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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

Phase 3
Completed
Conditions
Influenza
Interventions
Biological: Non-Influenza Comparator (Boostrix)
Biological: MF59-adjuvanted Quadrivalent Subunit Inactivated Egg-derived Influenza Vaccine (aQIV)
Registration Number
NCT02587221
Lead Sponsor
Seqirus
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
6790
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Non-influenza Comparator VaccineNon-Influenza Comparator (Boostrix)Non-influenza comparator vaccine
aQIVMF59-adjuvanted Quadrivalent Subunit Inactivated Egg-derived Influenza Vaccine (aQIV)MF59-adjuvanted Quadrivalent Influenza Vaccine (aQIV)
Primary Outcome Measures
NameTimeMethod
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.Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

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.

Safety Endpoint: The Percentage of Subjects in the Solicited Safety Subset With Solicited Local and Systemic Adverse Events (AE)Day 1 through Day 7

Safety of vaccination was assessed in terms of percentage of subjects reporting solicited local and systemic AEs up to 7 days after vaccination.

Safety Endpoint: Percentage of Subjects With Medically-attended Adverse Events (MAAEs)Within 30 days after of first occurrence RT-PCR confirmed Influenza

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.

Safety Endpoint: Percentages of Subjects With Any Unsolicited AEDay 1 through Day 366

Safety of vaccination was assessed in terms of percentage of subjects reporting unsolicited AEs up to 21 days after vaccination.

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)Day 1 to Day 366

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.

Secondary Outcome Measures
NameTimeMethod
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.Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

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.

Immunogenicity Endpoint: Geometric Mean Hemagglutination Inhibition (HI) Titers (GMT)Days 1 and 22

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.

Immunogenicity Endpoint: Percentages of Subjects With an HI Titer ≥1:40Day 22

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.

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.Day 7 to Day 180 after vaccination or end of influenza season, whichever is longer

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.

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.Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

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.

Immunogenicity Endpoint: Percentages of Subjects Who Achieved Seroconversion (SCR)Day 22

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.

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.Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

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.

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.Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

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.

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.Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

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.

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.Day 21 to Day 180 after vaccination or end of influenza season, whichever is longer

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.

Immunogenicity Endpoint: Geometric Mean Ratio (GMR) of Post-vaccination HI Titer Over the Pre-vaccination HI TiterDay 22/Day 1

The GMR was assessed as the postvaccination HI titer divided by the prevaccination HI titer (Day 22/Day 1).

Trial Locations

Locations (88)

Mhat Silistra

🇧🇬

Silistra, Bulgaria

Mc Avicena Sofia

🇧🇬

Sofia, Bulgaria

Medical center Synexus Sofia EOOD

🇧🇬

Sofia, Bulgaria

Medical Centre Orpheus OOD (Synexus)

🇧🇬

Stara Zagora, Bulgaria

Hospital General de Medellín-Luz Castro de Gutiérrez - E.S.E

🇨🇴

Medellín, Antioquia, Colombia

Fundacion Cardiomet CEQUIN - Internal Medicine

🇨🇴

Armenia, Colombia

Clinica de la Costa

🇨🇴

Barranquilla, Colombia

Centro de Atención e Investigación Médica S.A.S. - CAIMED S.A.S.

🇨🇴

Bogotá, Colombia

Asociacion IPS Medicos Internistas de Caldas

🇨🇴

Manizales, Colombia

CCBR Czech Brno, s.r.o.

🇨🇿

Brno, Czechia

FN Hradec Kralove

🇨🇿

Hradec Kralove, Czechia

Centrum ockovani a cestovni mediciny

🇨🇿

Hradec Králové, Czechia

CCBR Ostrava, s.r.o.

🇨🇿

Ostrava, Czechia

Center for Clinical and Basic Research

🇪🇪

Tallinn, Harjumaa, Estonia

CCBR Czech, a.s.

🇨🇿

Pardubice, Czechia

Clinical Research Center

🇪🇪

Tartu, Tartumaa, Estonia

Merelahe Family Doctors Centre

🇪🇪

Tallinn, Harjumaa, Estonia

Practice Dr Liga Kozlovska

🇱🇻

Balvi, Latvia

Family Doctors Pullerits & Gavronski

🇪🇪

Tartu, Tartumaa, Estonia

Practice Dr Ruta Eglite

🇱🇻

Kuldiga, Latvia

Family Doctor Andra Lasmane clinic "ALMA"

🇱🇻

Riga, Latvia

Practice Dr Inese Petrova

🇱🇻

Tukums, Latvia

Klaipeda University Hospital

🇱🇹

Klaipeda, Lithuania

JSC Saules seimos medicinos centras

🇱🇹

Kaunas, Lithuania

Lietuvos Sveikatos Mokslų Universitetas

🇱🇹

Kaunas, Lithuania

UAB InMedica

🇱🇹

Kaunas, Lithuania

CCBR

🇱🇹

Vilnius, Lithuania

Hospital Sultanah Bahiyah

🇲🇾

Alor Setar, Malaysia

Hospital Selayang

🇲🇾

Batu Caves, Malaysia

Klinik Kesihatan Greentown

🇲🇾

Ipoh, Malaysia

University Malaya Medical Centre (UMMC)

🇲🇾

Kuala Lumpur, Malaysia

Hospital Raja Perempuan Zainab II

🇲🇾

Kota Bharu, Malaysia

Hospital Seri Manjung

🇲🇾

Seri Manjung, Malaysia

Hospital Sibu

🇲🇾

Sibu, Malaysia

Klinik Kesihatan Seremban 2

🇲🇾

Seremban, Malaysia

De La Salle Health Sciences Institute

🇵🇭

Dasmariñas, Cavite, Philippines

West Visayas State University - Medical Center

🇵🇭

Jaro, Iloilo, Philippines

Quirino Memorial Medical Center

🇵🇭

Quezon, National Capital Region, Philippines

Marilao St. Michael Family Hospital

🇵🇭

Bulacan, Philippines

San Juan De Dios Hospital

🇵🇭

Pasay, Philippines

Philippine General Hospital

🇵🇭

Manila, Philippines

Niepubliczny Zaklad Opieki Zdrowotnej VITAMED

🇵🇱

Bydgoszcz, Kujawsko-pomorskie, Poland

Synexus Polska Sp. z o.o.

🇵🇱

Gdansk, Pomorskie, Poland

Centrum Medyczne Pratia Warszawa

🇵🇱

Warszawa, Mazowieckie, Poland

NZOZ Centrum Medyczne "OMEGA" sp. z o.o.

🇵🇱

Plock, Mazowieckie, Poland

Specjalistyczny Osrodek Medycyny Wieku Dojrzalego

🇵🇱

Warszawa, Mazowieckie, Poland

Centrum Medyczne Pratia Gdynia

🇵🇱

Gdynia, Pomorskie, Poland

Centrum Medyczne Pratia Katowice

🇵🇱

Katowice, Slaskie, Poland

Praktyka Lekarzy Rodzinnych SALUS

🇵🇱

Katowice, Slaskie, Poland

Synexus Polska Sp. z o.o

🇵🇱

Poznan, Wielkopolskie, Poland

Centrum Medyczne PRATIA Bydgoszcz

🇵🇱

Bydgoszcz, Poland

Specjalistyczny Osrodek Medycyny Wieku Dojrzalego sp. z o.o.

🇵🇱

Lodz, Poland

RCMed Oddzial Sochaczew

🇵🇱

Sochaczew, Poland

Cabinet Medical Individual Craciun-Nicodin Maria Marcela

🇷🇴

Bucuresti, Romania

Centrul Medical Sana

🇷🇴

Bucuresti, Romania

Spitalul Clinic C.F. Cluj-Napoca

🇷🇴

Cluj, Romania

Clintrial Medical Center

🇷🇴

Resca, Romania

Mahidol University (MU) - Faculty of Tropical Medicine

🇹🇭

Bangkok, Thailand

Khon Kaen University - Srinagarind Hospital - Medicine

🇹🇭

Khon Kaen, Thailand

Ramathibodi Hospital

🇹🇭

Bangkok, Thailand

Istanbul University Cerrahpasa Medical Faculty

🇹🇷

Cerrahpaşa, Turkey

Ankara Training and Research Hospital

🇹🇷

Ankara, Turkey

Bamrasnaradura Infectious Diseases Institute (BIDI)

🇹🇭

Mueang Nonthaburi, Thailand

Hacettepe University Medical Faculty

🇹🇷

Ankara, Turkey

Ege University Medical Faculty

🇹🇷

Izmir, Turkey

Kocaeli University Research and Application Hospital

🇹🇷

Kocaeli, Turkey

Ataturk University Medical Faculty

🇹🇷

Erzurum, Turkey

Sakarya Training and Research Hospital

🇹🇷

Sakarya, Turkey

Medical Trials Institute

🇵🇱

Torun, Poland

Cabinet dr. Dana OLAR

🇷🇴

Arad, Romania

Mc Smolyan

🇧🇬

Smolyan, Bulgaria

Akdeniz University Medical Faculty

🇹🇷

Antalya, Turkey

Fundatia Cardioprevent

🇷🇴

Timisoara, Romania

Clinica Medicala Synexus

🇷🇴

Bucuresti, Romania

Medical Center Excelsior

🇧🇬

Sofia, Bulgaria

Medplus Medicina Prepagada

🇨🇴

Bogotá, Colombia

MHAT Sv Nikolay Chudotvoretz Lom

🇧🇬

Lom, Bulgaria

MBAL TRIMONCIUM (Synexus)

🇧🇬

Plovdiv, Bulgaria

Caja de Compesanción Familiar CAFAM

🇨🇴

Bogotá, Cundinamarca, Colombia

Kauno klinikine ligonine

🇱🇹

Kaunas, Lithuania

RCMed Oddział Nowy Duninow

🇵🇱

Nowy Duninow, Poland

MHAT St. Ekaterina

🇧🇬

Dimitrovgrad, Bulgaria

SHATPPD-Ruse

🇧🇬

Ruse, Bulgaria

SHATPPD-Sofia, City

🇧🇬

Sofia, Bulgaria

Medicum AS

🇪🇪

Tallinn, Harjumaa, Estonia

Vee Family Doctors Centre

🇪🇪

Paide, Järvamaa, Estonia

Republican Siauliai Hospital

🇱🇹

Siauliai, Lithuania

Centrul Medical de Diagnostic si Tratament Ambulator NEOMED

🇷🇴

Brasov, Romania

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