Clinical trial NCT03859141: Clinical Trial to Evaluate the Safety and Immunogenicity of Quadrivalent Influenza Vaccine (7.5μg/0.25ml)
Official title: Open Phase I and Randomized, Double-blind, Controlled Phase III Clinical Trial to Evaluate the Safety and Immunogenicity of Quadrivalent Influenza Vaccine in Healthy Subjects Aged 6-35 Months
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Seasonal Influenza
Keywords: Influenza Vaccine
Quadrivalent
Trivalent
Children
Lead sponsor: Sinovac Biotech Co., Ltd
Sponsor class: INDUSTRY
First posted: 2019-03-01
Enrollment: 2340
Sex: ALL
Minimum age (years): 6
Maximum age (years): 35
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The phase Ⅰ clinical trial was a single arm.The phase Ⅲ was 3 parallel arms.
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the safety and immunogenicity of quadrivalent influenza vaccine in healthy children aged 6-35 months.

Detailed description: The study includes open-labelled phase I and randomized, double-blind, controlled phase III clinical trial. In the phase I, 20 healthy Chinese children aged 6-35 months were administered with two doses of QIV (7.5μg/0.25ml). In the phase Ⅲ clinical trial, 2320 children were assigned to QIV group, TIV (B/Victoria) group and TIV (B/Yamagata) group in a 2:1:1 ratio. All vaccines were manufactured by Sinovac Biotech Co., Ltd.

Eligibility criteria: Inclusion Criteria:

* Healthy volunteer between 6 - 35 months old; Term birth; Birth weight \>2500g;
* Proven legal identity;
* Written consent of the guardian(s) of the volunteer;

Exclusion Criteria:

* Received seasonal influenza vaccine in the current year;
* Suffering from seasonal influenza in the past 6 moths;
* Axillaty temperature \> 37.0 °C;
* History of allergy to any vaccine or vaccine ingredient;
* History of serious adverse reaction(s) to vaccination, such as urticaria, difficulty in breathing, angioneurotic edema, abdominal pain, etc;
* Autoimmune disease or immunodeficiency;
* Congenital malformation, developmental disorders;
* Severe malnutrition;
* Diagnosed coagulation function abnormal (e.g., coagulation factor deficiency, coagulation disorder, or platelet abnormalities) , or obvious bruising or coagulation disorders;
* History of epilepsy (except febrile seizures occurred \< 2 years of age or pure epilepsy occurred within the past 3 years that does not need treatment)
* Chronic diseases (e.g., viral hepatitis, tuberculosis, diabetes, blood diseases, or neurological disorders)
* Acute disease or acute stage of chronic disease;
* Receipt of any of the following products:

  1. Any subunit vaccine or inactivated vaccine (e.g., pneumococcal vaccine) or treatment of allergy within 14 days prior to study entry;
  2. Any live attenuated vaccine within 30 days prior to study entry;
  3. Any other investigational medicine(s) or vaccine within 30 days prior to study entry;
  4. Blood product within 3 months prior to study entry;
  5. 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;
* Participate or will participate in other clinical trial(s) during this study;
* Based on the judgment of investigator(s) or the Ethic Committee, there was any condition indicating that the subject should be excluded;

Primary outcomes:
measure: The lower limit of 95% confidence intervals (95%CI) of geometric mean titer (GMT) ratio (experimental group/control group) of hemagglutination inhibition (HI) antibody titer≥2/3.
timeFrame: 28 days after two doses immunization
measure: The lower limit of 95% CI of the seroconversion rate difference (experimental group-control group)≥-10%.
timeFrame: 28 days after two doses immunization
Secondary outcomes:
measure: The lower limit of 95%CI of the ratio of GMT (experimental group/control group) >1.5.
timeFrame: 28 days after two doses immunization
measure: The lower limit of 95% CI of the difference of HI antibody seroconversion rate (experimental group-control group)>10%
timeFrame: 28 days after two doses immunization
measure: The lower limit of 95% CI of seroconversion rate for each HI antibody after two doses immunization≥40%.
timeFrame: 28 days after two doses immunization
measure: The seroprotective rate (HI antibody titer≥1:40) of each HI antibody after two doses immunization≥70%.
timeFrame: 28 days after two doses immunization
measure: The geometric mean increase (GMI) of each HI antibody after two doses immunization >2.5.
timeFrame: 28 days after two doses immunization
measure: The lower limit of 95%CI of the ratio of GMT(experimental group/control group)≥2/3, in the subjects whose pre-immune HI antibody titer<1:40
timeFrame: 28 days after two doses immunization
measure: The lower limit of 95% CI of the difference of HI antibody seroconversion rate (experimental group-control group)≥-10%, in the subjects whose pre-immune HI antibody titer<1:40.
timeFrame: 28 days after two doses immunization
measure: The incidence of the solicited local and general adverse reactions 0-7 days after each immunization.
timeFrame: 0-7 days
measure: The incidence of the unsolicited adverse events 0-28 days after each immunization
timeFrame: 0-28 days after each dose immunization
measure: The incidence of the serious adverse events within 7 months after the first immunization.
timeFrame: Within 7 months after the first dose immunization
Other outcomes:
Locations:
city: Lianyungang
country: China
facility: Guanyun Center for Disease Prevention and Control
state: Jiangsu
city: Pizhou
country: China
facility: Pizhou Center for Disease Prevention and Control
state: Jiangsu
Study officials:
affiliation: Jiangsu Provincial Center for Disease Prevention and Control
name: Yuemei Hu, Bachelor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hu Y, Shao M, Hu Y, Liang Q, Jia N, Chu K, Xu L, Li J, Li C, Zhu F. Immunogenicity and safety of an inactivated quadrivalent influenza vaccine: a randomized, double-blind, controlled phase III clinical trial in children aged 6-35 months in China. Hum Vaccin Immunother. 2020 Jul 2;16(7):1691-1698. doi: 10.1080/21645515.2020.1721994. Epub 2020 Apr 29.