Asthma
Conditions
Keywords
Inadequately controlled asthma, brodalumab, AMG 827
Brief summary
The purpose of this study is to determine if brodalumab (AMG 827) is safe and effective compared to placebo as measured by change in Asthma Control Questionnaire (ACQ) composite scores.
Interventions
BIOLOGICALPlacebo
Placebo administered subcutaneously
BIOLOGICALBrodalumab
Brodalumab administered subcutaneously
Sponsors
Kyowa Kirin Co., Ltd.
AstraZeneca
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of asthma, and presently has reversibility over pre-bronchodilator forced expiratory volume in 1 second (FEV1) of ≥ 20% at screening * Percent of predicted FEV1 ≥ 40% and ≤ 80% at screening * Inhaled corticosteroid (ICS) ≥ 200 and ≤ 1000/μg/day fluticasone powder or equivalent * Ongoing asthma symptoms with asthma control questionnaire (ACQ) composite score at screening and baseline ≥ 1.5 points
Exclusion criteria
* History of chronic obstructive pulmonary disease (COPD) or other chronic pulmonary condition other than asthma * History of allergic bronchopulmonary aspergillosis * Respiratory infection within 4 weeks of screening or 1 week of baseline visit * Subject has known history of Crohn's disease * Subject has any other significant concurrent medical condition of laboratory abnormalities, as defined in the study protocol * Subject has previously used any anti-interleukin-17 (IL17) biologic therapy * Subject is pregnant or breastfeeding, or planning to become pregnant while enrolled in the study * Female subject is unwilling to use highly effective methods of birth control unless 2 years post-menopausal or surgically sterile * Subject has severe depression measured by Personal Health Questionnaire Depression Scale (PHQ-8) or suicidal ideation/behavior as measured by and Columbia Suicide Severity Rating Scale (e-CSSRS) * Subject has a history or evidence of psychiatric disorder or substance abuse considered by the Investigator to pose a risk to subject safety
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Score at Week 24 | Baseline and week 24 | The ACQ is a validated instrument used in clinical research and practice to evaluate asthma control/impairment. The ACQ assesses disease control by evaluating 7 questions: night time awakenings, asthma symptoms upon wakening, activity limitation, shortness of breath, wheeze frequency, short-acting bronchodilator use, and FEV1. All seven items are scored on a 7-point scale, with 0 indicating good control and 6 indicating poor control; the total score is the mean of the seven items and ranges from 0 (totally-controlled) to 6 (extremely poorly controlled). A negative change from baseline indicates improvement. A change of 0.50 points is considered clinically meaningful and a total score of \< 1.0 indicates good asthma control. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Asthma Exacerbation Rate | Baseline to week 24 | The asthma exacerbation event rate is defined as the number of events per subject-year during the 24 week treatment period. An asthma exacerbation was defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study; distinct asthma exacerbations were defined as events with start dates more than 10 days apart from each other. |
| Change From Baseline in ACQ Composite Score at Week 24 in ICS+LABA Subpopulation | Baseline and week 24 | The ACQ is a validated instrument used in clinical research and practice to evaluate asthma control/impairment. The ACQ assesses disease control by evaluating 7 questions: night time awakenings, asthma symptoms upon wakening, activity limitation, shortness of breath, wheeze frequency, short-acting bronchodilator use, and FEV1. All seven items are scored on a 7-point scale, with 0 indicating good control and 6 indicating poor control; the total score is the mean of the seven items and ranges from 0 (totally-controlled) to 6 (extremely poorly controlled). A negative change from baseline indicates improvement. A change of 0.50 points is considered clinically meaningful and a total score of \< 1.0 indicates good asthma control. |
| Asthma Exacerbation Rate in ICS+LABA Subpopulation | Baseline to week 24 | The asthma exacerbation event rate is defined as the number of events per subject-year during the 24 week treatment period. An asthma exacerbation was defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study; distinct asthma exacerbations were defined as events with start dates more than 10 days apart from each other. |
| Change From Baseline in Daily Asthma Symptom Score (7-day Average Score) | Baseline and week 24 | The Asthma Symptom Diary (ASD) consists of 23 questions answered on a handheld device, including 10 asthma symptom-related items (5 answered in the morning and 5 in the evening). The morning diary comprises questions on 4 asthma-related symptoms (wheezing, shortness of breath, cough, chest tightness), rated on a 5-point severity scale from 0 (no symptom) to 4 (very severe symptoms), and 1 question on nocturnal awakenings, rated from 0 (did not wake up) to 4 (unable to sleep due to asthma). The evening diary has questions on the same 4 asthma-related symptoms and 1 question on limitations of activities, rated from 0 (not at all) to 4 (extremely). The ASD daily score is computed by averaging the responses to the 10 symptom-related items, and the mean 7-day ASD score is calculated by averaging the 7 daily scores, with the final score ranging from 0 (minimal symptoms) to 4 (very severe symptoms). |
| Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) | Baseline and week 24 | — |
| Change From Baseline in Daily Rescue Short-acting Beta-agonist Use | Baseline and week 24 | Participants were permitted allowed to use their inhaled rescue medication (SABA) as needed throughout the study and the use was captured in the daily electronic diary (eDiary). |
| Number of Participants Who Experienced an Asthma Exacerbation | Baseline to week 24 | An asthma exacerbation is defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study. |
| Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Overall Score | Baseline and week 24 | The AQLQ is an asthma-specific instrument that includes evaluations of both symptoms and health-related quality of life measures. The 32-item instrument measures 4 domains affected by asthma including activity limitations, emotional function, exposure to environmental stimuli, and symptoms. Participants were asked to recall their experiences during the last 2 weeks and to respond to each question on a 7-point scale (7=no impairment, 1=severe impairment). The overall score was calculated as mean of the responses to the 32 questions and ranges from 1 (severe impairment) to 7 (no impairment). A positive change from baseline indicates improvement. |
| Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) | Baseline and week 24 | Peak expiratory flow rate was measured by the participant twice daily at approximately the same time each day (eg, within 1 hour of waking and immediately before bedtime) using a peak flow meter. |
| Change From Baseline in Variation of Peak Flow | Baseline and week 24 | Peak flow was measured by the participant twice daily at approximately the same time each day (eg, within 1 hour of waking and immediately before bedtime) using a peak flow meter. The variation of peak flow is defined as the absolute value of the difference between the A.M. and P.M. peak flow in one day for an individual participant. |
| Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Baseline (the 4 weeks prior to first dose) and 4-week intervals up to week 24 | Asthma symptom-free days is defined as days that a participant had a score of zero in their daily asthma symptom diary score. The ASD consists of 23 questions answered on a handheld device, including 10 asthma symptom-related items (5 answered in the morning and 5 in the evening). The morning diary comprises questions on 4 asthma-related symptoms (wheezing, shortness of breath, cough, chest tightness), rated on a 5-point severity scale from 0 (no symptom) to 4 (very severe symptoms), and 1 question on nocturnal awakenings, rated from 0 (did not wake up) to 4 (unable to sleep due to asthma). The evening diary has questions on the same 4 asthma-related symptoms and 1 question on limitations of activities, rated from 0 (not at all) to 4 (extremely). The daily score is the average of the responses to the 10 items. |
| Serum Brodalumab Concentration | Day 1 and weeks 1, 2, 4, 8, 12, 16, and 22 at predose, week 2 + 3 days, week 22 + 3, 7, 10, and 14 days | Serum brodalumab concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) = 0.0500 µg/mL; values below the LLOQ were set to zero. |
| Time to First Asthma Exacerbation | From first dose of study drug to week 24 | An asthma exacerbation is defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study. Median time to first asthma exacerbation could not be estimated, the percentage of participants with an asthma exacerbation is reported. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug up to the end of study, 28 weeks | Adverse events were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. The investigator assessed whether the adverse event was possibly related to the investigational product. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: * fatal; * life threatening; * requires in-patient hospitalization or prolongation of existing hospitalization; * results in persistent or significant disability/incapacity; * congenital anomaly/birth defect; * other medically important serious event. |
Countries
Australia, Canada, France, Germany, Greece, Hong Kong, Ireland, Italy, New Zealand, Poland, Puerto Rico, Russia, South Korea, Taiwan, United States
Participant flow
Recruitment details
This study was conducted at 157 centers in Asia, Australia, Canada, Europe, and the United States.
Pre-assignment details
Participants underwent 3 run-in visits over 4 weeks after completing screening assessments and meeting eligibility criteria. After the run-in visits, eligibility of asthma control questionnaire (ACQ), forced expiratory volume in 1 second (FEV1), and reversibility were confirmed. Eligible participants were randomized in a 1:1 ratio to 1 of 2 arms, stratified based on the current use of long acting β-agonist (LABAs) and number of prior exacerbations (≤ 2 or \> 2) in the past year before screening.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22. | 207 |
| Brodalumab 210 mg Participants received brodalumab 210 mg administered by subcutaneous injection on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22. | 208 |
| Total | 415 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Sponsor Decision | 26 | 24 |
| Overall Study | Withdrawal by Subject | 19 | 27 |
Baseline characteristics
| Characteristic | Placebo | Brodalumab 210 mg | Total |
|---|---|---|---|
| Age, Continuous | 47.3 years STANDARD_DEVIATION 13.3 | 47.2 years STANDARD_DEVIATION 14 | 47.3 years STANDARD_DEVIATION 13.6 |
| Duration of Asthma | 22.20 years STANDARD_DEVIATION 14.89 | 22.92 years STANDARD_DEVIATION 14.44 | 22.56 years STANDARD_DEVIATION 14.66 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 13 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 199 Participants | 195 Participants | 394 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 10 Participants | 13 Participants | 23 Participants |
| Race/Ethnicity, Customized Black or African American | 29 Participants | 19 Participants | 48 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 162 Participants | 174 Participants | 336 Participants |
| Randomization Strata LABA -No; ≤ 2 asthma exacerbation prior year | 30 Participants | 37 Participants | 67 Participants |
| Randomization Strata LABA -No; > 2 asthma exacerbation prior year | 0 Participants | 1 Participants | 1 Participants |
| Randomization Strata LABA -Yes; ≤ 2 asthma exacerbation prior year | 160 Participants | 153 Participants | 313 Participants |
| Randomization Strata LABA -Yes; > 2 asthma exacerbation prior year | 17 Participants | 17 Participants | 34 Participants |
| Sex: Female, Male Female | 120 Participants | 122 Participants | 242 Participants |
| Sex: Female, Male Male | 87 Participants | 86 Participants | 173 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 104 / 207 | 129 / 208 |
| serious Total, serious adverse events | 8 / 207 | 7 / 208 |
Outcome results
Primary
Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Score at Week 24
The ACQ is a validated instrument used in clinical research and practice to evaluate asthma control/impairment. The ACQ assesses disease control by evaluating 7 questions: night time awakenings, asthma symptoms upon wakening, activity limitation, shortness of breath, wheeze frequency, short-acting bronchodilator use, and FEV1. All seven items are scored on a 7-point scale, with 0 indicating good control and 6 indicating poor control; the total score is the mean of the seven items and ranges from 0 (totally-controlled) to 6 (extremely poorly controlled). A negative change from baseline indicates improvement. A change of 0.50 points is considered clinically meaningful and a total score of \< 1.0 indicates good asthma control.
Time frame: Baseline and week 24
Population: Full analysis set with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Score at Week 24 | -0.815 score on a scale | Standard Error 0.073 |
| Brodalumab 210 mg | Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Score at Week 24 | -0.865 score on a scale | Standard Error 0.074 |
p-value: 0.521995% CI: [-0.203, 0.103]Mixed-effect model
Secondary
Asthma Exacerbation Rate
The asthma exacerbation event rate is defined as the number of events per subject-year during the 24 week treatment period. An asthma exacerbation was defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study; distinct asthma exacerbations were defined as events with start dates more than 10 days apart from each other.
Time frame: Baseline to week 24
Population: Full analysis set with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Asthma Exacerbation Rate | 0.57 exacerbations per subject-year |
| Brodalumab 210 mg | Asthma Exacerbation Rate | 0.81 exacerbations per subject-year |
p-value: 0.10295% CI: [0.93, 2.12]Generalized linear model
Secondary
Asthma Exacerbation Rate in ICS+LABA Subpopulation
The asthma exacerbation event rate is defined as the number of events per subject-year during the 24 week treatment period. An asthma exacerbation was defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study; distinct asthma exacerbations were defined as events with start dates more than 10 days apart from each other.
Time frame: Baseline to week 24
Population: Full analysis set participants taking both ICS and LABA at baseline with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Asthma Exacerbation Rate in ICS+LABA Subpopulation | 0.60 exacerbations per subject-year |
| Brodalumab 210 mg | Asthma Exacerbation Rate in ICS+LABA Subpopulation | 0.89 exacerbations per subject-year |
p-value: 0.09695% CI: [0.94, 2.24]Generalized linear model
Secondary
Change From Baseline in ACQ Composite Score at Week 24 in ICS+LABA Subpopulation
The ACQ is a validated instrument used in clinical research and practice to evaluate asthma control/impairment. The ACQ assesses disease control by evaluating 7 questions: night time awakenings, asthma symptoms upon wakening, activity limitation, shortness of breath, wheeze frequency, short-acting bronchodilator use, and FEV1. All seven items are scored on a 7-point scale, with 0 indicating good control and 6 indicating poor control; the total score is the mean of the seven items and ranges from 0 (totally-controlled) to 6 (extremely poorly controlled). A negative change from baseline indicates improvement. A change of 0.50 points is considered clinically meaningful and a total score of \< 1.0 indicates good asthma control.
Time frame: Baseline and week 24
Population: Full analysis set participants who were taking both inhaled corticosteroids (ICS) and a long-acting β-agonist (LABA) at baseline with available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in ACQ Composite Score at Week 24 in ICS+LABA Subpopulation | -0.793 score on a scale | Standard Error 0.084 |
| Brodalumab 210 mg | Change From Baseline in ACQ Composite Score at Week 24 in ICS+LABA Subpopulation | -0.831 score on a scale | Standard Error 0.088 |
p-value: 0.663295% CI: [-0.21, 0.134]Mixed-effect model
Secondary
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Overall Score
The AQLQ is an asthma-specific instrument that includes evaluations of both symptoms and health-related quality of life measures. The 32-item instrument measures 4 domains affected by asthma including activity limitations, emotional function, exposure to environmental stimuli, and symptoms. Participants were asked to recall their experiences during the last 2 weeks and to respond to each question on a 7-point scale (7=no impairment, 1=severe impairment). The overall score was calculated as mean of the responses to the 32 questions and ranges from 1 (severe impairment) to 7 (no impairment). A positive change from baseline indicates improvement.
Time frame: Baseline and week 24
Population: Full analysis set with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Overall Score | 0.804 score on a scale | Standard Error 0.085 |
| Brodalumab 210 mg | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Overall Score | 0.803 score on a scale | Standard Error 0.087 |
p-value: 0.98795% CI: [-0.174, 0.171]Mixed-effects model
Secondary
Change From Baseline in Daily Asthma Symptom Score (7-day Average Score)
The Asthma Symptom Diary (ASD) consists of 23 questions answered on a handheld device, including 10 asthma symptom-related items (5 answered in the morning and 5 in the evening). The morning diary comprises questions on 4 asthma-related symptoms (wheezing, shortness of breath, cough, chest tightness), rated on a 5-point severity scale from 0 (no symptom) to 4 (very severe symptoms), and 1 question on nocturnal awakenings, rated from 0 (did not wake up) to 4 (unable to sleep due to asthma). The evening diary has questions on the same 4 asthma-related symptoms and 1 question on limitations of activities, rated from 0 (not at all) to 4 (extremely). The ASD daily score is computed by averaging the responses to the 10 symptom-related items, and the mean 7-day ASD score is calculated by averaging the 7 daily scores, with the final score ranging from 0 (minimal symptoms) to 4 (very severe symptoms).
Time frame: Baseline and week 24
Population: Full analysis set with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Daily Asthma Symptom Score (7-day Average Score) | -0.397 score on a scale | Standard Error 0.042 |
| Brodalumab 210 mg | Change From Baseline in Daily Asthma Symptom Score (7-day Average Score) | -0.443 score on a scale | Standard Error 0.043 |
p-value: 0.32995% CI: [-0.137, 0.046]Mixed-effect model
Secondary
Change From Baseline in Daily Rescue Short-acting Beta-agonist Use
Participants were permitted allowed to use their inhaled rescue medication (SABA) as needed throughout the study and the use was captured in the daily electronic diary (eDiary).
Time frame: Baseline and week 24
Population: Full analysis set with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Daily Rescue Short-acting Beta-agonist Use | -1.359 puffs | Standard Error 0.243 |
| Brodalumab 210 mg | Change From Baseline in Daily Rescue Short-acting Beta-agonist Use | -1.231 puffs | Standard Error 0.246 |
p-value: 0.631795% CI: [-0.396, 0.653]Mixed-effect model
Secondary
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR)
Peak expiratory flow rate was measured by the participant twice daily at approximately the same time each day (eg, within 1 hour of waking and immediately before bedtime) using a peak flow meter.
Time frame: Baseline and week 24
Population: Full analysis set with available data
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) | Morning peak flow | 0.072 L/min | Standard Error 5.813 |
| Placebo | Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) | Evening peak flow | -10.008 L/min | Standard Error 5.719 |
| Brodalumab 210 mg | Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) | Evening peak flow | -4.089 L/min | Standard Error 5.771 |
| Brodalumab 210 mg | Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) | Morning peak flow | 0.706 L/min | Standard Error 5.885 |
Comparison: Analysis of morning peak flowp-value: 0.905395% CI: [-9.82, 11.089]Mixed-effect model
Comparison: Analysis of evening peak flowp-value: 0.266195% CI: [-4.515, 16.354]Mixed-effects model
Secondary
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1)
Time frame: Baseline and week 24
Population: Full analysis set with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) | 0.207 L/s | Standard Error 0.045 |
| Brodalumab 210 mg | Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) | 0.237 L/s | Standard Error 0.046 |
p-value: 0.454995% CI: [-0.049, 0.109]Mixed-effect model
Secondary
Change From Baseline in Variation of Peak Flow
Peak flow was measured by the participant twice daily at approximately the same time each day (eg, within 1 hour of waking and immediately before bedtime) using a peak flow meter. The variation of peak flow is defined as the absolute value of the difference between the A.M. and P.M. peak flow in one day for an individual participant.
Time frame: Baseline and week 24
Population: Full analysis set with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Variation of Peak Flow | -0.872 L/min | Standard Error 2.135 |
| Brodalumab 210 mg | Change From Baseline in Variation of Peak Flow | -4.892 L/min | Standard Error 2.169 |
p-value: 0.087195% CI: [-8.627, 0.586]Mixed-effect model
Secondary
Number of Participants Who Experienced an Asthma Exacerbation
An asthma exacerbation is defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study.
Time frame: Baseline to week 24
Population: Full analysis set with available data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Experienced an Asthma Exacerbation | 41 Participants |
| Brodalumab 210 mg | Number of Participants Who Experienced an Asthma Exacerbation | 49 Participants |
p-value: 0.35195% CI: [0.78, 2.01]Regression, Logistic
Secondary
Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period
Asthma symptom-free days is defined as days that a participant had a score of zero in their daily asthma symptom diary score. The ASD consists of 23 questions answered on a handheld device, including 10 asthma symptom-related items (5 answered in the morning and 5 in the evening). The morning diary comprises questions on 4 asthma-related symptoms (wheezing, shortness of breath, cough, chest tightness), rated on a 5-point severity scale from 0 (no symptom) to 4 (very severe symptoms), and 1 question on nocturnal awakenings, rated from 0 (did not wake up) to 4 (unable to sleep due to asthma). The evening diary has questions on the same 4 asthma-related symptoms and 1 question on limitations of activities, rated from 0 (not at all) to 4 (extremely). The daily score is the average of the responses to the 10 items.
Time frame: Baseline (the 4 weeks prior to first dose) and 4-week intervals up to week 24
Population: Full analysis set with available data during each 4-week interval
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Week 8 | 0.174 proportion of days | Standard Deviation 0.302 |
| Placebo | Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Week 16 | 0.211 proportion of days | Standard Deviation 0.328 |
| Placebo | Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Week 4 | 0.122 proportion of days | Standard Deviation 0.239 |
| Placebo | Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Week 20 | 0.222 proportion of days | Standard Deviation 0.346 |
| Placebo | Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Week 12 | 0.191 proportion of days | Standard Deviation 0.319 |
| Placebo | Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Week 24 | 0.237 proportion of days | Standard Deviation 0.371 |
| Placebo | Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Baseline | 0.071 proportion of days | Standard Deviation 0.179 |
| Brodalumab 210 mg | Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Week 24 | 0.204 proportion of days | Standard Deviation 0.342 |
| Brodalumab 210 mg | Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Baseline | 0.041 proportion of days | Standard Deviation 0.125 |
| Brodalumab 210 mg | Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Week 4 | 0.083 proportion of days | Standard Deviation 0.195 |
| Brodalumab 210 mg | Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Week 8 | 0.132 proportion of days | Standard Deviation 0.268 |
| Brodalumab 210 mg | Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Week 12 | 0.164 proportion of days | Standard Deviation 0.298 |
| Brodalumab 210 mg | Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Week 16 | 0.194 proportion of days | Standard Deviation 0.335 |
| Brodalumab 210 mg | Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period | Week 20 | 0.203 proportion of days | Standard Deviation 0.339 |
Secondary
Serum Brodalumab Concentration
Serum brodalumab concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) = 0.0500 µg/mL; values below the LLOQ were set to zero.
Time frame: Day 1 and weeks 1, 2, 4, 8, 12, 16, and 22 at predose, week 2 + 3 days, week 22 + 3, 7, 10, and 14 days
Population: Participants who received brodalumab with available concentration data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Brodalumab Concentration | Day 1 predose | 0 µg/mL | Standard Deviation 0 |
| Placebo | Serum Brodalumab Concentration | Week 1 predose | 8.48 µg/mL | Standard Deviation 5.55 |
| Placebo | Serum Brodalumab Concentration | Week 2 predose | 16.8 µg/mL | Standard Deviation 9.85 |
| Placebo | Serum Brodalumab Concentration | Week 2 day 3 | 24.9 µg/mL | Standard Deviation 15.8 |
| Placebo | Serum Brodalumab Concentration | Week 4 predose | 14.5 µg/mL | Standard Deviation 9.28 |
| Placebo | Serum Brodalumab Concentration | Week 8 predose | 11.1 µg/mL | Standard Deviation 9.03 |
| Placebo | Serum Brodalumab Concentration | Week 12 predose | 10.6 µg/mL | Standard Deviation 9.86 |
| Placebo | Serum Brodalumab Concentration | Week 16 predose | 8.93 µg/mL | Standard Deviation 9.06 |
| Placebo | Serum Brodalumab Concentration | Week 22 predose | 8.94 µg/mL | Standard Deviation 9.32 |
| Placebo | Serum Brodalumab Concentration | Week 22 day 3 | 18.0 µg/mL | Standard Deviation 15.4 |
| Placebo | Serum Brodalumab Concentration | Week 22 day 7 | 14.8 µg/mL | Standard Deviation 13.3 |
| Placebo | Serum Brodalumab Concentration | Week 22 day 10 | 12.5 µg/mL | Standard Deviation 12.2 |
| Placebo | Serum Brodalumab Concentration | Week 22 day 14 | 9.06 µg/mL | Standard Deviation 9.78 |
Secondary
Time to First Asthma Exacerbation
An asthma exacerbation is defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study. Median time to first asthma exacerbation could not be estimated, the percentage of participants with an asthma exacerbation is reported.
Time frame: From first dose of study drug to week 24
Population: Full analysis set with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Time to First Asthma Exacerbation | 20.1 percentage of participants |
| Brodalumab 210 mg | Time to First Asthma Exacerbation | 23.9 percentage of participants |
p-value: 0.23895% CI: [0.843, 1.936]Log Rank
Other Pre-specified
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Adverse events were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. The investigator assessed whether the adverse event was possibly related to the investigational product. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: * fatal; * life threatening; * requires in-patient hospitalization or prolongation of existing hospitalization; * results in persistent or significant disability/incapacity; * congenital anomaly/birth defect; * other medically important serious event.
Time frame: From first dose of study drug up to the end of study, 28 weeks
Population: Randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Fatal adverse events | 1 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious adverse events | 8 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related treatment-emergent adverse events | 27 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment related fatal adverse events | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAE ≥ 2 | 17 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to discontinuation of study drug | 9 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related serious adverse events | 4 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAE leading to discontinuation of study drug | 5 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE ≥ 2 | 97 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related life-threatening adverse events | 1 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Life-threatening adverse events | 2 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-emergent adverse event | 134 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment related fatal adverse events | 0 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-emergent adverse event | 156 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE ≥ 2 | 103 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious adverse events | 7 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to discontinuation of study drug | 13 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Life-threatening adverse events | 1 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Fatal adverse events | 0 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related treatment-emergent adverse events | 44 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAE ≥ 2 | 14 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related TEAE leading to discontinuation of study drug | 8 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related life-threatening adverse events | 0 Participants |
| Brodalumab 210 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-related serious adverse events | 0 Participants |