Study to Assess the Immune Response and the Safety Profile of a High-Dose Quadrivalent Influenza Vaccine (QIV-HD) Compared to a Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD) in Japanese Adults 60 Years of Age and Older

Immunogenicity and Safety of High-Dose Quadrivalent Influenza Vaccine (SP0178) Administered by Intramuscular Route Versus Standard-Dose Quadrivalent Influenza Vaccine by Subcutaneous Route in Subjects 60 Years of Age and Older in Japan

Primary Objective:

To demonstrate that QIV-HD induced an immune response (as assessed by hemagglutination inhibition [HAI] geometric mean titers [GMTs] and seroconversion rates) that was superior to responses induced by QIV-SD for the 4 virus strains at 28 days post-vaccination in all participants.

Secondary Objective:

• To describe the immune response induced by QIV-HD and QIV-SD by HAI measurement method in all participants.
• To describe the safety profile of all participants in each study group.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Influenza Immunization
• Intervention / Treatment: Biological: High-Dose Quadrivalent Influenza Vaccine, (Zonal Purified, Split Virus) 2020-2021 Strains (QIV-HD); Biological: Local Standard-Dose Inactivated Quadrivalent Influenza Vaccine, 2020-2021 Strains (QIV-SD)

Detailed Description

Study duration per participant was approximately 28 days including: 1 day of screening and vaccination, a safety follow-up telephone call and an end of study visit approximately at Day 8 and 28 after vaccination, respectively.

• Study Type: Interventional
• Enrollment (Actual): 2100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka-Shi, Japan
    • Investigational Site Number 3920005
  • Koganei-Shi, Japan
    • Investigational Site Number 3920004
  • Kumamoto-Shi, Japan
    • Investigational Site Number 3920006
  • Osaka-Shi, Japan
    • Investigational Site Number 3920001
  • Shinjuku-Ku, Japan
    • Investigational Site Number 3920003
  • Shinjuku-Ku, Japan
    • Investigational Site Number 3920008
  • Shinjuku-Ku, Japan
    • Investigational Site Number 3920009
  • Suita-Shi, Japan
    • Investigational Site Number 3920002
  • Toshima-Ku, Japan
    • Investigational Site Number 3920007
  • Yokohama-Shi, Japan
    • Investigational Site Number 3920010

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria :

• Aged greater than or equal to (>=) 60 years on the day of inclusion.
• Able to attend all scheduled visits and complied with all study procedures.

Exclusion criteria:

• Participation at the time of study enrollment (or in the 4 weeks preceding the study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure.
• Receipt of any vaccination with live vaccines within the past 27 days preceding the study vaccination or any vaccination with inactivated vaccines within the past 6 days preceding the study vaccination, or planned receipt of any vaccine prior to Visit 02.
• 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 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 eggs, chicken proteins, or any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the study or to a vaccine containing any of the same substances.
• Thrombocytopenia or bleeding disorder, contraindicating IM vaccination based on Investigator's judgment.
• Alcohol or substance abuse 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 study conduct or completion.
• 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, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.
• Personal or family history of Guillain-Barré syndrome.
• Neoplastic disease or any hematologic malignancy (except localized skin or prostate cancer that is stable at the time of vaccination in the absence of therapy and participants who have a history of neoplastic disease and have been disease free for >=5 years).
• Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature >=37.5 degree Celsius). A prospective participant was not be included in the study until the condition had resolved or the febrile event had subsided.
• History of convulsions.
• Any condition that in the opinion of the Investigator could interfere with the evaluation of the vaccine.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: QIV-HD; Participants received a single injection of 0.7 milliliters (mL) high dose quadrivalent influenza vaccine (QIV-HD), intramuscularly (IM) at Day 0.	Biological: High-Dose Quadrivalent Influenza Vaccine, (Zonal Purified, Split Virus) 2020-2021 Strains (QIV-HD); Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM; Other Names: QIV-HD
Active Comparator: Group 2: QIV-SD; Participants received a single injection of 0.5 mL standard-dose quadrivalent influenza vaccine (QIV-SD), subcutaneously (SC) at Day 0.	Biological: Local Standard-Dose Inactivated Quadrivalent Influenza Vaccine, 2020-2021 Strains (QIV-SD); Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: SC; Other Names: QIV-SD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 28	GMTs of anti-influenza antibodies were measured using hemagglutination inhibition (HAI) assay for 4 influenza virus strains: A/H1N1, A/H3N2-like, B/Victoria-like, and B/Yamagata. Titers were expressed in terms of 1/dilution.	Day 28 (post-vaccination)
Percentage of Participants Achieving Seroconversion Against Influenza Virus Antigens: Superiority Analysis	Anti-influenza antibodies were measured by HAI assay for 4 influenza virus strains: A/H1N1, A/H3N2-like, B/Victoria-like, and B/Yamagata. Seroconversion was defined as either a pre-vaccination HAI titer less than (<) 10 (1/dilution) and a post-vaccination titer >=40 (1/dilution) or a pre-vaccination titer >=10 (1/dilution) and a >= four-fold increase in post-vaccination titer at Day 28.	Day 28 (post-vaccination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMTs of Influenza Vaccine Antibodies at Day 0 and Day 28	GMTs of anti-influenza antibodies were measured using HAI assay for 6 influenza virus strains: A/H1N1, A/H3N2, A/H3N2-like, B/Victoria, B/Victoria-like, and B/Yamagata. Titers were expressed in terms of 1/dilution.	Day 0 (pre-vaccination) and Day 28 (post-vaccination)
Geometric Mean Titers Ratio (GMTR) of Influenza Vaccine Antibodies	GMTs of anti-influenza antibodies were measured using HAI assay for 6 influenza virus strains: A/H1N1, A/H3N2, A/H3N2-like, B/Victoria, B/Victoria-like, and B/Yamagata. GMTRs were calculated as the ratio of GMTs post-vaccination (on Day 28) and pre-vaccination (on Day 0).	Day 0 (pre-vaccination), Day 28 (post-vaccination)
Percentage of Participants Achieving Seroconversion Against Influenza Virus Antigens	Anti-influenza antibodies were measured by HAI assay for 6 influenza virus strains: A/H1N1, A/H3N2, A/H3N2-like, B/Victoria, B/Victoria-like, and B/Yamagata. Seroconversion was defined as either a pre-vaccination HAI titer <10 (1/dilution) and a post-vaccination titer >=40 (1/dilution) or a pre-vaccination titer >=10 (1/dilution) and a >= four-fold increase in post-vaccination titer at Day 28.	Day 28 (post-vaccination)
Percentage of Participants With HAI Titers >=40 (1/Dilution) Against Influenza Antigens	Anti-influenza antibodies were measured using HAI assay method for 6 influenza virus strains: A/H1N1, A/H3N2, A/H3N2-like, B/Victoria, B/Victoria-like, and B/Yamagata. Percentage of participants with HAI titers >=40 (1/dilution) is reported in the outcome measure.	Day 0 (pre-vaccination), Day 28 (post-vaccination)
Number of Participants Reporting Immediate Unsolicited Adverse Events (AEs)	An AE was any untoward medical occurrence in a patient or in a clinical investigation participant administered a medicinal product and which did not necessarily have a casual relationship with the treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination. All participants were observed for 30 minutes after vaccination, and any unsolicited AEs that occurred during that time were recorded as immediate unsolicited AEs in the CRB.	Within 30 minutes post-vaccination
Number of Participants Reporting Solicited Injection Site and 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 CRB and considered as related to the product administered. Solicited injection site reactions included injection site pain, injection site erythema, injection site swelling, injection site induration, and injection site bruising. Solicited systemic reactions included fever, headache, malaise, myalgia and shivering.	Within 7 days post-vaccination
Number of Participants Reporting Unsolicited Adverse Events (AEs)	An AE was any untoward medical occurrence in a patient or in a clinical investigation participant administered a medicinal product and which did not necessarily have a casual relationship with the treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination.	Within 28 days post-vaccination
Number of Participants Reporting Serious Adverse Events (SAEs)	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.	From Day 0 up to Day 28 post-vaccination

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Sanchez L, Nakama T, Nagai H, Matsuoka O, Inoue S, Inoue T, Shrestha A, Pandey A, Chang LJ, De Bruijn I; QHD00010 Study Group. Superior immunogenicity of high-dose quadrivalent inactivated influenza vaccine versus Standard-Dose vaccine in Japanese Adults >/= 60 years of age: Results from a phase III, randomized clinical trial. Vaccine. 2023 Apr 6;41(15):2553-2561. doi: 10.1016/j.vaccine.2023.02.071. Epub 2023 Mar 10.

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2020
• Primary Completion (Actual): January 14, 2021
• Study Completion (Actual): January 14, 2021

Study Registration Dates

• First Submitted: July 31, 2020
• First Submitted That Met QC Criteria: July 31, 2020
• First Posted (Actual): August 5, 2020

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: EFC15150; U1111-1225-1085 (Other Identifier: UTN); QHD00010 (Other Identifier: Sanofi Pasteur)

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