Study With Quadrivalent Recombinant Influenza Vaccine (RIV4) Compared With Egg-Based Quadrivalent Influenza Vaccine (IIV4) in Participants Aged 3 to 8 Years

Immunogenicity and Safety of Quadrivalent Recombinant Influenza Vaccine Compared With Egg-Based Standard-Dose Quadrivalent Influenza Vaccine in Children 3 to 8 Years of Age.

The purpose of this study was to demonstrate the non-inferior HAI immune response of quadrivalent recombinant influenza vaccine (RIV4) vs licensed Egg-Based Quadrivalent Influenza Vaccine (IIV4) for the 4 strains based on the egg-derived antigen in all participants aged 3 to 8 years and to describe the immunogenicity and safety profile of RIV4 compared to IIV4 in participants aged 3 to 8 years.

Study Overview

• Status: Terminated
• Conditions: Influenza Immunization
• Intervention / Treatment: Biological: Recombinant influenza vaccine (RIV4); Biological: Quadrivalent influenza vaccine (IIV4)

Detailed Description

Participants were enrolled on the day of their first vaccination and received 1 or 2 doses 28 days apart of either RIV4 or IIV4; depending on if they were previously vaccinated against influenza or previously unvaccinated against influenza, respectively; and were followed for 6 months after the last vaccination.

• Study Type: Interventional
• Enrollment (Actual): 366
• Phase: Phase 3

Contacts and Locations

Study Locations

• Poland
  • Bydgoszcz, Poland, 85-796
    • Investigational Site Number : 6160003
  • Tarnów, Poland, 33-100
    • Investigational Site Number : 6160006
  • Warsaw, Poland, 02-647
    • Investigational Site Number : 6160001
  • Wroclaw, Poland, 53-149
    • Investigational Site Number : 6160012
  • Kuyavian-Pomeranian Voivodeship
    • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-048
      • Investigational Site Number : 6160010
    • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-079
      • Investigational Site Number : 6160007
  • Silesian Voivodeship
    • Siemianowice Śląskie, Silesian Voivodeship, Poland, 41-103
      • Investigational Site Number : 6160005
• Spain
  • Madrid, Spain, 28041
    • Investigational Site Number : 7240004
  • Madrid, Spain, 28660
    • Investigational Site Number : 7240018
  • Málaga, Spain, 29015
    • Investigational Site Number : 7240005
  • Móstoles, Spain, 28938
    • Investigational Site Number : 7240001
  • Seville, Spain, 41014
    • Investigational Site Number : 7240007
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28046
      • Investigational Site Number : 7240014
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Birmingham Pediatric Associates Site Number : 8400023
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • The Children's Clinic Of Jonesboro PA Site Number : 8400025
  • California
    • San Diego, California, United States, 92123-1881
      • California Research Foundation Site Number : 8400003
  • Iowa
    • Sioux City, Iowa, United States, 51106
      • Meridian Clinical Research- Sioux City Site Number : 8400007
  • Kansas
    • Newton, Kansas, United States, 67114
      • AMR - Newton Site Number : 8400021
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Kentucky Pediatrics / Adult Research Site Number : 8400010
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • Velocity Clinical Research- New Orleans Site Number : 8400012
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Velocity Clinical Research Lincoln Site Number : 8400013
    • Omaha, Nebraska, United States, 68134
      • Velocity Clinical Research Omaha Site Number : 8400009
  • New York
    • Binghamton, New York, United States, 13905
      • Meridian Clinical Research Site Number : 8400006
    • Vestal, New York, United States, 13850
      • Velocity Clinical Research Vestal Site Number : 8400016
  • Ohio
    • Dayton, Ohio, United States, 45414
      • Ohio Pediatric Research Site Number : 8400020
  • South Carolina
    • Barnwell, South Carolina, United States, 29812
      • Rainbow Pediatrics Site Number : 8400014
    • Charleston, South Carolina, United States, 29414
      • Coastal Pediatric Research Charleston Site Number : 8400005
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center Site Number : 8400022
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • JBR Clinical Research Site Number : 8400001
    • Salt Lake City, Utah, United States, 84109
      • J. Lewis Research Site Number : 8400017
    • Syracuse, Utah, United States, 84075-9645
      • Alliance for Multispecialty Research Syracuse Site Number : 8400027

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 8 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged 3 to 8 years on the day of inclusion
• Assent form has been signed and dated by the participant (according to local regulations), and informed consent form has been signed and dated by the parent(s) or another legally acceptable representative and by an independent witness, if required by local regulations

Exclusion Criteria:

• Known or suspected congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances
• Thrombocytopenia
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination based on the Investigator's judgment
• Personal or family history of Guillain-Barre Syndrome (GBS)
• Personal history of clinically significant development delay (at the discretion of the Investigator), neurologic disorder, or seizure disorder NOTE: The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RIV4 cohort; RIV4 single injection at Day 1	Biological: Recombinant influenza vaccine (RIV4); Pharmaceutical form: solution for injection Route of administration: intramuscular; Other Names: Supemtek / Flublok Quadrivalent
Active Comparator: IIV4 cohort; IIV4, single injection at Day 1	Biological: Quadrivalent influenza vaccine (IIV4); Pharmaceutical form: suspension for injection Route of administration: intramuscular; Other Names: Fluarix Tetra / Fluarix® Quadrivalent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies 28 Days After the Last Vaccination	GMTs of influenza vaccine antibodies were measured using individual hemagglutination inhibition (HAI) assay for 4 influenza virus strains: A/H1N1 strain, A/H3N2 strain, B/Victoria lineage strain, and B/Yamagata lineage strain.	Day 29 [participants previously vaccinated] or Day 57 [participants previously unvaccinated]
Percentage of Participants With Seroconversion (SC) Against Antigens 28 Days After the Last Vaccination	Anti-influenza antibodies were measured using HAI assay for 4 influenza virus strains: A/H1N1 strain, A/H3N2 strain, B/Victoria lineage strain, and B/Yamagata lineage strain. SC was defined as either a pre-vaccination HAI titer less than (<) 10 (1/dilution) and a post-vaccination titer greater than or equal to (≥) 40 (1/dilution) or a pre-vaccination titer ≥ 10 (1/dilution) and a ≥ 4-fold increase in post-vaccination titer.	Day 29 [participants previously vaccinated] or Day 57 [participants previously unvaccinated]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMTs of Influenza Vaccine Antibodies at Day 1	GMTs of influenza vaccine antibodies were measured using HAI assay for 4 influenza virus strains: A/H1N1 strain, A/H3N2 strain, B/Victoria lineage strain, and B/Yamagata lineage strain.	Pre-vaccination on Day 1
Percentage of Participants With Detectable HAI Titer ≥ 10 and ≥ 40 for Influenza Vaccine Antibodies at Day 1 and 28 Days After the Last Vaccination	Antibody titers were measured using HAI assay for 4 influenza virus strains: A/H1N1 strain, A/H3N2 strain, B/Victoria lineage strain, and B/Yamagata lineage strain.	Day 1 (all participants) and Day 29 (participants previously vaccinated) or Day 57 (participants previously unvaccinated)
Geometric Mean Titer Ratio (GMTR) of Influenza Vaccine Antibodies	GMTR was the ratio of the individual titers post-vaccination over pre-vaccination. The GMTs of influenza vaccine antibodies were measured using HAI assay for 4 influenza virus strains: A/H1N1 strain, A/H3N2 strain, B/Victoria lineage strain, and B/Yamagata lineage strain.	Day 1 (all participants) and Day 29 (participants previously vaccinated) or Day 57 (participants previously unvaccinated)
Number of Participants With Immediate Unsolicited Adverse Events (AEs)	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, i.e., pre-listed in the case report form (CRF) in terms of diagnosis and onset window post-vaccination. Immediate events were recorded to capture medically relevant unsolicited systemic AEs which occurred within the first 30 minutes after vaccination.	Within 30 minutes post-vaccination on Day 1 (all participants) and Day 29 (participants previously unvaccinated)
Number of Participants With Solicited Injection Site Reactions and Systemic Reactions	Solicited injection site reactions were reactions at and around the injection/administration site of the investigational medicinal product (IMP) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF and considered as being related to the IMP administered at that site. Solicited systemic reactions were systemic AEs observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF, and those occurring during the specified collection period were always considered related to the IMP even if there was evidence of alternative etiology.	Day 1 to Day 8 (all participants); Day 29 to Day 36 (participants previously unvaccinated)
Number of Participants With Unsolicited AEs	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, i.e., pre-listed in the CRF in terms of diagnosis and onset window post-vaccination.	Up to Day 29 (all participants); Up to Day 57 (participants previously unvaccinated)
Number of Participants With Medically Attended Adverse Events (MAAEs)	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An MAAE was a new onset or a worsening of a condition that prompted the participant or participant's parent/legally acceptable representative to seek unplanned medical advice at a physician's office or emergency department.	Up to Day 29 (all participants); Up to Day 57 (participants previously unvaccinated)
Number of Participants With Serious Adverse Events (SAEs) And Adverse Events of Special Interest (AESI)	An SAE was defined as any adverse event that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was other medically important event. An AESI was defined as one of scientific and medical concern specific to the Sponsor's study intervention or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate.	From the first vaccination up to 6 months after the last vaccination, 209 days

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi Pasteur, a Sanofi Company

Publications and helpful links

Helpful Links

• VAP00026 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2022
• Primary Completion (Actual): October 3, 2023
• Study Completion (Actual): October 3, 2023

Study Registration Dates

• First Submitted: August 22, 2022
• First Submitted That Met QC Criteria: August 23, 2022
• First Posted (Actual): August 24, 2022

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: September 5, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; Influenza Vaccines
• Other Study ID Numbers: VAP00026 (Other Identifier: Sanofi Identifier); U1111-1256-8841 (Registry Identifier: ICTRP); 2022-000576-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No