Immunogenicity of High-dose Inactivated, Split-virion Influenza Vaccine Versus Standard Fluzone Vaccine in the Elderly

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00391053
First received: October 20, 2006
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

Compared to young adults, the elderly mount a lower antibody response to vaccination. Thus, improvement of the immune response to influenza vaccination in this age group, which is at higher risk for influenza-related morbidity and mortality, represents an important unmet need.

Primary Objectives:

Immunogenicity:

  • To demonstrate lot consistency of the Fluzone High Dose (Fluzone HD) manufacturing process through evaluation of the immune responses elicited by three different lots.
  • To demonstrate the superiority of Fluzone HD vaccine compared to standard-dose Fluzone® vaccine.

Secondary Objectives:

Immunogenicity:

  • To describe the seroprotection of Fluzone HD compared to that of standard dose Fluzone® vaccine.

Safety:

  • To describe the safety profile of Fluzone HD, in terms of solicited -, unsolicited adverse and serious adverse events post-vaccination.
  • To describe clinical information on some additional defined criteria during the six months following vaccination.

Condition Intervention Phase
Orthomyxoviridae Infection
Influenza
Myxovirus Infection
Biological: High-Dose Inactivated, Split-Virion Influenza Vaccine
Biological: Inactivated, Split-Virion Influenza Vaccine
Phase 3

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: Phase III Lot Consistency, Immunogenicity and Safety Study of Three Lots of Fluzone High Dose Vaccine Compared With One Lot of Standard Fluzone® in Adults ≥ 65 Years of Age.

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines. [ Time Frame: Day 0 and Day 28 Post-vaccination ] [ Designated as safety issue: No ]
    Antibodies against each of three Influenza antigens (virus) in Fluzone® High-Dose and Standard Fluzone® vaccines (A/H1N1 New-Caledonia; A/H3N2 Wisconsin; and B Malaysia) were determined by the Hemagglutination inhibition assay method.

  • Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. [ Time Frame: Day 28 Post-vaccination ] [ Designated as safety issue: No ]
    Seroconversion was defined as a Hemagglutination Inhibition Antibody Titers of Titer ≥40 (1/dil) on Day 28 if pre-vaccination (Day 0) titer <10 (1/dil); or a four-fold increase of titer on Day 28, if pre-vaccination (Day 0) titer is ≥10 (1/dil) for each of the three Influenza vaccine antigens (A/H1N1 New-Caledonia; A/H3N2 Wisconsin; and B Malaysia).


Secondary Outcome Measures:
  • Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines. [ Time Frame: Day 0 and Day 28 Post-vaccination ] [ Designated as safety issue: No ]
    Seroprotection was defined as a Hemagglutination Inhibition Titers of at least 40 (≥ 1:40) for each of the Influenza vaccine antigens (A/H1N1 New-Caledonia; A/H3N2 Wisconsin; and B Malaysia) pre- or post-vaccination with Fluzone® High-Dose or Standard Fluzone® vaccines.

  • Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination [ Time Frame: Day 0 to Day 7 Post-vaccination ] [ Designated as safety issue: Yes ]
    The occurrence, time to onset, number of days of occurrence, and severity of solicited injection site reactions: Injection Site Pain, Erythema, and Swelling; Solicited systemic reactions: Fever (temperature), Headache, Malaise, and Myalgia were collected.


Enrollment: 3851
Study Start Date: October 2006
Study Completion Date: February 2008
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Study Group 1
Participants will receive the High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1
Biological: High-Dose Inactivated, Split-Virion Influenza Vaccine
0.5 mL, IM
Other Name: Fluzone® High-Dose
Experimental: Study Group 2
Participants will receive the High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2
Biological: High-Dose Inactivated, Split-Virion Influenza Vaccine
0.5 mL, IM
Other Name: Fluzone® High-Dose
Experimental: Study Group 3
Participants will receive the High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3
Biological: High-Dose Inactivated, Split-Virion Influenza Vaccine
0.5 mL, IM
Other Name: Fluzone® High-Dose
Active Comparator: Group 4
Participants will receive the Standard Fluzone® vaccine
Biological: Inactivated, Split-Virion Influenza Vaccine
0.5 mL, IM
Other Name: Fluzone® 2006-2007 formulation

  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.
  • Medically stable. (Subjects may have underlying chronic conditions such as hypertension, diabetes, ischemic heart disease, or hypothyroidism, as long as their symptoms/signs are controlled. If they are on medication for a condition, the medication dose must have been stable for at least 3 weeks preceding vaccination.)
  • Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

  • Systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components, or a history of a life-threatening reaction to the standard-dose Fluzone® vaccine or a vaccine containing any of the same substances.
  • Congenital or history of acquired immunodeficiency, or immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding six months.
  • Systemic corticosteroid therapy, as follows:

Continuous use with a dosage equivalent to > 15 mg/day of oral prednisone for 90 days preceding vaccination.

Sporadic use with a dosage equivalent to > 40 mg/day of oral prednisone for > 14 consecutive days in the 90 days preceding vaccination.

Note:Use of topical or inhalant corticosteroids is acceptable.

  • Neoplastic disease or any hematologic malignancy (except localized skin or prostate cancer that is stable at the time of vaccination in the absence of therapy, as well as subjects who have a history of neoplastic disease and who have been disease-free for ≥ 5 years).
  • Current alcohol abuse or drug addiction that in the opinion of the investigator may interfere with the subject's ability to comply with trial procedures.
  • Receipt of blood or blood-derived products in the past three months.
  • Participation in a trial of a high-dose influenza vaccine in the past 12 months.
  • Receipt of influenza vaccine in the past six months.
  • Receipt of any other vaccine in the past four weeks.
  • Planned receipt of any other vaccine in the four weeks following the trial vaccination.
  • Participation in another clinical trial in the past four weeks.
  • Planned participation in another clinical trial during the present trial period.

Note:Concomitant participation in an observational trial (not involving drugs, vaccines, or medical devices) is acceptable.

  • Thrombocytopenia or bleeding disorder contraindicating intramuscular (IM) vaccination.
  • History of Guillain-Barré syndrome.
  • Subject deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.
  • An acute febrile illness (oral temperature ≥ 99.5ºF [≥ 37.5ºC]) within 24 hours prior to vaccination. If this contraindication exists, vaccination will be deferred until the participant has been afebrile 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: NCT00391053

  Show 28 Study Locations
Sponsors and Collaborators
Sanofi Pasteur, a Sanofi Company
Investigators
Study Director: Medical Director Sanofi Pasteur Inc.
  More Information

Additional Information:
Publications:
Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00391053     History of Changes
Other Study ID Numbers: FIM05
Study First Received: October 20, 2006
Results First Received: January 14, 2010
Last Updated: January 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Influenza
Orthomyxoviruses
Inactivated Split-virion influenza vaccine
Adults

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 July 24, 2014