Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine in Participants ≥65 Years in the US

Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine Administered by Intramuscular Route in Participants Aged 65 Years and Older

This randomized, modified double-blind, active-controlled, multi-center trial assessed the safety and immunogenicity of the high-dose quadrivalent influenza vaccine (QIV-HD) compared to either the licensed or investigational high-dose trivalent influenza vaccine (TIV-HD) in adults.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: QIV-HD; Biological: Licensed TIV-HD1; Biological: Investigational TIV-HD2

Detailed Description

This randomized, modified double-blind, active-controlled, multi-center trial was conducted in healthy adults (greater than and equal to [>=] 65 years) to assess the safety and immunogenicity (geometric mean titers and seroconversion for the 4 virus strains at 28 days post vaccination) of the QIV-HD compared to one of the TIV-HDs containing either the B strain from the primary lineage (TIV-HD1; licensed vaccine [Fluzone® High-Dose] for the 2017-2018 Northern Hemisphere [NH] influenza season) or the B strain from the alternate lineage (TIV-HD2, investigational TIV-HD containing an alternate B strain).

• Study Type: Interventional
• Enrollment (Actual): 2670
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Sanofi Pasteur Investigational Site 037
    • Redding, California, United States, 96001
      • Sanofi Pasteur Investigational Site 029
    • San Diego, California, United States, 92117
      • Sanofi Pasteur Investigational Site 003
  • Colorado
    • Colorado Springs, Colorado, United States, 80920
      • Sanofi Pasteur Investigational Site 016
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • Sanofi Pasteur Investigational Site 035
  • Florida
    • Hollywood, Florida, United States, 33024
      • Sanofi Pasteur Investigational Site 031
    • Jacksonville, Florida, United States, 32205
      • Sanofi Pasteur Investigational Site 009
    • Jacksonville, Florida, United States, 32216
      • Sanofi Pasteur Investigational Site 017
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Sanofi Pasteur Investigational Site 030
  • Idaho
    • Boise, Idaho, United States, 83712
      • Sanofi Pasteur Investigational Site 010
    • Meridian, Idaho, United States, 83642
      • Sanofi Pasteur Investigational Site 034
  • Iowa
    • Council Bluffs, Iowa, United States, 51501
      • Sanofi Pasteur Investigational Site 021
  • Kansas
    • Wichita, Kansas, United States, 67205
      • Sanofi Pasteur Investigational Site 023
    • Wichita, Kansas, United States, 67207
      • Sanofi Pasteur Investigational Site 028
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Sanofi Pasteur Investigational Site 012
  • Louisiana
    • Metairie, Louisiana, United States, 70427
      • Sanofi Pasteur Investigational Site 018
  • Mississippi
    • Biloxi, Mississippi, United States, 39531
      • Sanofi Pasteur Investigational Site 026
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Sanofi Pasteur Investigational Site 014
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Sanofi Pasteur Investigational Site 011
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • Sanofi Pasteur Investigational Site 024
  • New York
    • Rochester, New York, United States, 14609
      • Sanofi Pasteur Investigational Site 008
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Sanofi Pasteur Investigational Site 005
    • Winston-Salem, North Carolina, United States, 27045
      • Sanofi Pasteur Investigational Site 036
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Sanofi Pasteur Investigational Site 004
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Sanofi Pasteur Investigational Site 015
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Sanofi Pasteur Investigational Site 013
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Sanofi Pasteur Investigational Site 033
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Sanofi Pasteur Investigational Site 001
  • Texas
    • Dallas, Texas, United States, 75234
      • Sanofi Pasteur Investigational Site 002
    • Tomball, Texas, United States, 77375
      • Sanofi Pasteur Investigational Site 025
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • Sanofi Pasteur Investigational Site 027
    • Salt Lake City, Utah, United States, 84121
      • Sanofi Pasteur Investigational Site 006
    • Salt Lake City, Utah, United States, 84123
      • Sanofi Pasteur Investigational Site 019
    • South Jordan, Utah, United States, 84095
      • Sanofi Pasteur Investigational Site 020
    • West Jordan, Utah, United States, 83642
      • Sanofi Pasteur Investigational Site 022
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sanofi Pasteur Investigational Site 038

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged >= 65 years on the day of inclusion.
• Informed consent form had been signed and dated.
• Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

• Participation at the time of trial enrollment (or in the 4 weeks preceding the trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.
• Receipt of any vaccine in the 4 weeks (28 days) preceding the trial vaccination or planned receipt of any vaccine prior to Visit 2.
• Previous vaccination against influenza (in the preceding 6 months) with either the trial 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 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 or bleeding disorder, contraindicating IM vaccination based on investigator's judgment.
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
• Alcohol or substance abuse that, in the opinion of the investigator, might interfere with the trial conduct or completion.
• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.
• Identified as an Investigator or employee of the Investigator or trial center with direct involvement in the proposed trial, 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 trial.
• 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 >= 38.0°C [>= 100.4°F]). A prospective participant should not be included in the trial until the condition has resolved or the febrile event had subsided.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: QIV-HD; Participants randomized to receive a single injection of 0.7 mL QIV-HD by intramuscular (IM) route at Day 0.	Biological: QIV-HD; 0.7 mL-dose was administered intramuscularly (IM) into the upper arm area.; Other Names: High-dose quadrivalent influenza vaccine
ACTIVE_COMPARATOR: TIV-HD1 (Licensed TIV-HD1); Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Biological: Licensed TIV-HD1; 0.5 mL-dose was administered IM into the upper arm area.; Other Names: High-dose trivalent influenza vaccine
ACTIVE_COMPARATOR: TIV-HD2 (Investigational TIV-HD2); Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	Biological: Investigational TIV-HD2; 0.5 mL-dose was administered IM into the upper arm area.; Other Names: High-dose trivalent influenza vaccine (alternate B strain)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine	GMTs of anti-influenza antibodies were measured using an hemagglutination inhibition (HAI) assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). For each A strain, the comparison was made with the pooled TIV-HD groups. For each B strain, the comparison was made with the TIV-HD group containing the corresponding B strain. TIV-HD 1 did not contain B2 strain; TIV-HD2 did not contain B1 strain.	Day 28 post-vaccination
Percentage of Participants Achieving Seroconversion Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine	Anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Seroconversion was defined as either a HAI titer less than (<) 10 (1/dilution) at Day 0 and post-injection titer greater than or equal to (>=) 40 (1/dilution) at Day 28, or HAI titer >=10 (1/dilution) at Day 0 and a >=4-fold increase in HAI titer (1/dilution) at Day 28. For each A strain, the comparison was made with the pooled TIV-HD groups. For each B strain, the comparison was made with the TIV-HD group containing the corresponding B strain. TIV-HD 1 did not contain B2 strain; TIV-HD2 did not contain B1 strain.	Day 28 post-vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMTs of B Strains Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine	Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). For each B strain, the immunogenicity of QIV-HD was compared to that of TIV-HD group which contains the corresponding B strain. TIV-HD1 did not contain B2 strain; TIV-HD2 did not contain B1 strain.	Day 28 post-vaccination
GMT Ratios of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine	GMTs of anti-influenza antibodies using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Geometric Mean Titers Ratios (GMTRs) were calculated as the ratio of GMTs post vaccination and pre-vaccination.	Day 0 (pre-vaccination) and Day 28 post-vaccination
Percentage of Participants Achieving Seroconversion Against Antigens of B Strains After Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine	Seroconversion was defined as either a HAI titer <10 (1/dilution) at Day 0 and post-injection titer >=40 (1/dilution) at Day 28, or HAI titer >=10 (1/dilution) at Day 0 and a >=4-fold increase in HAI titer (1/dilution) at Day 28.	Day 28 post-vaccination
Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine	Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). Seroprotection was defined as a HAI titer >=40 (1/dilution) at Day 0 and Day 28.	Day 0 (pre-vaccination) and Day 28 post-vaccination
Geometric Mean Titers of Influenza Antibodies (Seroneutralization [SN] Assay) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine	GMTs of anti-influenza antibodies were measured using SN assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2).	Day 0 (pre-vaccination) and Day 28 post-vaccination
GMTRs of Influenza Antibodies (SN Assay) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine	GMTRs of anti-influenza antibodies were measured using SN assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). GMTRs were calculated as the ratio of GMTs post vaccination and pre-vaccination.	Day 0 (pre-vaccination) and Day 28 post-vaccination
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28	Neutralizing Antibody titer was measured for each influenza strain with the SN method for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Neutralizing antibody was defined as titers >=20 (1/dilution), >=40 (1/dilution), >=80 (1/dilution) at Day 0 and Day 28.	Day 0, Day 28
Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer at Day 28	Neutralizing Antibody titer was measured for each influenza strain with the SN method for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). 2-fold and 4-fold rise was defined as the computed value = post-vaccination computed value / baseline computed value.	Day 28
Number of Participants With Detectable Neutralization Antibody Titers at Day 0 and Day 28	Neutralizing Antibody titer was measured for each influenza strain with the SN method for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Detectable neutralization antibody titer >= 1:10 (1/dilution) at Day 0 and Day 28.	Day 0, Day 28
Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine	Solicited injection site: Pain, Erythema, Swelling, Induration, and Bruising. Grade 3 reactions: Pain - interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention; Erythema, Swelling, Induration, and Bruising: >100 millimeters (mm). Systemic reactions: Fever, Headache, Malaise, Myalgia, and Shivering. Grade 3 reactions: Fever: >=39°C; Headache, Malaise, Myalgia, and Shivering: interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.	Within 7 days after vaccination
Number of Participants With Immediate Adverse Event (AEs)	Participants were observed for 30 minutes after vaccination, and any unsolicited systemic AEs occurring during that time was recorded as immediate unsolicited systemic AEs (AEs that were related to the investigational product) in the case report book (CRB). Unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRB in terms of symptom and/ or onset post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. A serious adverse event was any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event.	Within 30 minutes after vaccination
Number of Participant With Unsolicited Adverse Event (AE)	An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRB in terms of symptom and/or onset post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. A serious adverse event was any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event.	Within 28 days after vaccination
Number of Participant With Serious Adverse Event	An serious adverse event was any untoward medical occurrence that at any dose results in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity,is a congenital anomaly/birth defect, or was an important medical event.	Up to 6 months after vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Chang LJ, Meng Y, Janosczyk H, Landolfi V, Talbot HK; QHD00013 Study Group. Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults >/=65 years of age: A phase 3 randomized clinical trial. Vaccine. 2019 Sep 16;37(39):5825-5834. doi: 10.1016/j.vaccine.2019.08.016. Epub 2019 Aug 17.

Helpful Links

• Related Info
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Study record dates

Study Major Dates

• Study Start (ACTUAL): September 8, 2017
• Primary Completion (ACTUAL): November 2, 2017
• Study Completion (ACTUAL): April 19, 2018

Study Registration Dates

• First Submitted: September 12, 2017
• First Submitted That Met QC Criteria: September 12, 2017
• First Posted (ACTUAL): September 13, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 7, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Influenza
• 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: QHD00013; U1111-1183-5556 (OTHER: World Health Organization Universal Trial 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