Clinical Trial to Evaluate the Safety and Immunogenicity of Quadrivalent Influenza Vaccine (15µg/0.5ml)

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 Over 3 Years.

The purpose of this study is to evaluate the safety and immunogenicity of quadrivalent influenza vaccine in healthy subjects aged over 3 years

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

This study is a phase I& III clinical trial. Phase I is open-labelled, and phase III is randomized, double-blind, active-controlled. The purpose of this study is to evaluate the safety and immunogenicity of the quadrivalent influenza vaccine (QIV) (experimental vaccine) manufactured by Sinovac Biotech Co., Ltd in subjects aged over 3 years. In phase I, 60 volunteers received single dose QIV (15µg/0.5ml). In phase III, 2320 volunteers were assigned to receive single dose QIV (15µg/0.5ml) or two commercial trivalent influenza vaccines (TIVs) (15µg/0.5ml) in a ratio of 2:1:1. The commercial TIVs were also manufactured by Sinovac Biotech Co., Ltd.

• Study Type: Interventional
• Enrollment (Actual): 2380
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers aged ≥3 years;
• Proven legal identity;
• Participants or (and) 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 influenza vaccine of the current year;
• History of influenza within 6 months prior to study entry;
• Axillary temperature > 37.0 °C;
• History of allergy to any vaccine, or any ingredient of the experimental vaccine, especially eggs, egg albumin, etc.;
• Serious adverse reaction(s) to vaccination, such as urticaria, dyspnea, angioneurotic edema, abdominal pain, etc.;
• Severe/uncontrollable nervous system disease (epilepsy, seizures or convulsions) or mental illness;
• Autoimmune disease or immunodeficiency/immunosuppressive, or any immunosuppressant receipt within 6 months prior to the study entry;
• History of asthma, thyroidectomy, angioedema, diabetes or malignancy;
• No spleen, or functional no spleen, or splenectomy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• 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; Received single dose QIV (15µg/0.5ml)
Experimental: Experimental group-phase III; Quadrivalent influenza vaccine	Biological: Quadrivalent influenza vaccine; Received single dose QIV (15µg/0.5ml)
Active Comparator: Control group-1-phase III; Trivalent influenza vaccine (contains B/Victoria strain)	Biological: Trivalent influenza vaccine (contains B/Victoria strain); Received single dose TIV which contains B/Victoria strain (15µg/0.5ml)
Active Comparator: Control group-2-phase III; Trivalent influenza vaccine (contains B/Yamagata strain)	Biological: Trivalent influenza vaccine (contains B/Yamagata strain); Received single dose TIV which contains B/Yamagata strain (15µg/0.5ml)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The lower limit of 95% confidence intervals (95%CI) of the ratio of geometric mean titer of hemagglutination inhibition (HI) antibody titer (experimental group/control group)≥2/3.	Immunogenicity index, One of the standard to evaluate the experimental vaccine is non-inferior to the control vaccines	28 days after the injection
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 non-inferior to the control vaccines	28 days after the injection

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 the injection
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 the injection
The 95% CI lower limit of seroconversion rate of HI antibodies in the subjects aged 3-59 years≥40%	Immunogenicity index	28 days after the injection
The 95% CI lower limit of seroconversion rate of HI antibodies in the subjects aged over 60 years≥30%	Immunogenicity index	28 days after the injection
The seroprotective rate (HI antibody titer≥1:40) in the subjects aged 3-59 years ≥70%	Immunogenicity index	28 days after the injection
The seroprotective rate (HI antibody titer≥1:40) in the subjects aged over 60 years ≥60%	Immunogenicity index	28 days after the injection
The geometric mean increase (GMI) in the subjects aged 3-59 years >2.5	Immunogenicity index	28 days after the injection
The geometric mean increase (GMI) in the subjects aged over 60 years >2.0	Immunogenicity index	28 days after the injection
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 the injection
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 the injection
The incidence of the solicited local and general adverse reactions on day 0-7	Safety index, The adverse reactions refers to the adverse events which considered related to the vaccination	0-7 days after the injection
The incidence of the unsolicited adverse events on day 0-28	Safety Index	0-28 days after the injection
The incidence of the serious adverse events within 6 months after the injection	Safety Index	Within 6 months after the injection

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Chu K, Xu K, Tang R, Tian X, Hu J, Yang T, Li C, Hu Y, Zeng G. Immunogenicity and safety of an inactivated quadrivalent influenza vaccine: A randomized, double-blind, controlled phase III study in healthy population aged >/=3 years. Vaccine. 2020 Aug 18;38(37):5940-5946. doi: 10.1016/j.vaccine.2020.06.071. Epub 2020 Jul 27.

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2018
• Primary Completion (Actual): August 17, 2018
• Study Completion (Actual): October 8, 2018

Study Registration Dates

• First Submitted: February 21, 2019
• First Submitted That Met QC Criteria: February 21, 2019
• First Posted (Actual): February 26, 2019

Study Record Updates

• Last Update Posted (Actual): February 27, 2019
• Last Update Submitted That Met QC Criteria: February 25, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: 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-3001

Drug and device information, study documents

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