Phase 3 Safety and Immunogenicity Study of aQIV in Elderly Adults

A Phase 3, Randomized, Double-Blind, Controlled, Multicenter, Clinical Study to Evaluate Safety and Immunogenicity of an MF59-Adjuvanted Quadrivalent Subunit Influenza Vaccine in Comparison With an MF59-Adjuvanted Trivalent Subunit Influenza Vaccine and an MF59-Adjuvanted Trivalent Subunit Influenza Vaccine Containing the Alternate B Strain, in Adults Aged 65 Years and Above

This phase 3 study is a randomized, double-blinded, comparator controlled, parallel-group, multicenter study of aQIV versus the US-licensed 2017-2018 adjuvanted trivalent influenza vaccine (aTIV-1, Fluad), and versus an adjuvanted trivalent influenza vaccine (aTIV-2), containing the alternate B strain.

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Biological: MF59-adjuvanted Quadrivalent Subunit Inactivated Egg-derived Influenza Vaccine (aQIV); Biological: Licensed MF59-adjuvanted Trivalent Subunit Inactivated Egg-derived Influenza Vaccine (aTIV-1); Biological: MF59-adjuvanted Trivalent Subunit Inactivated Egg-derived Influenza Vaccine Containing the Alternate B Strain (aTIV-2)

• Study Type: Interventional
• Enrollment (Actual): 1778
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research, Inc.
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials
    • Redding, California, United States, 96001
      • Paradigm Clinical Research Centers, Inc
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida, an AMR Company
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Meridan Clinical Research, LLC
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Advanced Clinical Research
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County Clin-Trials
    • Newton, Kansas, United States, 67114
      • Heartland Research Associates, LLC - An AMR Company
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC - An AMR Company
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Center for Pharmaceutical Research, LLC
    • Saint Louis, Missouri, United States, 63141
      • Sundance Clinical Research, LLC
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research, LLC
  • New York
    • Binghamton, New York, United States, 13901
      • United Medical Associates
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research, Inc.
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Medical Research South
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Center for Clinical Research
  • Texas
    • Fort Worth, Texas, United States, 76135
      • Benchmark Research
    • San Angelo, Texas, United States, 76904
      • Benchmark Research
    • Tomball, Texas, United States, 77375
      • Martin Diagnostic Clinic
  • Utah
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research

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:

• Males and females ≥ 65 years old who are healthy or have co-morbidities
• Individuals who or whose legal representative(s) have voluntarily given written consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry
• Ability to attend all scheduled visits and to comply with study procedures including diary card completion and follow-up

Exclusion Criteria:

• History of behavioral or cognitive impairment or psychiatric condition
• Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study
• Abnormal function of the immune system
• Receipt of any influenza vaccine within 6 months prior to enrollment in this study, or plan to receive influenza vaccine prior to the Day 22 blood collection
• Any other clinical condition that, in the opinion of the Investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study

Additional eligibility criteria may be discussed by contacting the site.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: aQIV; MF59-adjuvanted Quadrivalent Subunit Inactivated Egg-derived Influenza Vaccine (aQIV) contains each of the 2 influenza type A strains and each of the two influenza type B strains in the vaccine.	Biological: MF59-adjuvanted Quadrivalent Subunit Inactivated Egg-derived Influenza Vaccine (aQIV); The strain composition is that recommended by the World Health Organization for the 2017-2018 Northern Hemisphere influenza season (WHO, 2017) for quadrivalent vaccines.
Experimental: aTIV-1; Licensed MF59-adjuvanted Trivalent Subunit Inactivated Egg-derived Influenza Vaccine (aTIV-1) contains each of the 2 influenza type A strains and one influenza type B strain in the vaccine.	Biological: Licensed MF59-adjuvanted Trivalent Subunit Inactivated Egg-derived Influenza Vaccine (aTIV-1); The strain composition is that recommended by the World Health Organization for the 2017-2018 Northern Hemisphere influenza season (WHO, 2017) for trivalent vaccines.
Experimental: aTIV-2; MF59-adjuvanted Trivalent Subunit Inactivated Egg-derived Influenza Vaccine contains each of the 2 influenza type A strains and alternate influenza type B strain in the vaccine.	Biological: MF59-adjuvanted Trivalent Subunit Inactivated Egg-derived Influenza Vaccine Containing the Alternate B Strain (aTIV-2); The strain composition is that recommended by the World Health Organization for the 2017-2018 Northern Hemisphere influenza season (WHO, 2017) for trivalent vaccines except the B strain present in this vaccine is the second/alternate B strain recommended for inclusion in quadrivalent vaccines (ie, Alternate B strain).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity Endpoint: The Geometric Mean Titer (GMT) and GMT Ratio for the Four Strains Included in the Vaccine, Non-inferiority Analysis.	The GMT of the post-vaccination (Day 22) hemagglutination inhibition (HI) titer. The GMT ratio was defined as the GMT for aTIV-1 (or aTIV-2) over the GMT for aQIV for all of the four strains.	Day 22
Immunogenicity Endpoint: The Difference Between the Seroconversion Rate (SCR) for the Four Strains Included in the Vaccine, Non-inferiority Analysis	The SCR is defined as the percentage of subjects with either a pre-vaccination HI titer < 1:10 and a post-vaccination HI titer >= 1:40 or a pre-vaccination HI titer >= 1:10 and a >= 4-fold increase in post-vaccination HI titer. The SCR Difference is defined as the difference between the SCR of post- vaccination (Day 22) HI titer for aTIV-1 (or aTIV-2) and the SCR of post-vaccination (Day 22) HI titer for aQIV. aTIV-1 and aTIV-2 vaccine groups are pooled for the analysis of A-H1N1 and A-H3N2 strains. For B/Victoria TIV=TIV-1. For B/Yamagata TIV=TIV-2.	Day 22
Immunogenicity Endpoint: The Percentage of Subjects Achieving SCR for Hemagglutination Inhibition (HI) Antibody for the Four Strains Included in the Vaccine.	The percentage of subjects vaccinated with aQIV achieving SCR at Day 22 was assessed for each of the 4 strains. SCR was defined as the percentage of subjects with either a pre-vaccination HI titer <1:10 and a post-vaccination HI titer ≥1:40 or a pre-vaccination HI titer ≥1:10 and a ≥4-fold increase in post-vaccination HI titer. Assessment criteria was considered fulfilled if the lower bound of the two-sided 95% confidence interval for the percentage of subjects achieving SCR for HI antibody should meet or exceed 30%.	Day 22
Immunogenicity Endpoint: The Percent of Subjects Achieving an HI Antibody Titer ≥ 1:40 for the Four Strains Included in the Vaccines.	The percentage of subjects vaccinated with aQIV achieving HI antibody titers ≥ 1:40 at Day 22 was assessed for each of the 4 strains. Assessment criteria was considered fulfilled if the lower bound of the two-sided 95% confidence interval for the percentage of subjects achieving a post-vaccination HI antibody titer ≥ 1:40 should meet or exceed 60%.	Day 22

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity Endpoint: Geometric Mean Titers (GMT) Against Homologous Strains	For the assessment of GMTs using HI assay, aTIV-1 and aTIV-2 vaccine groups were pooled for the analysis of A-H1N1 and A-H3N2 strains. aTIV-1 and aTIV-2 vaccine groups are pooled for the analysis of A-H1N1 and A-H3N2 strains. For B-Victoria TIV=aTIV-1. For B-Yamagata TIV=aTIV-2. The immunologic superiority in HI antibody responses for the alternate B strain (eg, the influenza B strain included in the aQIV but not in the aTIV formulation) were assessed for each aTIV separately, using the GMT ratio (aTIV/aQIV) at Day 22.	Day 1 and Day 22
Immunogenicity Endpoint: Geometric Mean Ratio (GMR) of Post Vaccination HI Titer Over the Pre-vaccination HI Titer Against Homologous Strains	The GMR was assessed as the postvaccination HI titer divided by the prevaccination HI titer (Day 22/Day 1). aTIV-1 and aTIV-2 vaccine groups were pooled for the analysis of A-H1N1 and A-H3N2 strains. For B-Victoria TIV=aTIV-1. For B-Yamagata TIV=aTIV-2.	Day 22/Day 1
Immunogenicity Endpoint: The Percentage of Subjects With a Titer ≥1:40 Against Homologous Strains	The percentage of subjects with HI titer of ≥1:40 at Day 1 (prevaccination) and Day 22 (postvaccination) was assessed for homologous strains. aTIV-1 and aTIV-2 vaccine groups are pooled for the analysis of A-H1N1 and A-H3N2 strains. For B/Victoria TIV=TIV-1. For B/Yamagata TIV=TIV-2.	Day 1 and Day 22
Immunogenicity Endpoint: The Percentage of Subjects With SCR Against Homologous Strains	The SCR was defined as the percentage of subjects with either a prevaccination HI titer <1:10 and a postvaccination HI titer ≥1:40 or a prevaccination HI titer ≥1:10 and a ≥4-fold increase in postvaccination HI titer. For assessment if SCR using HI assay, aTIV-1 and aTIV-2 vaccine groups were pooled for the analysis of A-H1N1 and A-H3N2 strains. For B-Victoria TIV=aTIV-1. For B-Yamagata TIV=aTIV-2. The immunologic superiority in HI antibody responses for the alternate B strain (eg, the influenza B strain included in the aQIV but not in the aTIV formulation) were assessed for each aTIV separately, using the difference in SCR (aTIV-aQIV) at Day 22.	Day 22
Safety Endpoint: Number of Subjects With Solicited Local and Systemic Adverse Events (AEs) Following Vaccination	Safety of vaccination was assessed in terms of percentage of subjects reporting solicited AEs up to 7 days after vaccination.	Day 1 through Day 7
Safety Endpoint: Number of Subjects With Unsolicited AEs	Safety of vaccination was assessed in terms of percentage of subjects reporting unsolicited AEs up to 21 days after vaccination.	Day 1 through Day 22
Safety Endpoint: Number of Subjects With Serious AEs (SAEs), AEs Leading to Withdrawal From the Study, New Onset of Chronic Diseases (NOCDs) and AEs of Special Interest (AESIs)	Safety of vaccination was assessed in terms of percentage of subjects reporting SAEs, AEs leading to withdrawal, NOCDs, and AESIs and medically attended AE up to 180 days after vaccination.	Day 1 through Day 181

Collaborators and Investigators

• Sponsor: Seqirus

Publications and helpful links

General Publications

• Essink B, Fierro C, Rosen J, Figueroa AL, Zhang B, Verhoeven C, Edelman J, Smolenov I. Immunogenicity and safety of MF59-adjuvanted quadrivalent influenza vaccine versus standard and alternate B strain MF59-adjuvanted trivalent influenza vaccines in older adults. Vaccine. 2020 Jan 10;38(2):242-250. doi: 10.1016/j.vaccine.2019.10.021. Epub 2019 Oct 18.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2017
• Primary Completion (Actual): December 11, 2017
• Study Completion (Actual): May 17, 2018

Study Registration Dates

• First Submitted: October 16, 2017
• First Submitted That Met QC Criteria: October 16, 2017
• First Posted (Actual): October 19, 2017

Study Record Updates

• Last Update Posted (Actual): July 22, 2020
• Last Update Submitted That Met QC Criteria: July 20, 2020
• Last Verified: July 1, 2020

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; Adjuvants, Immunologic; Vaccines; MF59 oil emulsion
• Other Study ID Numbers: V118_20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No