Hand, Foot and Mouth DiseasePhase 3NCT03909074

Clinical Trial of Enterovirus 71（EV71） Inactivated Vaccine in Children Aged 36-71 Months

A Phase 3 study testing 36-71 months old children-experimental EV71 vaccine. and 6-35 months old children-experimental EV71 vaccine. in people with Hand, Foot and Mouth Disease, run by Sinovac Biotech Co., Ltd at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 6 to 71 monthsHealthy volunteers can take part
Conditions the study is for: Hand, Foot and Mouth Disease
What is being tested?: 36-71 months old children-experimental EV71 vaccine. and 6-35 months old children-experimental EV71 vaccine.
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 900 participants
Where: 1 siteChina
Study dates: 10 Mar 2019to 13 Nov 2019
Phase: Phase 3
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 71 months
All sexes
Healthy volunteers accepted
Child

Who may be able to join

Healthy volunteers ≥ 2 years old;
Proven legal identity;
Participants or guardians of the participants should be capable of understanding the written consent form, and such form should be signed prior to enrolment.

Who cannot join

Prior vaccination with EV71 vaccine;
History of hand, foot and mouth disease;
History of allergy to any vaccine or vaccine ingredient, asthma, serious adverse reactions to vaccination, such as urticaria, dyspnea, angioneurotic edema, abdominal pain, etc;
Congenital malformation, developmental disorders, genetic defects, or severe malnutrition;
Autoimmune disease or immunodeficiency/immunosuppressive;
Severe/uncontrollable nervous system disease (epilepsy, seizures or convulsions) or mental illness;

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History of thyroidectomy, no spleen and functional spleen;
Diagnosed coagulation function abnormal (e.g., coagulation factor deficiency, coagulation disorder, or platelet abnormalities) , or obvious bruising or coagulation disorders;
Receipt of any of the following products:
Any immunosuppressant, cytotoxic medicine, or inhaled corticosteroids (except corticosteroid spray for treatment of allergic rhinitis or corticosteroid treatment on surface for acute non-complicated dermatitis) within 6 month prior to study entry
Blood products within 2 months prior to study entry
Any other investigational products (drug or vaccine）within 30 days prior to study entry
Any live attenuated vaccine within 14 days prior to study entry
Any subunit vaccine or inactivated vaccine within 7 days prior to study entry;
Acute disease or acute stage of chronic disease within 7 days prior to study entry;
Axillary temperature > 37.0 °C;
Any other factor that suggesting the volunteer is unsuitable for this study based on the opinions of investigators.

Trial locations and contacts

1 site in 1 country.

China1 site

Yun County Center for Disease Control and Prevention
Lincang, Yunnan, 675800

Other trials in China

About this study

Official title: A Phase III Clinical Trial With Randomized, Double-blinded, Controlled Design as Well as Bridging Design to Evaluate the Safety and Immunogenicity of EV71 Vaccine in Children Aged 36-71 Months

The purpose of this study is to evaluate the non-inferiority of experimental EV71 vaccine compared to the control EV71 vaccine in children aged 36-71 months, to evaluate the non-inferiority of EV71 vaccine used in children aged 36-71 months compared to 6-35 months. The experimental vaccine was manufactured by Sinovac Biotech Co., Ltd, and the control vaccine was manufactured by Institute of Medical Biology Chinese Academy of Medical Sciences.

Read the detailed description

This study is a randomized, double-blind, single-center, controlled phase III clinical trial in children aged 36-71 months, and bridging trial between agegroup of 6-35 and 36-71 months. The purpose of this study is to evaluate the immunogenicity and safety of the experimental EV71 vaccine in children aged 36-71 months. The primary objective of this study is to evaluate the non-inferiority of experimental EV71 vaccine compared to the control EV71 vaccine in children aged 36-71 months, and the non-inferiority of EV71 vaccine used in children aged 36-71 months compared to 6-35 months. The secondary objective is to evaluate the safety of the experimental vaccine used in children aged 36-71 months. The experimental vaccine is manufactured by Sinovac Biotech Co., Ltd, and the control vaccine is manufactured by Institute of Medical Biology Chinese Academy of Medical Sciences. 600 children aged 36-71 months will be randomly assigned in to receive the experimental vaccine or control vaccine, and 300 children aged 6-35 months will receive the experimental vaccine.

Conditions: Hand, Foot and Mouth Disease
Being tested: 36-71 months old children-experimental EV71 vaccine., 36-71 months old children-control EV71 vaccine., 6-35 months old children-experimental EV71 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.

36-71 months old children-experimental EV71 vaccine.Biological
Two doses experimental EV71 vaccine at the 0, 30 days vaccination schedule.
36-71 months old children-control EV71 vaccine.Biological
Two doses control EV71 vaccine at the 0, 30 days vaccination schedule.
6-35 months old children-experimental EV71 vaccine.Biological
Two doses experimental EV71 vaccine at the 0, 30 days vaccination schedule.

Study groups in NCT03909074
Study group	Role	What they receive
Experimental group	Experimental	36-71 months old children-experimental EV71 vaccine. Receives: Biological: 36-71 months old children-experimental EV71 vaccine.
Vaccine-controlled group	Active comparator	36-71 months old children-control EV71 vaccine. Receives: Biological: 36-71 months old children-control EV71 vaccine.
Age-controlled group	Active comparator	6-35 months old children-experimental EV71 vaccine. Receives: Biological: 6-35 months old children-experimental EV71 vaccine.

What is being measured

The primary outcome is the main question the study is designed to answer.

The seroconversion rates (SCR) of the EV71 neutralizing antibody calculated based on the cutoff value of 1:8
Subjects whose pre-immune antibody titer < 1:8 and post-immune antibody titer ≥ 1:8, or those whose pre-immune antibody titer ≥ 1:8 and the increase of post-immune antibody level ≥ 4 folds are considered seroconverted.
Measured: 30 days after two doses
The Geometric mean titer (GMT) of the EV71 neutralizing antibody in the susceptible population
The susceptible population refer to the subjects whose pre-immune antibody titer <1:8
Measured: 30 days after two doses

Secondary outcomes (4)

The overall incidence of adverse reactions
After each dose, a 30-minute safety observation will be conducted immediately. The body temperature, solicited local and general adverse events (AE) on day 0-7 were reported. The solicited local symptoms include pain, induration, redness, swelling, rash, and pruritus. The solicited general adverse symptoms include allergy, fatigue, irritability, inappetence, vomiting, diarrhea, and fever. Unsolicited adverse events on day 0-30 were also reported, which include the unsolicited symptoms happened within 0-7 days, and any symptoms happened within the 8-28 days. Each AE case will be reviewed by the investigator to determine whether it was an adverse reaction (The vaccination-related AE). The incidence of adverse reactions=Number of subjects who have adverse reactions of any symptoms/number of all the subjects whose safety information are collected.
Measured: 0-30 days after each dose
The incidence of the serious adverse events (SAE)
After each dose, the serious adverse events in the safety observation period will be reported. The SAE incidence=Number of subjects who have SAE of any symptoms/Number of subjects whose safety information are collected.
Measured: 0-30 days after each dose
The seroconversion rates (SCR) of the EV71 neutralizing antibody calculated based on the cutoff value of 1:16, 1:32, and 1:64 respectively
Subjects whose pre-immune antibody titer <1:16(1:32/1:64) and post-immune antibody titer ≥1:16(1:32/1:64), or those whose pre-immune antibody titer ≥ 1:16(1:32/1:64) and the increase of post-immune antibody level ≥ 4 folds are considered seroconverted.
Measured: 30 days after two doses
The Geometric mean titer (GMT) of the EV71 neutralizing antibody
The GMT 30 days after two doses.
Measured: 30 days after two doses

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Mar 201913 Nov 2019

First posted9 Apr 2019
Study start10 Mar 2019
Primary completion17 Jun 2019
Study completion13 Nov 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hand, Foot and Mouth DiseaseStudies of the same condition, open and under way.
More trials run by Sinovac Biotech Co., LtdThe sponsor's other registered studies.
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 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 900 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03909074
Sponsor's protocol ID: PRO-EV71-3003
Status last verified: Jan 2020
First submitted: 29 Mar 2019
Last updated: 26 May 2022
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Zhang L, Gao F, Zeng G, Yang H, Zhu T, Yang S, Meng X, Mao Q, Liu X. Immunogenicity and Safety of Inactivated Enterovirus 71 Vaccine in Children Aged 36-71 Months: A Double-Blind, Randomized, Controlled, Non-inferiority Phase III Trial. J Pediatric Infect Dis Soc. 2021 Apr 30;10(4):440-447. doi: 10.1093/jpids/piaa129.
PubMed 33269798

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
CHIPCAT and HFMD-PREP for HFMD Prevention in Childcare Centres in Kota Kinabalu
Hand, Foot and Mouth Disease, Infection Control
Not yet recruiting
Bridging Clinical Trial of EV71 Vaccine in Vietnamese Children
Hand, Foot, and Mouth Disease (HFMD), Enterovirus 71 Infection
Not yet recruitingPhase 3
Protective Efficacy , Immunogenicity and Safety of the Tetravalent Inactivated Enterovirus Vaccine (Vero Cell).
Hand, Foot, and Mouth Disease(HFMD), Herpangina
Not yet recruitingPhase 1
Phase I Clinical Trial of Enterovirus Type71 - Coxsackievirus Type A16 Bivalent Vaccine
Hand, Foot and Mouth Disease (HFMD), HFMD
Enrolling by invitationObservational study
Study on the Persistence of Immunity Following EV71 Vaccination
Hand, Foot, and Mouth Disease, Hand, Foot, and Mouth Disease (HFMD)

All Hand, Foot and Mouth Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 26 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III Clinical Trial With Randomized, Double-blinded, Controlled Design as Well as Bridging Design to Evaluate the Safety and Immunogenicity of EV71 Vaccine in Children Aged 36-71 Months
ClinicalTrials.gov ID: NCT03909074
Acronym / sponsor ID: PRO-EV71-3003
Conditions: Hand, Foot and Mouth Disease
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 900 participants (actual)
Lead sponsor: Sinovac Biotech Co., LtdIndustry (pharma, biotech, devices)
Study start: 10 Mar 2019 (actual)
Primary completion: 17 Jun 2019 (actual)
Study completion: 13 Nov 2019 (actual)
First posted: 9 Apr 2019 (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.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
Experimental group	Experimental	Biological: 36-71 months old children-experimental EV71 vaccine.36-71 months old children-experimental EV71 vaccine.
Vaccine-controlled group	Active comparator	Biological: 36-71 months old children-control EV71 vaccine.36-71 months old children-control EV71 vaccine.
Age-controlled group	Active comparator	Biological: 6-35 months old children-experimental EV71 vaccine.6-35 months old children-experimental EV71 vaccine.

Who may qualify

Ages: 6 to 71 months
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (3 listed)

Healthy volunteers ≥ 2 years old;
Proven legal identity;
Participants or guardians of the participants should be capable of understanding the written consent form, and such form should be signed prior to enrolment.

Key exclusion criteria (17 listed)

Prior vaccination with EV71 vaccine;
History of hand, foot and mouth disease;
History of allergy to any vaccine or vaccine ingredient, asthma, serious adverse reactions to vaccination, such as urticaria, dyspnea, angioneurotic edema, abdominal pain, etc;
Congenital malformation, developmental disorders, genetic defects, or severe malnutrition;
Autoimmune disease or immunodeficiency/immunosuppressive;

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
36-71 months old children-experimental EV71 vaccine.Two doses experimental EV71 vaccine at the 0, 30 days vaccination schedule.	Biological	Experimental group
36-71 months old children-control EV71 vaccine.Two doses control EV71 vaccine at the 0, 30 days vaccination schedule.	Biological	Vaccine-controlled group
6-35 months old children-experimental EV71 vaccine.Two doses experimental EV71 vaccine at the 0, 30 days vaccination schedule.	Biological	Age-controlled group

Primary outcome

The seroconversion rates (SCR) of the EV71 neutralizing antibody calculated based on the cutoff value of 1:8
Time frame: 30 days after two doses
Subjects whose pre-immune antibody titer < 1:8 and post-immune antibody titer ≥ 1:8, or those whose pre-immune antibody titer ≥ 1:8 and the increase of post-immune antibody level ≥ 4 folds are considered seroconverted.
The Geometric mean titer (GMT) of the EV71 neutralizing antibody in the susceptible population
Time frame: 30 days after two doses
The susceptible population refer to the subjects whose pre-immune antibody titer <1:8

4 secondary outcomes

The overall incidence of adverse reactions
Time frame: 0-30 days after each dose
The incidence of the serious adverse events (SAE)
Time frame: 0-30 days after each dose
The seroconversion rates (SCR) of the EV71 neutralizing antibody calculated based on the cutoff value of 1:16, 1:32, and 1:64 respectively
Time frame: 30 days after two doses
The Geometric mean titer (GMT) of the EV71 neutralizing antibody
Time frame: 30 days after two doses

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 26 May 2022.
Derived from this study: PubMed 33269798Zhang L, Gao F, Zeng G, Yang H, Zhu T, Yang S, Meng X, Mao Q, Liu X. Immunogenicity and Safety of Inactivated Enterovirus 71 Vaccine in Children Aged 36-71 Months: A Double-Blind, Randomized, Controlled, Non-inferiority Phase III Trial. J Pediatric Infect Dis Soc. 2021 Apr 30;10(4):440-447. doi: 10.1093/jpids/piaa129.

Related trials for Hand, Foot and Mouth Disease

Not yet recruiting
CHIPCAT and HFMD-PREP for HFMD Prevention in Childcare Centres in Kota Kinabalu
Hand, Foot and Mouth Disease, Infection Control
Not yet recruiting
Bridging Clinical Trial of EV71 Vaccine in Vietnamese Children
Hand, Foot, and Mouth Disease (HFMD), Enterovirus 71 Infection
Not yet recruitingPhase 3
Protective Efficacy , Immunogenicity and Safety of the Tetravalent Inactivated Enterovirus Vaccine (Vero Cell).
Hand, Foot, and Mouth Disease(HFMD), Herpangina
Not yet recruitingPhase 1
Phase I Clinical Trial of Enterovirus Type71 - Coxsackievirus Type A16 Bivalent Vaccine
Hand, Foot and Mouth Disease (HFMD), HFMD
Enrolling by invitationObservational study
Study on the Persistence of Immunity Following EV71 Vaccination
Hand, Foot, and Mouth Disease, Hand, Foot, and Mouth Disease (HFMD)

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.

Lifen Zhang, Master principal investigator

Yunnan Center for Disease Control and Prevention

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 3 inclusion and 17 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 26 May 2022. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

The seroconversion rates (SCR) of the EV71 neutralizing antibody calculated based on the cutoff value of 1:8 (time frame: 30 days after two doses). The study lists 2 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 NCT03909074, which also lists 1 linked publication.

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 26 May 2022.