Immunogenicity, Safety, Reactogenicity, Efficacy, Effectiveness and Lot Consistency of FluBlok

Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT00539981
Collaborator
Protein Sciences Corporation (Industry)
4,648
24
2
8.4
193.7
23

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate a single dose of FluBlok in terms of safety, efficacy and effectiveness in prevention of influenza and influenza-like illness and assess clinical lot-to-lot consistency in manufacturing by evaluating and comparing the immunogenicity of three different lots of FluBlok in a subset of participants.

Condition or Disease Intervention/Treatment Phase
  • Biological: FluBlok®
  • Biological: Placebo
Phase 3

Detailed Description

All currently licensed influenza vaccines in the United States were produced in embryonated hen's eggs. There were several well-recognized disadvantages to the use of eggs as the substrate for influenza vaccine. Eggs required specialized manufacturing facilities and could be difficult to scale up rapidly in response to an emerging need such as a pandemic. It was usually necessary to adapt candidate vaccine viruses for high-yield growth in eggs, a process that could be time consuming, was not always successful, and could select receptor variants that might have suboptimal immunogenicity. In addition, agricultural diseases that affected chicken flocks, and that might be an important issue in a pandemic due to an avian influenza virus strain, could easily disrupt the supply of eggs for vaccine manufacturing. Therefore, development of alternative substrates for influenza vaccine production had been identified as a high-priority objective.

One potential alternative method for production of influenza vaccine was expression of the influenza virus hemagglutinin (HA) using recombinant deoxyribonucleic acid (DNA) techniques. This alternative avoided dependence on eggs and was very efficient because of the high levels of protein expression under the control of the baculovirus polyhedrin promoter.

Study Design

Study Type:
Interventional
Actual Enrollment :
4648 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Prevention
Official Title:
Evaluation of the Immunogenicity, Safety, Reactogenicity, Efficacy, Effectiveness and Lot Consistency of FluBlok® Trivalent Recombinant Baculovirus-Expressed Hemagglutinin Influenza Vaccine in Healthy Adults Aged 18 to 49 Years
Actual Study Start Date :
Sep 15, 2007
Actual Primary Completion Date :
May 28, 2008
Actual Study Completion Date :
May 28, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: FluBlok (Lots A, B, C)

Participants received a single 0.5 milliliters (mL) dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination.

Biological: FluBlok®
Dose: 0.5 mL, single dose; Route of administration: intramuscular. Recombinant Trivalent Hemagglutinin Influenza Vaccine containing 45 microgram (mcg) of each hemagglutinin derived from A/Solomon Islands/3/2006 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004
Other Names:
  • rHA Trivalent Recombinant Hemagglutinin Influenza Vaccine
  • Placebo Comparator: Placebo

    Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination.

    Biological: Placebo
    Dose: 0.5 mL normal saline for injection, single dose; Route of administration: intramuscular

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants Reporting Solicited Injection Site (Local) Reactions [Within 7 days post vaccination]

      Solicited reaction (reactogenicity event) was an adverse event (AE) that was pre-listed in electronic case report form(eCRF), considered to be related to vaccination and recorded by participant by means of memory aid. Injection sites reaction included pain,bruising,redness,swelling. Pain and bruising:Grade0: didn't have it at all; Grade1: noticed it, but it didn't interfere with usual activities at all; Grade2: had it, and it was bad enough to prevent a significant part of usual activities; Grade3: had it, and it prevented most or all of normal activities, or had to see a doctor for prescription medicine, Redness and swelling: participants measured largest diameter of any injection site reaction and grade them from 0 to 3, where Grade0: measured less than(<)10 milliliters(mm); Grade1: larger than or equal to(>=) 10mm and <20mm; Grade 2: >=20mm and <50mm; Grade3: >=50mm. Participants with multiple symptoms in same category were counted once per category using symptom with maximum grade

    2. Number of Participants Reporting Solicited Systemic Reactions [Within 7 days post vaccination]

      Solicited reaction (reactogenicity event) was an AE that was pre-listed in eCRF, considered to be related to vaccination recorded by the participant by means of a memory aid between the day of vaccination (Day 0) and Day 7 post vaccination. Systemic events included fever, fatigue, shivering, joint pain, muscle pain, headache, and nausea. Fever: >=100.4 degree Fahrenheit (ºF) to <101.1ºF; >=101.2ºF to <102.2ºF; >=102.2ºF; Fatigue, shivering, joint pain, muscle pain, headache and nausea: Grade 0: didn't have it at all; Grade 1: noticed it, but it didn't interfere with usual activities at all; Grade 2: had it, and it was bad enough to prevent a significant part of usual activities; and Grade 3: had it, and it prevented most or all of normal activities, or had to see a doctor for prescription medicine. Participants with multiple symptoms in the same category were counted once per category using the symptom with the maximum grade.

    3. Number of Participants Reporting Unsolicited Adverse Events [From Day 0 (post-vaccination) through Day 28 post vaccination]

      An AE was defined as any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a study vaccine, whether or not considered to be related to the study vaccine. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination, ascertained during follow-up visit or telephone contact up to (and including) the Day 28 contact, whether reported spontaneously by the participant or in response to general questions about current or interim health status.

    4. Lot Consistency: Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies Following FluBlok Vaccination [Day 28 post vaccination]

      GMTs of anti-influenza antibodies were measured using a single radial immunodiffusion (SRID) assay for 3 strains: A/Solomon Islands [H1N1], A/Wisconsin [H3N2], and B/Malaysia. Titers were expressed in terms of 1/dilution.

    5. Percentage of Participants With Positive Cell Culture/Culture-Confirmed Influenza Like Illness as Defined by Centers for Disease Control and Prevention (CDC-ILI) [14 days post vaccination through and up to 6 months]

      CDC-defined ILI was defined as fever (body temperature >=100ºF oral accompanied by cough and/or sore throat, on the same day or on consecutive days) due to strains represented in the vaccine.

    Secondary Outcome Measures

    1. Percentage of Participants With Seroprotection to Influenza Vaccine Antigens After Vaccination With FluBlok [28 days post vaccination]

      Anti-influenza antibodies were measured using an HAI assay for 3 strains: A/Solomon Islands [H1N1], A/Wisconsin [H3N2] and B/Malaysia. Seroprotection was defined as a post-vaccination HAI antibody titer of >=1:40.

    2. Percentage of Participants With Seroconversion to Influenza Vaccine Antigens After Vaccination With FluBlok [28 days post vaccination]

      Anti-influenza antibodies were measured using an HAI assay for 3 strains: A/Solomon Islands [H1N1], A/Wisconsin [H3N2] and B/Malaysia. Seroconversion was defined as a post-vaccination titer of >=1:40 in participants with undetectable baseline antibody (HI titer = <1:10) or a >=4-fold rise in antibody in participants with a baseline titer of >=1:10, with the achievement of post-vaccination titer of at least 1:40.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 49 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Healthy adult aged 18-49 years.

    • Provided informed consent prior to any study procedures.

    • Able to comply with all study procedures.

    • Available for follow-up for the duration of the influenza season.

    • Women of child-bearing potential must have had a negative urine pregnancy test at the time of randomization and must be willing to use an adequate form of contraception (includes abstinence, condom with spermicide, licensed hormonal contraceptive, intrauterine device [IUD], monogamous relationship with a vasectomized partner) during the course of the study.

    Exclusion Criteria:
    • Long-term use of oral steroids, parenteral steroids, or high-dose inhaled steroids (greater than [>] 800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (Nasal and topical steroids were allowed).

    • Presence of high-risk conditions or other characteristics were considered to be indication for influenza vaccination, as defined by the Advisory Committee on Immunization Practices.

    • Acute febrile illness (defined as having a temperature greater than or equal to [>=]100 degrees Fahrenheit) or upper respiratory tract illness within 72 hours of vaccination. Participants with acute febrile illness were rescheduled after fever resolved.

    • Use of experimental vaccines or any influenza vaccine other than FluBlOk after May 31st 2007 for the 2008 Southern Hemisphere or 2007 to 2008 Northern hemisphere epidemic seasons.

    • Immunosuppression as a result of an underlying illness or treatment, or used anticancer chemotherapy or radiation therapy within the preceding 36 months.

    • Any malignancy diagnosed or treated actively during the past five (5) years, with two (2) exceptions. Participant with any history of lymphoproliferative disorder were excluded. However, participants with a history of localized non-melanotic skin cancer were eligible.

    • Receipt of any other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study.

    • Receipt of an experimental agent (vaccine, drug, biologic, device, blood product or medication) within 1 month prior to enrollment in this study, or expected to receive an experimental agent during study period.

    • Receipt of parenteral immunoglobulin or other blood product within the three months prior to study vaccination.

    • Major psychiatric diagnosis including schizophrenia, bipolar disease or other major depression, or any diagnosis of dementia or associated concomitant medications (e.g., Aricept) used for treating dementia.

    • Known active human immunodeficiency virus, hepatitis B, or hepatitis C infection.

    • History of alcohol or drug abuse in the last 5 years.

    • Not available for three or more consecutive weeks during flu surveillance period.

    • Any acute or chronic condition that, in the opinion of the investigator, would render vaccination unsafe or interfere with the evaluation of responses or render the participant unable to meet the requirements of the protocol.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Impact Clinical Trials Beverly Hills California United States 90211
    2 Benchmark Research - Sacramento Sacramento California United States 95816
    3 Benchmark Research - San Francisco San Francisco California United States 94102
    4 University Clinical Research, Inc Pembroke Pines Florida United States 33024
    5 Vince and Associates Overland Park Kansas United States 66212
    6 Kentucky pediatric /Adult Research Bardstown Kentucky United States 40004
    7 Benchmarch Research - New Orleans Metairie Louisiana United States 70006
    8 University of Maryland - Baltimore Baltimore Maryland United States 21201
    9 Saint Louis University Saint Louis Missouri United States 63110
    10 Meridian Clinical Research Omaha Nebraska United States 68134
    11 Regional Clinical Research, Inc. Endwell New York United States 13760
    12 Rochester Medical Center Rochester New York United States 14642
    13 Carolina Medical Trials Winston-Salem North Carolina United States 27103
    14 Sterling Research Cincinnati Ohio United States 45246
    15 Primary Physicians Research - Pediatric Alliance St. Clair Pittsburgh Pennsylvania United States 15241
    16 Primary Physicians Research Pittsburgh Pennsylvania United States 15241
    17 Vanderbilt University Medical Center Nashville Tennessee United States 37232
    18 Benchmarch Research - Austin Austin Texas United States 78705
    19 Benchmark Research - Fort Worth Fort Worth Texas United States 76135
    20 Baylor College of Medicine Houston Texas United States 77030
    21 Benchmark Research - San Angelo San Angelo Texas United States 76904
    22 Jean Brown Research Salt Lake City Utah United States 84124
    23 University of Virginia Health System Charlottesville Virginia United States 22908
    24 Marshfield Clinic Marshfield Wisconsin United States 54449

    Sponsors and Collaborators

    • Sanofi
    • Protein Sciences Corporation

    Investigators

    • Principal Investigator: John J Treanor, MD, University of Rochester

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Sanofi
    ClinicalTrials.gov Identifier:
    NCT00539981
    Other Study ID Numbers:
    • PSC04
    First Posted:
    Oct 5, 2007
    Last Update Posted:
    Apr 6, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Sanofi
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details The study was conducted at 24 active centers in the United States from 15-September-2007 to 28-May-2008.
    Pre-assignment Detail A total of 4648 participants were randomized in the study. Participants were randomized in 1:1 ratio to receive FluBlok or Placebo. The FluBlok assignment was further stratified into three lots, A, B and C to assess lot consistency.
    Arm/Group Title FluBlok (Lots A, B, C) Placebo
    Arm/Group Description Participants received a single 0.5 milliliters (mL) dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination.
    Period Title: Overall Study
    STARTED 2344 2304
    COMPLETED 2049 2022
    NOT COMPLETED 295 282

    Baseline Characteristics

    Arm/Group Title FluBlok (Lots A, B, C) Placebo Total
    Arm/Group Description Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. Total of all reporting groups
    Overall Participants 2344 2304 4648
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    2344
    100%
    2304
    100%
    4648
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    1391
    59.3%
    1349
    58.6%
    2740
    59%
    Male
    953
    40.7%
    955
    41.4%
    1908
    41%
    Race/Ethnicity, Customized (Count of Participants)
    White/Caucasian
    1570
    67%
    1530
    66.4%
    3100
    66.7%
    Black/African-American
    430
    18.3%
    447
    19.4%
    877
    18.9%
    Latino/Hispanic
    250
    10.7%
    239
    10.4%
    489
    10.5%
    Asian
    62
    2.6%
    52
    2.3%
    114
    2.5%
    American Indian/Alaska Native
    7
    0.3%
    9
    0.4%
    16
    0.3%
    Native Hawaiian/Pacific Islander
    6
    0.3%
    8
    0.3%
    14
    0.3%
    Other-unspecified
    19
    0.8%
    19
    0.8%
    38
    0.8%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants Reporting Solicited Injection Site (Local) Reactions
    Description Solicited reaction (reactogenicity event) was an adverse event (AE) that was pre-listed in electronic case report form(eCRF), considered to be related to vaccination and recorded by participant by means of memory aid. Injection sites reaction included pain,bruising,redness,swelling. Pain and bruising:Grade0: didn't have it at all; Grade1: noticed it, but it didn't interfere with usual activities at all; Grade2: had it, and it was bad enough to prevent a significant part of usual activities; Grade3: had it, and it prevented most or all of normal activities, or had to see a doctor for prescription medicine, Redness and swelling: participants measured largest diameter of any injection site reaction and grade them from 0 to 3, where Grade0: measured less than(<)10 milliliters(mm); Grade1: larger than or equal to(>=) 10mm and <20mm; Grade 2: >=20mm and <50mm; Grade3: >=50mm. Participants with multiple symptoms in same category were counted once per category using symptom with maximum grade
    Time Frame Within 7 days post vaccination

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population.
    Arm/Group Title FluBlok (Lots A, B, C) Placebo
    Arm/Group Description Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination.
    Measure Participants 2344 2304
    Injection site pain- Grade 0
    1421
    60.6%
    2050
    89%
    Injection site pain- Grade 1
    797
    34%
    177
    7.7%
    Injection site pain- Grade 2
    52
    2.2%
    3
    0.1%
    Injection site pain- Grade 3
    2
    0.1%
    1
    0%
    Injection site bruising- Grade 0
    2197
    93.7%
    2172
    94.3%
    Injection site bruising- Grade 1
    68
    2.9%
    57
    2.5%
    Injection site bruising- Grade 2
    6
    0.3%
    1
    0%
    Injection site bruising- Grade 3
    1
    0%
    1
    0%
    Injection site redness- Grade 0
    2181
    93%
    2184
    94.8%
    Injection site redness- Grade 1
    72
    3.1%
    40
    1.7%
    Injection site redness- Grade 2
    15
    0.6%
    6
    0.3%
    Injection site redness- Grade 3
    4
    0.2%
    1
    0%
    Injection site swelling- Grade 0
    2195
    93.6%
    2189
    95%
    Injection site swelling- Grade 1
    55
    2.3%
    34
    1.5%
    Injection site swelling- Grade 2
    16
    0.7%
    6
    0.3%
    Injection site swelling- Grade 3
    6
    0.3%
    2
    0.1%
    2. Primary Outcome
    Title Number of Participants Reporting Solicited Systemic Reactions
    Description Solicited reaction (reactogenicity event) was an AE that was pre-listed in eCRF, considered to be related to vaccination recorded by the participant by means of a memory aid between the day of vaccination (Day 0) and Day 7 post vaccination. Systemic events included fever, fatigue, shivering, joint pain, muscle pain, headache, and nausea. Fever: >=100.4 degree Fahrenheit (ºF) to <101.1ºF; >=101.2ºF to <102.2ºF; >=102.2ºF; Fatigue, shivering, joint pain, muscle pain, headache and nausea: Grade 0: didn't have it at all; Grade 1: noticed it, but it didn't interfere with usual activities at all; Grade 2: had it, and it was bad enough to prevent a significant part of usual activities; and Grade 3: had it, and it prevented most or all of normal activities, or had to see a doctor for prescription medicine. Participants with multiple symptoms in the same category were counted once per category using the symptom with the maximum grade.
    Time Frame Within 7 days post vaccination

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population.
    Arm/Group Title FluBlok (Lots A, B, C) Placebo
    Arm/Group Description Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination.
    Measure Participants 2344 2304
    Fever (>=100.4ºF)
    2238
    95.5%
    2188
    95%
    Fever (>=100.4 to <101.1ºF)
    8
    0.3%
    5
    0.2%
    Fever (>=101.2 to <102.2ºF)
    5
    0.2%
    6
    0.3%
    Fever (>=102.2ºF)
    4
    0.2%
    1
    0%
    Fatigue- Grade 0
    1932
    82.4%
    1898
    82.4%
    Fatigue- Grade 1
    250
    10.7%
    256
    11.1%
    Fatigue- Grade 2
    78
    3.3%
    66
    2.9%
    Fatigue- Grade 3
    12
    0.5%
    11
    0.5%
    Shivering- Grade 0
    2202
    93.9%
    2160
    93.8%
    Shivering- Grade 1
    52
    2.2%
    54
    2.3%
    Shivering- Grade 2
    12
    0.5%
    13
    0.6%
    Shivering- Grade 3
    6
    0.3%
    4
    0.2%
    Joint pain- Grade 0
    2183
    93.1%
    2148
    93.2%
    Joint pain- Grade 1
    69
    2.9%
    67
    2.9%
    Joint pain- Grade 2
    14
    0.6%
    12
    0.5%
    Joint pain- Grade 3
    6
    0.3%
    4
    0.2%
    Muscle pain- Grade 0
    2033
    86.7%
    2077
    90.1%
    Muscle pain- Grade 1
    197
    8.4%
    124
    5.4%
    Muscle pain- Grade 2
    36
    1.5%
    22
    1%
    Muscle pain- Grade 3
    6
    0.3%
    8
    0.3%
    Headache- Grade 0
    1923
    82%
    1877
    81.5%
    Headache- Grade 1
    264
    11.3%
    273
    11.8%
    Headache- Grade 2
    70
    3%
    68
    3%
    Headache- Grade 3
    15
    0.6%
    13
    0.6%
    Nausea- Grade 0
    2143
    91.4%
    2122
    92.1%
    Nausea- Grade 1
    94
    4%
    74
    3.2%
    Nausea- Grade 2
    29
    1.2%
    25
    1.1%
    Nausea- Grade 3
    6
    0.3%
    10
    0.4%
    3. Primary Outcome
    Title Number of Participants Reporting Unsolicited Adverse Events
    Description An AE was defined as any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a study vaccine, whether or not considered to be related to the study vaccine. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination, ascertained during follow-up visit or telephone contact up to (and including) the Day 28 contact, whether reported spontaneously by the participant or in response to general questions about current or interim health status.
    Time Frame From Day 0 (post-vaccination) through Day 28 post vaccination

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population.
    Arm/Group Title FluBlok (Lots A, B, C) Placebo
    Arm/Group Description Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination.
    Measure Participants 2344 2304
    Count of Participants [Participants]
    61
    2.6%
    67
    2.9%
    4. Primary Outcome
    Title Lot Consistency: Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies Following FluBlok Vaccination
    Description GMTs of anti-influenza antibodies were measured using a single radial immunodiffusion (SRID) assay for 3 strains: A/Solomon Islands [H1N1], A/Wisconsin [H3N2], and B/Malaysia. Titers were expressed in terms of 1/dilution.
    Time Frame Day 28 post vaccination

    Outcome Measure Data

    Analysis Population Description
    Analysis was done on evaluable population that included all participants who had met the study entry criteria and had titers taken at Baseline (Day 0) and after vaccination (Day 28). Data for this outcome measure was planned to be collected and analyzed for each FluBlok lot separately and not planned to be collected for placebo, as pre-specified in protocol.
    Arm/Group Title FluBlok: Lot A FluBlok: Lot B FluBlok: Lot C
    Arm/Group Description Participants received a single 0.5 mL dose of FluBlok vaccine from Lot A, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. Participants received a single 0.5 mL dose of FluBlok vaccine from Lot B, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. Participants received a single 0.5 mL dose of FluBlok vaccine from Lot C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination.
    Measure Participants 150 151 147
    A/Solomon Islands (H1N1)
    346.15
    322.95
    381.00
    A/Wisconsin (H3N2)
    390.34
    192.25
    240.01
    B/Malaysia
    182.10
    205.95
    215.34
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection FluBlok (Lots A, B, C), Placebo
    Comments A/Solomon Islands (H1N1): FluBlok: Lot A versus FluBlok: Lot B
    Type of Statistical Test Equivalence
    Comments Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot A vs. B falls within 0.67 to 1.5.
    Statistical Test of Hypothesis p-Value 0.009
    Comments Threshold for significance of p value was 0.05.
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter GMT ratio
    Estimated Value 1.07
    Confidence Interval (2-Sided) 95%
    0.85 to 1.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection FluBlok (Lots A, B, C), FluBlok: Lot C
    Comments A/Solomon Islands (H1N1): FluBlok: Lot A versus FluBlok: Lot C
    Type of Statistical Test Equivalence
    Comments Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot A vs. C falls within 0.67 to 1.5.
    Statistical Test of Hypothesis p-Value 0.009
    Comments Threshold for significance of p value was 0.05.
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter GMT ratio
    Estimated Value 0.91
    Confidence Interval (2-Sided) 0.91%
    0.71 to 1.15
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, FluBlok: Lot C
    Comments A/Solomon Islands (H1N1): FluBlok: Lot B versus FluBlok: Lot C
    Type of Statistical Test Equivalence
    Comments Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot B vs. C falls within 0.67 to 1.5.
    Statistical Test of Hypothesis p-Value 0.009
    Comments
    Method ANOVA
    Comments Threshold for significance of p value was 0.05.
    Method of Estimation Estimation Parameter GMT ratio
    Estimated Value 0.85
    Confidence Interval (2-Sided) 95%
    0.67 to 1.07
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection FluBlok (Lots A, B, C), Placebo
    Comments A/Wisconsin (H3N2): FluBlok: Lot A versus FluBlok: Lot B
    Type of Statistical Test Equivalence
    Comments Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot A vs. B falls within 0.67 to 1.5.
    Statistical Test of Hypothesis p-Value 0.065
    Comments Threshold of significance for p value was 0.05.
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter GMT ratio
    Estimated Value 2.03
    Confidence Interval (2-Sided) 95%
    1.56 to 2.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection FluBlok (Lots A, B, C), FluBlok: Lot C
    Comments A/Wisconsin (H3N2): FluBlok: Lot A versus FluBlok: Lot C
    Type of Statistical Test Equivalence
    Comments Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot A vs. C falls within 0.67 to 1.5.
    Statistical Test of Hypothesis p-Value 0.065
    Comments
    Method ANOVA
    Comments Threshold of significance for p value was 0.05.
    Method of Estimation Estimation Parameter GMT ratio
    Estimated Value 1.63
    Confidence Interval (2-Sided) 95%
    1.26 to 2.11
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, FluBlok: Lot C
    Comments A/Wisconsin (H3N2): FluBlok: Lot B versus FluBlok: Lot C
    Type of Statistical Test Equivalence
    Comments Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot B vs. C falls within 0.67 to 1.5.
    Statistical Test of Hypothesis p-Value 0.065
    Comments
    Method ANOVA
    Comments Threshold of significance for p value was 0.05.
    Method of Estimation Estimation Parameter GMT ratio
    Estimated Value 0.80
    Confidence Interval (2-Sided) 95%
    0.62 to 1.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection FluBlok (Lots A, B, C), Placebo
    Comments B/Malaysia: FluBlok: Lot A versus FluBlok: Lot B
    Type of Statistical Test Equivalence
    Comments Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot A vs. B falls within 0.67 to 1.5.
    Statistical Test of Hypothesis p-Value 0.011
    Comments
    Method ANOVA
    Comments Threshold of significance for p value was 0.05.
    Method of Estimation Estimation Parameter GMT ratio
    Estimated Value 0.88
    Confidence Interval (2-Sided) 95%
    0.69 to 1.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection FluBlok (Lots A, B, C), FluBlok: Lot C
    Comments B/Malaysia: FluBlok: Lot A versus FluBlok: Lot C
    Type of Statistical Test Equivalence
    Comments Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot A vs. C falls within 0.67 to 1.5.
    Statistical Test of Hypothesis p-Value 0.011
    Comments
    Method ANOVA
    Comments Threshold of significance for p value was 0.05.
    Method of Estimation Estimation Parameter GMT ratio
    Estimated Value 0.85
    Confidence Interval (2-Sided) 95%
    0.65 to 1.09
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, FluBlok: Lot C
    Comments B/Malaysia: FluBlok: Lot B versus FluBlok: Lot C
    Type of Statistical Test Equivalence
    Comments Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot B vs. C falls within 0.67 to 1.5.
    Statistical Test of Hypothesis p-Value 0.011
    Comments
    Method ANOVA
    Comments Threshold of significance for p value was 0.05.
    Method of Estimation Estimation Parameter GMT ratio
    Estimated Value 0.96
    Confidence Interval (2-Sided) 95%
    0.75 to 1.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Primary Outcome
    Title Percentage of Participants With Positive Cell Culture/Culture-Confirmed Influenza Like Illness as Defined by Centers for Disease Control and Prevention (CDC-ILI)
    Description CDC-defined ILI was defined as fever (body temperature >=100ºF oral accompanied by cough and/or sore throat, on the same day or on consecutive days) due to strains represented in the vaccine.
    Time Frame 14 days post vaccination through and up to 6 months

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on safety population.
    Arm/Group Title FluBlok (Lots A, B, C) Placebo
    Arm/Group Description Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination.
    Measure Participants 2344 2304
    Number [percentage of participants]
    0.04
    0%
    0.2
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection FluBlok (Lots A, B, C), Placebo
    Comments FluBlok versus Placebo
    Type of Statistical Test Superiority
    Comments Relative protective efficacy is equivalent to absolute efficacy which is defined as the reduction in the influenza rate for Flublok relative to placebo.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Relative protective efficacy
    Estimated Value 75.4
    Confidence Interval (2-Sided) 95%
    -148.0 to 99.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Percentage of Participants With Seroprotection to Influenza Vaccine Antigens After Vaccination With FluBlok
    Description Anti-influenza antibodies were measured using an HAI assay for 3 strains: A/Solomon Islands [H1N1], A/Wisconsin [H3N2] and B/Malaysia. Seroprotection was defined as a post-vaccination HAI antibody titer of >=1:40.
    Time Frame 28 days post vaccination

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on evaluable population. Data for this outcome measure was not planned to be collected and analyzed for placebo group, as pre-specified in protocol.
    Arm/Group Title FluBlok (Lots A, B, C)
    Arm/Group Description Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination.
    Measure Participants 448
    A/Solomon Islands (H1N1)
    99
    4.2%
    A/Wisconsin (H3N2)
    97
    4.1%
    B/Malaysia
    96
    4.1%
    7. Secondary Outcome
    Title Percentage of Participants With Seroconversion to Influenza Vaccine Antigens After Vaccination With FluBlok
    Description Anti-influenza antibodies were measured using an HAI assay for 3 strains: A/Solomon Islands [H1N1], A/Wisconsin [H3N2] and B/Malaysia. Seroconversion was defined as a post-vaccination titer of >=1:40 in participants with undetectable baseline antibody (HI titer = <1:10) or a >=4-fold rise in antibody in participants with a baseline titer of >=1:10, with the achievement of post-vaccination titer of at least 1:40.
    Time Frame 28 days post vaccination

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on evaluable population. Data for this outcome measure was not planned to be collected and analyzed for placebo group, as pre-specified in protocol.
    Arm/Group Title FluBlok (Lots A, B, C)
    Arm/Group Description Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination.
    Measure Participants 448
    A/Solomon Islands (H1N1)
    78
    3.3%
    A/Wisconsin (H3N2)
    81
    3.5%
    B/Malaysia
    52
    2.2%

    Adverse Events

    Time Frame Unsolicited non-serious AEs: Day 0 to Day 28 post vaccination, Solicited reactions: within 7 days post vaccination, SAE: through the end of influenza season (up to 6 months)
    Adverse Event Reporting Description Solicited reaction was AE that was prelisted (i.e., solicited) in the eCRF and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination. Analysis was performed on Safety population.
    Arm/Group Title FluBlok (Lots A, B, C) Placebo
    Arm/Group Description Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination.
    All Cause Mortality
    FluBlok (Lots A, B, C) Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/2344 (0%) 1/2304 (0%)
    Serious Adverse Events
    FluBlok (Lots A, B, C) Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 30/2344 (1.3%) 34/2304 (1.5%)
    Blood and lymphatic system disorders
    Iron deficiency anaemia 1/2344 (0%) 0/2304 (0%)
    Lymphadenopathy 0/2344 (0%) 1/2304 (0%)
    Cardiac disorders
    Angina pectoris 1/2344 (0%) 0/2304 (0%)
    Myocardial infarction 0/2344 (0%) 1/2304 (0%)
    Pericardial effusion 1/2344 (0%) 0/2304 (0%)
    Sinus tachycardia 1/2344 (0%) 0/2304 (0%)
    Supraventricular tachycardia 0/2344 (0%) 1/2304 (0%)
    Congenital, familial and genetic disorders
    Rathke's cleft cyst 0/2344 (0%) 1/2304 (0%)
    Eye disorders
    Retinal haemorrhage 1/2344 (0%) 0/2304 (0%)
    Gastrointestinal disorders
    Abdominal pain 1/2344 (0%) 1/2304 (0%)
    Crohn's disease 0/2344 (0%) 1/2304 (0%)
    Inflammatory bowel disease 0/2344 (0%) 1/2304 (0%)
    Small intestinal obstruction 1/2344 (0%) 0/2304 (0%)
    Vomiting 1/2344 (0%) 0/2304 (0%)
    General disorders
    Accidental death 0/2344 (0%) 1/2304 (0%)
    Chest pain 0/2344 (0%) 1/2304 (0%)
    Non-cardiac chest pain 1/2344 (0%) 0/2304 (0%)
    Hepatobiliary disorders
    Biliary colic 0/2344 (0%) 1/2304 (0%)
    Cholelithiasis 1/2344 (0%) 0/2304 (0%)
    Infections and infestations
    Appendicitis 1/2344 (0%) 2/2304 (0.1%)
    Cellulitis 0/2344 (0%) 1/2304 (0%)
    Hepatitis viral 1/2344 (0%) 0/2304 (0%)
    Infected insect bite 0/2344 (0%) 1/2304 (0%)
    Infectious mononucleosis 0/2344 (0%) 1/2304 (0%)
    Kidney infection 0/2344 (0%) 2/2304 (0.1%)
    Perianal abscess 0/2344 (0%) 1/2304 (0%)
    Peritonsillar abscess 0/2344 (0%) 1/2304 (0%)
    Pharyngitis streptococcal 0/2344 (0%) 1/2304 (0%)
    Pneumonia 0/2344 (0%) 1/2304 (0%)
    Postoperative infection 0/2344 (0%) 1/2304 (0%)
    Pyelonephritis acute 1/2344 (0%) 0/2304 (0%)
    Staphylococcal abscess 0/2344 (0%) 1/2304 (0%)
    Tonsillitis 1/2344 (0%) 0/2304 (0%)
    Injury, poisoning and procedural complications
    Acetabulum fracture 1/2344 (0%) 0/2304 (0%)
    Cervical vertebral fracture 1/2344 (0%) 0/2304 (0%)
    Fibula fracture 1/2344 (0%) 0/2304 (0%)
    Hand fracture 1/2344 (0%) 0/2304 (0%)
    Head injury 0/2344 (0%) 1/2304 (0%)
    Injury 1/2344 (0%) 0/2304 (0%)
    Ligament injury 1/2344 (0%) 0/2304 (0%)
    Open fracture 1/2344 (0%) 0/2304 (0%)
    Tibia fracture 1/2344 (0%) 0/2304 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/2344 (0%) 2/2304 (0.1%)
    Hyperglycaemic hyperosmolar nonketotic syndrome 0/2344 (0%) 1/2304 (0%)
    Musculoskeletal and connective tissue disorders
    Aseptic necrosis bone 1/2344 (0%) 0/2304 (0%)
    Back pain 1/2344 (0%) 0/2304 (0%)
    Intervertebral disc protrusion 0/2344 (0%) 2/2304 (0.1%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 0/2344 (0%) 1/2304 (0%)
    Liposarcoma 1/2344 (0%) 0/2304 (0%)
    Uterine leiomyoma 2/2344 (0.1%) 0/2304 (0%)
    Nervous system disorders
    Headache 0/2344 (0%) 1/2304 (0%)
    Hypoaesthesia 1/2344 (0%) 0/2304 (0%)
    Pregnancy, puerperium and perinatal conditions
    Ectopic pregnancy 0/2344 (0%) 1/2304 (0%)
    Pregnancy induced hypertension 0/2344 (0%) 1/2304 (0%)
    Psychiatric disorders
    Adjustment disorder 1/2344 (0%) 0/2304 (0%)
    Bipolar disorder 1/2344 (0%) 0/2304 (0%)
    Depression 0/2344 (0%) 3/2304 (0.1%)
    Suicidal ideation 0/2344 (0%) 1/2304 (0%)
    Suicide attempt 2/2344 (0.1%) 1/2304 (0%)
    Depression 0/2344 (0%) 1/2304 (0%)
    Renal and urinary disorders
    Nephrolithiasis 0/2344 (0%) 1/2304 (0%)
    Reproductive system and breast disorders
    Adnexa uteri mass 1/2344 (0%) 0/2304 (0%)
    Dysfunctional uterine bleeding 1/2344 (0%) 0/2304 (0%)
    Dysmenorrhoea 1/2344 (0%) 1/2304 (0%)
    Dyspareunia 0/2344 (0%) 1/2304 (0%)
    Endometrial disorder 1/2344 (0%) 0/2304 (0%)
    Menometrorrhagia 0/2344 (0%) 1/2304 (0%)
    Menorrhagia 1/2344 (0%) 0/2304 (0%)
    Ovarian cyst 1/2344 (0%) 0/2304 (0%)
    Uterine haemorrhage 1/2344 (0%) 0/2304 (0%)
    Uterine prolapse 0/2344 (0%) 1/2304 (0%)
    Prolapsed bladder 1/2344 (0%) 0/2304 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 1/2344 (0%) 0/2304 (0%)
    Pulmonary embolism 1/2344 (0%) 0/2304 (0%)
    Other (Not Including Serious) Adverse Events
    FluBlok (Lots A, B, C) Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 152/2344 (6.5%) 120/2304 (5.2%)
    Nervous system disorders
    Headache 35/2344 (1.5%) 42/2304 (1.8%)
    Respiratory, thoracic and mediastinal disorders
    Cough 48/2344 (2%) 37/2304 (1.6%)
    Nasal congestion 37/2344 (1.6%) 31/2304 (1.3%)
    Pharyngolaryngeal pain 42/2344 (1.8%) 49/2304 (2.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.

    Results Point of Contact

    Name/Title Trial Transparency Team
    Organization Sanofi Pasteur
    Phone 800-633-1610 ext 1#
    Email Contact-US@sanofi.com
    Responsible Party:
    Sanofi
    ClinicalTrials.gov Identifier:
    NCT00539981
    Other Study ID Numbers:
    • PSC04
    First Posted:
    Oct 5, 2007
    Last Update Posted:
    Apr 6, 2022
    Last Verified:
    Mar 1, 2022