A Study of Fluzone® High-Dose Vaccine Compared With Fluzone® Vaccine In Elderly Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT01427309
First received: August 30, 2011
Last updated: August 5, 2014
Last verified: August 2014
  Purpose

The aim of this study is to determine the efficacy of Fluzone High-Dose compared to standard dose Fluzone for laboratory-confirmed or culture-confirmed influenza caused by influenza types/subtypes that are similar (for laboratory-confirmed) or antigenically similar (for culture-confirmed) to those contained in the respective annual vaccine formulations.

Primary Objective:

  • To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to laboratory-confirmed influenza caused by any influenza viral types/subtypes, associated with the occurrence of a protocol-defined influenza-like-illnesses (ILI).

Secondary Objectives:

  • To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to laboratory-confirmed influenza, caused by any influenza viral types/subtypes, associated with the occurrence of a protocol-defined ILI.
  • To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to culture-confirmed influenza, caused by any influenza viral types/subtypes, associated with the occurrence of a protocol-defined ILI.
  • To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to culture-confirmed influenza caused by viral types/subtypes antigenically similar to those contained in the respective annual vaccine formulations, associated with the occurrence of a modified Centers for Disease Control and Prevention (CDC)-defined ILI.
  • To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to culture-confirmed influenza caused by any influenza viral types/subtypes, associated with the occurrence of a modified CDC-defined ILI.
  • To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to culture-confirmed influenza caused by viral types/subtypes antigenically similar to those contained in the respective annual vaccine formulations, associated with the occurrence of a respiratory illness.
  • To compare the clinical efficacy of Fluzone High-Dose to that of Fluzone in elderly adults, with respect to culture-confirmed influenza caused by any influenza viral types/subtypes, associated with the occurrence of a respiratory illness.

Condition Intervention Phase
Influenza
Biological: High Dose Trivalent Inactivated Influenza Vaccine
Biological: Trivalent Inactivated Influenza Vaccine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Efficacy Study of Fluzone® High-Dose Vaccine Compared With Fluzone® Vaccine In Elderly Adults

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Occurrences of Culture- or Polymerase Chain Reaction (PCR)-Confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Protocol-defined Influenza-like Illness (ILI). [ Time Frame: ≥14 days post-vaccination ] [ Designated as safety issue: No ]

    Influenza positive cultures were confirmed using direct immunofluorescence techniques with influenza type-specific antibodies. 3 culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney cells, Classic Flu A and B culture using Rhesus Monkey Kidney cells, and R Mix Flu A and B culture). The initial molecular test (PCR) was the validated ProFlu+™ assay by Prodesse, Inc., Waukesha, WI, which had been approved by the Food and Drug Administration through a 510K evaluation for specific detection of Influenza A, B or Respiratory Syncytial Virus.

    A protocol-defined influenza-like illness was determined by the occurrence of at least 1 of the following respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing; concurrently with at least one of the following systemic symptoms: fever (defined as temperature > 99.0°F [> 37.2°C]), chills (shivering), tiredness (fatigue), headache, or myalgia (muscle aches).



Secondary Outcome Measures:
  • Occurrences of Culture-confirmed Influenza Caused by Influenza Viral Types/Subtypes That Are Antigenically Similar to Those Contained in the Vaccine Formulations, in Association With a Protocol-defined Influenza-like Illness (ILI) [ Time Frame: ≥14 days post-vaccination ] [ Designated as safety issue: No ]
    Influenza positive cultures were confirmed by using direct immunofluorescence techniques with influenza type-specific (i.e., for Influenza A and Influenza B) antibodies. For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney [MDCK] cells, Classic Flu A and B culture using Rhesus Monkey Kidney [RhMK] cells, and R Mix Flu A and B culture. For antigenic similarity determinations, a standard hemagglutination inhibition test using a panel of ferret antisera (ferret antigenicity testing) was used.

  • Occurrences of Culture-confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Protocol-defined Influenza-like Illness [ Time Frame: ≥14 days post-vaccination ] [ Designated as safety issue: No ]

    For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney [MDCK] cells, Classic Flu A and B culture using Rhesus Monkey Kidney [RhMK] cells, and R Mix Flu A and B culture).

    A protocol-defined influenza-like illness (ILI) was determined by the occurrence of at least one of the following respiratory symptoms: sore throat, cough, sputum production, wheezing, or difficulty breathing; concurrently with at least one of the following systemic symptoms: fever (defined as temperature > 99.0°F [> 37.2°C]), chills (shivering), tiredness (fatigue), headache, or myalgia (muscle aches).


  • Occurrences of Culture-confirmed Influenza Caused by Influenza Viral Types/Subtypes That Are Antigenically Similar to Those Contained in the Vaccine Formulations, in Association With a Modified CDC-defined Influenza-like Illness. [ Time Frame: ≥14 days post-vaccination ] [ Designated as safety issue: No ]

    Influenza positive cultures were confirmed by using direct immunofluorescence techniques with influenza type-specific antibodies. For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney cells, Classic Flu A and B culture using Rhesus Monkey Kidney cells, and R Mix Flu A and B culture). For antigenic similarity determinations, a standard hemagglutination inhibition test using a panel of ferret antisera (ferret antigenicity testing) was used.

    The modified Centers for Disease Control and Prevention-defined influenza-like illness is the occurrence of fever (defined as temperature > 99.0°F [> 37.2°C]) with cough or sore throat.


  • Occurrences of Culture-confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Modified CDC-defined Influenza-like Illness [ Time Frame: ≥14 days post-vaccination ] [ Designated as safety issue: No ]

    Influenza positive cultures were confirmed by using direct immunofluorescence techniques with influenza type-specific antibodies. For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney cells, Classic Flu A and B culture using Rhesus Monkey Kidney cells, and R Mix Flu A and B culture). For antigenic similarity determinations, a standard hemagglutination inhibition test using a panel of ferret antisera (ferret antigenicity testing) was used.

    The modified Centers for Disease Control and Prevention-defined influenza-like illness is the occurrence of fever (defined as temperature > 99.0°F [> 37.2°C]) with cough or sore throat.


  • Occurrences of Culture-confirmed Influenza Caused by Influenza Viral Types/Subtypes That Are Antigenically Similar to Those Contained in the Vaccine Formulations, in Association With a Respiratory Illness [ Time Frame: ≥14 days post-vaccination ] [ Designated as safety issue: No ]

    Influenza positive cultures were confirmed by using direct immunofluorescence techniques with influenza type-specific antibodies. For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney cells, Classic Flu A and B culture using Rhesus Monkey Kidney cells, and R Mix Flu A and B culture). For antigenic similarity determinations, a standard hemagglutination inhibition test using a panel of ferret antisera (ferret antigenicity testing) was used.

    Respiratory illness was defined as the occurrence of a new onset (or exacerbation of a pre-existing condition/symptom) of one or more of the following symptoms (that persist for or reoccur after a period of at least 12 hours): sneezing, stuffy or runny nose (nasal congestion), sore throat, cough, sputum production, wheezing, or difficulty breathing.


  • Occurrences of Culture-confirmed Influenza Caused by Any Influenza Viral Types/Subtypes, in Association With a Respiratory Illness [ Time Frame: ≥14 days post-vaccination ] [ Designated as safety issue: No ]

    Influenza positive cultures were confirmed by using direct immunofluorescence techniques with influenza type-specific (i.e., for Influenza A and Influenza B) antibodies. For culture confirmation of influenza, 3 different culture methods were utilized for each NP sample (Classic Flu A and B culture using Madin Darby Canine Kidney cells, Classic Flu A and B culture using Rhesus Monkey Kidney cells, and R Mix Flu A and B culture).

    Respiratory illness is defined as the occurrence of a new onset (or exacerbation of a pre-existing condition/symptom) of one or more of the following symptoms (that persist for or reoccur after a period of at least 12 hours): sneezing, stuffy or runny nose (nasal congestion), sore throat, cough, sputum production, wheezing, or difficulty breathing.



Other Outcome Measures:
  • Safety Overview After Injection With Either Fluzone High Dose or Fluzone Vaccine Through the End of Surveillance Period [ Time Frame: Day 0 up to Day 240 post-vaccination ] [ Designated as safety issue: No ]
    All serious adverse events, including deaths and adverse events (AEs) of special interest (Guillain Barre Syndrome, Bell's Palsy, encephalitis/myelitis, optic neuritis, Stevens Johnson Syndrome, and toxic epidermal necrolysis) were collected.


Enrollment: 31989
Study Start Date: September 2011
Study Completion Date: November 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High Dose Trivalent Inactivated Influenza Vaccine
Participants will receive an injection of High Dose Trivalent Inactivated Influenza Vaccine
Biological: High Dose Trivalent Inactivated Influenza Vaccine
0.5 mL Intramuscular
Other Name: Fluzone® High Dose
Active Comparator: Trivalent Inactivated Influenza Vaccine
Participants will receive an injection of the Trivalent Inactivated Influenza vaccine
Biological: Trivalent Inactivated Influenza Vaccine
0.5 mL, Intramuscular
Other Name: Fluzone®

Detailed Description:

The trial will span 2 influenza seasons. Each study year, participants will be randomized to receive one dose of either Fluzone® High-Dose or Fluzone® vaccine prior to the start of the influenza season and will be followed until the end of each season.

The duration of each participant's participation in the respective study year will be 6 to 8 months, depending on the time of enrollment.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Aged ≥ 65 years on the day of vaccination
  • Informed consent form signed and dated
  • Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

  • Participation at the time of study enrollment (or in the 4 weeks preceding the trial vaccination), or planned participation during each year of the trial period, in another clinical trial investigating a vaccine, drug, medical device, or medical procedure (Note: Concomitant participation in an observational trial is acceptable)
  • Vaccination against influenza in the 6 months preceding the trial vaccination
  • Systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components, or a history of a life-threatening reaction to Fluzone High-Dose or Fluzone vaccine or to a vaccine containing any of the same substances
  • Personal history of Guillain-Barré Syndrome
  • Dementia or any other cognitive condition at a stage that could interfere with following the trial procedures
  • Thrombocytopenia contraindicating intramuscular (IM) vaccination, as judged by the investigator
  • Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination, as judged by the investigator
  • Current alcohol abuse or drug addiction
  • Subject deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
  • Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study
  • Moderate or severe acute illness with or without fever (oral temperature > 99.0ºF [> 37.2ºC]). If this contraindication exists, vaccination will be deferred until the individual has been medically stable and/or afebrile (temperature ≤ 99.0 ºF [≤ 37.2ºC]) for at least 24 hours
  • Signs and symptoms of an acute infectious respiratory illness. If this exists, vaccination will be deferred until the symptoms resolve.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01427309

  Hide Study Locations
Locations
United States, Alabama
Mobile, Alabama, United States, 36608
United States, Arizona
Chandler, Arizona, United States, 85224
Glendale, Arizona, United States, 85306
Glendale, Arizona, United States, 85308
Mesa, Arizona, United States, 85213
Mesa, Arizona, United States, 85203
Phoenix, Arizona, United States, 85050
Phoenix, Arizona, United States, 85028
Phoenix, Arizona, United States, 85020
Scottsdale, Arizona, United States, 85251
Tempe, Arizona, United States, 85283
United States, Arkansas
Harrisburg, Arkansas, United States, 72432
United States, California
Anaheim, California, United States, 92801
La Mesa, California, United States, 91942
Oceanside, California, United States, 92056
Redding, California, United States, 96001
San Diego, California, United States, 92103
Santa Rosa, California, United States, 95405
United States, Colorado
Aurora, Colorado, United States, 80045
Colorado Springs, Colorado, United States, 80907
Colorado Springs, Colorado, United States, 80922
United States, Connecticut
Milford, Connecticut, United States, 06460
Milford, Connecticut, United States, 01757
United States, Florida
Brooksville, Florida, United States, 34601
Clearwater, Florida, United States, 33761
Clearwater, Florida, United States, 33756
Coral Gables, Florida, United States, 33134
Crystal River, Florida, United States, 34429
DeLand, Florida, United States, 32720
Jacksonville, Florida, United States, 32216
Melbourne, Florida, United States, 32935
Pembroke Pine, Florida, United States, 33026
Pinellas Park, Florida, United States, 33781
Sarasota, Florida, United States, 34231
United States, Georgia
Stockbridge, Georgia, United States, 30281
United States, Idaho
Boise, Idaho, United States, 83642
United States, Illinois
Chicago, Illinois, United States, 60654
Peoria, Illinois, United States, 61602
United States, Indiana
Mishawaka, Indiana, United States, 46545
United States, Kansas
Lenexa, Kansas, United States, 66219
Newton, Kansas, United States, 67114
Overland Park, Kansas, United States, 66212
Prairie Village, Kansas, United States, 66206
Wichita, Kansas, United States, 67205
Wichita, Kansas, United States, 67207
United States, Kentucky
Bardstown, Kentucky, United States, 40004
Lexington, Kentucky, United States, 40504
United States, Maryland
Columbia, Maryland, United States, 21045
Elkridge, Maryland, United States, 21075
Rockville, Maryland, United States, 20850
United States, Massachusetts
Brockton, Massachusetts, United States, 02301
Haverhill, Massachusetts, United States, 01830
United States, Minnesota
Edina, Minnesota, United States, 55435
United States, Missouri
Kansas City, Missouri, United States, 64114
St. Louis, Missouri, United States, 63141
United States, Montana
Missoula, Montana, United States, 59808
United States, Nebraska
Bellevue, Nebraska, United States, 68005
Omaha, Nebraska, United States, 68114
United States, Nevada
Las Vega, Nevada, United States, 89104
United States, New Hampshire
Newington, New Hampshire, United States, 03801
United States, New Jersey
Edison, New Jersey, United States, 08817
United States, New Mexico
Albuquerque, New Mexico, United States, 87018
United States, New York
Binghamton, New York, United States, 13901
Endwell, New York, United States, 13760
Rochester, New York, United States, 14609
Rochester, New York, United States, 14642
United States, North Carolina
Cary, North Carolina, United States, 27518
Charlotte, North Carolina, United States, 28209
Hickory, North Carolina, United States, 28602
Raleigh, North Carolina, United States, 27612
Raleigh, North Carolina, United States, 27609
Salisbury, North Carolina, United States, 28144
Wilmington, North Carolina, United States, 28401
Winston Salem, North Carolina, United States, 27103
United States, North Dakota
Fargo, North Dakota, United States, 58104
Idaho Falls, North Dakota, United States, 83404
United States, Ohio
Akron, Ohio, United States, 44311
Cincinnati, Ohio, United States, 45259
Cincinnati, Ohio, United States, 45227
Cleveland, Ohio, United States, 44122
Columbus, Ohio, United States, 43213
United States, Oklahoma
Norman, Oklahoma, United States, 73069
United States, Pennsylvania
Erie, Pennsylvania, United States, 16506
Pittsburgh, Pennsylvania, United States, 15241
Scranton, Pennsylvania, United States, 18510
United States, Rhode Island
Warwick, Rhode Island, United States, 02886
United States, South Carolina
Anderson, South Carolina, United States, 29621
Clinton, South Carolina, United States, 29325
Greer, South Carolina, United States, 29650
Mt. Pleasant, South Carolina, United States, 29464
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
Bristol, Tennessee, United States, 37620
Nashville, Tennessee, United States, 37203
Nashville, Tennessee, United States, 37212
United States, Texas
Fort Worth, Texas, United States, 76107
San Antonio, Texas, United States, 78229
Tomball, Texas, United States, 77375
United States, Utah
Salt Lake City, Utah, United States, 84124
Salt Lake City, Utah, United States, 84109
Salt Lake City, Utah, United States, 84121
South Jordan, Utah, United States, 84095
West Jordan, Utah, United States, 84088
United States, Virginia
Norfolk, Virginia, United States, 23507
Williamsburg, Virginia, United States, 23185
Winchester, Virginia, United States, 22601
Canada, British Columbia
Coquitlam, British Columbia, Canada, V3K3P4
Canada, Newfoundland and Labrador
Mount Pearl, Newfoundland and Labrador, Canada, A1N1W7
Canada, Nova Scotia
Truro, Nova Scotia, Canada, B2N1L2
Canada, Ontario
Sudbury, Ontario, Canada, P3E1H5
Toronto, Ontario, Canada, M9W4L6
Canada, Quebec
Sherbrooke, Quebec, Canada, J1H4J6
Puerto Rico
Bayamon, Puerto Rico, 00961
San Juan, Puerto Rico, 00909
Sponsors and Collaborators
Sanofi Pasteur, a Sanofi Company
Investigators
Study Director: Medical Director Sanofi Pasteur Inc.
  More Information

Additional Information:
No publications provided by Sanofi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT01427309     History of Changes
Other Study ID Numbers: FIM12, U1111-1120-1300
Study First Received: August 30, 2011
Results First Received: July 8, 2014
Last Updated: August 5, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Sanofi:
Influenza
Trivalent Inactivated Influenza Vaccine
High-Dose Trivalent Inactivated Influenza Vaccine
Fluzone® High-Dose
Influenza vaccines

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on August 28, 2014