Clinical trial NCT00391053: Immunogenicity of High-dose Inactivated, Split-virion Influenza Vaccine Versus Standard Fluzone Vaccine in the Elderly
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Orthomyxoviridae Infection
Influenza
Myxovirus Infection
Keywords: Influenza
Orthomyxoviruses
Inactivated Split-virion influenza vaccine
Adults
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2006-10-23
Enrollment: 3851
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines.
timeFrame: Day 0 and Day 28 Post-vaccination
measure: Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines.
timeFrame: Day 28 Post-vaccination
Secondary outcomes:
measure: Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines.
timeFrame: Day 0 and Day 28 Post-vaccination
measure: Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination
timeFrame: Day 0 to Day 7 Post-vaccination
Other outcomes:
Locations:
city: Mesa
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Tempe
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: San Diego
country: United States
state: California
city: Stratford
country: United States
state: Connecticut
city: Clearwater
country: United States
state: Florida
city: Coral Gables
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Wichita
country: United States
state: Kansas
city: Rockville
country: United States
state: Maryland
city: Rochester
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: St. Louis
country: United States
state: Missouri
city: Endwell
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Cary
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Downington
country: United States
state: Pennsylvania
city: Erie
country: United States
state: Pennsylvania
city: Warwick
country: United States
state: Rhode Island
city: Dallas
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: West Jordan
country: United States
state: Utah
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Marshfield
country: United States
state: Wisconsin
Study officials:
affiliation: Sanofi Pasteur Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Falsey AR, Treanor JJ, Tornieporth N, Capellan J, Gorse GJ. Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older. J Infect Dis. 2009 Jul 15;200(2):172-80. doi: 10.1086/599790.