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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

Primary Purpose

Influenza Immunization, Healthy Volunteers

Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
High-Dose Quadrivalent Influenza Vaccine, (Zonal Purified, Split Virus) 2020-2021 Strains (QIV-HD)
Local Standard-Dose Inactivated Quadrivalent Influenza Vaccine, 2020-2021 Strains (QIV-SD)
Sponsored by
Sanofi Pasteur, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Influenza Immunization

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Investigational Site Number 3920005
  • Investigational Site Number 3920004
  • Investigational Site Number 3920006
  • Investigational Site Number 3920001
  • Investigational Site Number 3920003
  • Investigational Site Number 3920008
  • Investigational Site Number 3920009
  • Investigational Site Number 3920002
  • Investigational Site Number 3920007
  • Investigational Site Number 3920010

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Group 1: QIV-HD

Group 2: QIV-SD

Arm Description

Participants received a single injection of 0.7 milliliters (mL) high dose quadrivalent influenza vaccine (QIV-HD), intramuscularly (IM) at Day 0.

Participants received a single injection of 0.5 mL standard-dose quadrivalent influenza vaccine (QIV-SD), subcutaneously (SC) at Day 0.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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).
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.
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.
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.
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.
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.
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.

Full Information

First Posted
July 31, 2020
Last Updated
September 26, 2023
Sponsor
Sanofi Pasteur, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT04498832
Brief Title
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
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
October 21, 2020 (Actual)
Primary Completion Date
January 14, 2021 (Actual)
Study Completion Date
January 14, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi Pasteur, a Sanofi Company

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza Immunization, Healthy Volunteers

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Participants randomized in each group were stratified by site and age (60 to 64, 65 to 74, and 75 years of age and older).
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Modified double-blind: the participant and the Investigator remain unaware of the treatment assignments throughout the study. An unblinded qualified trial staff member will administer the appropriate vaccine but will not be involved in the immunogenicity and safety evaluations.
Allocation
Randomized
Enrollment
2100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1: QIV-HD
Arm Type
Experimental
Arm Description
Participants received a single injection of 0.7 milliliters (mL) high dose quadrivalent influenza vaccine (QIV-HD), intramuscularly (IM) at Day 0.
Arm Title
Group 2: QIV-SD
Arm Type
Active Comparator
Arm Description
Participants received a single injection of 0.5 mL standard-dose quadrivalent influenza vaccine (QIV-SD), subcutaneously (SC) at Day 0.
Intervention Type
Biological
Intervention Name(s)
High-Dose Quadrivalent Influenza Vaccine, (Zonal Purified, Split Virus) 2020-2021 Strains (QIV-HD)
Other Intervention Name(s)
QIV-HD
Intervention Description
Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM
Intervention Type
Biological
Intervention Name(s)
Local Standard-Dose Inactivated Quadrivalent Influenza Vaccine, 2020-2021 Strains (QIV-SD)
Other Intervention Name(s)
QIV-SD
Intervention Description
Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: SC
Primary Outcome Measure Information:
Title
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 28
Description
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.
Time Frame
Day 28 (post-vaccination)
Title
Percentage of Participants Achieving Seroconversion Against Influenza Virus Antigens: Superiority Analysis
Description
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.
Time Frame
Day 28 (post-vaccination)
Secondary Outcome Measure Information:
Title
GMTs of Influenza Vaccine Antibodies at Day 0 and Day 28
Description
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.
Time Frame
Day 0 (pre-vaccination) and Day 28 (post-vaccination)
Title
Geometric Mean Titers Ratio (GMTR) of Influenza Vaccine Antibodies
Description
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).
Time Frame
Day 0 (pre-vaccination), Day 28 (post-vaccination)
Title
Percentage of Participants Achieving Seroconversion Against Influenza Virus Antigens
Description
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.
Time Frame
Day 28 (post-vaccination)
Title
Percentage of Participants With HAI Titers >=40 (1/Dilution) Against Influenza Antigens
Description
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.
Time Frame
Day 0 (pre-vaccination), Day 28 (post-vaccination)
Title
Number of Participants Reporting Immediate Unsolicited Adverse Events (AEs)
Description
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.
Time Frame
Within 30 minutes post-vaccination
Title
Number of Participants Reporting Solicited Injection Site and Systemic Reactions
Description
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.
Time Frame
Within 7 days post-vaccination
Title
Number of Participants Reporting Unsolicited Adverse Events (AEs)
Description
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.
Time Frame
Within 28 days post-vaccination
Title
Number of Participants Reporting Serious Adverse Events (SAEs)
Description
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.
Time Frame
From Day 0 up to Day 28 post-vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 3920005
City
Fukuoka-Shi
Country
Japan
Facility Name
Investigational Site Number 3920004
City
Koganei-Shi
Country
Japan
Facility Name
Investigational Site Number 3920006
City
Kumamoto-Shi
Country
Japan
Facility Name
Investigational Site Number 3920001
City
Osaka-Shi
Country
Japan
Facility Name
Investigational Site Number 3920003
City
Shinjuku-Ku
Country
Japan
Facility Name
Investigational Site Number 3920008
City
Shinjuku-Ku
Country
Japan
Facility Name
Investigational Site Number 3920009
City
Shinjuku-Ku
Country
Japan
Facility Name
Investigational Site Number 3920002
City
Suita-Shi
Country
Japan
Facility Name
Investigational Site Number 3920007
City
Toshima-Ku
Country
Japan
Facility Name
Investigational Site Number 3920010
City
Yokohama-Shi
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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
Citations:
PubMed Identifier
36906404
Citation
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.
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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

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