Phase 3 Safety and Immunogenicity Study of aQIV in Elderly Adults

Phase 3

Completed

Conditions: Influenza, Human

Interventions: 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)

Registration Number: NCT03314662

Lead Sponsor: Seqirus

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1778

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
aQIV	MF59-adjuvanted Quadrivalent Subunit Inactivated Egg-derived Influenza Vaccine (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.
aTIV-1	Licensed MF59-adjuvanted Trivalent Subunit Inactivated Egg-derived Influenza Vaccine (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.
aTIV-2	MF59-adjuvanted Trivalent Subunit Inactivated Egg-derived Influenza Vaccine Containing the Alternate B Strain (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.

Primary Outcome Measures

Name	Time	Method
Immunogenicity Endpoint: The Geometric Mean Titer (GMT) and GMT Ratio for the Four Strains Included in the Vaccine, Non-inferiority Analysis.	Day 22	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.
Immunogenicity Endpoint: The Percentage of Subjects Achieving SCR for Hemagglutination Inhibition (HI) Antibody for the Four Strains Included in the Vaccine.	Day 22	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%.
Immunogenicity Endpoint: The Difference Between the Seroconversion Rate (SCR) for the Four Strains Included in the Vaccine, Non-inferiority Analysis	Day 22	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.
Immunogenicity Endpoint: The Percent of Subjects Achieving an HI Antibody Titer ≥ 1:40 for the Four Strains Included in the Vaccines.	Day 22	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%.

Secondary Outcome Measures

Name	Time	Method
Safety Endpoint: Number of Subjects With Solicited Local and Systemic Adverse Events (AEs) Following Vaccination	Day 1 through Day 7	Safety of vaccination was assessed in terms of percentage of subjects reporting solicited AEs up to 7 days after vaccination.
Immunogenicity Endpoint: Geometric Mean Titers (GMT) Against Homologous Strains	Day 1 and Day 22	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.
Immunogenicity Endpoint: Geometric Mean Ratio (GMR) of Post Vaccination HI Titer Over the Pre-vaccination HI Titer Against Homologous Strains	Day 22/Day 1	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.
Immunogenicity Endpoint: The Percentage of Subjects With a Titer ≥1:40 Against Homologous Strains	Day 1 and Day 22	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.
Safety Endpoint: Number of Subjects With Unsolicited AEs	Day 1 through Day 22	Safety of vaccination was assessed in terms of percentage of subjects reporting unsolicited AEs up to 21 days after vaccination.
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)	Day 1 through Day 181	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.
Immunogenicity Endpoint: The Percentage of Subjects With SCR Against Homologous Strains	Day 22	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.

Trial Locations

Locations (17): Advanced Clinical Research
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West Jordan, Utah, United States
Paradigm clinical Research Centers, Inc
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Redding, California, United States
Meridan Clinical Research, LLC
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Savannah, Georgia, United States
Coastal Clinical Research, Inc.
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Mobile, Alabama, United States
Anaheim Clinical Trials
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Anaheim, California, United States
New Orleans Center for Clinical Research
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Knoxville, Tennessee, United States
Benchmark Research
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San Angelo, Texas, United States
Clinical Research of South Florida, an AMR Company
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Coral Gables, Florida, United States
Martin Diagnostic Clinic
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Tomball, Texas, United States
Heartland Research Associates, LLC - An AMR Company
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Wichita, Kansas, United States
Johnson County Clin-Trials
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Lenexa, Kansas, United States
Sundance Clinical Research, LLC
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Saint Louis, Missouri, United States
United Medical Associates
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Binghamton, New York, United States
Rapid Medical Research, Inc.
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Cleveland, Ohio, United States
Center for Pharmaceutical Research, LLC
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Kansas City, Missouri, United States
Meridian Clinical Research, LLC
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Omaha, Nebraska, United States
Medical Research South
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Charleston, South Carolina, United States