Trial Outcomes & Findings for Study of Efficacy and Safety of Brodalumab Compared With Placebo in Adults With Inadequately Controlled Asthma With High Bronchodilator Reversibility (NCT NCT01902290)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

421 participants

Primary outcome timeframe

Baseline and week 24

Results posted on

2022-09-21

Participant Flow

This study was conducted at 157 centers in Asia, Australia, Canada, Europe, and the United States.

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.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Overall Study STARTED	210	211
Overall Study Received Study Drug	207	208
Overall Study COMPLETED	162	158
Overall Study NOT COMPLETED	48	53

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Overall Study Withdrawal by Subject	19	27
Overall Study Lost to Follow-up	2	2
Overall Study Death	1	0
Overall Study Sponsor Decision	26	24

Baseline Characteristics

Study of Efficacy and Safety of Brodalumab Compared With Placebo in Adults With Inadequately Controlled Asthma With High Bronchodilator Reversibility

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=207 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=208 Participants 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.	Total n=415 Participants Total of all reporting groups
Age, Continuous	47.3 years STANDARD_DEVIATION 13.3 • n=93 Participants	47.2 years STANDARD_DEVIATION 14.0 • n=4 Participants	47.3 years STANDARD_DEVIATION 13.6 • n=27 Participants
Sex: Female, Male Female	120 Participants n=93 Participants	122 Participants n=4 Participants	242 Participants n=27 Participants
Sex: Female, Male Male	87 Participants n=93 Participants	86 Participants n=4 Participants	173 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=93 Participants	13 Participants n=4 Participants	21 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	199 Participants n=93 Participants	195 Participants n=4 Participants	394 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Asian	10 Participants n=93 Participants	13 Participants n=4 Participants	23 Participants n=27 Participants
Race/Ethnicity, Customized Black or African American	29 Participants n=93 Participants	19 Participants n=4 Participants	48 Participants n=27 Participants
Race/Ethnicity, Customized Multiple	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race/Ethnicity, Customized White	162 Participants n=93 Participants	174 Participants n=4 Participants	336 Participants n=27 Participants
Race/Ethnicity, Customized Other	3 Participants n=93 Participants	0 Participants n=4 Participants	3 Participants n=27 Participants
Randomization Strata LABA -No; ≤ 2 asthma exacerbation prior year	30 Participants n=93 Participants	37 Participants n=4 Participants	67 Participants n=27 Participants
Randomization Strata LABA -No; > 2 asthma exacerbation prior year	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Randomization Strata LABA -Yes; ≤ 2 asthma exacerbation prior year	160 Participants n=93 Participants	153 Participants n=4 Participants	313 Participants n=27 Participants
Randomization Strata LABA -Yes; > 2 asthma exacerbation prior year	17 Participants n=93 Participants	17 Participants n=4 Participants	34 Participants n=27 Participants
Duration of Asthma	22.20 years STANDARD_DEVIATION 14.89 • n=93 Participants	22.92 years STANDARD_DEVIATION 14.44 • n=4 Participants	22.56 years STANDARD_DEVIATION 14.66 • n=27 Participants

PRIMARY outcome

Timeframe: Baseline and week 24

Population: Full analysis set with available data

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.

Outcome measures

Outcome measures
Measure	Placebo n=147 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=137 Participants 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.
Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Score at Week 24	-0.815 score on a scale Standard Error 0.073	-0.865 score on a scale Standard Error 0.074

SECONDARY outcome

Timeframe: Baseline to week 24

Population: Full analysis set with available data

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.

Outcome measures

Outcome measures
Measure	Placebo n=204 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=205 Participants 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.
Asthma Exacerbation Rate	0.57 exacerbations per subject-year	0.81 exacerbations per subject-year

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=121 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=108 Participants 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.
Change From Baseline in ACQ Composite Score at Week 24 in ICS+LABA Subpopulation	-0.793 score on a scale Standard Error 0.084	-0.831 score on a scale Standard Error 0.088

SECONDARY outcome

Timeframe: Baseline to week 24

Population: Full analysis set participants taking both ICS and LABA at baseline with available data

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.

Outcome measures

Outcome measures
Measure	Placebo n=174 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=167 Participants 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.
Asthma Exacerbation Rate in ICS+LABA Subpopulation	0.60 exacerbations per subject-year	0.89 exacerbations per subject-year

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Full analysis set with available data

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).

Outcome measures

Outcome measures
Measure	Placebo n=121 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=117 Participants 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.
Change From Baseline in Daily Asthma Symptom Score (7-day Average Score)	-0.397 score on a scale Standard Error 0.042	-0.443 score on a scale Standard Error 0.043

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Full analysis set with available data

Outcome measures

Outcome measures
Measure	Placebo n=148 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=137 Participants 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.
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1)	0.207 L/s Standard Error 0.045	0.237 L/s Standard Error 0.046

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Full analysis set with available data

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).

Outcome measures

Outcome measures
Measure	Placebo n=121 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=117 Participants 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.
Change From Baseline in Daily Rescue Short-acting Beta-agonist Use	-1.359 puffs Standard Error 0.243	-1.231 puffs Standard Error 0.246

SECONDARY outcome

Timeframe: From first dose of study drug to week 24

Population: Full analysis set with available data

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.

Outcome measures

Outcome measures
Measure	Placebo n=204 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=205 Participants 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.
Time to First Asthma Exacerbation	20.1 percentage of participants	23.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline to week 24

Population: Full analysis set with available data

An asthma exacerbation is defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study.

Outcome measures

Outcome measures
Measure	Placebo n=204 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=205 Participants 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.
Number of Participants Who Experienced an Asthma Exacerbation	41 Participants	49 Participants

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Full analysis set with available data

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.

Outcome measures

Outcome measures
Measure	Placebo n=147 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=137 Participants 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.
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Overall Score	0.804 score on a scale Standard Error 0.085	0.803 score on a scale Standard Error 0.087

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Full analysis set with available data

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.

Outcome measures

Outcome measures
Measure	Placebo n=146 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=129 Participants 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.
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) Morning peak flow	0.072 L/min Standard Error 5.813	0.706 L/min Standard Error 5.885
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) Evening peak flow	-10.008 L/min Standard Error 5.719	-4.089 L/min Standard Error 5.771

SECONDARY outcome

Timeframe: Baseline and week 24

Population: Full analysis set with available data

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.

Outcome measures

Outcome measures
Measure	Placebo n=121 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=115 Participants 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.
Change From Baseline in Variation of Peak Flow	-0.872 L/min Standard Error 2.135	-4.892 L/min Standard Error 2.169

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Placebo n=204 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=205 Participants 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.
Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period Baseline	0.071 proportion of days Standard Deviation 0.179	0.041 proportion of days Standard Deviation 0.125
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	0.083 proportion of days Standard Deviation 0.195
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	0.132 proportion of days Standard Deviation 0.268
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	0.164 proportion of days Standard Deviation 0.298
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	0.194 proportion of days Standard Deviation 0.335
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	0.203 proportion of days Standard Deviation 0.339
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	0.204 proportion of days Standard Deviation 0.342

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=196 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Serum Brodalumab Concentration Day 1 predose	0 µg/mL Standard Deviation 0	—
Serum Brodalumab Concentration Week 1 predose	8.48 µg/mL Standard Deviation 5.55	—
Serum Brodalumab Concentration Week 2 predose	16.8 µg/mL Standard Deviation 9.85	—
Serum Brodalumab Concentration Week 2 day 3	24.9 µg/mL Standard Deviation 15.8	—
Serum Brodalumab Concentration Week 4 predose	14.5 µg/mL Standard Deviation 9.28	—
Serum Brodalumab Concentration Week 8 predose	11.1 µg/mL Standard Deviation 9.03	—
Serum Brodalumab Concentration Week 12 predose	10.6 µg/mL Standard Deviation 9.86	—
Serum Brodalumab Concentration Week 16 predose	8.93 µg/mL Standard Deviation 9.06	—
Serum Brodalumab Concentration Week 22 predose	8.94 µg/mL Standard Deviation 9.32	—
Serum Brodalumab Concentration Week 22 day 3	18.0 µg/mL Standard Deviation 15.4	—
Serum Brodalumab Concentration Week 22 day 7	14.8 µg/mL Standard Deviation 13.3	—
Serum Brodalumab Concentration Week 22 day 10	12.5 µg/mL Standard Deviation 12.2	—
Serum Brodalumab Concentration Week 22 day 14	9.06 µg/mL Standard Deviation 9.78	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=207 Participants Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=208 Participants 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any treatment-emergent adverse event	134 Participants	156 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE ≥ 2	97 Participants	103 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Serious adverse events	8 Participants	7 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) TEAE leading to discontinuation of study drug	9 Participants	13 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Life-threatening adverse events	2 Participants	1 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Fatal adverse events	1 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Treatment-related treatment-emergent adverse events	27 Participants	44 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Treatment-related TEAE ≥ 2	17 Participants	14 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Treatment-related serious adverse events	4 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Treatment-related TEAE leading to discontinuation of study drug	5 Participants	8 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Treatment-related life-threatening adverse events	1 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Treatment related fatal adverse events	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 104 other events

Deaths: 0 deaths

Brodalumab 210 mg

Serious events: 7 serious events

Other events: 129 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=207 participants at risk Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=208 participants at risk 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.
Blood and lymphatic system disorders Microcytic anaemia	0.00% 0/207 • From first dose of study drug until the end of study, week 28.	0.48% 1/208 • From first dose of study drug until the end of study, week 28.
Cardiac disorders Atrial fibrillation	0.00% 0/207 • From first dose of study drug until the end of study, week 28.	0.48% 1/208 • From first dose of study drug until the end of study, week 28.
Cardiac disorders Cardiac arrest	0.48% 1/207 • From first dose of study drug until the end of study, week 28.	0.00% 0/208 • From first dose of study drug until the end of study, week 28.
Infections and infestations Appendicitis	0.48% 1/207 • From first dose of study drug until the end of study, week 28.	0.48% 1/208 • From first dose of study drug until the end of study, week 28.
Infections and infestations Pneumonia	0.48% 1/207 • From first dose of study drug until the end of study, week 28.	0.48% 1/208 • From first dose of study drug until the end of study, week 28.
Injury, poisoning and procedural complications Pneumothorax traumatic	0.48% 1/207 • From first dose of study drug until the end of study, week 28.	0.00% 0/208 • From first dose of study drug until the end of study, week 28.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bile duct adenocarcinoma	0.48% 1/207 • From first dose of study drug until the end of study, week 28.	0.00% 0/208 • From first dose of study drug until the end of study, week 28.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.48% 1/207 • From first dose of study drug until the end of study, week 28.	0.00% 0/208 • From first dose of study drug until the end of study, week 28.
Nervous system disorders Paraesthesia	0.00% 0/207 • From first dose of study drug until the end of study, week 28.	0.48% 1/208 • From first dose of study drug until the end of study, week 28.
Psychiatric disorders Depression	0.48% 1/207 • From first dose of study drug until the end of study, week 28.	0.00% 0/208 • From first dose of study drug until the end of study, week 28.
Psychiatric disorders Suicidal behaviour	0.48% 1/207 • From first dose of study drug until the end of study, week 28.	0.00% 0/208 • From first dose of study drug until the end of study, week 28.
Psychiatric disorders Suicidal ideation	0.48% 1/207 • From first dose of study drug until the end of study, week 28.	0.00% 0/208 • From first dose of study drug until the end of study, week 28.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.48% 1/207 • From first dose of study drug until the end of study, week 28.	0.00% 0/208 • From first dose of study drug until the end of study, week 28.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/207 • From first dose of study drug until the end of study, week 28.	0.48% 1/208 • From first dose of study drug until the end of study, week 28.
Respiratory, thoracic and mediastinal disorders Status asthmaticus	0.48% 1/207 • From first dose of study drug until the end of study, week 28.	0.48% 1/208 • From first dose of study drug until the end of study, week 28.

Measure	Placebo n=207 participants at risk Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	Brodalumab 210 mg n=208 participants at risk 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.
Gastrointestinal disorders Nausea	1.4% 3/207 • From first dose of study drug until the end of study, week 28.	2.9% 6/208 • From first dose of study drug until the end of study, week 28.
General disorders Fatigue	2.4% 5/207 • From first dose of study drug until the end of study, week 28.	0.96% 2/208 • From first dose of study drug until the end of study, week 28.
General disorders Injection site erythema	1.4% 3/207 • From first dose of study drug until the end of study, week 28.	2.9% 6/208 • From first dose of study drug until the end of study, week 28.
Infections and infestations Bronchitis	6.8% 14/207 • From first dose of study drug until the end of study, week 28.	6.2% 13/208 • From first dose of study drug until the end of study, week 28.
Infections and infestations Influenza	0.48% 1/207 • From first dose of study drug until the end of study, week 28.	3.8% 8/208 • From first dose of study drug until the end of study, week 28.
Infections and infestations Nasopharyngitis	9.2% 19/207 • From first dose of study drug until the end of study, week 28.	11.5% 24/208 • From first dose of study drug until the end of study, week 28.
Infections and infestations Sinusitis	4.8% 10/207 • From first dose of study drug until the end of study, week 28.	2.4% 5/208 • From first dose of study drug until the end of study, week 28.
Infections and infestations Upper respiratory tract infection	9.2% 19/207 • From first dose of study drug until the end of study, week 28.	11.5% 24/208 • From first dose of study drug until the end of study, week 28.
Infections and infestations Viral upper respiratory tract infection	2.9% 6/207 • From first dose of study drug until the end of study, week 28.	1.9% 4/208 • From first dose of study drug until the end of study, week 28.
Musculoskeletal and connective tissue disorders Arthralgia	0.97% 2/207 • From first dose of study drug until the end of study, week 28.	3.8% 8/208 • From first dose of study drug until the end of study, week 28.
Musculoskeletal and connective tissue disorders Back pain	2.4% 5/207 • From first dose of study drug until the end of study, week 28.	2.9% 6/208 • From first dose of study drug until the end of study, week 28.
Nervous system disorders Headache	5.3% 11/207 • From first dose of study drug until the end of study, week 28.	3.8% 8/208 • From first dose of study drug until the end of study, week 28.
Respiratory, thoracic and mediastinal disorders Asthma	30.4% 63/207 • From first dose of study drug until the end of study, week 28.	34.6% 72/208 • From first dose of study drug until the end of study, week 28.
Respiratory, thoracic and mediastinal disorders Cough	2.9% 6/207 • From first dose of study drug until the end of study, week 28.	5.3% 11/208 • From first dose of study drug until the end of study, week 28.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.4% 3/207 • From first dose of study drug until the end of study, week 28.	3.4% 7/208 • From first dose of study drug until the end of study, week 28.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	2.4% 5/207 • From first dose of study drug until the end of study, week 28.	1.4% 3/208 • From first dose of study drug until the end of study, week 28.
Respiratory, thoracic and mediastinal disorders Wheezing	0.48% 1/207 • From first dose of study drug until the end of study, week 28.	3.8% 8/208 • From first dose of study drug until the end of study, week 28.