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Not yet recruitingNCT07611513Updated May 28, 2026

Protective Efficacy , Immunogenicity and Safety of the Tetravalent Inactivated Enterovirus Vaccine (Vero Cell).

A Phase 3 interventional study of Tetravalent Inactivated Enterovirus Vaccine (Vero Cell) and Placebo in Hand, Foot, and Mouth Disease(HFMD) and Herpangina, sponsored by Sinovac Biotech Co., Ltd. Not yet recruiting at 5 sites in China. Open to participants aged 6 Months to 71 Months, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-05-28.

Sponsored by Sinovac Biotech Co., Ltd · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
6,000
Allocation
Randomized
Ages
6 Months to 71 Months
Sex
All
01

Study summary

This multicenter, randomized, double-blind, placebo-controlled phase IIIa clinical trial aims to evaluate the protective efficacy , immunogenicity and safety of the Tetravalent Inactivated Enterovirus Vaccine (Vero Cell) in Children aged 6 to 71 months.

Participants will be randomly assigned in a 1:1 ratio to the trial group and the placebo group, receiving two doses of experimental vaccine or placebo , with a one-month interval between the two doses.

Read the detailed description

This trial employs a multicenter, randomized, double-blind, placebo-controlled design.With informed consent, 6000 children participants aged 6 to 71 months will be enrolled, with 2800 participants aged 6 to 23 months and 3200 participants aged 24 to 71 months, maintaining a balanced gender ratio. All participants will be randomly assigned to the trial and placebo groups at a 1:1 ratio, receiving two doses of experimental vaccine or placebo , with a one-month interval between the two doses.

Protective Efficacy Assessment: Each participant enters the case monitoring period after receiving the first dose of vaccination, which lasts until the end of two consecutive hand, foot and mouth disease (HFMD) epidemic seasons (i.e., the peak incidence period; bimodal epidemics occurring within the same year shall be regarded as one single epidemic season).

The valid case monitoring period commences on Day 15 after the second dose, and the period prior thereto is defined as the surveillance window period. During case monitoring , suspected cases identified through active follow-up by investigators or spontaneous reports from participants' guardians shall be subjected to nucleic acid testing using pharyngeal swabs and/or anal swabs collected once within 3 days after the initial onset of symptoms, with subsequent follow-up and specimen sampling conducted according to test results.

Safety Assessment: Adverse events (AEs) occurring within 30 minutes after each vaccination shall be collected from all participants. Serious adverse events (SAEs) will be monitored from the first dose administration until 6 months after the last dose, with SAE follow-up visits conducted once monthly. All AEs identified via spontaneous reports from participants' guardians or any other sources from the first dose up to 30 days after the last dose will be closely monitored, truthfully recorded and included in the analysis.

A total of 3000 participants will be enrolled in the reactogenicity subgroup, including 1400 children aged 6-23 months and 1600 children aged 24-71 months. On the basis of the above safety observations, participants in the reactogenicity subgroup shall record solicited and unsolicited AEs within 0 to 7 days after each vaccination using diary cards, and collect AEs occurring from Day 8 to Day 30 after each vaccination via contact cards.

Humoral Immunogenicity Assessment: A total of 600 participants will be selected from the reactogenicity subgroup into the humoral immunogenicity subgroup, consisting of 280 children aged 6-23 months and 320 children aged 24-71 months. Venous blood samples of 3.0 (±0.5) mL will be collected from participants in this subgroup at baseline before the first dose, 30 days, 6 months and 12 months after the second dose respectively. Sera isolated at the above four time points will be tested for neutralizing antibodies against EV71, CA16, CA10 and CA6 to evaluate immunogenicity and immune persistence. Sera collected before the first dose and 30 days after the second dose will be used to detect neutralizing antibodies against different enterovirus subtypes so as to explore cross-protective capacity. Meanwhile, 60 participants aged less than 12 months from this subgroup will receive all vaccinations at the anterolateral thigh, while the remaining participants will be vaccinated via the deltoid muscle of the upper arm, to analyze the differences in immunogenicity and immune persistence between different vaccination sites.

Cellular Immunogenicity Assessment:Another 80 participants aged 24-71 months will be enrolled from the reactogenicity subgroup into the cellular immunogenicity subgroup. Venous blood samples of 3.0 (±0.5) mL will be collected before each vaccination and on Day 14 after each dose administration. Blood samples from the first 40 randomly numbered participants will be used to detect the expression levels of EV71 and CA16-specific IFN-γ and IL-4 in T cells, and samples from the latter 40 randomly numbered participants will be applied to measure T cell expression levels of CA10 and CA6-specific IFN-γ and IL-4.

The primary protective efficacy analysis will be conducted when case monitoring for at least one epidemic season is completed, the total number of hand, foot and mouth disease cases caused by any serotype of EV71, CA16, CA10 and CA6 identified during the valid case surveillance period reaches no less than 73, and the number of HFMD cases induced by CA16 and CA6 infection reaches no less than 38 respectively.

02

Conditions studied

  • Hand, Foot, and Mouth Disease(HFMD)
  • Herpangina

Keywords

  • Hand, Foot, and Mouth Disease (HFMD)
  • Herpangina
  • phase IIIa
  • immunogenicity
  • safety
  • protective efficacy
03

Who can participate

Ages eligible
6 Months to 71 Months
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  1. Healthy children aged 6 to 71 months.
  2. Guardians who can understand and voluntarily sign the informed consent form
  3. Willing and able to comply with all visit schedules, sample collection, vaccinations, and other trial procedures。
  4. Provide legal identification for the participant and their guardian

Exclusion criteria

Exclusion Criteria:

  1. A known history of HFMD/HA
  2. Uncontrolled chronic diseases or a history of severe illnesses, including but not limited to cardiovascular diseases, blood disorders, liver or kidney diseases, digestive system diseases, respiratory system diseases, malignant tumors, or a history of major functional organ transplantation.
  3. Autoimmune diseases, immunodeficiency diseases (including but not limited to systemic lupus erythematosus, ankylosing spondylitis, autoimmune thyroid diseases, asplenia, functional asplenia, and HIV infection).
  4. Abnormal coagulation function (such as coagulation factor deficiencies,and platelet abnormalities).
  5. Suffering from/having a history of severe neurological diseases (epilepsy, convulsions, or seizures [excluding a history of febrile seizures]) ,psychiatric disorders, or a family history of psychiatric disorders
  6. Various acute diseases or exacerbations of chronic diseases within the last 3 days.
  7. Having been vaccinated with a vaccine containing any of the components EV71, CA16, CA10, CA6.
  8. Having received ≥14 days of immunosuppressive or other immunomodulatory treatment (prednisone ≥2mg/kg/day, or its equivalent; local or inhaled corticosteroids excluded) within the past 6 months, or cytotoxic treatment, or planning to receive such treatment during the trial.
  9. Having received immunoglobulin or other blood products(excluding hepatitis B immunoglobulin) within the past 6 months, or planning to receive such treatment during the trial.
  10. Having received other investigational drugs or vaccines within the past 30 days, or planning to receive such drugs or vaccines during the trial.
  11. Having received live attenuated vaccines or nucleic acid vaccines within the past 14 days, or subunit or inactivated vaccines within the past 7 days.
  12. Known allergy to any component of the investigational vaccine (inactivated EV71 virus, inactivated CA16 virus, , inactivated CA10 virus,, inactivated CA6 virus,aluminum hydroxide, sodium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate, injectable water).
  13. On the day of planned vaccination with the investigational vaccine, having an axillary temperature ≥37.3°C before vaccination, or other vital sign measurements outside the normal range,or the physical examination is not qualified.
  14. According to the investigator's judgment, participants have any other factors that make them unsuitable for participation in the clinical trial.
04

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
6,000 participants (estimated)

Study arms

  • Experimental
    Tetravalent Inactivated Enterovirus Vaccine (Vero Cell)

    3000 participants aged 6-71 months will receive Tetravalent Inactivated Enterovirus Vaccine (Vero Cell).Route of administration is intramuscular injection at anterolateral thigh for infants aged younger than 12 months, and at deltoid muscle of upper arm for children aged older than 12 months.

    Biological: Tetravalent Inactivated Enterovirus Vaccine (Vero Cell)

  • Placebo comparator
    placebo

    3000 participants aged 6-71 months will receive placebo .Route of administration is intramuscular injection at anterolateral thigh for infants aged younger than 12 months, and at deltoid muscle of upper arm for children aged older than 12 months.

    Biological: Placebo

Interventions

  • BiologicalTetravalent Inactivated Enterovirus Vaccine (Vero Cell)

    Two doses are administered with a one-month interval between each dose.

  • BiologicalPlacebo

    Two doses are administered with a one-month interval between each dose.

05

What researchers measure

Primary outcomes

  1. Evaluate the protective efficacy of the investigational vaccine against HFMD caused by any serotype of EV71, CA16, CA10 and CA6 infection compared to placebo.

    Evaluate the protective efficacy of the investigational vaccine versus placebo against RT-PCR-confirmed primary HFMD caused by any serotype of EV71, CA16, CA10 and CA6 in children aged 6 to 71 months starting from Day 15 after full-course vaccination during the primary protective efficacy analysis stage.

    Time frame: From day 15 after full-course vaccination to the data cutoff date when the pre-specified number of primary HFMD cases is reached (case-driven primary analysis)

  2. Evaluate the protective efficacy of the investigational vaccine against HFMD caused by CA6 infection compared to placebo.

    Evaluate the protective efficacy of the investigational vaccine versus placebo against RT-PCR-confirmed primary HFMD caused by CA6 in children aged 6 to 71 months starting from Day 15 after full-course vaccination during the primary protective efficacy analysis stage.

    Time frame: From day 15 after full-course vaccination to the data cutoff date when the pre-specified number of primary HFMD cases is reached (case-driven primary analysis)From day 15 after the full-course vaccination to data cutoff date of primary analysis

  3. Evaluate the protective efficacy of the investigational vaccine against HFMD caused by CA16 infection compared to placebo.

    Evaluate the protective efficacy of the investigational vaccine versus placebo against RT-PCR-confirmed primary HFMD caused by CA16 in children aged 6 to 71 months starting from Day 15 after full-course immunization during the primary protective efficacy analysis stage.

    Time frame: From day 15 after full-course vaccination to the data cutoff date when the pre-specified number of primary HFMD cases is reached (case-driven primary analysis)

Secondary outcomes

  1. Evaluate the safety of the investigational vaccine

    Incidence of adverse reactions within 0-30 days after each dose of investigational vaccine

    Time frame: From day 0 to day 30 after vaccination (The day of vaccination is defined as Day 0)

  2. Evaluate the safety of the investigational vaccine

    Incidence of serious adverse events (SAEs) from the start of vaccination until 6 months after the full vaccination.

    Time frame: From day of vaccination to 6 months after vaccination

  3. Evaluate the seroconversion rate of neutralizing antibodies against EV71, CA16, CA10, CA6

    Assess the seroconversion rate of neutralizing antibodies against EV71, CA16, CA10, CA6 at day 30 after full-course vaccination

    Time frame: At day 30 after full-course vaccination

  4. Evaluate the seropositivity rate of neutralizing antibodies against EV71, CA16, CA10, CA6

    Assess the seropositivity rate of neutralizing antibodies against EV71, CA16, CA10, CA6 at day 30 after full-course vaccination

    Time frame: At day 30 after full-course vaccination

  5. Evaluate the GMT of neutralizing antibodies against EV71, CA16, CA10, CA6

    Assess the GMT of neutralizing antibodies against EV71, CA16, CA10, CA6 at 30 days after full-course vaccination

    Time frame: At day 30 after full-course vaccination

  6. Evaluate the GMI of neutralizing antibodies against EV71, CA16, CA10, CA6

    Assess the GMI of neutralizing antibodies against EV71, CA16, CA10, CA6 at 30 days after full-course vaccination

    Time frame: At day 30 after full-course vaccination

  7. Evaluate the seroconversion rate of neutralizing antibodies against EV71, CA16, CA10, CA6

    Assess the seroconversion rate of neutralizing antibodies against EV71, CA16, CA10, CA6 at 6 months after full-course vaccination

    Time frame: At 6 months after full-course vaccinaton

  8. Evaluate the seroconversion rate of neutralizing antibodies against EV71, CA16, CA10, CA6

    Assess the seroconversion rate of neutralizing antibodies against EV71, CA16, CA10, CA6 at 12 months after full-course vaccination

    Time frame: At 12 months after full-course vaccinaton

  9. Evaluate the seropositivity rate of neutralizing antibodies against EV71, CA16, CA10, CA6

    Assess the seropositivity rate of neutralizing antibodies against EV71, CA16, CA10, CA6 at 6 months after full-course vaccination

    Time frame: At 6 months after full-course vaccination

  10. Evaluate the seropositivity rate of neutralizing antibodies against EV71, CA16, CA10, CA6

    Assess the seropositivity rate of neutralizing antibodies against EV71, CA16, CA10, CA6 at 12 months after full-course vaccination

    Time frame: At 12 months after full-course vaccination

  11. Evaluate the GMT of neutralizing antibodies against EV71, CA16, CA10, CA6

    Assess the GMT of neutralizing antibodies against EV71, CA16, CA10, CA6 at 6 months after full-course vaccination

    Time frame: At 6 months after full-course vaccination

  12. Evaluate the GMT of neutralizing antibodies against EV71, CA16, CA10, CA6

    Assess the GMT of neutralizing antibodies against EV71, CA16, CA10, CA6 at 12 months after full-course vaccination

    Time frame: At 12 months after full-course vaccination

  13. Evaluate the GMI of neutralizing antibodies against EV71, CA16, CA10, CA6

    Assess the GMI of neutralizing antibodies against EV71, CA16, CA10, CA6 at 6 months after full-course vaccination

    Time frame: At 6 months after full-course vaccination

  14. Evaluate the GMI of neutralizing antibodies against EV71, CA16, CA10, CA6

    Assess the GMI of neutralizing antibodies against EV71, CA16, CA10, CA6 at 12 months after full-course vaccination

    Time frame: At 12 months after full-course vaccination

  15. Evaluate the protective efficacy of the investigational vaccine against diseases caused by any serotype of EV71, CA16, CA10 and CA6 infection compared to placebo.

    The protective efficacy of the investigational vaccine versus placebo against RT-PCR-confirmed diseases caused by any serotype of EV71, CA16, CA10 and CA6 in children aged 6 to 71 months starting from Day 15 after full-course immunization during the primary protective efficacy analysis stage.

    Time frame: From day 15 after full-course vaccination to the data cutoff date when the pre-specified number of primary HFMD cases is reached (case-driven primary analysis)

  16. Evaluate the protective efficacy of the investigational vaccine against severe cases caused by any serotype of EV71, CA16, CA10 and CA6 infection compared to placebo.

    The protective efficacy of the investigational vaccine versus placebo against RT-PCR-confirmed severe cases caused by any serotype of EV71, CA16, CA10 and CA6 in children aged 6 to 71 months starting from Day 15 after full-course immunization during the primary protective efficacy analysis stage.

    Time frame: From day 15 after full-course vaccination to the data cutoff date when the pre-specified number of primary HFMD cases is reached (case-driven primary analysis)

  17. Evaluate the protective efficacy of the investigational vaccine against hospitalized cases caused by any serotype of EV71, CA16, CA10 and CA6 infection compared to placebo.

    The protective efficacy of the investigational vaccine versus placebo against RT-PCR-confirmed hospitalized cases caused by any serotype of EV71, CA16, CA10 and CA6 in children aged 6 to 71 months starting from Day 15 after full-course immunization during the primary protective efficacy analysis stage.

    Time frame: From day 15 after full-course vaccination to the data cutoff date when the pre-specified number of primary HFMD cases is reached (case-driven primary analysis)

  18. Evaluate the protective efficacy of the investigational vaccine against HFMD caused by any serotype of EV71, CA16, CA10 and CA6 infection compared to placebo.

    Evaluate the protective efficacy of the investigational vaccine versus placebo against RT-PCR-confirmed HFMD caused by any serotype of EV71, CA16, CA10 and CA6 in children aged 6 to 71 months, from Day 15 after full-course immunization until the end of two consecutive epidemic seasons.

    Time frame: From day 15 after full-course vaccination to the end of case surveillance period (December 31, 2027)

  19. Evaluate the protective efficacy of the investigational vaccine against herpangina caused by any serotype of EV71, CA16, CA10 and CA6 infection compared to placebo.

    Evaluate the protective efficacy of the investigational vaccine versus placebo against RT-PCR-confirmed herpangina caused by any serotype of EV71, CA16, CA10 and CA6 in children aged 6 to 71 months, from Day 15 after full-course immunization until the end of two consecutive epidemic seasons.

    Time frame: From day 15 after full-course vaccination to the end of case surveillance period (December 31, 2027)

  20. Evaluate the protective efficacy of the investigational vaccine against diseases caused by any serotype of EV71, CA16, CA10 and CA6 infection compared to placebo.

    Evaluate the protective efficacy of the investigational vaccine versus placebo against RT-PCR-confirmed diseases caused by any serotype of EV71, CA16, CA10 and CA6 in children aged 6 to 71 months, from Day 15 after full-course immunization until the end of two consecutive epidemic seasons.

    Time frame: From day 15 after full-course vaccination to the end of case surveillance period (December 31, 2027)

  21. Evaluate the protective efficacy of the investigational vaccine against severe cases caused by any serotype of EV71, CA16, CA10 and CA6 infection compared to placebo.

    Evaluate the protective efficacy of the investigational vaccine versus placebo against RT-PCR-confirmed severe cases caused by any serotype of EV71, CA16, CA10 and CA6 in children aged 6 to 71 months, from Day 15 after full-course immunization until the end of two consecutive epidemic seasons.

    Time frame: From day 15 after full-course vaccination to the end of case surveillance period (December 31, 2027)

  22. Evaluate the protective efficacy of the investigational vaccine against hospitalized cases caused by any serotype of EV71, CA16, CA10 and CA6 infection compared to placebo.

    Evaluate the protective efficacy of the investigational vaccine versus placebo against RT-PCR-confirmed hospitalized cases caused by any serotype of EV71, CA16, CA10 and CA6 in children aged 6 to 71 months, from Day 15 after full-course immunization until the end of two consecutive epidemic seasons.

    Time frame: From day 15 after full-course vaccination to the end of case surveillance period (December 31, 2027)

  23. Evaluate the protective efficacy of the investigational vaccine versus placebo against HFMD caused by EV71 infection compared to placebo.

    Evaluate the protective efficacy of the investigational vaccine versus placebo against RT-PCR-confirmed HFMD caused by EV71 infection in children aged 6 to 71 months, from Day 15 after full-course immunization until the end of two consecutive epidemic seasons.

    Time frame: From day 15 after full-course vaccination to the end of case surveillance period (December 31, 2027)

  24. Evaluate the protective efficacy of the investigational vaccine versus placebo against HFMD caused by CA10 infection compared to placebo.

    Evaluate the protective efficacy of the investigational vaccine versus placebo against RT-PCR-confirmed HFMD caused by CA10 infection in children aged 6 to 71 months, from Day 15 after full-course immunization until the end of two consecutive epidemic seasons.

    Time frame: From day 15 after full-course vaccination to the end of case surveillance period (December 31, 2027)

  25. Evaluate the protective efficacy of the investigational vaccine versus placebo against HFMD caused by CA16 infection compared to placebo.

    Evaluate the protective efficacy of the investigational vaccine versus placebo against RT-PCR-confirmed HFMD caused by CA16 infection in children aged 6 to 71 months, from Day 15 after full-course immunization until the end of two consecutive epidemic seasons.

    Time frame: From day 15 after full-course vaccination to the end of case surveillance period (December 31, 2027)

  26. Evaluate the protective efficacy of the investigational vaccine versus placebo against HFMD caused by CA6 infection compared to placebo.

    Evaluate the protective efficacy of the investigational vaccine versus placebo against RT-PCR-confirmed HFMD caused by CA6 infection in children aged 6 to 71 months, from Day 15 after full-course immunization until the end of two consecutive epidemic seasons.

    Time frame: From day 15 after full-course vaccination to the end of case surveillance period (December 31, 2027)

Other outcomes

  1. Evaluate the protective efficacy of the investigational vaccine compared to placebo against diseases caused by infections with other untyped enteroviruses excluding EV71, CA16, CA10 and CA6 .

    Evaluate the protective efficacy of the investigational vaccine compared to placebo against RT-PCR-confirmed diseases caused by infections with other untyped enteroviruses excluding EV71, CA16, CA10 and CA6 in children aged 6 to 71 months, from Day 15 after full-course immunization until the end of two consecutive epidemic seasons.

    Time frame: From day 15 after full-course vaccination to the end of case surveillance period (December 31, 2027)

  2. Evaluate the seroconversion rate of neutralizing antibodies against different subtype strains

    Assess the seroconversion rate of neutralizing antibodies against different subtype strains at 30 days after full-course vaccination

    Time frame: Day 30 after full-course vaccination

  3. Evaluate the seropositivity rate of neutralizing antibodies against different subtype strains

    Assess the seropositivity rate of neutralizing antibodies against different subtype strains at 30 days after full-course vaccination

    Time frame: Day 30 after full-course vaccination

  4. Evaluate the GMT of neutralizing antibodies against different subtype strains

    Assess the GMT of neutralizing antibodies against different subtype strains at 30 days after full-course vaccination

    Time frame: Day 30 after full-course vaccination

  5. Evaluate the GMI of neutralizing antibodies against different subtype strains

    Assess the GMI of neutralizing antibodies against different subtype strains at 30 days after full-course vaccination

    Time frame: Day 30 after full-course vaccination

  6. Evaluate the cellular immunity induced by the investigational vaccine

    Measure the number of EV71, CA16, CA10 and CA6-specific IFN-γ and IL-4 spot-forming cells per 3×10\^6 peripheral blood mononuclear cells (PBMCs) from participants aged 24 to 71 months , before each immunization and on the 14th day after each vaccination.

    Time frame: Pre-vaccination on each dosing day; day 14 after each dose

  7. Evaluate the cellular immunity induced by the investigational vaccine

    Evaluate the Fold increase from baseline in EV71, CA16, CA10 and CA6-specific IFN-γ and IL-4 spot-forming cell counts per 3×10\^6 PBMCs among children aged 24 to 71 months at day 14 after the first dose, before the second dose, and at day 14 after the second dose.

    Time frame: Pre-vaccination on each dosing day; day 14 after each dose

06

Study locations

5 sites
  • Anhui Provincial Center for Disease Control and Prevention
    Hefei, Anhui, China
  • Fujian Provincial Center for Disease Control and Prevention
    Fujian, China
  • Henan Provincial Center for Disease Control and Prevention
    Henan, China
  • Hubei Provincial Center for Disease Control and Prevention
    Hubei, China
  • Sichuan Provincial Center for Disease Control and Prevention
    Sichuan, China
07

Registry details

Key details

Study ID
NCT07611513
Lead sponsor
Sinovac Biotech Co., Ltd
Responsible party
Sponsor
First posted
May 28, 2026
Start date
May 2026 (estimated)
Primary completion
Dec 2027 (estimated)
Completion
Sep 2028 (estimated)
Last update
May 28, 2026

Study contacts

Yanxia Wang
Contact
wangyanxia99@163.com
13613816598
Yanxia Wang
principal investigator · Henan Provincial Center for Disease Control and Prevention

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
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