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

Sponsor

Sinovac Biotech Co., Ltd (Industry)

Overall Status

Completed

CT.gov ID

NCT03859141

Collaborator

(none)

2,340

Enrollment

Locations

Arms

8.8

Actual Duration (Months)

1170

Patients Per Site

132.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Seasonal Influenza	Biological: Quadrivalent influenza vaccine Biological: Quadrivalent influenza vaccine Biological: Trivalent influenza vaccine (contains B/Victoria strain) Biological: Trivalent influenza vaccine (contains B/Yamagata strain)	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

2340 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The phase Ⅰ clinical trial was a single arm.The phase Ⅲ was 3 parallel arms.The phase Ⅰ clinical trial was a single arm.The phase Ⅲ was 3 parallel arms.

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

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

Actual Study Start Date :

Feb 6, 2018

Actual Primary Completion Date :

Apr 17, 2018

Actual Study Completion Date :

Nov 2, 2018

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

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

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 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 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 geometric mean increase (GMI) of each HI antibody after two doses immunization >2.5. [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
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 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 incidence of the unsolicited adverse events 0-28 days after each immunization [0-28 days after each dose immunization]
Safety Index
The incidence of the serious adverse events within 7 months after the first immunization. [Within 7 months after the first dose immunization]
Safety Index

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 35 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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:

Any subunit vaccine or inactivated vaccine (e.g., pneumococcal vaccine) or treatment of allergy within 14 days prior to study entry;
Any live attenuated vaccine within 30 days prior to study entry;
Any other investigational medicine(s) or vaccine within 30 days prior to study entry;
Blood product within 3 months prior to study entry;
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;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Guanyun Center for Disease Prevention and Control	Lianyungang	Jiangsu	China	222200
2	Pizhou Center for Disease Prevention and Control	Pizhou	Jiangsu	China	221300