Hand Foot & Mouth DiseasePhase 1/2NCT04467541
Safety & Immunogenicity of Enterovirus Type 71 Vaccine in Healthy Adults and Children 6-71months
A Phase 1/2 study testing Inactivated Enterovirus Type 71 (EV71) Vaccine (Vero Cell) in people with Hand Foot & Mouth Disease, run by International Centre for Diarrhoeal Disease Research, Bangladesh at 1 site in Bangladesh.
Trial summary
1. Burden: Hand-foot-and-mouth disease (HFMD) characterized by skin rash in extremities, mouth ulcer and fever among <5 years children.Primarily caused by Enterovirus- predominantly human Enterovirus (EV) 71 and Coxsackie virus (CoxA). Read more about this study
- Who is it for?
- Ages 6 months to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Hand Foot & Mouth Disease
- What is being tested?
- Inactivated Enterovirus Type 71 (EV71) Vaccine (Vero Cell)
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 430 participants
- Where
- 1 siteBangladesh
- Study dates
- 24 Dec 2019to 31 Jan 2020
- Phase
- Phase 1/2
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Bangladeshi healthy adults 18-45yrs and children aged 6-71 months on the day of screening;
- Either sex;
- The participant /parents or guardian of the participant properly informed about the study and having signed the informed consent form (ICF);
- Participant/Parents' or guardian's availability for the entire period of the study and reachability by study staff for post-vaccination follow-up
Who cannot join
- Whether the participant should be enrolled should be judged according to the following criteria. The participant cannot participate in the study if any of the following circumstances exists:
- Previous history of hand, foot and mouth disease;
- Allergy history to vaccine or components of the vaccine, previous history of asthma, serious adverse effects of the vaccine such as urticaria, dyspnea, angioneurotic edema or stomachache, etc;
- Congenital malformation or developmental disorder, genetic defect, serious malnutrition, etc;
- Autoimmune disease or immunodeficiency or immunosuppression;
- Severe neurological disorders (epilepsy, convulsion or tic) or family history of mental disease;
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- History of thyroidectomy, or asplenia or functional asplenia;
- Severely malnourished children
- Abnormal coagulation functions (such as coagulation factor deficiency, blood coagulation disease and blood platelet disorders) or obvious bruise or blood coagulation disorders diagnosed by the doctors;
- Received immunosuppressant therapy, cytotoxic drug therapy and inhaled corticosteroid therapy (excluding the corticosteroid aerosol therapy for allergic rhinitis and surface corticosteroid therapy for acute non-complicated dermatitis) in the past 6 months;
- Received blood products within 3 months before receiving the investigational vaccine;
- Received other study drugs or vaccines within 30 days before receiving the investigational vaccine;
- Received live attenuated vaccines within 14 days before receiving the investigational vaccine;
- Received subunit or inactivated vaccines within 7 days before receiving the investigational vaccine;
- Various acute diseases or acute exacerbation of chronic diseases within 7 days;
- Fever before vaccine inoculation, axillary temperature >37.5°C;
- Any other factors which are unsuitable for participation in the clinical trial as judged by the investigator.
- Exclusion Criteria for Inoculation of the Second Dose of Vaccine:
- Any serious adverse event related to the inoculation of the investigational product;
- Hypersensitivity after vaccine inoculation (including urticaria/rash appeared within 30 minutes after inoculation);
- Any confirmed or suspected autoimmune disease or immunodeficiency disease, including human immunodeficiency virus (HIV) infection;
- If acute or newly onset chronic disease occurs during vaccine inoculation;
- The investigator judged that other significant reactions occur (including serious pain, serious swelling, serious activity limitation, continuous hyperthermia, serious headache or other systemic or local reactions);
- The patient develops acute disease when vaccine is inoculated (acute diseases means the moderate or severe disease with or without fever);
- Axillary temperature >37.5°C when vaccine is inoculated;
- The patient has received subunit inactivated vaccine within 7 days or live attenuated vaccines within 14 days.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Open, Phase I/II to Evaluate the Inactivated EV 71 Vaccine Safety in Healthy Adults Followed by Safety and Immunogenicity Administered in 2 Consecutive Doses, 1 Month Apart Among Child Aged 6 to 71 Months.
- Burden: Hand-foot-and-mouth disease (HFMD) characterized by skin rash in extremities, mouth ulcer and fever among <5 years children.Primarily caused by Enterovirus- predominantly human Enterovirus (EV) 71 and Coxsackie virus (CoxA). Several large epidemics have been reported worldwide.Large Asia-Pacific epidemic-in China in 2008, approximately 490,000 infections and 126 deaths of children. EV71 contributes severe and fatal cases e.g. encephalitis.A recent outbreak of HFMD in Bhubaneswar, Odisha in India indicates there is a chance of HFMD outbreaks in Bangladesh. However there is not much report of HFMD from Bangladesh.
- Knowledge gap: EV71 is most commonly transmitted via close person-to-person contact. Since there is no known effective treatment for HFMD and as the causative virus is highly contagious, hand washing is the best defense for prevention. However, asymptomatic or mild nature of the infection leads to ineffectiveness of public health interventions like hand washing. Thus the symptomatic management remains the mainstay of treatment strategy for HFMD as of now. EV71 vaccine, an inactivated vaccine, developed by Sinovac Biotech Ltd has shown satisfactory safety and effectiveness through Phase III trials conducted in various regions of mainland China, This new vaccine has the potential to significantly reduce suffering and death from EV71 disease in China. However, it is not assessed on Bangladeshi child.
- Relevance: Due to the absence of effective public health strategy and proper treatment, the development of an effective vaccine may be the best way to control EV71 infection.
Read the detailed description
General objective:
- To evaluate the safety of EV71 vaccine in adults and in children age 6-71 months
- To evaluate the immunogenicity of the vaccine in children by assessing the neutralization antibody levels before immunization; then 7, 15, 30 days after the first inoculation; and also 7, 15, 30 days after the second inoculation.
- To assess the incidence rate of adverse reactions/events
Specific objective: To find out:
- Seroconversion rate of neutralization antibody on the day 30 after the whole-range immunization (i.e. after 2nd dose of vaccination);
- Positive rate and Geometric Mean Titer of neutralization antibody on the day 30 after the whole-range immunization;
- Seroconversion rate, positive rate and Geometric Mean Titer of serum neutralization antibody on the day 7, day 15, day 30 after the first inoculation;
- Seroconversion rate,positive rate and Geometric Mean Titer of serum neutralization antibody on the day 7, day 15 after the second inoculation;
- The incidence rate of adverse reactions \& serious adverse events during the observation period of safety;
- The incidence rate of adverse reactions 0-30 days after each inoculation of vaccine;
- The incidence rate of adverse events 0-7 days after each inoculation of vaccine;
- Conditions
- Hand Foot & Mouth Disease
- Being tested
- Inactivated Enterovirus Type 71 (EV71) Vaccine (Vero Cell)
- 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.
Inactivated Enterovirus Type 71 (EV71) Vaccine (Vero Cell)Biological
Also called Inlive
Inactivated Enterovirus Type 71 (EV71) Vaccine safety in healthy adults followed by safety and immunogenicity administered in two consecutive doses, one-month apart among children aged 6 to 71 months
| Study group | Role | What they receive |
|---|---|---|
| Inactivated enterovirus type 71 vaccine | Experimental | Inactivated enterovirus type 71 vaccine safety in healthy adults followed by safety and immunogenicity administered in two consecutive doses, one-month apart among children aged 6 to 71 months Receives: Biological: Inactivated Enterovirus Type 71 (EV71) Vaccine (Vero Cell) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neutralizing Antibody responses for evaluation of enterovirus 71( EV71) vaccines
Testing the neutralization antibody levels before immunization, 7, 15, 30 days after Ist inoculation, 7, 15, 30 days after the 2nd inoculation, calculate the positive seroconversion rate, the positive rate and geometric mean titre of neutralization antibody.
Vaccine recipients will have greater increase in neutralization antibody titers (NT) after the first dose, without a further increase in NT after the second dose. The seroconversion rate will be increased after Ist \& second inoculation
Detection Method of the Anti-EV71 Neutralizing Antibody
- Sample collection and processing
- Serum will be examined to determine the potency of the neutralizing antibody
- Treatment of the serum to be examined
- Dilution of the serum to be examined and virus used for neutralization:
- Serum and virus neutralizing and virus culture
- Observation of the cytopathic change and judgment results
Measured: before immunization, 7, 15, 30 days after the first inoculation, 7, 15, 30 days after the second inoculation
Secondary outcomes (1)
Safety Outcome
Solicited AE's (Local) e.g. Tenderness, Indurations, Redness, swelling Rash (Injection site), Pruritus with Grading \& Solicited AE's (Systemic) e.g. Allergic Reaction, Fatigue, Asthenia, Dysphoria, Loss of Appetite Nausea, Vomiting, Diarrhea Fever (Axillary Temp)with Grading will be assessed.
If any solicited or unsolicited AE's following vaccination in this study and will record adverse events at home in diary card.
Measured: After Ist vacctination (0 day) & 30 days after 2nd vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2020
- Study start24 Dec 2019
- Primary completion31 Jan 2020
- Study completion31 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hand Foot & Mouth DiseaseStudies 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 1/2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 430 participants (actual)
Sponsor and investigators
- Lead sponsor
- International Centre for Diarrhoeal Disease Research, Bangladesh
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wasif Ali Khan, MBBS, MHS, Principal investigator, International Centre for Diarrhoeal Disease Research, Bangladesh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04467541
- Sponsor's protocol ID
- PR-19055
- Status last verified
- Jun 2020
- First submitted
- 25 Jun 2020
- Last updated
- 2 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open, Phase I/II to Evaluate the Inactivated EV 71 Vaccine Safety in Healthy Adults Followed by Safety and Immunogenicity Administered in 2 Consecutive Doses, 1 Month Apart Among Child Aged 6 to 71 Months.
- ClinicalTrials.gov ID
- NCT04467541
- Acronym / sponsor ID
- PR-19055
- Conditions
- Hand Foot & Mouth Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 430 participants (actual)
- Lead sponsor
- International Centre for Diarrhoeal Disease Research, BangladeshUniversity, hospital or other
- Study start
- 24 Dec 2019 (actual)
- Primary completion
- 31 Jan 2020 (actual)
- Study completion
- 31 Jan 2020 (actual)
- First posted
- 13 Jul 2020 (actual)
- 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.
- Burden: Hand-foot-and-mouth disease (HFMD) characterized by skin rash in extremities, mouth ulcer and fever among <5 years children.Primarily caused by Enterovirus- predominantly human Enterovirus (EV) 71 and Coxsackie virus (CoxA). Several large epidemics have been reported worldwide.Large Asia-Pacific epidemic-in China in 2008, approximately 490,000 infections and 126 deaths of children. EV71 contributes severe and fatal cases e.g. encephalitis.A recent outbreak of HFMD in Bhubaneswar, Odisha in India indicates there is a chance of HFMD outbreaks in Bangladesh. However there is not much report of HFMD from Bangladesh.
- Knowledge gap: EV71 is most commonly transmitted via close person-to-person contact. Since there is no known effective treatment for HFMD and as the causative virus is highly contagious, hand washing is the best defense for prevention. However, asymptomatic or mild nature of the infection leads to ineffectiveness of public health interventions like hand washing. Thus the symptomatic management remains the mainstay of treatment strategy for HFMD as of now. EV71 vaccine, an inactivated vaccine, developed by Sinovac Biotech Ltd has shown satisfactory safety and effectiveness through Phase III trials conducted in various regions of mainland China, This new vaccine has the potential to significantly reduce suffering and death from EV71 disease in China. However, it is not assessed on Bangladeshi child.
- Relevance: Due to the absence of effective public health strategy and proper treatment, the development of an effective vaccine may be the best way to control EV71 infection.
Detailed description
General objective:
- To evaluate the safety of EV71 vaccine in adults and in children age 6-71 months
- To evaluate the immunogenicity of the vaccine in children by assessing the neutralization antibody levels before immunization; then 7, 15, 30 days after the first inoculation; and also 7, 15, 30 days after the second inoculation.
- To assess the incidence rate of adverse reactions/events
Specific objective: To find out:
- Seroconversion rate of neutralization antibody on the day 30 after the whole-range immunization (i.e. after 2nd dose of vaccination);
- Positive rate and Geometric Mean Titer of neutralization antibody on the day 30 after the whole-range immunization;
- Seroconversion rate, positive rate and Geometric Mean Titer of serum neutralization antibody on the day 7, day 15, day 30 after the first inoculation;
- Seroconversion rate,positive rate and Geometric Mean Titer of serum neutralization antibody on the day 7, day 15 after the second inoculation;
- The incidence rate of adverse reactions \& serious adverse events during the observation period of safety;
- The incidence rate of adverse reactions 0-30 days after each inoculation of vaccine;
- The incidence rate of adverse events 0-7 days after each inoculation of vaccine;
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Inactivated enterovirus type 71 vaccine | Experimental | Biological: Inactivated Enterovirus Type 71 (EV71) Vaccine (Vero Cell)Inactivated enterovirus type 71 vaccine safety in healthy adults followed by safety and immunogenicity administered in two consecutive doses, one-month apart among children aged 6 to 71 months |
Who may qualify
- Ages
- 6 months to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Bangladeshi healthy adults 18-45yrs and children aged 6-71 months on the day of screening;
- Either sex;
- The participant /parents or guardian of the participant properly informed about the study and having signed the informed consent form (ICF);
- Participant/Parents' or guardian's availability for the entire period of the study and reachability by study staff for post-vaccination follow-up
Key exclusion criteria (26 listed)
- Whether the participant should be enrolled should be judged according to the following criteria. The participant cannot participate in the study if any of the following circumstances exists:
- Previous history of hand, foot and mouth disease;
- Allergy history to vaccine or components of the vaccine, previous history of asthma, serious adverse effects of the vaccine such as urticaria, dyspnea, angioneurotic edema or stomachache, etc;
- Congenital malformation or developmental disorder, genetic defect, serious malnutrition, etc;
- Autoimmune disease or immunodeficiency or immunosuppression;
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 |
|---|---|---|
| Inactivated Enterovirus Type 71 (EV71) Vaccine (Vero Cell)Also: InliveInactivated Enterovirus Type 71 (EV71) Vaccine safety in healthy adults followed by safety and immunogenicity administered in two consecutive doses, one-month apart among children aged 6 to 71 months | Biological | Inactivated enterovirus type 71 vaccine |
Primary outcome
Neutralizing Antibody responses for evaluation of enterovirus 71( EV71) vaccines
Time frame: before immunization, 7, 15, 30 days after the first inoculation, 7, 15, 30 days after the second inoculation
Testing the neutralization antibody levels before immunization, 7, 15, 30 days after Ist inoculation, 7, 15, 30 days after the 2nd inoculation, calculate the positive seroconversion rate, the positive rate and geometric mean titre of neutralization antibody. Vaccine recipients will have greater increase in neutralization antibody titers (NT) after the first dose, without a further increase in NT after the second dose. The seroconversion rate will be increased after Ist \& second inoculation Detection Method of the Anti-EV71 Neutralizing Antibody * Sample collection and processing * Serum will be examined to determine the potency of the neutralizing antibody * Treatment of the serum to be examined * Dilution of the serum to be examined and virus used for neutralization: * Serum and virus neutralizing and virus culture * Observation of the cytopathic change and judgment results
1 secondary outcome
Safety Outcome
Time frame: After Ist vacctination (0 day) & 30 days after 2nd 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 2 Feb 2021.
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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.
Wasif Ali Khan, MBBS, MHS principal investigator
International Centre for Diarrhoeal Disease Research, Bangladesh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Inactivated Enterovirus Type 71 (EV71) Vaccine (Vero Cell) in people with Hand Foot & Mouth Disease, run by International Centre for Diarrhoeal Disease Research, Bangladesh at 1 site in Bangladesh.
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 4 inclusion and 26 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 2 Feb 2021. 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 Bangladesh. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Neutralizing Antibody responses for evaluation of enterovirus 71( EV71) vaccines (time frame: before immunization, 7, 15, 30 days after the first inoculation, 7, 15, 30 days after the second inoculation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Feb 2021.