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

• ClinicalTrials.gov Identifier: NCT03859141
• Recruitment Status: Completed
• First Posted: March 1, 2019
• Last Update Posted: March 1, 2019
• Sponsor: Sinovac Biotech Co., Ltd
• Information provided by (Responsible Party): Sinovac Biotech Co., Ltd

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: 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 (Clinical Trial)
• 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.
• 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: February 6, 2018
• Actual Primary Completion Date: April 17, 2018
• Actual Study Completion Date: November 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 :

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

1. The lower limit of 95%CI of the ratio of GMT (experimental group/control group) >1.5. [ Time Frame: 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.
2. The lower limit of 95% CI of the difference of HI antibody seroconversion rate (experimental group-control group)>10% [ Time Frame: 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.
3. The lower limit of 95% CI of seroconversion rate for each HI antibody after two doses immunization≥40%. [ Time Frame: 28 days after two doses immunization ]
   Immunogenicity index
4. The seroprotective rate (HI antibody titer≥1:40) of each HI antibody after two doses immunization≥70%. [ Time Frame: 28 days after two doses immunization ]
   Immunogenicity index
5. The geometric mean increase (GMI) of each HI antibody after two doses immunization >2.5. [ Time Frame: 28 days after two doses immunization ]
   Immunogenicity index
6. 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 [ Time Frame: 28 days after two doses immunization ]
   Immunogenicity index
7. 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. [ Time Frame: 28 days after two doses immunization ]
   Immunogenicity index
8. The incidence of the solicited local and general adverse reactions 0-7 days after each immunization. [ Time Frame: 0-7 days ]
   Safety index, The adverse reactions refers to the adverse events which were considered related to the vaccination.
9. The incidence of the unsolicited adverse events 0-28 days after each immunization [ Time Frame: 0-28 days after each dose immunization ]
   Safety Index
10. The incidence of the serious adverse events within 7 months after the first immunization. [ Time Frame: Within 7 months after the first dose immunization ]
    Safety Index

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 35 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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;

Contacts and Locations

Locations

China, Jiangsu

Guanyun Center for Disease Prevention and Control

Lianyungang, Jiangsu, China, 222200

Pizhou Center for Disease Prevention and Control

Pizhou, Jiangsu, China, 221300

Sponsors and Collaborators

Sinovac Biotech Co., Ltd

Investigators

• Principal Investigator: Yuemei Hu, Bachelor; Jiangsu Provincial Center for Disease Prevention and Control

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Sinovac Biotech Co., Ltd
• ClinicalTrials.gov Identifier: NCT03859141
• Other Study ID Numbers: PRO-QINF-3002
• First Posted: March 1, 2019
• Last Update Posted: March 1, 2019
• Last Verified: February 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sinovac Biotech Co., Ltd:

Influenza Vaccine; Quadrivalent; Trivalent; Children

Additional relevant MeSH terms:

Influenza, Human; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs