Clinical trial NCT03873740: Immunogenicity and Safety of Two Different Commercial EV71 Vaccines
Official title: A Opened，Randomized and Controlled Trial to Evaluate the Immunity and Safety of Sequential Vaccination of Two Different Commercial EV71 Inactived Vaccines in Healthy Infants Aged 6-35 Months
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hand, Foot and Mouth Disease
Keywords: Inactivated Enterovirus Type 71 (EV71) Vaccine
Sequential vaccination
Immunity
Safety
Lead sponsor: Sinovac Biotech Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Shandong Province Centers for Disease Control and Prevention
First posted: 2019-03-13
Enrollment: 300
Sex: ALL
Minimum age (years): 6
Maximum age (years): 35
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 immunogenicity and safety of sequential vaccination of two EV71 inactived vaccines in healthy infants aged 6-35 months.

Detailed description: This study is a opened,randomized and controlled phase Ⅳ clinical trial. The purpose of this study is to evaluate the immunogenicity and safety of sequential vaccination of two EV71 inactived vaccines in healthy infants aged 6-35 months. EV71 inactived vaccines(Vero cells）was manufactured by Sinovac Biotech Co., Ltd and EV71 inactived vaccines(Human diploid cells）was manufactured by Institute of Medical Biology Chinese Academy of Medical Sciences.300 infants aged between 6-35 months will be randomly assigned into experimental group in the ratio 1:1:1:1.The experimental group 1 received two doses EV71 inactived vaccines(Vero cells）on day 0 and 30. The experimental group 2 received two doses EV71 inactived vaccines (Human diploid cells）on day 0 and 30. The experimental group 3 received one dose EV71 inactived vaccines (Vero cells）on day 0 and one dose EV71 inactived vaccines (Human diploid cells）on day 30.The experimental group 4 received one dose EV71 inactived vaccines (Human diploid cells）on day 0 and one dose EV71 inactived vaccines (Vero cells）on day 30. To evaluate the immunogenicity of the vaccine, venous blood will be collected for the EV71 neutralizing antibody detection prior to vaccination and 30 days after the 2nd dose vaccination.

Eligibility criteria: Inclusion Criteria:

* Healthy volunteer aged 6-35 months;
* Proven legal identity;
* Guardians of the participants should be capable of understanding the written consent form, and such form should be signed before the infant being included into this study.

Exclusion Criteria:

* Prior vaccination with EV71 vaccine;
* History of hand，foot and mouth disease;
* Allergy to gentamicin; history of allergy to any vaccine or vaccine ingredient, or serious adverse reaction(s) to vaccination, such as urticaria,difficulty in breathing, angioneurotic edema, pain, etc;
* Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc;
* Autoimmune diseases or immunodeficiency/immunosuppression;
* Severe neurological disorders (epilepsy, convulsions or convulsions) or psychosis;
* History of thyroidectomy, absence of spleen, functional absence of spleen, and any circumstances leading to absence of spleen or splenectomy;
* Diagnosed coagulation function abnormal (e.g., coagulation factor deficiency, coagulation disorder, or platelet abnormalities) , or obvious bruising or coagulation disorders;
* 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) in the past 6 months;
* Receipt of any of the following products:

  1. Blood product within 3 months prior to study entry;
  2. Any live attenuated vaccine within 14 days prior to study entry;
  3. Any subunit vaccine or inactivated vaccine within 7 days prior to study entry;
  4. Any other study drugs within 30 days prior to study entry;
* Acute disease or acute stage of chronic disease within 7 days prior to study entry;
* Axillary temperature \> 37.0℃;
* 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
Secondary outcomes:
measure: The incidences of adverse reactions after each does
timeFrame: 0-30 days after each dose
measure: The incidence of solicited local and general adverse events after each does
timeFrame: 0-7 days after each dose
measure: Incidence of serious adverse events (SAEs) during the period of safety monitoring
timeFrame: 0-30 days after each dose
measure: EV71 neutralizing antibody positive rate of each group after two doses.
timeFrame: 30 days after two doses
measure: The Geometric mean titer (GMT) of the EV71 neutralizing antibody
timeFrame: 30 days after two doses
measure: The geometric mean fold increase (GMI) of the EV71 neutralizing antibody
timeFrame: 30 days after two doses
Other outcomes:
Locations:
city: Rushan
country: China
facility: Rushan City Center for Disease Control and Prevention
state: Shandong
Study officials:
affiliation: Shandong Provincal Center for Disease Control and Preventione
name: AIqiang Xu
role: PRINCIPAL_INVESTIGATOR
References:
citation: Xu Q, Cao Q, Yang W, Liu X, Liu H, Tian X, Li J, Fang X, Jia N, Zeng G, Xu A. Interchangeability of two Enterovirus 71 inactivated vaccines in Chinese children: A phase IV, open-label, and randomized controlled trial. Vaccine. 2020 Mar 10;38(12):2671-2677. doi: 10.1016/j.vaccine.2020.02.013. Epub 2020 Feb 14.