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CompletedNCT00391053Updated Apr 14, 2016Results posted

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

A Phase 3 interventional study of High-Dose Inactivated, Split-Virion Influenza Vaccine and High-Dose Inactivated, Split-Virion Influenza Vaccine in Orthomyxoviridae Infection, Influenza and Myxovirus Infection, sponsored by Sanofi Pasteur, a Sanofi Company. Completed at 28 sites in United States. Open to participants aged 65 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-04-14.

Sponsored by Sanofi Pasteur, a Sanofi Company · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
3,851
Allocation
Randomized
Ages
65 Years and older
Sex
All
01

Study 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.
02

Conditions studied

  • Orthomyxoviridae Infection
  • Influenza
  • Myxovirus Infection

Keywords

  • Influenza
  • Orthomyxoviruses
  • Inactivated Split-virion influenza vaccine
  • Adults
03

In context

Infections

6,687 studies on the registry are indexed under Infections; 807 are open to participants now.

This study's enrollment of 3,851 is above the median of 120 across 4,200 interventional studies indexed under Infections.

Browse Infections studies →

Lead sponsor

Sanofi Pasteur, a Sanofi Company is the lead sponsor of 366 studies on the registry; 4 are open to participants now.

Of its 94 completed or terminated interventional studies of FDA-regulated products, 73 (78%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
65 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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.
05

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
3,851 participants (actual)

Study arms

  • 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

  • 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

  • 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

  • Active comparator
    Group 4

    Participants will receive the Standard Fluzone® vaccine

    Biological: Inactivated, Split-Virion Influenza Vaccine

Interventions

  • BiologicalHigh-Dose Inactivated, Split-Virion Influenza Vaccine

    0.5 mL, IM

    Also known as: Fluzone® High-Dose

  • BiologicalHigh-Dose Inactivated, Split-Virion Influenza Vaccine

    0.5 mL, IM

    Also known as: Fluzone® High-Dose

  • BiologicalHigh-Dose Inactivated, Split-Virion Influenza Vaccine

    0.5 mL, IM

    Also known as: Fluzone® High-Dose

  • BiologicalInactivated, Split-Virion Influenza Vaccine

    0.5 mL, IM

    Also known as: Fluzone® 2006-2007 formulation

06

What researchers measure

Primary outcomes

  1. Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines.

    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.

    Time frame: Day 0 and Day 28 Post-vaccination

  2. Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines.

    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).

    Time frame: Day 28 Post-vaccination

Secondary outcomes

  1. Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines.

    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.

    Time frame: Day 0 and Day 28 Post-vaccination

  2. Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination

    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.

    Time frame: Day 0 to Day 7 Post-vaccination

07

Results

Posted Apr 30, 2010

Participant flow

Participants were enrolled from 09 October 2006 to 21 December 2006 at 30 US sites.

Participant flow — Overall Study
MilestoneHigh-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3Active Comparator (Standard Fluzone®)
Started8578488701262
Completed8488478681252
Not completed91210
Withdrew: Serious adverse events1014
Withdrew: Protocol violation2000
Withdrew: Lost to follow-up1005
Withdrew: Withdrawal by subject5111

Outcome measures

PrimaryGeometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines.

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.

Time frame:
Day 0 and Day 28 Post-vaccination
Reported as:
Geometric mean · Titers
Geometric Mean Titers (GMTs) of Hemagglutination Inhibition Antibody Titers Pre- and Post-vaccination With Fluzone® High Dose or Standard Fluzone® Vaccines.
TitersHigh-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3Active Comparator (Standard Fluzone®)
A/H1N1 New Caledonia Pre-Dose28.25 (26.37 to 30.26)29.41 (27.39 to 31.57)27.86 (25.94 to 29.93)29.36 (27.72 to 31.11)
A/H1N1 New Caledonia Post-Dose112.77 (105.64 to 120.37)114.63 (107.18 to 122.61)120.02 (112.12 to 128.48)67.29 (63.65 to 71.13)
A/H3N2 Wisconsin Pre-Dose74.53 (67.29 to 82.55)77.3 (69.5 to 85.97)72.07 (65.12 to 79.77)74.74 (68.64 to 81.37)
A/H3N2 Wisconsin Post-Dose595.03 (552.8 to 640.49)628.54 (583.21 to 677.4)603.59 (561.33 to 649.03)332.46 (310.44 to 356.05)
B/Malaysia Pre-Dose19.24 (17.98 to 20.58)18.96 (17.71 to 20.29)19.78 (18.49 to 21.16)18.96 (17.93 to 20.04)
B/Malaysia Post-Dose68.98 (64.77 to 73.47)69.26 (64.99 to 73.81)68.93 (64.81 to 73.3)52.34 (49.48 to 55.35)
PrimaryPercentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines.

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).

Time frame:
Day 28 Post-vaccination
Reported as:
Number · Percentage of Participants
Percentage of Participants With Seroconversion Post-vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines.
Percentage of ParticipantsHigh-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3Active Comparator (Standard Fluzone®)
A/H1N1 New Caledonia47475223
A/H3N2 Wisconsin70687051
B/Malaysia43414230
SecondaryPercentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines.

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.

Time frame:
Day 0 and Day 28 Post-vaccination
Reported as:
Number · Percentage of Participants
Percentage of Participants With Seroprotection Pre- and Post-Vaccination With Fluzone® High-Dose or Standard Fluzone® Vaccines.
Percentage of ParticipantsHigh-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3Active Comparator (Standard Fluzone®)
A/H1N1 New Caledonia Pre-Dose44464246
A/H1N1 New Caledonia Post-Dose91899077
A/H3N2 Wisconsin Pre-Dose70696869
A/H3N2 Wisconsin Post-Dose99999997
B/Malaysia Pre-Dose27283027
B/Malaysia Post-Dose80788068
SecondaryPercentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination

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.

Time frame:
Day 0 to Day 7 Post-vaccination
Reported as:
Number · Percentage of Participants
Percentage of Participants Reporting Solicited Injection Site and Systemic Reactions After Fluzone® High-Dose or Standard Fluzone® Vaccination
Percentage of ParticipantsHigh-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3Active Comparator (Standard Fluzone®)
Any Solicited Injection Site Reaction41424331
Any Swelling9996
Grade 3 Swelling (≥ 5 cm)1211
Any Erythema16151411
Grade 3 Erythema (≥ 5 cm)3121
Any Pain35343824
Grade 3 Pain (Incapacitating)1000
Any Solicited Systemic Reaction37333329
Any Fever4342
Grade 3 Fever (>102.2 ºF or >39.0 ºC)0000
Any Headache17161714
Grade 3 Headache (Prevents Daily Activities)1210
Any Malaise20181614
Grade 3 Malaise (Prevents Daily Activities)1221
Any Myalgia23212118
Grade 3 Myalgia (Prevents Daily Activities)1120

Adverse events

Collected over Adverse events data were collected from day of vaccination (Day 0) for 6 months post-vaccination. Non-serious events are listed at a 5.0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1—56/855 (6.5%)455/855 (53.2%)
High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2—56/848 (6.6%)454/848 (53.5%)
High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3—44/870 (5.1%)449/870 (51.6%)
Standad Dose Inactivated, Split-Virion Influenza Vaccine—93/1,260 (7.4%)544/1,260 (43.2%)
Most frequent serious events
Showing 10 of 157
Most frequent serious events
EventHigh-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3Standad Dose Inactivated, Split-Virion Influenza Vaccine
PneumoniaInfections and infestations6/8555/8486/8704/1260
Cerebrovascular accidentNervous system disorders0/8555/8480/8701/1260
Cardiac failure congestiveCardiac disorders4/8553/8480/8702/1260
Chest painGeneral disorders0/8552/8480/8705/1260
SyncopeNervous system disorders1/8550/8480/8705/1260
Coronary artery diseaseCardiac disorders2/8553/8480/8704/1260
GastroenteritisInfections and infestations0/8553/8481/8700/1260
Pleural effusionRespiratory, thoracic and mediastinal disorders0/8553/8480/8702/1260
Mental status changesPsychiatric disorders3/8550/8480/8700/1260
Small intestinal obstructionGastrointestinal disorders0/8551/8483/8701/1260
Most frequent other events
Most frequent other events
EventHigh-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3Standad Dose Inactivated, Split-Virion Influenza Vaccine
Injection site painGeneral disorders295/855292/848328/870306/1260
MyalgiaMusculoskeletal and connective tissue disorders197/855175/848178/870230/1260
MalaiseGeneral disorders173/855150/848139/870176/1260
HeadacheNervous system disorders146/855138/848147/870182/1260
Injection site erythemaGeneral disorders136/855125/848123/870136/1260
Injection site swellingGeneral disorders79/85576/84875/87073/1260

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3Active Comparator (Standard Fluzone®)Total
<=18 years00000
Between 18 and 65 years00000
>=65 years85584887012603833
Age, Continuous
Age, Continuous(Years)High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3Active Comparator (Standard Fluzone®)Total
Mean72.9 ± 6.1572.9 ± 6.2072.9 ± 6.1772.9 ± 5.9972.9 ± 6.17
Sex: Female, Male
Sex: Female, Male(Participants)High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3Active Comparator (Standard Fluzone®)Total
Female4374384456882008
Male4184104255721825
Region of Enrollment
Region of Enrollment(participants)High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 1High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 2High-Dose Inactivated, Split-Virion Influenza Vaccine Lot 3Active Comparator (Standard Fluzone®)Total
United States85584887012603833
08

Study locations

28 sites
  • Mesa, Arizona, United States
  • Phoenix, Arizona, United States
  • Tempe, Arizona, United States
  • Tucson, Arizona, United States
  • San Diego, California, United States
  • Stratford, Connecticut, United States
  • Clearwater, Florida, United States
  • Coral Gables, Florida, United States
  • Orlando, Florida, United States
  • Pembroke Pines, Florida, United States
  • Wichita, Kansas, United States
  • Rockville, Maryland, United States
  • Rochester, Minnesota, United States
  • Kansas City, Missouri, United States
  • St. Louis, Missouri, United States
  • Endwell, New York, United States
  • Rochester, New York, United States
  • Cary, North Carolina, United States
  • Raleigh, North Carolina, United States
  • Downington, Pennsylvania, United States
  • Erie, Pennsylvania, United States
  • Warwick, Rhode Island, United States
  • Dallas, Texas, United States
  • Plano, Texas, United States
  • West Jordan, Utah, United States
  • Norfolk, Virginia, United States
  • Richmond, Virginia, United States
  • Marshfield, Wisconsin, United States
09

References and documents

Publications

  • 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. PubMed 19508159 ↗

Related links

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 14, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00391053
Lead sponsor
Sanofi Pasteur, a Sanofi Company
Responsible party
Sponsor
First posted
Oct 23, 2006
Start date
Oct 2006
Primary completion
Jul 2007
Completion
Feb 2008
Results posted
Apr 30, 2010
Last update
Apr 14, 2016

Study contacts

Medical Director
study director · Sanofi Pasteur Inc.

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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