Asthma
Conditions
Keywords
Male and female adolescent patients, severe asthma
Brief summary
This is a randomized, double-blind, parallel group, placebo-controlled study designed to investigate the potential effect of a fixed dose of benralizumab administered subcutaneously (SC) on antibody responses following seasonal influenza virus vaccination
Detailed description
This study is designed to investigate the potential effect of benralizumab on the antibody response to the seasonal influenza virus vaccine in patients 12-21 years of age with asthma. Benralizumab will be given subcutaneously (SC) at Weeks 0, 4, and 8 weeks, at which time benralizumab levels will reach steady state. Patients will then receive 1 dose of intramuscular (IM) seasonal influenza virus vaccine at Week 8 and samples drawn at Week 8 and Week 12 to measure the antibody response to the influenza virus
Interventions
DRUGBenralizumab
Benralizumab SC administered every 4 weeks for 3 doses (Weeks 0, 4, and 8).
Placebo administered every 4 weeks for 3 doses (Weeks 0, 4, and 8).
DRUGSeasonal influenza virus vaccine
Patients will receive 1 dose of seasonal influenza virus vaccine Intramuscular (IM) at Week 8.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Female and male patients aged 12 to 21 years, inclusive, at the time of Visit 1 * Weight of ≥40 kg * Documented history of current treatment with Inhaled corticosteroids (ICS) and long-acting β2 agonists (LABA) * Morning pre-bronchodilator forced expiratory volume in 1 second (FEV1) of \>50% predicted at Visit 1 or Visit 2. * Airway reversibility (FEV1 \>12% and 200 ml) demonstrated at Visit 1 or Visit 2 using the Maximum Post-bronchodilator Procedure OR * Airway reversibility documented in the previous 12 months prior to Visit 1 * An exacerbation, 1 or more, that required oral corticosteroids in the previous year OR * Any condition assessed by patient recall over the previous 2-4 weeks
Exclusion criteria
* Clinically important pulmonary disease other than asthma * Known history of allergy or reaction to the Investigational Product formulation or influenza vaccine * Receipt of an influenza vaccine within 90 days prior to randomization * Poorly controlled asthma during the screening period that requires treatment with oral corticosteroids or a hospitalization/emergency room visit for the treatment of asthma * Acute illness or evidence of significant active infection or known influenza infection during the current flu season
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | 4 weeks | To compare the geometric mean fold rises in influenza strain-specific hemagglutination-inhibition responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean \[log(z) x\]), where x is the postdose HAI antibody titer fold rise from Week 8 and z is the natural logarithm. |
| Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 | 12 weeks | To compare the geometric mean titers of hemagglutination-inhibition antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. |
| Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12 | 4 weeks | To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in hemagglutination-inhibition antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. |
| Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 | 12 weeks | To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥40-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 | 12 weeks | To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥320-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. |
| Change From Baseline in Mean Asthma Control Questionnaire 6 (ACQ-6) Score at Week 12 | 12 weeks | To compare the change from baseline at Week 12 in mean ACQ-6 score between patients receiving benralizumab 30mg and patients receiving placebo. The ACQ-6 assesses asthma symptoms (nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and short-acting β2 agonist use). Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses to each question. Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and ≤1.5 indicate partly controlled asthma, and a score \>1.5 indicates not well controlled asthma |
| Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | 4 weeks | To compare the geometric mean fold rises in influenza strain-specific microneutralization antibody responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean \[log(z) x\]), where x is the postdose microneutralization antibody titer fold rise from Week 8 and z is the natural logarithm. |
| Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 | 12 weeks | To compare the geometric mean titers of microneutralization antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. |
| Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12 | 4 weeks | To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in microneutralization antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 30 study centers in the United States between 01 July 2016 and 24 January 2017
Pre-assignment details
The study duration was up to 23 weeks, consisting of an initial screening period lasting up to 3 weeks, a 12-week treatment period, and a follow-up visit 8 weeks after the last dose of study drug
Participants by arm
| Arm | Count |
|---|---|
| Benralizumab 30mg Benralizumab 30mg/day subcutaneous | 51 |
| Placebo Placebo to benralizumab subcutaneous | 52 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Benralizumab 30mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 16.0 Years STANDARD_DEVIATION 2.65 | 15.7 Years STANDARD_DEVIATION 2.99 | 15.9 Years STANDARD_DEVIATION 2.82 |
| Age, Customized ≥12 to ≤17 | 36 Participants | 36 Participants | 72 Participants |
| Age, Customized ≥18 to ≤21 | 15 Participants | 16 Participants | 31 Participants |
| Race/Ethnicity, Customized American Indian Or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black Or African American | 13 Participants | 13 Participants | 26 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 38 Participants | 36 Participants | 74 Participants |
| Sex/Gender, Customized Female | 21 Participants | 21 Participants | 42 Participants |
| Sex/Gender, Customized Male | 30 Participants | 31 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 52 |
| other Total, other adverse events | 28 / 51 | 23 / 52 |
| serious Total, serious adverse events | 0 / 51 | 2 / 52 |
Outcome results
Primary
Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12
To compare the geometric mean titers of hemagglutination-inhibition antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time frame: 12 weeks
Population: The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Benralizumab 30mg | Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 | Influenza A H1N1 | 521.06 Antibody titer | Standard Error 1.13 |
| Benralizumab 30mg | Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 | Influenza A H3N2 | 170.73 Antibody titer | Standard Error 1.15 |
| Benralizumab 30mg | Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 | Influenza B Yamagata lineage | 61.47 Antibody titer | Standard Error 1.13 |
| Benralizumab 30mg | Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 | Influenza B Victoria lineage | 53.10 Antibody titer | Standard Error 1.14 |
| Placebo | Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 | Influenza B Victoria lineage | 66.85 Antibody titer | Standard Error 1.14 |
| Placebo | Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 | Influenza A H1N1 | 518.60 Antibody titer | Standard Error 1.13 |
| Placebo | Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 | Influenza B Yamagata lineage | 63.15 Antibody titer | Standard Error 1.13 |
| Placebo | Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 | Influenza A H3N2 | 219.35 Antibody titer | Standard Error 1.15 |
Comparison: Influenza A H1N190% CI: [0.76, 1.31]ANCOVA
Comparison: Influenza A H3N290% CI: [0.93, 1.77]ANCOVA
Comparison: Influenza B Yamagata lineage90% CI: [0.79, 1.34]ANCOVA
Comparison: Influenza B Victoria lineage90% CI: [0.93, 1.7]ANCOVA
Primary
Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12
To compare the geometric mean fold rises in influenza strain-specific hemagglutination-inhibition responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean \[log(z) x\]), where x is the postdose HAI antibody titer fold rise from Week 8 and z is the natural logarithm.
Time frame: 4 weeks
Population: The vaccine immunogenicity analysis set included all randomized patients who received ≥1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or microneutralization antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Benralizumab 30mg | Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza A H1N1 | 3.60 Fold change | Standard Error 1.22 |
| Benralizumab 30mg | Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza A H3N2 | 3.25 Fold change | Standard Error 1.18 |
| Benralizumab 30mg | Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza B Yamagata lineage | 3.42 Fold change | Standard Error 1.16 |
| Benralizumab 30mg | Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza B Victoria lineage | 4.08 Fold change | Standard Error 1.19 |
| Placebo | Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza B Victoria lineage | 3.27 Fold change | Standard Error 1.19 |
| Placebo | Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza A H1N1 | 3.13 Fold change | Standard Error 1.22 |
| Placebo | Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza B Yamagata lineage | 3.17 Fold change | Standard Error 1.16 |
| Placebo | Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza A H3N2 | 3.85 Fold change | Standard Error 1.18 |
Comparison: Influenza A H1N190% CI: [0.56, 1.35]ANCOVA
Comparison: Influenza A H3N290% CI: [0.82, 1.71]ANCOVA
Comparison: Influenza B Yamagata lineage90% CI: [0.67, 1.29]ANCOVA
Comparison: Influenza B Victoria lineage90% CI: [0.54, 1.19]ANCOVA
Primary
Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12
To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥40-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time frame: 12 weeks
Population: The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Benralizumab 30mg | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 | Influenza A H1N1 | 1.00 Proportion of Participants | 90% Confidence Interval 251.9 |
| Benralizumab 30mg | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 | Influenza A H3N2 | 0.980 Proportion of Participants | 90% Confidence Interval 136.2 |
| Benralizumab 30mg | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 | Influenza B Victoria lineage | 0.780 Proportion of Participants | 90% Confidence Interval 178.7 |
| Benralizumab 30mg | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 | Influenza B Yamagata lineage | 0.860 Proportion of Participants | 90% Confidence Interval 144.9 |
| Placebo | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 | Influenza B Yamagata lineage | 0.796 Proportion of Participants | 90% Confidence Interval 115 |
| Placebo | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 | Influenza A H1N1 | 1.00 Proportion of Participants | 90% Confidence Interval 191.3 |
| Placebo | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 | Influenza B Victoria lineage | 0.878 Proportion of Participants | 90% Confidence Interval 162.2 |
| Placebo | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 | Influenza A H3N2 | 0.980 Proportion of Participants | 90% Confidence Interval 168.6 |
Primary
Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12
To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in hemagglutination-inhibition antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time frame: 4 weeks
Population: The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Benralizumab 30mg | Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12 | Influenza A H1N1 | 0.440 Proportion of Participants |
| Benralizumab 30mg | Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12 | Influenza A H3N2 | 0.500 Proportion of Participants |
| Benralizumab 30mg | Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12 | Influenza B Yamagata lineage | 0.480 Proportion of Participants |
| Benralizumab 30mg | Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12 | Influenza B Victoria lineage | 0.560 Proportion of Participants |
| Placebo | Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12 | Influenza B Victoria lineage | 0.408 Proportion of Participants |
| Placebo | Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12 | Influenza A H1N1 | 0.306 Proportion of Participants |
| Placebo | Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12 | Influenza B Yamagata lineage | 0.490 Proportion of Participants |
| Placebo | Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12 | Influenza A H3N2 | 0.490 Proportion of Participants |
Secondary
Change From Baseline in Mean Asthma Control Questionnaire 6 (ACQ-6) Score at Week 12
To compare the change from baseline at Week 12 in mean ACQ-6 score between patients receiving benralizumab 30mg and patients receiving placebo. The ACQ-6 assesses asthma symptoms (nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and short-acting β2 agonist use). Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses to each question. Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and ≤1.5 indicate partly controlled asthma, and a score \>1.5 indicates not well controlled asthma
Time frame: 12 weeks
Population: The full analysis set included all patients who were randomized and received any investigational product.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Benralizumab 30mg | Change From Baseline in Mean Asthma Control Questionnaire 6 (ACQ-6) Score at Week 12 | -0.50 Score on a scale |
| Placebo | Change From Baseline in Mean Asthma Control Questionnaire 6 (ACQ-6) Score at Week 12 | -0.42 Score on a scale |
Secondary
Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12
To compare the geometric mean fold rises in influenza strain-specific microneutralization antibody responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean \[log(z) x\]), where x is the postdose microneutralization antibody titer fold rise from Week 8 and z is the natural logarithm.
Time frame: 4 weeks
Population: The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Benralizumab 30mg | Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza A H1N1 | 5.1 Fold change | Geometric Coefficient of Variation 521.4 |
| Benralizumab 30mg | Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza A H3N2 | 3.2 Fold change | Geometric Coefficient of Variation 149.8 |
| Benralizumab 30mg | Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza B Yamagata lineage | 2.8 Fold change | Geometric Coefficient of Variation 148.9 |
| Benralizumab 30mg | Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza B Victoria lineage | 3.8 Fold change | Geometric Coefficient of Variation 224.1 |
| Placebo | Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza B Victoria lineage | 3.5 Fold change | Geometric Coefficient of Variation 195.3 |
| Placebo | Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza A H1N1 | 4.4 Fold change | Geometric Coefficient of Variation 329.4 |
| Placebo | Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza B Yamagata lineage | 3.2 Fold change | Geometric Coefficient of Variation 141.3 |
| Placebo | Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 | Influenza A H3N2 | 3.6 Fold change | Geometric Coefficient of Variation 210 |
Secondary
Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12
To compare the geometric mean titers of microneutralization antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time frame: 12 weeks
Population: The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Benralizumab 30mg | Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 | Influenza A H1N1 | 3774.1 Antibody titer | Geometric Coefficient of Variation 181.7 |
| Benralizumab 30mg | Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 | Influenza A H3N2 | 4307.5 Antibody titer | Geometric Coefficient of Variation 169 |
| Benralizumab 30mg | Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 | Influenza B Yamagata lineage | 350.2 Antibody titer | Geometric Coefficient of Variation 103.6 |
| Benralizumab 30mg | Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 | Influenza B Victoria lineage | 164.5 Antibody titer | Geometric Coefficient of Variation 178.5 |
| Placebo | Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 | Influenza B Victoria lineage | 234.4 Antibody titer | Geometric Coefficient of Variation 135 |
| Placebo | Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 | Influenza A H1N1 | 3969.1 Antibody titer | Geometric Coefficient of Variation 154 |
| Placebo | Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 | Influenza B Yamagata lineage | 336.2 Antibody titer | Geometric Coefficient of Variation 114.3 |
| Placebo | Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 | Influenza A H3N2 | 4351.3 Antibody titer | Geometric Coefficient of Variation 171 |
Secondary
Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12
To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥320-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time frame: 12 weeks
Population: The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Benralizumab 30mg | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 | Influenza B Yamagata lineage | 0.020 Proportion of Participants |
| Benralizumab 30mg | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 | Influenza A H3N2 | 0.500 Proportion of Participants |
| Benralizumab 30mg | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 | Influenza B Victoria lineage | 0.080 Proportion of Participants |
| Benralizumab 30mg | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 | Influenza A H1N1 | 0.840 Proportion of Participants |
| Placebo | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 | Influenza B Victoria lineage | 0.041 Proportion of Participants |
| Placebo | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 | Influenza A H3N2 | 0.612 Proportion of Participants |
| Placebo | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 | Influenza B Yamagata lineage | 0.020 Proportion of Participants |
| Placebo | Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 | Influenza A H1N1 | 0.857 Proportion of Participants |
Secondary
Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12
To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in microneutralization antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.
Time frame: 4 weeks
Population: The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Benralizumab 30mg | Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12 | Influenza A H1N1 | 0.420 Proportion of Participants | 90% Confidence Interval 251.9 |
| Benralizumab 30mg | Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12 | Influenza A H3N2 | 0.440 Proportion of Participants | 90% Confidence Interval 136.2 |
| Benralizumab 30mg | Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12 | Influenza B Yamagata lineage | 0.280 Proportion of Participants | 90% Confidence Interval 144.9 |
| Benralizumab 30mg | Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12 | Influenza B Victoria lineage | 0.400 Proportion of Participants | 90% Confidence Interval 178.7 |
| Placebo | Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12 | Influenza B Victoria lineage | 0.388 Proportion of Participants | 90% Confidence Interval 162.2 |
| Placebo | Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12 | Influenza A H1N1 | 0.408 Proportion of Participants | 90% Confidence Interval 191.3 |
| Placebo | Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12 | Influenza B Yamagata lineage | 0.388 Proportion of Participants | 90% Confidence Interval 115 |
| Placebo | Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12 | Influenza A H3N2 | 0.429 Proportion of Participants | 90% Confidence Interval 168.6 |