Phase 3 Safety and Immunogenicity Study of aQIV in Elderly Adults

Seqirus1,778 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

1,778

Conditions

Influenza, Human

Interventions

MF59-adjuvanted Quadrivalent Subunit Inactivated Egg-derived Influenza Vaccine (aQIV)BIOLOGICAL

The strain composition is that recommended by the World Health Organization for the 2017-2018 Northern Hemisphere influenza season (WHO, 2017) for quadrivalent vaccines.

Licensed MF59-adjuvanted Trivalent Subunit Inactivated Egg-derived Influenza Vaccine (aTIV-1)BIOLOGICAL

The strain composition is that recommended by the World Health Organization for the 2017-2018 Northern Hemisphere influenza season (WHO, 2017) for trivalent vaccines.

MF59-adjuvanted Trivalent Subunit Inactivated Egg-derived Influenza Vaccine Containing the Alternate B Strain (aTIV-2)

Eligibility

Sex: ALLMin age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (20)

Coastal Clinical Research, Inc.

Mobile, Alabama, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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%.

Time frame: 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%.

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Day 1 through Day 181