Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of an MF59-Adjuvanted Quadrivalent Influenza Vaccine Compared to Non-influenza Vaccine Comparator in Adults ≥ 65 Years of Age

A Phase III, Randomized, Observer-Blind, Controlled, Multicenter Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of an MF59-Adjuvanted Quadrivalent Influenza Vaccine Compared to Non-influenza Vaccine Comparator in Adults ≥ 65 Years of Age

A Phase III, Randomized, Observer-Blind, Controlled, Multicenter Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of an MF59-Adjuvanted Quadrivalent Influenza Vaccine Compared to Non-influenza Vaccine Comparator in Adults ≥ 65 Years of Age.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: MF59-adjuvanted Quadrivalent Subunit Inactivated Egg-derived Influenza Vaccine (aQIV); Biological: Non-Influenza Comparator (Boostrix)

• Study Type: Interventional
• Enrollment (Actual): 6790
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Dimitrovgrad, Bulgaria
    • MHAT St. Ekaterina
  • Lom, Bulgaria
    • MHAT Sv Nikolay Chudotvoretz Lom
  • Plovdiv, Bulgaria
    • MBAL TRIMONCIUM (Synexus)
  • Ruse, Bulgaria, 7000
    • SHATPPD-Ruse
  • Silistra, Bulgaria
    • Mhat Silistra
  • Smolyan, Bulgaria
    • Mc Smolyan
  • Sofia, Bulgaria
    • Mc Avicena Sofia
  • Sofia, Bulgaria
    • Medical Center Excelsior
  • Sofia, Bulgaria
    • Medical Center Synexus Sofia EOOD
  • Sofia, Bulgaria
    • SHATPPD-Sofia, City
  • Stara Zagora, Bulgaria
    • Medical Centre Orpheus OOD (Synexus)
• Colombia
  • Armenia, Colombia, NAP
    • Fundacion Cardiomet CEQUIN - Internal Medicine
  • Barranquilla, Colombia, NAP
    • Clinica De La Costa
  • Bogotá, Colombia, NAP
    • Centro de Atención e Investigación Médica S.A.S. - CAIMED S.A.S.
  • Bogotá, Colombia, NAP
    • Medplus Medicina Prepagada
  • Manizales, Colombia, 170004
    • Asociacion IPS Medicos Internistas de Caldas
  • Antioquia
    • Medellín, Antioquia, Colombia, 0500515
      • Hospital General de Medellín-Luz Castro de Gutiérrez - E.S.E
  • Cundinamarca
    • Bogotá, Cundinamarca, Colombia, 74136-3367
      • Caja de Compesanción Familiar CAFAM
• Czechia
  • Brno, Czechia
    • CCBR Czech Brno, s.r.o.
  • Hradec Kralove, Czechia
    • FN Hradec Králové
  • Hradec Králové, Czechia
    • Centrum ockovani a cestovni mediciny
  • Ostrava, Czechia
    • CCBR Ostrava, s.r.o.
  • Pardubice, Czechia
    • CCBR Czech, a.s.
• Estonia
  • Harjumaa
    • Tallinn, Harjumaa, Estonia
      • Center for Clinical and Basic Research
    • Tallinn, Harjumaa, Estonia
      • Medicum AS
    • Tallinn, Harjumaa, Estonia
      • Merelahe Family Doctors Centre
  • Järvamaa
    • Paide, Järvamaa, Estonia
      • Vee Family Doctors Centre
  • Tartumaa
    • Tartu, Tartumaa, Estonia
      • Clinical Research Center
    • Tartu, Tartumaa, Estonia
      • Family Doctors Pullerits & Gavronski
• Latvia
  • Balvi, Latvia
    • Practice Dr Liga Kozlovska
  • Kuldiga, Latvia
    • Practice Dr Ruta Eglite
  • Riga, Latvia
    • Family Doctor Andra Lasmane clinic "ALMA"
  • Tukums, Latvia
    • Practice Dr Inese Petrova
• Lithuania
  • Kaunas, Lithuania
    • JSC Saules seimos medicinos centras
  • Kaunas, Lithuania
    • Kauno klinikine ligonine
  • Kaunas, Lithuania
    • Lietuvos sveikatos mokslų universitetas
  • Kaunas, Lithuania
    • UAB InMedica
  • Klaipeda, Lithuania
    • Klaipeda university hospital
  • Siauliai, Lithuania
    • Republican Siauliai Hospital
  • Vilnius, Lithuania
    • CCBR
• Malaysia
  • Alor Setar, Malaysia
    • Hospital Sultanah Bahiyah
  • Batu Caves, Malaysia
    • Hospital Selayang
  • Ipoh, Malaysia
    • Klinik Kesihatan Greentown
  • Kota Bharu, Malaysia
    • Hospital Raja Perempuan Zainab II
  • Kuala Lumpur, Malaysia
    • University Malaya Medical Centre (UMMC)
  • Seremban, Malaysia
    • Klinik Kesihatan Seremban 2
  • Seri Manjung, Malaysia
    • Hospital Seri Manjung
  • Sibu, Malaysia
    • Hospital Sibu
• Philippines
  • Bulacan, Philippines, 3019
    • Marilao St. Michael Family Hospital
  • Manila, Philippines, 1000
    • Philippine General Hospital
  • Pasay, Philippines, 1300
    • San Juan De Dios Hospital
  • Cavite
    • Dasmariñas, Cavite, Philippines, 4114
      • De La Salle Health Sciences Institute
  • Iloilo
    • Jaro, Iloilo, Philippines, 5000
      • West Visayas State University - Medical Center
  • National Capital Region
    • Quezon, National Capital Region, Philippines, 1109
      • Quirino Memorial Medical Center
• Poland
  • Bydgoszcz, Poland
    • Centrum medyczne Pratia Bydgoszcz
  • Lodz, Poland
    • Specjalistyczny Osrodek Medycyny Wieku Dojrzalego sp. z o.o.
  • Nowy Duninow, Poland
    • RCMed Oddział Nowy Duninow
  • Sochaczew, Poland
    • RCMed Oddzial Sochaczew
  • Torun, Poland
    • Medical Trials Institute
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland
      • Synexus Polska Sp. z o.o.
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland
      • Niepubliczny Zaklad Opieki Zdrowotnej VITAMED
  • Mazowieckie
    • Plock, Mazowieckie, Poland
      • NZOZ Centrum Medyczne "OMEGA" sp. z o.o.
    • Warszawa, Mazowieckie, Poland
      • Centrum Medyczne Pratia Warszawa
    • Warszawa, Mazowieckie, Poland
      • Specjalistyczny Osrodek Medycyny Wieku Dojrzalego
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-382
      • Synexus Polska Sp. z o.o.
    • Gdynia, Pomorskie, Poland
      • Centrum Medyczne Pratia Gdynia
  • Slaskie
    • Katowice, Slaskie, Poland
      • Centrum Medyczne Pratia Katowice
    • Katowice, Slaskie, Poland
      • Praktyka Lekarzy Rodzinnych SALUS
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland
      • Synexus Polska sp. z o.o
• Romania
  • Arad, Romania
    • Cabinet dr. Dana OLAR
  • Brasov, Romania
    • Centrul Medical de Diagnostic si Tratament Ambulator Neomed
  • Bucuresti, Romania
    • Cabinet Medical Individual Craciun-Nicodin Maria Marcela
  • Bucuresti, Romania
    • Centrul Medical Sana
  • Bucuresti, Romania
    • Clinica Medicala Synexus
  • Cluj, Romania
    • Spitalul Clinic C.F. Cluj-Napoca
  • Resca, Romania
    • Clintrial Medical Center
  • Timisoara, Romania
    • Fundatia Cardioprevent
• Thailand
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital
  • Bangkok, Thailand
    • Mahidol University (MU) - Faculty of Tropical Medicine
  • Khon Kaen, Thailand, 40002
    • Khon Kaen University - Srinagarind Hospital - Medicine
  • Mueang Nonthaburi, Thailand
    • Bamrasnaradura Infectious Diseases Institute (BIDI)
• Turkey
  • Ankara, Turkey
    • Hacettepe University Medical Faculty
  • Ankara, Turkey
    • Ankara Training and Research Hospital
  • Antalya, Turkey
    • Akdeniz University Medical Faculty
  • Cerrahpaşa, Turkey
    • Istanbul University Cerrahpasa Medical Faculty
  • Erzurum, Turkey
    • Ataturk University Medical Faculty
  • Izmir, Turkey
    • Ege University Medical Faculty
  • Kocaeli, Turkey
    • Kocaeli University Research and Application Hospital
  • Sakarya, Turkey
    • Sakarya Training and Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females ≥ 65 years old who are healthy or have co-morbidities
2. Individuals who or whose legal guardian have voluntarily given written consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry.
3. Ability to attend all scheduled visits and to comply with study procedures

Exclusion Criteria:

1. Hypersensitivity, including allergy to any component of vaccines foreseen in this study
2. Abnormal function of the immune system.
3. Receipt of any influenza vaccine within 6 months prior to enrolment in this study or who plan to receive influenza vaccine while participating in the study.
4. 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: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: aQIV; MF59-adjuvanted Quadrivalent Influenza Vaccine (aQIV)	Biological: MF59-adjuvanted Quadrivalent Subunit Inactivated Egg-derived Influenza Vaccine (aQIV); 1 dose approximately 0.5 mL of aQIV
Placebo Comparator: Non-influenza Comparator Vaccine; Non-influenza comparator vaccine	Biological: Non-Influenza Comparator (Boostrix); 1 dose approximately 0.5 mL dose of Non-influenza comparator vaccine (Boostrix)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on RT-PCR-confirmed Influenza Due to Any Strain Using Protocol Defined ILI Definition.	The primary efficacy endpoint was the time of first-occurrence of RT-PCR-confirmed influenza due to any strain of influenza regardless of antigenic match to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using protocol defined ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the primary endpoint.	Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer
Safety Endpoint: The Percentage of Subjects in the Solicited Safety Subset With Solicited Local and Systemic Adverse Events (AE)	Safety of vaccination was assessed in terms of percentage of subjects reporting solicited local and systemic AEs up to 7 days after vaccination.	Day 1 through Day 7
Safety Endpoint: Percentage of Subjects With Medically-attended Adverse Events (MAAEs)	Safety of vaccination was assessed in terms of percentage of subjects reporting medically attended AEs within 30 days after of first occurrence RT-PCR confirmed influenza.	Within 30 days after of first occurrence RT-PCR confirmed Influenza
Safety Endpoint: Percentages of Subjects With Any Unsolicited AE	Safety of vaccination was assessed in terms of percentage of subjects reporting unsolicited AEs up to 21 days after vaccination.	Day 1 through Day 366
Safety Endpoint: Percentages of Subjects With Serious Adverse Events (SAE), AEs Leading to Withdrawal, New Onset of Chronic Disease (NOCD), and Adverse Events of Special Interest (AESI)	Safety of vaccination was assessed in terms of percentage of subjects reporting SAEs, AEs leading to withdrawal, NOCDs, and AESIs up to 366 days after vaccination.	Day 1 to Day 366

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on RT-PCR-confirmed Influenza Due to Any Strain Using Modified CDC ILI Definition.	The secondary efficacy endpoint was the time of first-occurrence of RT-PCR-confirmed influenza due to any strain of influenza regardless of antigenic match to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using modified CDC ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary efficacy endpoint.	Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on Culture Confirmed Influenza Due to Any Strain of Influenza Antigenically Matched to the Strains Selected for the Seasonal Vaccine Using Protocol Defined ILI Definition.	The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza antigenically matched to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using protocol defined ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.	Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on Culture Confirmed Influenza Due to Any Strain of Influenza Antigenically Matched to the Strains Selected for the Seasonal Vaccine Using Modified CDC ILI Definition.	The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza antigenically matched to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using modified CDC ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.	Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on Culture Confirmed Influenza Due to Any Strain of Influenza Regardless of Antigenic Match Using Protocol Defined ILI Definition.	The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza regardless of antigenic match from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using protocol defined ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.	Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on Culture Confirmed Influenza Due to Any Strain of Influenza Regardless of Antigenic Match Using Modified CDC ILI Definition.	The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza regardless of antigenic match from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using modified CDC ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.	Day 7 to Day 180 after vaccination or end of influenza season, whichever is longer
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on Culture Confirmed Influenza Due to Any Strain of Influenza Antigenically Unmatched to the Strains Selected for the Seasonal Vaccine Using Protocol Defined ILI Definition.	The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza antigenically unmatched to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using protocol defined ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.	Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer
Absolute Vaccine Efficacy (VE) of aQIV Versus Non-influenza Comparator Based on Culture Confirmed Influenza Due to Any Strain of Influenza Antigenically Unmatched to the Strains Selected for the Seasonal Vaccine Using Modified CDC ILI Definition.	The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza antigenically unmatched to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using modified CDC ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.	Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer
Immunogenicity Endpoint: Geometric Mean Hemagglutination Inhibition (HI) Titers (GMT)	The log-transformed antibody titers (GMT) at Day 1 and Day 22 were evaluated using an analysis of covariance (ANCOVA) model including factors for site/country, pre-vaccination titer, age, and comorbidity.	Days 1 and 22
Immunogenicity Endpoint: Geometric Mean Ratio (GMR) of Post-vaccination HI Titer Over the Pre-vaccination HI Titer	The GMR was assessed as the postvaccination HI titer divided by the prevaccination HI titer (Day 22/Day 1).	Day 22/Day 1
Immunogenicity Endpoint: Percentages of Subjects With an HI Titer ≥1:40	The percentage of subjects vaccinated with aQIV with a HI antibody titers ≥1:40 was assessed for each of the 4 strains Assessment criteria was considered fulfilled if the lower bound of the two-sided 95% CI for percent of subjects with HI antibody titer ≥1:40 met or exceeded 60% at Day 22.	Day 22
Immunogenicity Endpoint: Percentages of Subjects Who Achieved Seroconversion (SCR)	The percentage of subjects achieving SCR at Day 22 was assessed for each of the 4 strains. SCR is defined as HI titer ≥1:40 for subjects seronegative at baseline (HI titer <1:10) or a minimum 4-fold increase in HI titer for subjects seropositive at baseline (HI titer ≥1:10) on Day 22. Assessment criteria was considered fulfilled if the lower bound of the two-sided 95% CI for the percentage of subjects achieving an HI antibody SCR met or exceeded 30% at Day 22.	Day 22

Collaborators and Investigators

• Sponsor: Seqirus
• Investigators: Study Director: Clinical Program Manager, Seqirus

Publications and helpful links

General Publications

• Beran J, Reynales H, Poder A, Yu CY, Pitisuttithum P, Yuan LL, Vermeulen W, Verhoeven C, Leav B, Zhang B, Sawlwin D, Hamers-Heijnen E, Edelman J, Smolenov I. Prevention of influenza during mismatched seasons in older adults with an MF59-adjuvanted quadrivalent influenza vaccine: a randomised, controlled, multicentre, phase 3 efficacy study. Lancet Infect Dis. 2021 Jul;21(7):1027-1037. doi: 10.1016/S1473-3099(20)30694-0. Epub 2021 Feb 9.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2016
• Primary Completion (Actual): July 23, 2018
• Study Completion (Actual): July 23, 2018

Study Registration Dates

• First Submitted: October 15, 2015
• First Submitted That Met QC Criteria: October 26, 2015
• First Posted (Estimate): October 27, 2015

Study Record Updates

• Last Update Posted (Actual): June 17, 2020
• Last Update Submitted That Met QC Criteria: June 8, 2020
• Last Verified: June 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
• Other Study ID Numbers: V118_18; 2015-000728-27 (EudraCT Number)