Clinical trial NCT03909074: Clinical Trial of Enterovirus 71（EV71） Inactivated Vaccine in Children Aged 36-71 Months
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hand, Foot and Mouth Disease
Lead sponsor: Sinovac Biotech Co., Ltd
Sponsor class: INDUSTRY
First posted: 2019-04-09
Enrollment: 900
Sex: ALL
Minimum age (years): 6
Maximum age (years): 71
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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;
* 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:

  1. 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
  2. Blood products within 2 months prior to study entry
  3. Any other investigational products (drug or vaccine）within 30 days prior to study entry
  4. Any live attenuated vaccine within 14 days prior to study entry
  5. 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.

Primary outcomes:
measure: The seroconversion rates (SCR) of the EV71 neutralizing antibody calculated based on the cutoff value of 1:8
timeFrame: 30 days after two doses
measure: The Geometric mean titer (GMT) of the EV71 neutralizing antibody in the susceptible population
timeFrame: 30 days after two doses
Secondary outcomes:
measure: The overall incidence of adverse reactions
timeFrame: 0-30 days after each dose
measure: The incidence of the serious adverse events (SAE)
timeFrame: 0-30 days after each dose
measure: The seroconversion rates (SCR) of the EV71 neutralizing antibody calculated based on the cutoff value of 1:16, 1:32, and 1:64 respectively
timeFrame: 30 days after two doses
measure: The Geometric mean titer (GMT) of the EV71 neutralizing antibody
timeFrame: 30 days after two doses
Other outcomes:
Locations:
city: Lincang
country: China
facility: Yun County Center for Disease Control and Prevention
state: Yunnan
Study officials:
affiliation: Yunnan Center for Disease Control and Prevention
name: Lifen Zhang, Master
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.