Hand, Foot and Mouth DiseasePhase 4NCT06146088
Lot-to-lot Consistency Study of Three Commercial Batches of Enterovirus 71 Vaccine
A Phase 4 study testing EV71 Vaccine in people with Hand, Foot and Mouth Disease, run by Institute of Medical Biology, Chinese Academy of Medical Sciences at 4 sites in China.
Trial summary
This study is a randomized, blinded study to evaluate the lot-to-lot consistency of immunogenicity, safety, and immune persistence of three consecutive manufacturing lots of EV71 vaccine, in 1500 children aged 6-35 months. Read more about this study
- Who is it for?
- Ages 6 to 35 monthsHealthy volunteers can take part
- Conditions the study is for
- Hand, Foot and Mouth Disease
- What is being tested?
- EV71 Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,500 participants
- Where
- 4 sitesChina
- Study dates
- 25 Nov 2023to 15 Jul 2026
- Phase
- Phase 4
- 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 to 35 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Age Requirement: Children aged 6 to 35 months at the time of enrollment.
- Provision of legal Identification: Volunteers and their legal guardians or appointed representatives must provide valid legal identification documents.
- Informed Consent: Legal guardians or appointed representatives of volunteers must have the capacity to understand the informed consent document and the research process, voluntarily participate, sign the informed consent form, and be able to comply with the study's requirements and complete relevant visits on time.
- Temperature Requirement: Axillary body temperature prior to vaccination is less than 37.3°C.
Who cannot join
- [First Dose Exclusion Criterions] Subjects meeting any of the following exclusion criteria will not be eligible for enrollment
- Allergic History: Subjects have a previous history of allergies to any component of the vaccine (e.g., aluminum hydroxide, glycine), or previous or suspected allergy to any vaccine or other serious adverse reaction (e.g., anaphylactic shock, laryngeal edema, anaphylactic purpura, thrombocytopenic purpura, local anaphylactic necrosis reaction, dyspnea, angioedema, systemic rash and/or urticaria, etc.).
- Vaccination History: Subjects received any inactivated vaccine or subunit vaccine within 7 days prior to the first dose of the investigational vaccine or any live attenuated vaccine within 14 days prior to the first dose of the investigational vaccine.
- Neurological and Mental Health: Subjects with a history or family history of convulsion, epilepsy, encephalopathy, and psychosis.
- Health Conditions: Subjects with known severe congenital malformation or developmental disorder (e.g., Down syndrome, sickle cell anemia, congenital neurological disorders).
- Acute Illness: Subjects have experienced acute illness (e.g., fever) or acute onset of chronic illness within 3 days before the first dose of investigational vaccine, or use of antipyretic, analgesic, or antiallergic drugs within 3 days before the first dose of the investigational vaccine.
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- Coagulation Abnormalities: Subjects with genetic bleeding tendency, coagulopathy, or a history of bleeding disorders.
- Organ Removal History: Subjects have a history of surgical removal of the spleen or other vital immune organs for any reason.
- Blood Conditions: Subjects with blood loss (≥400mL) or receipt of blood transfusion, immune globulin (other than hepatitis B immune globulin), or blood products within 3 months prior to the first dose of the investigational vaccine.
- Drug Administration: Subjects use any investigational or unregistered product (drug, biological product, or device) within 3 months prior to the first dose of the investigational vaccine, or planned use during the study, except the investigational vaccine.
- Immune Therapy: Subjects have a treatment with immunosuppressive agents within 6 months before the first dose of the investigational vaccine, such as long-term treatment with systemic glucocorticoids (e.g., prednisone or a similar agent for more than 2 consecutive weeks within 6 months), but topical use (e.g., ointments, eye drops, inhalers, or nasal sprays) would be allowed.
- Previous history of receipt of other EV71 vaccines.
- Previous history of hand-foot-mouth disease.
- Immune-related Disease: Subjects have been diagnosed with an infectious disease that may interfere with the conduct or completion of the study (e.g., tuberculosis, viral hepatitis, human immunodeficiency virus infection, etc.).
- Investigators' Discretion: The final exclusion criterion is the investigator's discretion to determine whether a subject is suitable for participation in the study.
- [Contraindication of the second dose of vaccine] Subjects meeting any of the following exclusion criteria will not be eligible for the second dose of the investigational vaccine
- Meeting allergic conditions that are mentioned in the First Dose Exclusion Criteria after the first dose.
- Severe Adverse Reactions: Subjects experienced serious adverse reactions after receiving the previous vaccine dose.
- Other Exclusion Reasons as Determined by the Investigator: The investigator determines other reasons for exclusion.
Trial locations and contacts
4 sites in 1 country.
China4 sites, 4 recruiting
- Not yet recruiting
Chencang Center for Disease Prevention and Control
Baoji, Shaan XI
MIn Yang, 0917-6298067 ext. +86, ccqcdcfy@163.com
- Recruiting
Ningqiang Center for Disease Prevention and Control
Hanzhong, Shaan XI
Hui Zhang, 0916-4228039 ext. +86, 412111748@qq.com
- Not yet recruiting
Fuping Center for Disease Prevention and Control
Weinan, Shaan XI
liqi Shi, 0913-8212134 ext. +86, 469001182@qq.com
- Recruiting
Jingyang Center for Disease Prevention and Control
Xianyang, Shaan XI
Xiaohua Zhai, 029-36212531, jingyangcdc@163.com
About this study
Official title: To Evaluate the Lot-to-lot Consistency of Immunogenicity, Safety, and Immune Persistence of Three Consecutive Commercial Manufacturing Batches of Inactivated Enterovirus 71 Vaccine (Human Diploid Cell) in Children Aged 6-35 Months in a Randomized, Blinded Study
This study is a randomized, blinded study to evaluate the lot-to-lot consistency of immunogenicity, safety, and immune persistence of three consecutive manufacturing lots of EV71 vaccine, in 1500 children aged 6-35 months. The primary immunogenicity endpoint is the anti-EV71 neutralizing antibody geometric mean titer (GMT) 30 days after the final dose. The secondary immunogenicity endpoints are the geometric mean fold increases and seroconversion rates of anti-EV71 neutralizing antibodies 30 days after the final dose. The immune persistence endpoints are the seropositive rates as well as GMT of anti-EV71 neutralizing antibodies 12 and 24 months after the final dose. The safety endpoints are the number of adverse events/reactions within 30 minutes after each dose, the number of solicited adverse events/reactions within 7 days after each dose, the number of unsolicited adverse events/reactions within 30 days after each dose, and the number of serious adverse events (SAE) from the first dose to 6 months post the final dose.
Read the detailed description
This study is a randomized, blinded study to evaluate the lot-to-lot consistency of immunogenicity, safety, and immune persistence of three consecutive manufacturing lots of EV71 vaccine, in children aged 6-35 months. The study is conducted to enroll 1500 healthy participants, including 600 infants aged 6-11 months, 600 toddlers aged 12-23 months, and 300 children aged 24-35 months. Eligibility will be assessed through medical history and physical examination. Participants from each age group will be randomly assigned to three different batch groups in a ratio of 1:1:1, that is, 500 participants in total will be in each lot arm, respectively.
All participants will receive an injection of the EV71 vaccine in the anterolateral midthigh or deltoid muscle of the upper arm on Day 0 and Day 30, respectively. The duration of interventions for each participant is approximately 1 month, thus, the duration of the immune persistence study for each participant is approximately 25 months.
For immunogenicity and immune persistence assessment, neutralizing antibodies against EV71 of all participants will be assessed on the first day (Day 0) before administration, 30 days after the final dose, and 12 and 24 months after the final dose, respectively.
For safety assessment, observation of adverse events (AE) from Day 0 to Day 30 after each dose of vaccination will be evaluated by diary or contact cards. Simultaneously, the serious adverse event (SAE) between the first dose of the vaccine to 6 months after the final dose will be evaluated by diary or contact cards, active reports, investigators' phone calls, or on-site visits. Meanwhile, participants will be observed at clinical sites for at least 30 minutes.
- Conditions
- Hand, Foot and Mouth Disease
- Being tested
- EV71 Vaccine
- Keywords
- Enterovirus 71, Inactivated enterovirus 71 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.
EV71 VaccineBiological
Inactivated enterovirus 71 vaccine (human diploid cell) of 3.0EU/0.5mL on Day 0,30
| Study group | Role | What they receive |
|---|---|---|
| Batch 1 (6-35 months old, 2 doses) | Experimental | Inactivated Enterovirus 71 Vaccine (human diploid cell) in children aged 6-35 months old on Day 0 and Day 30 approved by the National Institute for Food and Drug Control Receives: Biological: EV71 Vaccine |
| Batch 2 (6-35 months old, 2 doses) | Experimental | Inactivated Enterovirus 71 Vaccine (human diploid cell) in children aged 6-35 months old on Day 0 and Day 30 approved by the National Institute for Food and Drug Control Receives: Biological: EV71 Vaccine |
| Batch 3 (6-35 months old, 2 doses) | Experimental | Inactivated Enterovirus 71 Vaccine (human diploid cell) in children aged 6-35 months old on Day 0 and Day 30 approved by the National Institute for Food and Drug Control Receives: Biological: EV71 Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immunogenicity index-geometric mean titer (GMT) of neutralizing antibody
Neutralizing antibody assay will be performed using the neutralization and Microneutralization test method
Measured: Day 30 after the second vaccination
Secondary outcomes (10)
Immunogenicity index-geometric mean fold increase (GMFI) of neutralizing antibody
Neutralizing antibody assay will be performed using the neutralization and Microneutralization test method
Measured: Between baseline and Day 30 after the second vaccination
Immunogenicity index-seroconversion rates of neutralizing antibody
Neutralizing antibody assay will be performed using the neutralization and Microneutralization test method.
Seroconversion will be defined as a change from seronegative (<1:8) to seropositive (≥1:8), or ≥4-fold increase from baseline
Measured: Between baseline and Day 30 after the second vaccination
Immunogenicity index-seropositive rates of neutralizing antibody
Neutralizing antibody assay will be performed using the neutralization and Microneutralization test method. Seropositive will be defined as the positive results with ties≥1:8
Measured: Day 30, 12 months, and 24 months after the second vaccination
Safety index-incidence of adverse reactions/events
Incidence of adverse reactions/events after the first dose vaccination
Measured: 0-30 minutes after the first dose vaccination
Safety index-incidence of adverse reactions/events
Incidence of adverse reactions/events after the second dose vaccination
Measured: 0-30 minutes after the second dose vaccination
Safety index-incidence of adverse reactions/events
Incidence of solicited adverse reactions/events after the first dose vaccination
Measured: Day 0 to Day 7 after the first dose vaccination
Safety index-incidence of adverse reactions/events
Incidence of solicited adverse reactions/events after the second dose vaccination
Measured: Day 0 to Day 7 after the second dose vaccination
Safety index-incidence of adverse reactions/events
Incidence of unsolicited adverse reactions/events after the first dose vaccination
Measured: Day 0 to Day 30 after the first dose vaccination
Safety index-incidence of adverse reactions/events
Incidence of unsolicited adverse reactions/events after the second dose vaccination
Measured: Day 0 to Day 30 after the second dose vaccination
Safety index-incidence of serious adverse reactions/events
Occurrence of serious adverse reactions/events after vaccination
Measured: From the first dose to 6 months post the last dose of vaccination completed
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2023
- Study start25 Nov 2023
- Primary completion31 Mar 2024 (estimated)
- Study completion15 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hand, Foot and 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 1,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute of Medical Biology, Chinese Academy of Medical Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Centers for Disease Control and Prevention, China
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06146088
- Sponsor's protocol ID
- EV71-401
- Status last verified
- Jan 2024
- First submitted
- 17 Nov 2023
- Last updated
- 3 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- To Evaluate the Lot-to-lot Consistency of Immunogenicity, Safety, and Immune Persistence of Three Consecutive Commercial Manufacturing Batches of Inactivated Enterovirus 71 Vaccine (Human Diploid Cell) in Children Aged 6-35 Months in a Randomized, Blinded Study
- ClinicalTrials.gov ID
- NCT06146088
- Acronym / sponsor ID
- EV71-401
- Conditions
- Hand, Foot and Mouth Disease
- Keywords
- Enterovirus 71, Inactivated enterovirus 71 vaccine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,500 participants (estimated)
- Lead sponsor
- Institute of Medical Biology, Chinese Academy of Medical SciencesUniversity, hospital or other
- Collaborators
- Centers for Disease Control and Prevention, China
- Study start
- 25 Nov 2023 (actual)
- Primary completion
- 31 Mar 2024 (estimated)
- Study completion
- 15 Jul 2026 (estimated)
- First posted
- 24 Nov 2023 (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.
This study is a randomized, blinded study to evaluate the lot-to-lot consistency of immunogenicity, safety, and immune persistence of three consecutive manufacturing lots of EV71 vaccine, in 1500 children aged 6-35 months. The primary immunogenicity endpoint is the anti-EV71 neutralizing antibody geometric mean titer (GMT) 30 days after the final dose. The secondary immunogenicity endpoints are the geometric mean fold increases and seroconversion rates of anti-EV71 neutralizing antibodies 30 days after the final dose. The immune persistence endpoints are the seropositive rates as well as GMT of anti-EV71 neutralizing antibodies 12 and 24 months after the final dose. The safety endpoints are the number of adverse events/reactions within 30 minutes after each dose, the number of solicited adverse events/reactions within 7 days after each dose, the number of unsolicited adverse events/reactions within 30 days after each dose, and the number of serious adverse events (SAE) from the first dose to 6 months post the final dose.
Detailed description
This study is a randomized, blinded study to evaluate the lot-to-lot consistency of immunogenicity, safety, and immune persistence of three consecutive manufacturing lots of EV71 vaccine, in children aged 6-35 months. The study is conducted to enroll 1500 healthy participants, including 600 infants aged 6-11 months, 600 toddlers aged 12-23 months, and 300 children aged 24-35 months. Eligibility will be assessed through medical history and physical examination. Participants from each age group will be randomly assigned to three different batch groups in a ratio of 1:1:1, that is, 500 participants in total will be in each lot arm, respectively.
All participants will receive an injection of the EV71 vaccine in the anterolateral midthigh or deltoid muscle of the upper arm on Day 0 and Day 30, respectively. The duration of interventions for each participant is approximately 1 month, thus, the duration of the immune persistence study for each participant is approximately 25 months.
For immunogenicity and immune persistence assessment, neutralizing antibodies against EV71 of all participants will be assessed on the first day (Day 0) before administration, 30 days after the final dose, and 12 and 24 months after the final dose, respectively.
For safety assessment, observation of adverse events (AE) from Day 0 to Day 30 after each dose of vaccination will be evaluated by diary or contact cards. Simultaneously, the serious adverse event (SAE) between the first dose of the vaccine to 6 months after the final dose will be evaluated by diary or contact cards, active reports, investigators' phone calls, or on-site visits. Meanwhile, participants will be observed at clinical sites for at least 30 minutes.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Batch 1 (6-35 months old, 2 doses) | Experimental | Biological: EV71 VaccineInactivated Enterovirus 71 Vaccine (human diploid cell) in children aged 6-35 months old on Day 0 and Day 30 approved by the National Institute for Food and Drug Control |
| Batch 2 (6-35 months old, 2 doses) | Experimental | Biological: EV71 VaccineInactivated Enterovirus 71 Vaccine (human diploid cell) in children aged 6-35 months old on Day 0 and Day 30 approved by the National Institute for Food and Drug Control |
| Batch 3 (6-35 months old, 2 doses) | Experimental | Biological: EV71 VaccineInactivated Enterovirus 71 Vaccine (human diploid cell) in children aged 6-35 months old on Day 0 and Day 30 approved by the National Institute for Food and Drug Control |
Who may qualify
- Ages
- 6 to 35 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Age Requirement: Children aged 6 to 35 months at the time of enrollment.
- Provision of legal Identification: Volunteers and their legal guardians or appointed representatives must provide valid legal identification documents.
- Informed Consent: Legal guardians or appointed representatives of volunteers must have the capacity to understand the informed consent document and the research process, voluntarily participate, sign the informed consent form, and be able to comply with the study's requirements and complete relevant visits on time.
- Temperature Requirement: Axillary body temperature prior to vaccination is less than 37.3°C.
Key exclusion criteria (19 listed)
- [First Dose Exclusion Criterions] Subjects meeting any of the following exclusion criteria will not be eligible for enrollment
- Allergic History: Subjects have a previous history of allergies to any component of the vaccine (e.g., aluminum hydroxide, glycine), or previous or suspected allergy to any vaccine or other serious adverse reaction (e.g., anaphylactic shock, laryngeal edema, anaphylactic purpura, thrombocytopenic purpura, local anaphylactic necrosis reaction, dyspnea, angioedema, systemic rash and/or urticaria, etc.).
- Vaccination History: Subjects received any inactivated vaccine or subunit vaccine within 7 days prior to the first dose of the investigational vaccine or any live attenuated vaccine within 14 days prior to the first dose of the investigational vaccine.
- Neurological and Mental Health: Subjects with a history or family history of convulsion, epilepsy, encephalopathy, and psychosis.
- Health Conditions: Subjects with known severe congenital malformation or developmental disorder (e.g., Down syndrome, sickle cell anemia, congenital neurological disorders).
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 |
|---|---|---|
| EV71 VaccineInactivated enterovirus 71 vaccine (human diploid cell) of 3.0EU/0.5mL on Day 0,30 | Biological | Batch 1 (6-35 months old, 2 doses), Batch 2 (6-35 months old, 2 doses), Batch 3 (6-35 months old, 2 doses) |
Primary outcome
Immunogenicity index-geometric mean titer (GMT) of neutralizing antibody
Time frame: Day 30 after the second vaccination
Neutralizing antibody assay will be performed using the neutralization and Microneutralization test method
10 secondary outcomes
Immunogenicity index-geometric mean fold increase (GMFI) of neutralizing antibody
Time frame: Between baseline and Day 30 after the second vaccination
Immunogenicity index-seroconversion rates of neutralizing antibody
Time frame: Between baseline and Day 30 after the second vaccination
Immunogenicity index-seropositive rates of neutralizing antibody
Time frame: Day 30, 12 months, and 24 months after the second vaccination
Safety index-incidence of adverse reactions/events
Time frame: 0-30 minutes after the first dose vaccination
Safety index-incidence of adverse reactions/events
Time frame: 0-30 minutes after the second dose vaccination
Safety index-incidence of adverse reactions/events
Time frame: Day 0 to Day 7 after the first dose vaccination
Safety index-incidence of adverse reactions/events
Time frame: Day 0 to Day 7 after the second dose vaccination
Safety index-incidence of adverse reactions/events
Time frame: Day 0 to Day 30 after the first dose vaccination
Safety index-incidence of adverse reactions/events
Time frame: Day 0 to Day 30 after the second dose vaccination
Safety index-incidence of serious adverse reactions/events
Time frame: From the first dose to 6 months post the last dose of vaccination completed
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2024.
- Individual participant dataSharing planned: No
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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.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing EV71 Vaccine in people with Hand, Foot and Mouth Disease, run by Institute of Medical Biology, Chinese Academy of Medical Sciences at 4 sites 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 4 inclusion and 19 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: status not confirmed, as of the sponsor's last update on 3 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Weijun Hu (029-82221350 ext. +86, huweijun0828@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immunogenicity index-geometric mean titer (GMT) of neutralizing antibody (time frame: Day 30 after the second vaccination). 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 3 Jan 2024.