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Safety and Immunogenicity of MF59C.1 Adjuvanted Trivalent Subunit Influenza Vaccine in Elderly Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01162122
Recruitment Status : Completed
First Posted : July 14, 2010
Results First Posted : June 12, 2014
Last Update Posted : June 26, 2014
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )

Tracking Information
First Submitted Date  ICMJE July 13, 2010
First Posted Date  ICMJE July 14, 2010
Results First Submitted Date  ICMJE January 28, 2014
Results First Posted Date  ICMJE June 12, 2014
Last Update Posted Date June 26, 2014
Study Start Date  ICMJE August 2010
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2014)
  • Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 13, 2010)
  • Immunologic equivalence of 3 consecutive production lots of MF59-adjuvanted subunit seasonal influenza vaccine, as measured by Hemagglutination Inhibition (HI) Geometric Mean Titers (GMTs) for each virus strain after a single 0.5mL IM injection [ Time Frame: 21 days post immunization ]
  • Antibody response to homologous antigens as measured by HI [ Time Frame: 21 days, 180 days, and 365 days post immunization ]
Change History Complete list of historical versions of study NCT01162122 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2014)
  • Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-PPS [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2010)
  • Antibody response to heterologous antigens as measured by HI [ Time Frame: 21 days, 180 days, and 365 days post immunization ]
  • Antibody response to homologous antigens as measured by HI in a subset of subjects with pre-defined chronic disease [ Time Frame: 21 days, 180 days, and 365 days post immunization ]
  • Clinical Effectiveness of MF59-adjuvanted subunit seasonal influenza vaccine compared to non-adjuvanted seasonal influenza vaccine [ Time Frame: Days 23 to 365 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Immunogenicity of MF59C.1 Adjuvanted Trivalent Subunit Influenza Vaccine in Elderly Subjects
Official Title  ICMJE A Phase III, Randomized, Controlled, Observer-Blind, Multicenter Study to Evaluate the Safety and Immunogenicity and the Consistency of Three Consecutive Lots of a MF59C.1 Adjuvanted Trivalent Subunit Influenza Vaccine in Elderly Subjects Aged 65 Years and Older
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Influenza
Intervention  ICMJE
  • Biological: MF59 adjuvanted trivalent subunit influenza vaccine (aTIV)
    one dose 0.5 mL administered IM in the deltoid muscle of (preferably) the non-dominant arm
    Other Name: Fluad
  • Biological: Non-adjuvanted trivalent subunit influenza vaccine (TIV)
    one 0.5 mL dose administered IM in the deltoid muscle of (preferably) the non-dominant arm
    Other Name: Agriflu
Study Arms  ICMJE
  • Experimental: 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).
    Intervention: Biological: MF59 adjuvanted trivalent subunit influenza vaccine (aTIV)
  • Experimental: Licensed TIV
    Subjects received one dose of non-adjuvanted trivalent subunit influenza vaccine (TIV).
    Intervention: Biological: Non-adjuvanted trivalent subunit influenza vaccine (TIV)
Publications * Frey SE, Reyes MR, Reynales H, Bermal NN, Nicolay U, Narasimhan V, Forleo-Neto E, Arora AK. Comparison of the safety and immunogenicity of an MF59®-adjuvanted with a non-adjuvanted seasonal influenza vaccine in elderly subjects. Vaccine. 2014 Sep 3;32(39):5027-34. doi: 10.1016/j.vaccine.2014.07.013. Epub 2014 Jul 18.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 30, 2011)
7109
Original Estimated Enrollment  ICMJE
 (submitted: July 13, 2010)
7000
Actual Study Completion Date  ICMJE November 2011
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Males and females subjects aged ≥65 years at day of vaccination who are willing and able to comply to study procedures.

Exclusion Criteria:

  1. 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.
  2. Individuals who were not able to comprehend and/or follow all required study procedures for the whole period of the study.
  3. Known or suspected impairment/alteration of immune function.
  4. Individuals with a known bleeding diathesis.
  5. History of Guillain-Barré syndrome.
  6. 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).
  7. 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.
  8. 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.
  9. Individuals who had received vaccination against seasonal influenza in the previous 6 months.
  10. Individuals with oral temperature ≥38.0°C (≥100.4°F) on day of study vaccination.
  11. Individuals with history of substance or alcohol abuse within the past 2 years.
  12. Individuals providing consent who did not consent to the retention of their serum samples after study completion.
  13. 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.
  14. Subjects from whom blood could not be drawn at visit 1.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 65 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Colombia,   Panama,   Philippines,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01162122
Other Study ID Numbers  ICMJE V70_27
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Vaccines )
Study Sponsor  ICMJE Novartis Vaccines
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Novartis Vaccines Novartis Vaccines
PRS Account Novartis
Verification Date June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP