Safety and Immunogenicity of MF59C.1 Adjuvanted Trivalent Subunit Influenza Vaccine in Elderly Subjects
- Conditions
- Influenza
- Interventions
- Biological: MF59 adjuvanted trivalent subunit influenza vaccine (aTIV)Biological: Non-adjuvanted trivalent subunit influenza vaccine (TIV)
- Registration Number
- NCT01162122
- Lead Sponsor
- Novartis Vaccines
- Brief Summary
The present phase III study aims to evaluate the safety and immunogenicity of MF59-adjuvanted subunit seasonal influenza vaccine and to evaluate the consistency in the manufacturing process of three consecutive lots of MF59-adjuvanted subunit seasonal influenza vaccine with respect to immunogenicity in subjects aged 65 years and older. The active comparator non-adjuvanted seasonal influenza vaccine is approved for use in this age group in the United States and will be used to provide a comparative assessment for immunogenicity and safety.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 7109
Males and females subjects aged ≥65 years at day of vaccination who are willing and able to comply to study procedures.
- Individuals with behavioral or cognitive impairment or a psychiatric condition or with a history of any illness that,in the opinion of the investigator, would have interfered with the subject's ability to participate in the study.
- Individuals who were not able to comprehend and/or follow all required study procedures for the whole period of the study.
- Known or suspected impairment/alteration of immune function.
- Individuals with a known bleeding diathesis.
- History of Guillain-Barré syndrome.
- Individuals with history of allergy to vaccine components and/or a history of any anaphylaxis, serious vaccine reactions or hypersensitivity to influenza viral proteins, egg proteins (including ovalbumin), polymyxin, neomycin, betapropiolactone, thimerosal/ sodium ethylmercurothiosalicylate/ mercury and nonylphenolethoxylate/ nonoxynol-9 (spermicide).
- Receipt of another investigational agent within 30 days prior to enrollment in the study or before completion of the safety follow-up period in another study.
- Individuals who had received any other vaccines within 2 weeks for inactivated vaccines or 4 weeks for live vaccines prior to enrollment in this study or who had planned to receive any vaccine within 3 weeks from the study vaccine.
- Individuals who had received vaccination against seasonal influenza in the previous 6 months.
- Individuals with oral temperature ≥38.0°C (≥100.4°F) on day of study vaccination.
- Individuals with history of substance or alcohol abuse within the past 2 years.
- Individuals providing consent who did not consent to the retention of their serum samples after study completion.
- Elective surgery or hospitalization planned to occur during the treatment phase or during the follow-up phase that, according to the opinion of the investigator, might have poses additional risk to the subject.
- Subjects from whom blood could not be drawn at visit 1.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description aTIV MF59 adjuvanted trivalent subunit influenza vaccine (aTIV) Subjects received one dose of MF59-adjuvanted trivalent subunit influenza vaccine (aTIV) from one of three consecutive lots (Lot 1, Lot 2 or Lot 3). Licensed TIV Non-adjuvanted trivalent subunit influenza vaccine (TIV) Subjects received one dose of non-adjuvanted trivalent subunit influenza vaccine (TIV).
- Primary Outcome Measures
Name Time Method Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV Day 22 post vaccination Immunologic equivalence of 3 consecutive production lots of aTIV (Lot 1, Lot 2 and Lot 3), was assessed in terms of Hemagglutination Inhibition (HI) Geometric Mean Titers (GMTs) in subjects, at three weeks after vaccination, against each vaccine strain.
Comparison of aTIV Versus TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains - PPS Day 22 post vaccination The non-inferiority of HI antibody responses of aTIV compared to TIV assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains.
Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS Day 22 post vaccination The non-inferiority of HI antibody responses of aTIV compared to TIV assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the three homologous vaccine strains.
Seroconversion defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.Comparison of aTIV Versus TIV in Terms of GMTs Against Homologous Strains-Full Analysis Set (FAS) Day 22 post vaccination The superiority of HI antibody responses of aTIV compared to TIV assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains.
Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS Day 22 post vaccination The superiority of HI antibody responses of aTIV compared to TIV assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the three homologous vaccine strains.
Seroconversion defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.Percentage of Subjects With HI Titers ≥40 Against Homologous Strains Day 22 post vaccination The percentage of subjects demonstrating HI titers ≥40, in overall group and in subjects with pre-defined co-morbidities (high risk group), against homologous strains, three weeks after vaccination with aTIV or TIV.
Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains Day 22 post vaccination The percentage of subjects achieving seroconversion in HI titers from baseline, in overall group and in subjects with pre-defined co-morbidities (high risk group), against homologous strains, three weeks after vaccination with aTIV or TIV.
Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains Day 22 post vaccination The GMR of post-vaccination versus pre-vaccination HI titers (day 22/day 1) in overall group and in subjects with pre-defined co-morbidities (high risk group), against homologous strains, three weeks after vaccination with aTIV or TIV.
Percentage of Subjects With HI Titers ≥40 Against Heterologous Strains Day 22 post vaccination The percentage of subjects demonstrating HI titers ≥40, in overall group and in subjects with pre-defined co-morbidities (high risk group), against heterologous strains, three weeks after vaccination with aTIV or TIV.
Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains Day 22 post vaccination The GMR of post-vaccination versus pre-vaccination HI titers (day 22/day 1) in overall group and in subjects with pre-defined co-morbidities (high risk group), against heterologous strains, three weeks after vaccination with aTIV or TIV.
Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains Day 22 post vaccination The percentage of subjects achieving seroconversion in HI titers from baseline, in overall group and in subjects with pre-defined co-morbidities (high risk group), against heterologous strains, three weeks after vaccination with aTIV or TIV.
Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.
- Secondary Outcome Measures
Name Time Method Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-PPS Day 22 post vaccination The non-inferiority of HI antibody responses of ATIV compared to TIV, in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains.
Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS Day 22 post vaccination The non-inferiority of HI antibody responses of ATIV compared to TIV, in subjects with pre-defined co-morbidities (high risk group), assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the homologous vaccine strains.
Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-FAS Day 22 post vaccination The superiority of HI antibody responses of aTIV compared to TIV, in subjects with predefined co-morbidities (high risk group) assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains.
Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS Day 22 postvaccination The superiority of HI antibody responses of aTIV compared to TIV, in subjects with pre-defined co-morbidities (high risk group), assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the homologous vaccine strains.
Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS Day 22 post vaccination The non-inferiority of HI antibody responses of aTIV compared to TIV against the heterologous vaccine strains, in overall group and in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of post vaccination GMTs at three weeks after vaccination .
Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS Day 22 post vaccination The superiority of HI antibody responses of aTIV compared to TIV against the heterologous vaccine strains, in overall group and in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of post vaccination GMTs at three weeks after vaccination.
Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS Day 22 postvaccination The non-inferiority of HI antibody responses of aTIV compared to TIV against the heterologous strains, in overall group and in subjects with pre-defined co-morbidities (high risk group), assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination.
Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS Day 22 post vaccination The superiority of HI antibody responses of aTIV compared to TIV against the heterologous vaccine strains, in overall group and in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of percentage of subjects achieving seroconversion, at three weeks after vaccination.
Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.Persistence of GMTs Against Homologous and Heterologous Strains Day 181, Day 366 post vaccination The GMTs against homologous and heterologous strains, persisting in subjects at six months (day 181) and one year (day 366) after vaccination with either aTIV or TIV.
Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains Day 181, Day 366 post vaccination The percentage of subjects demonstrating seroconversion in HI titers against homologous and heterologous strains, at six months (day 181) and one year (day 366) after vaccination with either aTIV or TIV.
Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40 or at least a 4-fold increase in HI titers from prevaccination HI titer ≥10.Number of Subjects Reporting Influenza Like Illness (ILI) Across Vaccine Groups Day 22 through Day 366 post vaccination The number of subjects reporting ILI from three weeks after vaccination to up to one year in aTIV group compared to TIV group, by country.
Number of High Risk Subjects With Exacerbation of Preexisting Chronic Disease, Across Vaccine Groups Day 1 through Day 366 post vaccination The number of high risk subjects reporting exacerbation of preexisting chronic conditions (i.e.congestive heart failure, Chronic Obstructive Pulmonary disease (COPD), asthma, hepatic disease, renal insufficiency, and neurological/neuromuscular or metabolic disorders including diabetes mellitus) in aTIV group compared to TIV group.
Number of Subjects Reporting Healthcare Utilization Across Vaccine Groups Day 1 through Day 366 post vaccination The number of subjects with emergency room visits, unscheduled physician visits, and hospitalizations due to community acquired influenza or pneumonia, cardiopulmonary disease, cardiac disease, respiratory or pulmonary disease,in aTIV group compared to TIV group.
All Cause Mortality Rate, Across Vaccine Groups Day 1 through Day 366 post vaccination The all-cause mortality rate (excluding injury)reported in aTIV group compared to TIV group, by country.
Number of Subjects Reporting Solicited Adverse Events Following Vaccination Day 1 through Day 7 post vaccination The number of subjects reporting solicited local and systemic adverse events and other adverse events in aTIV group compared to TIV group.
Trial Locations
- Locations (38)
323 PI Coor Clinical Research LCC, 10721 Main St Suite 1500
🇺🇸Fairfax, Virginia, United States
102, De La Salle Health Sciences Institute
🇵🇭Dbbb Dasmarinas, Cavite, Philippines
106, Our Lady of Lourdes Hospital, 46 P. Sanchez Street Sta.
🇵🇭Mesa, Manila, Philippines
104 Jose Reyes Memorial Medical Center
🇵🇭Rizal Avenue Avenida Cruz, Manila, Philippines
107 Philippine General Hospital
🇵🇭Taft Avenue, Manila, Philippines
110, San Juan de Dios Hospital, 2772 Roxas Blvd
🇵🇭Pasay City, Philippines
111, St Lukes Medical Center, 279 E Rodriguez Sr Boulevard
🇵🇭Quezon City, Philippines
318 Avail Clinical Research, 860 Peachwood Drive
🇺🇸Deland, Florida, United States
311 Regional Clinical Research INC, 415 Hooper Road
🇺🇸Endwell, New York, United States
330 Mercy Health Research, 12680 Olive Blvd Suite 200
🇺🇸Saint Louis, Missouri, United States
209, Centro de Investigacion CAFAM
🇨🇴Avenida Carrera 68, Bogota, Colombia
205, Medical and Research Center Calle 53 Urbanizacion Marbella
🇵🇦Consultorios Royal Center 108, Panama
206, Centro de Atencion e Investigacion Medica CAIMED
🇨🇴Carrera 42A, Bogota, Colombia
203, Health Research International HRI
🇵🇦Clayton ciudad del Saber Edificio 118, Panama
109, Research Institute for Tropical Medicine Department of Health Compound FILINVEST
🇵🇭Corporate City Alabang, Muntinlupa, Philippines
326 Triangle Medical Research, 5816 Creedmoor Rd. Suite 104
🇺🇸Raleigh, North Carolina, United States
314 Saint Louis Univ Med Div of Infectious Diseases Immunology, 1100 S Grand Blvd DRC- Rm 827
🇺🇸Saint Louis, Missouri, United States
213, Centro de Atencion e Investigacion Medica CAIMED
🇨🇴Carrera 42A, Bogota, Colombia
103, De La Salle Health Sciences Institute
🇵🇭DBB B Dasmarinas, Cavite, Philippines
207, Centro de Investigacion Cafesalud Medicina Prepagada
🇨🇴Cra 14 No Piso Sexto, Bogota, Colombia
312 Spartanburg Regional Medical Center, 485 Simuel Road
🇺🇸Spartanburg, South Carolina, United States
328 Miami Research Associates, 6141 Sunset Drive
🇺🇸Miami, Florida, United States
313 Clinical Research Center of Nevada, 7425 W Azure Suite 150
🇺🇸Las Vegas, Nevada, United States
320 Johnson County Clin-Trials, 15602 College Blvd
🇺🇸Lenexa, Kansas, United States
310 Heartland Research Associates LLC, 3730 N Ridge Road Suite 600
🇺🇸Wichita, Kansas, United States
316 Heartland Research Associates LLC - Axtell Clinic - PA, 700 Medical Center Dr
🇺🇸Newton, Kansas, United States
322 Heartland Research Associates Wichita, 1709 S. Rock Road
🇺🇸Wichita, Kansas, United States
325 Omega Medical Research, 400 Bald Hill Road
🇺🇸Warwick, Rhode Island, United States
306 Westside Center for Clinical Research, 810 Lane Avenue South
🇺🇸Jacksonville, Florida, United States
303 Prestige Clinical Research, 333 Conover Drive
🇺🇸Franklin, Ohio, United States
321 Jordan River Family Medicine, 1868 West 9800 South Ste 100
🇺🇸Jordan, Utah, United States
105, Manila Doctors Hospital, 667 United Nations Avenue
🇵🇭Ermita, Manila, Philippines
101, Asian Hospital and Medical Center 2205 Civic Drive Filinvest
🇵🇭Corporate City Alabang, Muntinlupa, Philippines
108, City Health Office 1 Rosa City
🇵🇭City Health Office 1, Rosa City, Philippines
305 Foothill Family Clinic South, 6360 South 3000 East
🇺🇸Salt Lake City, Utah, United States
301, Tatum Highlands Medical Associates PLLC, 26224 N Tatum Blvd 15A
🇺🇸Phoenix, Arizona, United States
332 Piedmont Medical Research, 1901 S. Hawthorne Rd. Suite 306
🇺🇸Winston-Salem, North Carolina, United States
317 J. Lewis Research Inc., 2295 Foothill Drive
🇺🇸Salt Lake City, Utah, United States