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

Influenza Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02587221
• Other study ID #: V118_18
• Secondary ID: 2015-000728-27
• Status: Completed
• Phase: Phase 3
• Start date: September 30, 2016
• Est. completion date: July 23, 2018

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6790
• Est. completion date: July 23, 2018
• Est. primary completion date: July 23, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• MF59-adjuvanted Quadrivalent Subunit Inactivated Egg-derived Influenza Vaccine (aQIV)
1 dose approximately 0.5 mL of aQIV
• Non-Influenza Comparator (Boostrix)
1 dose approximately 0.5 mL dose of Non-influenza comparator vaccine (Boostrix)

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Seqirus

Countries where clinical trial is conducted

Bulgaria,  Colombia,  Czechia,  Estonia,  Latvia,  Lithuania,  Malaysia,  Philippines,  Poland,  Romania,  Thailand,  Turkey, 

Outcome

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