Clinical Trial to Evaluate the Safety and Immunogenicity of Quadrivalent Influenza Vaccine (7.5μg/0.25ml)

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

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

Study Overview

• Status: Completed
• Conditions: Seasonal Influenza
• Intervention / Treatment: Biological: Quadrivalent influenza vaccine; Biological: Trivalent influenza vaccine (contains B/Victoria strain); Biological: Trivalent influenza vaccine (contains B/Yamagata strain)

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.

• Study Type: Interventional
• Enrollment (Actual): 2340
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Lianyungang, Jiangsu, China, 222200
      • Guanyun Center for Disease Prevention and Control
    • Pizhou, Jiangsu, China, 221300
      • Pizhou Center for Disease Prevention and Control

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 2 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental group-phase Ⅰ; Quadrivalent influenza vaccine	Biological: Quadrivalent influenza vaccine; One dose of quadrivalent influenza vaccine: 0.25 ml per dose containing 7.5μg antigen.
EXPERIMENTAL: Experimental group-phase Ⅲ; Quadrivalent influenza vaccine	Biological: Quadrivalent influenza vaccine; One dose of quadrivalent influenza vaccine: 0.25 ml per dose containing 7.5μg antigen.
ACTIVE_COMPARATOR: Control group 1-phase Ⅲ; Trivalent influenza vaccine (contains B/Victoria strain)	Biological: Trivalent influenza vaccine (contains B/Victoria strain); One dose of trivalent influenza vaccine (contains B/Victoria strain): 0.25 ml per dose containing 7.5μg antigen.
ACTIVE_COMPARATOR: Control group 2-phase Ⅲ; Trivalent influenza vaccine (contains B/Yamagata strain)	Biological: Trivalent influenza vaccine (contains B/Yamagata strain); One dose of trivalent influenza vaccine (contains B/Yamagata strain): 0.25 ml per dose containing 7.5μg antigen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Immunogenicity index, One of the standard to evaluate the experimental vaccine is non-inferior to the control vaccines.	28 days after two doses immunization
The lower limit of 95% CI of the seroconversion rate difference (experimental group-control group)≥-10%.	Immunogenicity index, Another standard to evaluate the experimental vaccine is non-inferior to the control vaccines.	28 days after two doses immunization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The lower limit of 95%CI of the ratio of GMT (experimental group/control group) >1.5.	Immunogenicity index, One of the standard to evaluate the experimental vaccine is superior to the control vaccines for specific antigen type.	28 days after two doses immunization
The lower limit of 95% CI of the difference of HI antibody seroconversion rate (experimental group-control group)>10%	Immunogenicity index, Another standard to evaluate the experimental vaccine is superior to the control vaccines for specific antigen type.	28 days after two doses immunization
The lower limit of 95% CI of seroconversion rate for each HI antibody after two doses immunization≥40%.	Immunogenicity index	28 days after two doses immunization
The seroprotective rate (HI antibody titer≥1:40) of each HI antibody after two doses immunization≥70%.	Immunogenicity index	28 days after two doses immunization
The geometric mean increase (GMI) of each HI antibody after two doses immunization >2.5.	Immunogenicity index	28 days after two doses immunization
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	Immunogenicity index	28 days after two doses immunization
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.	Immunogenicity index	28 days after two doses immunization
The incidence of the solicited local and general adverse reactions 0-7 days after each immunization.	Safety index, The adverse reactions refers to the adverse events which were considered related to the vaccination.	0-7 days
The incidence of the unsolicited adverse events 0-28 days after each immunization	Safety Index	0-28 days after each dose immunization
The incidence of the serious adverse events within 7 months after the first immunization.	Safety Index	Within 7 months after the first dose immunization

Collaborators and Investigators

• Sponsor: Sinovac Biotech Co., Ltd
• Investigators: Principal Investigator: Yuemei Hu, Bachelor, Jiangsu Provincial Center for Disease Prevention and Control

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 6, 2018
• Primary Completion (ACTUAL): April 17, 2018
• Study Completion (ACTUAL): November 2, 2018

Study Registration Dates

• First Submitted: February 28, 2019
• First Submitted That Met QC Criteria: February 28, 2019
• First Posted (ACTUAL): March 1, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 1, 2019
• Last Update Submitted That Met QC Criteria: February 28, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Children; Influenza Vaccine; Trivalent; Quadrivalent
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: PRO-QINF-3002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No