Study Describing the Immunogenicity and Safety of Quadrivalent Recombinant Influenza Vaccine (RIV4) Versus a Licensed Quadrivalent-inactivated Influenza Vaccine (IIV4) (Fluarix® Quadrivalent) in Participants 18 Years of Age and Older in South Korea

A Phase III Randomized, Modified Double-blind, Active-controlled, Multi-center Study to Describe the Immunogenicity and Safety of the Quadrivalent Recombinant Influenza Vaccine (RIV4) Versus a Quadrivalent-inactivated Influenza Vaccine (IIV4) (Fluarix® Quadrivalent) in Participants 18 Years of Age and Older in South Korea

• To describe the immune response induced by quadrivalent recombinant influenza vaccine (RIV4) and Quadrivalent-inactivated Influenza Vaccine (IIV4) in 18-49 and greater than or equal to (>=) 50 years of age participants by hemagglutination inhibition (HAI) measurement method.
• To describe the safety profile of all participants in RIV4 and IIV4 groups.

Study Overview

• Status: Completed
• Conditions: Influenza (Healthy Volunteers)
• Intervention / Treatment: Biological: Quadrivalent Recombinant Influenza Vaccine (RIV4); Biological: Quadrivalent inactivated influenza vaccine (IIV4)

Detailed Description

The duration of each participant's participation was approximately 6 months.

• Study Type: Interventional
• Enrollment (Actual): 301
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Korea
  • Seoul, South Korea, 07441
    • Investigational Site Number :4100002
  • Gyeonggi-do
    • Ansan-si, Gyeonggi-do, South Korea, 15355
      • Investigational Site Number :4100003
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, South Korea, 152-703
      • Investigational Site Number :4100001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged >=18 years on the day of inclusion.
• Participants who were overtly healthy as determined by medical evaluation including medical history, physical examination.
• Able to attend all scheduled visits and complied with all study procedures.
• Informed consent form was signed and dated.
• A female participant was eligible to participate if she was not pregnant or breastfeeding and one of the following conditions applies:

Was of non-childbearing potential. To be considered of non-childbearing potential, a female must be postmenopausal for at least 1 year, or surgically sterile OR Was of childbearing potential and agreed to use an effective contraceptive method or abstinence from at least 4 weeks prior to the study intervention administration until at least 4 weeks after study intervention administration.

A female participant of childbearing potential must had a negative highly sensitive pregnancy test (urine) before the first dose of study intervention.

Exclusion Criteria:

Participants were excluded from the study if any of the following criteria applied:

• Participation at the time of study enrollment, or in the 6 months preceding the study vaccination, or planned participation during the present study period in another clinical study investigating involving an Investigational Medical Product (IMP) (vaccine, drug), medical device, or medical procedure or in any other type of medical research.
• Receipt of any vaccine in the 4 weeks (28 days) preceding the study vaccination or planned receipt of any vaccine prior to Visit 2.
• Previous vaccination against influenza (in the preceding 6 months) with either the study vaccine or another vaccine.
• Receipt of immune globulins, blood, or blood-derived products in the past 3 months.
• Known or suspected abnormal immune function: immunosuppression, suspected congenital or acquired immunodeficiency based on medical history and physical examination, 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 study or to a vaccine containing any of the same substances.
• Thrombocytopenia or bleeding disorder, contraindicating IM vaccination based on the Investigator's judgment.
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
• Current alcohol abuse or drug addiction that in the opinion of the Investigator might interfere with the study conduct or completion.
• Chronic illness that, in the opinion of the Investigator, was at a stage where it might interfere with trial conduct or completion (Chronic illness may include, but is not limited to, cardiac disorders, renal disorders, auto-immune disorders, diabetes, psychiatric disorders, or chronic infection).
• Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature >=38.0°C). A prospective participant should not be included in the study until the condition had resolved or the febrile event had subsided.
• Personal or family history of Guillain-Barré syndrome.
• Neoplastic disease or any hematologic malignancy (except localized skin or prostate cancer that was stable at the time of vaccination in the absence of therapy and participants who had a history of neoplastic disease and had been disease-free for >= 5 years).
• Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse) of the Investigator or employee with direct involvement in the proposed study.

The above information was not intended to contain all considerations relevant to a 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: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Quadrivalent Recombinant Influenza Vaccine (RIV4); Participants received a single intramuscular (IM) injection of 0.5 milliliters (mL) RIV4 on Day 1.	Biological: Quadrivalent Recombinant Influenza Vaccine (RIV4); Solution for intramuscular injection
Active Comparator: Group 2: Quadrivalent-inactivated Influenza Vaccine (IIV4); Participants received a single IM injection of 0.5 mL IIV4 on Day 1.	Biological: Quadrivalent inactivated influenza vaccine (IIV4); Suspension for intramuscular injection; Other Names: Fluarix®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 1- Per Protocol Analysis Set (PPAS)	GMTs of anti-influenza antibodies were measured using hemagglutination inhibition (HAI) assay for 4 influenza virus strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata lineages. Titers were expressed in terms of 1/dilution.	Day 1 (pre-vaccination)
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 1- Full Analysis Set (FAS)	GMTs of anti-influenza antibodies were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata lineages. Titers were expressed in terms of 1/dilution.	Day 1 (pre-vaccination)
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 29- PPAS	GMTs of anti-influenza antibodies were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata lineages. Titers were expressed in terms of 1/dilution.	Day 29 (post-vaccination)
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 29- FAS	GMTs of anti-influenza antibodies were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata lineages. Titers were expressed in terms of 1/dilution.	Day 29 (post-vaccination)
Geometric Mean Fold-rise (GMFR) for Influenza Vaccine Antibodies-PPAS	GMTs of anti-influenza antibodies were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata lineages. GMFR were calculated as the ratio of GMTs post-vaccination (on Day 29) and pre-vaccination (on Day 1).	Day 1 (pre-vaccination) and Day 29 (post-vaccination)
Geometric Mean Fold-rise (GMFR) for Influenza Vaccine Antibodies-FAS	GMTs of anti-influenza antibodies were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata lineages. GMFR were calculated as the ratio of GMTs post-vaccination (on Day 29) and pre-vaccination (on Day 1).	Day 1 (pre-vaccination) and Day 29 (post-vaccination)
Percentage of Participants Achieving Seroconversion Against Influenza Vaccine Antibodies-PPAS	Anti-influenza antibodies were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata lineages. Seroconversion was defined as either a pre-vaccination titer less than (<) 1:10 (1/dilution) and a post-vaccination titer >=1:40 (1/dilution) or a pre-vaccination titer >= 1:10 (1/dilution) and a >= four-fold increase in post-vaccination titer at Day 29.	Day 29 (post-vaccination)
Percentage of Participants Achieving Seroconversion Against Influenza Vaccine Antibodies-FAS	Anti-influenza antibodies were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata lineages. Seroconversion was defined as either a pre-vaccination titer less than (<) 1:10 (1/dilution) and a post-vaccination titer >=1:40 (1/dilution) or a pre-vaccination titer >= 1:10 (1/dilution) and a >= four-fold increase in post-vaccination titer at Day 29.	Day 29 (post-vaccination)
Percentage of Participants With Antibody Titers Greater Than or Equal to (>=) 40 (1/Dilution) Against Influenza Vaccine Antibodies-PPAS	Antibody titers were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata lineages. Percentage of participants with antibody titers >=40 (1/dilution) against influenza vaccine antibodies at Day 1 and Day 29 were reported in this outcome measure.	Day 1 (pre-vaccination) and Day 29 (post-vaccination)
Percentage of Participants With Antibody Titers >=40 (1/Dilution) Against Influenza Vaccine Antibodies-FAS	Antibody titers were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata lineages. Percentage of participants with antibody titers >=40 (1/dilution) against influenza vaccine antibodies at Day 1 and Day 29 were reported in this outcome measure.	Day 1 (pre-vaccination) and Day 29 (post-vaccination)
Percentage of Participants With Detectable Antibody Titers >= 10 (1/Dilution) Against Influenza Vaccine Antibodies- PPAS	Antibody titers were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata lineages. Percentage of participants with antibody titers >=10 (1/dilution) against influenza vaccine antibodies at Day 1 and Day 29 were reported in this outcome measure.	Day 1 (pre-vaccination) and Day 29 (post-vaccination)
Percentage of Participants With Detectable Antibody Titers >= 10 (1/Dilution) Against Influenza Vaccine Antibodies- FAS	Antibody titers were measured using HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata lineages. Percentage of participants with antibody titers >=10 (1/dilution) against influenza vaccine antibodies at Day 1 and Day 29 were reported in this outcome measure.	Day 1 (pre-vaccination) and Day 29 (post-vaccination)
Number of Participants Reporting Immediate Unsolicited Adverse Events (AEs)	An AE was any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which did not had any casual relationship with the treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report form (CRF) in terms of diagnosis and/or onset window post-vaccination. All participants were observed for 30 minutes after vaccination, and any unsolicited AEs occurred during that time were recorded as immediate unsolicited AEs in the CRF.	Within 30 minutes post-vaccination
Number of Participants Reporting Solicited Systemic Reactions	A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRF and considered as related to the study intervention administered. Solicited systemic reactions included fever, headache, malaise, myalgia, shivering, fatigue, nausea, and arthralgia.	Within 7 days post-vaccination
Number of Participants Reporting Solicited Injection Site Reactions	A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRF and considered as related to the study intervention administered. Solicited injection site reactions included pain, erythema, swelling, induration, bruising and tenderness.	Within 7 days post-vaccination
Number of Participants Reporting Unsolicited Adverse Events (AEs)	An AE was any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which did not had any casual relationship with the treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRF in terms of diagnosis and/or onset window post-vaccination.	From Day 1 up to 28 days post-vaccination (i.e., up to Day 29)
Number of Participants Reporting Serious Adverse Events (SAEs) And Adverse Events of Special Interest (AESI)	A SAE was any untoward medical occurrence 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 an important medical event. A SAE which caused death of the participant was considered as fatal SAE. An AESIs were defined as one of scientific and medical concern specific to the Sponsor's study intervention, events for which ongoing monitoring and rapid communication by the investigator to the sponsor was done.	From Day 1 up to 6 months post-vaccination (i.e., up to Day 181)

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Choi WS, Lee J, Ottaviano C, Samson S, Peng L, Shin S, Choe S, Kim WJ. Immunogenicity and safety of quadrivalent recombinant influenza vaccine in Korean adults: Phase III, randomized study. Vaccine. 2025 Aug 1;62:127521. doi: 10.1016/j.vaccine.2025.127521. Online ahead of print.

Helpful Links

• VAP00016 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2021
• Primary Completion (Actual): September 1, 2022
• Study Completion (Actual): September 1, 2022

Study Registration Dates

• First Submitted: November 17, 2021
• First Submitted That Met QC Criteria: November 17, 2021
• First Posted (Actual): December 6, 2021

Study Record Updates

• Last Update Posted (Estimated): September 11, 2025
• Last Update Submitted That Met QC Criteria: September 10, 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; fluarix
• Other Study ID Numbers: VAP00016; U1111-1253-2122 (Registry Identifier: ICTRP)

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.: Yes