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

Phase 3

Completed

• Conditions: Seasonal Influenza
• Interventions: Biological: Trivalent influenza vaccine (contains B/Yamagata strain); Biological: Trivalent influenza vaccine (contains B/Victoria strain); Biological: Quadrivalent influenza vaccine

• Registration Number: NCT03859141
• Lead Sponsor: Sinovac Biotech Co., Ltd

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.

Study Timeline

• Study Start: 2018-02-06
• Primary Completion: 2018-04-17
• Study Completion: 2018-11-02
• Status Verified: 2019-02
• Study First Submitted: 2019-02-28
• Study First Submitted QC: 2019-02-28
• Last Update Submitted: 2019-02-28
• Study First Posted: 2019-03-01
• Last Update Posted: 2019-03-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2340

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group 2-phase Ⅲ	Trivalent influenza vaccine (contains B/Yamagata strain)	Trivalent influenza vaccine (contains B/Yamagata strain)
Control group 1-phase Ⅲ	Trivalent influenza vaccine (contains B/Victoria strain)	Trivalent influenza vaccine (contains B/Victoria strain)
Experimental group-phase Ⅰ	Quadrivalent influenza vaccine	Quadrivalent influenza vaccine
Experimental group-phase Ⅲ	Quadrivalent influenza vaccine	Quadrivalent influenza vaccine

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Guanyun Center for Disease Prevention and Control; 🇨🇳 Lianyungang, Jiangsu, China

Pizhou Center for Disease Prevention and Control; 🇨🇳 Pizhou, Jiangsu, China