Phase 3 Safety and Immunogenicity Study of aQIV in Elderly Adults

Influenza, Human Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03314662
• Other study ID #: V118_20
• Status: Completed
• Phase: Phase 3
• Start date: October 17, 2017
• Est. completion date: May 17, 2018

Study information

• Verified date: July 2020
• Source: Seqirus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1778
• Est. completion date: May 17, 2018
• Est. primary completion date: December 11, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Influenza, Human

Intervention

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.
• 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.
• 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).

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Seqirus

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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