccine, Human Diploid cell, Safety, Immunogenicity, Adverse reactions associated with vaccine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 660 participants (actual)
- Lead sponsor
- Institute of Medical Biology, Chinese Academy of Medical SciencesUniversity, hospital or other
- Collaborators
- Guangxi Center for Disease Control and Prevention
- Study start
- Jul 2011
- Primary completion
- Jan 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 19 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 15
| Arm | Type | Receives |
|---|---|---|
| 160Eu/0.5ml in infants (6-11 months old) | Experimental | Biological: 160Eu/0.5ml in infants (6-11 months old)inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 60 infants aged 6-11 months old on day 0, 28 |
| 320Eu/0.5ml in infants (6-11 months old) | Experimental | Biological: 320Eu/0.5ml in infants (6-11 months old)inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 60 infants aged 6-11 months old on day 0, 28 |
| 640Eu/0.5ml in infants (6-11 months old) | Experimental | Biological: 640Eu/0.5ml in infants (6-11 months old)inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 40 infants aged 6-11 months old on day 0, 28 |
| 1280Eu/0.5ml in infants (6-11 months old) | Experimental | Biological: 1280Eu/0.5ml (without adjuvant) in infants (6-11 months old)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 in infants (6-11 months old) | Placebo comparator | Biological: 0Eu/0.5ml in infants (6-11 months old)0Eu/0.5ml placebo in 80 infants aged 6-11 months old on day 0, 28 |
| 160Eu/0.5ml in infants (12-23 months old) | Experimental | Biological: 160Eu/0.5ml in infants (12-23 months old)inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 30 infants aged 12-23 months old on day 0, 28 |
| 320Eu/0.5ml in infants (12-23 months old) | Experimental | Biological: 320Eu/0.5ml in infants (12-23 months old)inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 30 infants aged 12-23 months old on day 0, 28 |
| 640Eu/0.5ml in infants (12-23 months old) | Experimental | Biological: 640Eu/0.5ml in infants (12-23 months old)inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 40 infants aged 12-23 months old on day 0, 28 |
| 1280Eu/0.5ml in infants (12-23 months old) | Experimental | Biological: 1280Eu/0.5ml (without adjuvant) in infants (12-23 months old)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 in infants (12-23 months old) | Placebo comparator | Biological: 0Eu/0.5ml in infants (12-23 months old)0Eu/0.5ml placebo in 50 infants aged 12-23 months old on day 0, 28 |
| 160Eu/0.5ml in children (24 months-5 years old) | Experimental | Biological: 160Eu/0.5ml in children (24 months-5 years old)inactivated EV71 vaccine (KMB-17) of 160Eu/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) | Experimental | Biological: 320Eu/0.5ml in children (24 months-5 years old)inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 30 children aged 24 months-5 years months old on day 0, 28 |
| 640Eu/0.5ml in children (24 months-5 years old) | Experimental | Biological: 640Eu/0.5ml in children (24 months-5 years old)inactivated EV71 vaccine (KMB-17) of 640Eu/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) | Experimental | Biological: 1280Eu/0.5ml (without adjuvant) in children (24 months-5 years old)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 |
| 0Eu/0.5ml in children (24 months-5 years old) | Placebo comparator | Biological: 0Eu/0.5ml in children (24 months-5 years old)0Eu/0.5ml placebo in 50 children aged 24 months-5 years old on day 0, 28 |
Who may qualify
- Ages
- 6 months to 5 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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℃
Key exclusion criteria (20 listed)
- Subject who has a clinical diagnosis history of Hand, Foot and Mouth Disease (HFMD)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 160Eu/0.5ml in infants (6-11 months old)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)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)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 (without adjuvant) in infants (6-11 months old)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 in infants (6-11 months old) |
| 0Eu/0.5ml in infants (6-11 months old)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)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)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)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 (without adjuvant) in infants (12-23 months old)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 in infants (12-23 months old) |
| 0Eu/0.5ml in infants (12-23 months old)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)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)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)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 (without adjuvant) in children (24 months-5 years old)inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml in 40 children aged 24 months-5 years months old on day 0, 28 | Biological | 1280Eu/0.5ml in children (24 months-5 years old) |
| 0Eu/0.5ml in children (24 months-5 years old)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) |
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
Adverse reactions associated with vaccine were observed in Chinese Infants (from 12 to 23 months old) 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)
Time frame: within the first 56 days after the second vaccination
Adverse reactions associated with vaccine were observed in Chinese children (from 24 months to 5 years old) after the second vaccination
10 secondary outcomes
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
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
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
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
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
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
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
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
Evaluate the vaccine-induced cellular immune responses in children and infant after first vaccination
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2023.
- Derived from this study: PubMed 26419198Zhang 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.
- Derived from this study: PubMed 23372725Liu 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zhaojun Mo, Master principal investigator
Guangxi Provincial Center for Diseases Control and Prevention
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 160Eu/0.5ml in infants (6-11 months old), 320Eu/0.5ml in infants (6-11 months old) and 640Eu/0.5ml in infants (6-11 months old) in people with The Study Focused on the Safety of Inactivated EV71 Vaccine (Human Diploid Cell) Against Hand, Foot and Mouth Disease in Chinese Children and Infants, run by Institute of Medical Biology, Chinese Academy of Medical Sciences at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01512706, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2023.