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

• Sponsor: Amgen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01902290
• Collaborator: Kyowa Kirin Co., Ltd. (Industry), AstraZeneca (Industry)
• Enrollment: 421
• Locations: 161
• Arms: 2
• Actual Duration (Months): 23.8
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Biological: Placebo; Biological: Brodalumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 421 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Brodalumab in Subjects With Inadequately Controlled Asthma and High Bronchodilator Reversibility
• Actual Study Start Date: May 22, 2013
• Actual Primary Completion Date: May 15, 2015
• Actual Study Completion Date: May 15, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received placebo administered by subcutaneous injection on day 1, week 1, week 2 and every 2 weeks thereafter for 24 weeks.	Biological: Placebo; Placebo administered subcutaneously
Experimental: Brodalumab 210 mg Participants received 210 mg brodalumab administered by subcutaneous injection on day 1, week 1, week 2, and every 2 weeks thereafter for 24 weeks.	Biological: Brodalumab; Brodalumab administered subcutaneously; Other Names: AMG 827

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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).

5. Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) [Baseline and week 24]

6. 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).

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

Other Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35209
2	Research Site	Glendale	Arizona	United States	85306
3	Research Site	Phoenix	Arizona	United States	85006
4	Research Site	Scottsdale	Arizona	United States	85251
5	Research Site	Little Rock	Arkansas	United States	72205
6	Research Site	Bakersfield	California	United States	93301
7	Research Site	Encinitas	California	United States	92024
8	Research Site	Los Angeles	California	United States	90025
9	Research Site	Los Angeles	California	United States	90048
10	Research Site	Newport Beach	California	United States	92663
11	Research Site	North Hollywood	California	United States	91606
12	Research Site	Orange	California	United States	92868
13	Research Site	Palmdale	California	United States	93551
14	Research Site	Rolling Hills Estates	California	United States	90274
15	Research Site	San Diego	California	United States	92103
16	Research Site	San Diego	California	United States	92108
17	Research Site	San Jose	California	United States	95117
18	Research Site	Santa Monica	California	United States	90404
19	Research Site	Stockton	California	United States	95207
20	Research Site	Colorado Springs	Colorado	United States	80907
21	Research Site	Waterbury	Connecticut	United States	06708
22	Research Site	Aventura	Florida	United States	33180
23	Research Site	Hialeah	Florida	United States	33012
24	Research Site	Jacksonville	Florida	United States	32256
25	Research Site	Lynn Haven	Florida	United States	32444
26	Research Site	Miami	Florida	United States	33173
27	Research Site	Orlando	Florida	United States	32806
28	Research Site	Port Orange	Florida	United States	32127
29	Research Site	Tallahassee	Florida	United States	32308
30	Research Site	Decatur	Georgia	United States	30033
31	Research Site	Lawrenceville	Georgia	United States	30046
32	Research Site	Eagle	Idaho	United States	83616
33	Research Site	Chicago	Illinois	United States	60616
34	Research Site	Chicago	Illinois	United States	60637
35	Research Site	Normal	Illinois	United States	61761
36	Research Site	Peoria	Illinois	United States	61603
37	Research Site	Iowa City	Iowa	United States	52242
38	Research Site	Paducah	Kentucky	United States	42003
39	Research Site	Baltimore	Maryland	United States	21224
40	Research Site	Baltimore	Maryland	United States	21236
41	Research Site	North Dartmouth	Massachusetts	United States	02747
42	Research Site	Plymouth	Minnesota	United States	55441
43	Research Site	Jackson	Mississippi	United States	39216
44	Research Site	Saint Louis	Missouri	United States	63110
45	Research Site	Bellevue	Nebraska	United States	68123
46	Research Site	Ocean City	New Jersey	United States	07712
47	Research Site	Albuquerque	New Mexico	United States	87109
48	Research Site	Rochester	New York	United States	14618
49	Research Site	Charlotte	North Carolina	United States	28207
50	Research Site	High Point	North Carolina	United States	27262
51	Research Site	Winston-Salem	North Carolina	United States	27103
52	Research Site	Cincinnati	Ohio	United States	45231
53	Research Site	Dublin	Ohio	United States	43016
54	Research Site	Middleburg Heights	Ohio	United States	44130
55	Research Site	Oklahoma City	Oklahoma	United States	73103
56	Research Site	Lake Oswego	Oregon	United States	97035
57	Research Site	Medford	Oregon	United States	97504
58	Research Site	Portland	Oregon	United States	97202
59	Research Site	Upland	Pennsylvania	United States	19013
60	Research Site	Rock Hill	South Carolina	United States	29732
61	Research Site	Spartanburg	South Carolina	United States	29303
62	Research Site	Bristol	Tennessee	United States	37620
63	Research Site	Nashville	Tennessee	United States	37203-1424
64	Research Site	Nashville	Tennessee	United States	37214
65	Research Site	Arlington	Texas	United States	76018
66	Research Site	Dallas	Texas	United States	75231
67	Research Site	El Paso	Texas	United States	79903
68	Research Site	McKinney	Texas	United States	75069
69	Research Site	San Antonio	Texas	United States	78229
70	Research Site	San Antonio	Texas	United States	78258
71	Research Site	Clinton	Utah	United States	84015
72	Research Site	Bellingham	Washington	United States	98225
73	Research Site	Milwaukee	Wisconsin	United States	53226
74	Research Site	New Lambton	New South Wales	Australia	2305
75	Research Site	Nedlands	Western Australia	Australia	6009
76	Research Site	Sherwood Park	Alberta	Canada	T8H 0N2
77	Research Site	Kelowna	British Columbia	Canada	V1W 1V3
78	Research Site	Surrey	British Columbia	Canada	V3T 0G9
79	Research Site	Vancouver	British Columbia	Canada	V5Z 1M9
80	Research Site	Vancouver	British Columbia	Canada	V6J 1S3
81	Research Site	Brampton	Ontario	Canada	L6T 0G1
82	Research Site	Hamilton	Ontario	Canada	L8N 3Z5
83	Research Site	Newmarket	Ontario	Canada	L3Y 5G8
84	Research Site	Sarnia	Ontario	Canada	N7T 4X3
85	Research Site	Toronto	Ontario	Canada	M5T 3A9
86	Research Site	Toronto	Ontario	Canada	M9V 4B4
87	Research Site	Trois Rivieres	Quebec	Canada	G8T 7A1
88	Research Site	Le Kremlin Bicetre		France	94270
89	Research Site	Marseille		France	13015
90	Research Site	Montpellier cedex 05		France	34295
91	Research Site	Pessac Cedex		France	33604
92	Research Site	Saint Herblain		France	44805
93	Research Site	Strasbourg cedex		France	67091
94	Research Site	Tours Cedex 9		France	37044
95	Research Site	Berlin		Germany	10717
96	Research Site	Berlin		Germany	12099
97	Research Site	Bonn		Germany	53119
98	Research Site	Cottbus		Germany	03050
99	Research Site	Frankfurt am Main		Germany	60596
100	Research Site	Hamburg		Germany	22299
101	Research Site	Hannover		Germany	30173
102	Research Site	Mainz		Germany	55131
103	Research Site	Radebeul		Germany	01445
104	Research Site	Rüdersdorf		Germany	15562
105	Research Site	Alexandroupoli		Greece	68100
106	Research Site	Athens		Greece	10676
107	Research Site	Athens		Greece	11527
108	Research Site	Athens		Greece	11528
109	Research Site	Athens		Greece	15125
110	Research Site	Chaidari, Athens		Greece	12462
111	Research Site	Heraklion - Crete		Greece	71110
112	Research Site	Thessaloniki		Greece	57010
113	Research Site	Hong Kong		Hong Kong
114	Research Site	New Territories		Hong Kong
115	Research Site	Cork		Ireland
116	Research Site	Dublin		Ireland	15
117	Research Site	Dublin		Ireland	24
118	Research Site	Dublin		Ireland
119	Research Site	Catania		Italy	95123
120	Research Site	Ferrara		Italy	44121
121	Research Site	Genova		Italy	16132
122	Research Site	Modena		Italy	41124
123	Research Site	Padova		Italy	35128
124	Research Site	Pavia		Italy	27100
125	Research Site	Pisa		Italy	56124
126	Research Site	Tradate (VA)		Italy	21049
127	Research Site	Bucheon-si, Gyeonggi-do		Korea, Republic of	420-767
128	Research Site	Incheon		Korea, Republic of	405-760
129	Research Site	Seoul		Korea, Republic of	142-703
130	Research Site	Wonju-si, Gangwon-do		Korea, Republic of	220-710
131	Research Site	Christchurch		New Zealand	8140
132	Research Site	Dunedin		New Zealand	9058
133	Research Site	Remuera		New Zealand	1051
134	Research Site	Bialystok		Poland	15-010
135	Research Site	Bialystok		Poland	15-044
136	Research Site	Gdynia		Poland	81-338
137	Research Site	Katowice		Poland	40-954
138	Research Site	Krakow		Poland	31-011
139	Research Site	Krakow		Poland	31-024
140	Research Site	Krakow		Poland	31-637
141	Research Site	Lublin		Poland	59-300
142	Research Site	Skierniewice		Poland	96-100
143	Research Site	Tarnow		Poland	33-100
144	Research Site	Warszawa		Poland	01-868
145	Research Site	Warszawa		Poland	02-097
146	Research Site	Warszawa		Poland	02-201
147	Research Site	Warszawa		Poland	04-141
148	Research Site	Zgierz		Poland	95-100
149	Research Site	San Juan		Puerto Rico	00917
150	Research Site	Moscow		Russian Federation	105077
151	Research Site	Moscow		Russian Federation	115280
152	Research Site	Moscow		Russian Federation	115446
153	Research Site	Moscow		Russian Federation	119991
154	Research Site	Moscow		Russian Federation	123182
155	Research Site	Moscow		Russian Federation	127018
156	Research Site	Saint Petersburg		Russian Federation	193231
157	Research Site	Saint Petersburg		Russian Federation	197022
158	Research Site	Saint-Petersburg		Russian Federation	195271
159	Research Site	Taipei		Taiwan	10002
160	Research Site	Taipei		Taiwan	112
161	Research Site	Taipei		Taiwan	22050

Sponsors and Collaborators

• Amgen
• Kyowa Kirin Co., Ltd.
• AstraZeneca

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01902290
• Other Study ID Numbers: 20120141; 2012-003351-11
• First Posted: Jul 18, 2013
• Last Update Posted: Feb 28, 2022
• Last Verified: Jan 1, 2022

• Keywords provided by Amgen: Inadequately controlled asthma, brodalumab, AMG 827
• Additional relevant MeSH terms: Asthma; Brodalumab

Study Results

Participant Flow

Recruitment Details

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

Pre-assignment Detail

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.

Arm/Group Title	Placebo	Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Period Title: Overall Study
STARTED	210	211
Received Study Drug	207	208
COMPLETED	162	158
NOT COMPLETED	48	53

Baseline Characteristics

Arm/Group Title	Placebo	Brodalumab 210 mg	Total
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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 of all reporting groups
Overall Participants	207	208	415
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.3 (13.3)	47.2 (14.0)	47.3 (13.6)
Sex: Female, Male (Count of Participants)
Female	120 58%	122 58.7%	242 58.3%
Male	87 42%	86 41.3%	173 41.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 3.9%	13 6.3%	21 5.1%
Not Hispanic or Latino	199 96.1%	195 93.8%	394 94.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 0.5%	0 0%	1 0.2%
Asian	10 4.8%	13 6.3%	23 5.5%
Black or African American	29 14%	19 9.1%	48 11.6%
Multiple	1 0.5%	1 0.5%	2 0.5%
Native Hawaiian or Other Pacific Islander	1 0.5%	1 0.5%	2 0.5%
White	162 78.3%	174 83.7%	336 81%
Other	3 1.4%	0 0%	3 0.7%
Randomization Strata (Count of Participants)
LABA -No; ≤ 2 asthma exacerbation prior year	30 14.5%	37 17.8%	67 16.1%
LABA -No; > 2 asthma exacerbation prior year	0 0%	1 0.5%	1 0.2%
LABA -Yes; ≤ 2 asthma exacerbation prior year	160 77.3%	153 73.6%	313 75.4%
LABA -Yes; > 2 asthma exacerbation prior year	17 8.2%	17 8.2%	34 8.2%
Duration of Asthma (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22.20 (14.89)	22.92 (14.44)	22.56 (14.66)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Score at Week 24
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set with available data

Arm/Group Title	Placebo	Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Measure Participants	147	137
Least Squares Mean (Standard Error) [score on a scale]	-0.815 (0.073)	-0.865 (0.074)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5219
	Comments
	Method	Mixed-effect model
	Comments	The model included fixed effects of treatment group, time, interaction of treatment group by time, stratification variables, and baseline ACQ score.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.050
	Confidence Interval	(2-Sided) 95%; -0.203 to 0.103
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference = Brodalumab - Placebo

2. Secondary Outcome

Title	Asthma Exacerbation Rate
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set with available data

Arm/Group Title	Placebo	Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Measure Participants	204	205
Number [exacerbations per subject-year]	0.57	0.81

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.102
	Comments
	Method	Generalized linear model
	Comments	Generalized linear model under a negative binomial distribution assumption adjusting for stratification factors.
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	1.41
	Confidence Interval	(2-Sided) 95%; 0.93 to 2.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Rate ratio = Brodalumab : Placebo

3. Secondary Outcome

Title	Change From Baseline in ACQ Composite Score at Week 24 in ICS+LABA Subpopulation
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set participants who were taking both inhaled corticosteroids (ICS) and a long-acting β-agonist (LABA) at baseline with available data.

Arm/Group Title	Placebo	Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Measure Participants	121	108
Least Squares Mean (Standard Error) [score on a scale]	-0.793 (0.084)	-0.831 (0.088)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6632
	Comments
	Method	Mixed-effect model
	Comments	The model included fixed effects of treatment group, time, interaction of treatment group by time, stratification factors, and baseline ACQ score.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.038
	Confidence Interval	(2-Sided) 95%; -0.210 to 0.134
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference = Brodalumab - Placebo

4. Secondary Outcome

Title	Asthma Exacerbation Rate in ICS+LABA Subpopulation
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Measure Participants	174	167
Number [exacerbations per subject-year]	0.60	0.89

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.096
	Comments
	Method	Generalized linear model
	Comments	Generalized linear model under a negative binomial distribution assumption adjusting for stratification factors.
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; 0.94 to 2.24
	Parameter Dispersion	Type: Value:
	Estimation Comments	Rate ratio = Brodalumab : Placebo

5. Secondary Outcome

Title	Change From Baseline in Daily Asthma Symptom Score (7-day Average Score)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set with available data

Arm/Group Title	Placebo	Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Measure Participants	121	117
Least Squares Mean (Standard Error) [score on a scale]	-0.397 (0.042)	-0.443 (0.043)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3290
	Comments
	Method	Mixed-effect model
	Comments	The model included fixed effects of treatment group, time, interaction of treatment group by time, stratification variables, and baseline score.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.046
	Confidence Interval	(2-Sided) 95%; -0.137 to 0.046
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference = Brodalumab - Placebo

6. Secondary Outcome

Title	Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1)
Time Frame	Baseline and week 24

Outcome Measure Data

Analysis Population Description

Full analysis set with available data

Arm/Group Title	Placebo	Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Measure Participants	148	137
Least Squares Mean (Standard Error) [L/s]	0.207 (0.045)	0.237 (0.046)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4549
	Comments
	Method	Mixed-effect model
	Comments	Model includes treatment, time, stratification factors, treatment by time and baseline value of age, gender, pooled race group, height and FEV1.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.030
	Confidence Interval	() 95%; -0.049 to 0.109
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference = Brodalumab - Placebo

7. Secondary Outcome

Title	Change From Baseline in Daily Rescue Short-acting Beta-agonist Use
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set with available data

Arm/Group Title	Placebo	Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Measure Participants	121	117
Least Squares Mean (Standard Error) [puffs]	-1.359 (0.243)	-1.231 (0.246)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6317
	Comments
	Method	Mixed-effect model
	Comments	The model included fixed effects of treatment group, time, interaction of treatment group by time, stratification variables, and baseline value.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.128
	Confidence Interval	() 95%; -0.396 to 0.653
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference = Brodalumab - Placebo

8. Secondary Outcome

Title	Time to First Asthma Exacerbation
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set with available data

Arm/Group Title	Placebo	Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Measure Participants	204	205
Number [percentage of participants]	20.1 9.7%	23.9 11.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.238
	Comments
	Method	Log Rank
	Comments	Log rank test stratified for baseline stratification factors.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.277
	Confidence Interval	(2-Sided) 95%; 0.843 to 1.936
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Number of Participants Who Experienced an Asthma Exacerbation
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set with available data

Arm/Group Title	Placebo	Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Measure Participants	204	205
Count of Participants [Participants]	41 19.8%	49 23.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.351
	Comments
	Method	Regression, Logistic
	Comments	Logistic regression adjusted for stratification factors.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.25
	Confidence Interval	() 95%; 0.78 to 2.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Overall Score
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set with available data

Arm/Group Title	Placebo	Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Measure Participants	147	137
Least Squares Mean (Standard Error) [score on a scale]	0.804 (0.085)	0.803 (0.087)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9870
	Comments
	Method	Mixed-effects model
	Comments	The model included fixed effects of treatment group, time, interaction of treatment group by time, stratification variables, and baseline AQLQ score.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.001
	Confidence Interval	() 95%; -0.174 to 0.171
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference = Brodalumab - Placebo

11. Secondary Outcome

Title	Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set with available data

Arm/Group Title	Placebo	Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Measure Participants	146	129
Morning peak flow	0.072 (5.813)	0.706 (5.885)
Evening peak flow	-10.008 (5.719)	-4.089 (5.771)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments	Analysis of morning peak flow
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9053
	Comments
	Method	Mixed-effect model
	Comments	Model includes treatment, time, stratification factors, treatment by time and baseline value of age, gender, pooled race group, height and AM PEFR.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.635
	Confidence Interval	(2-Sided) 95%; -9.820 to 11.089
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference = Brodalumab - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments	Analysis of evening peak flow
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2661
	Comments
	Method	Mixed-effects model
	Comments	Model includes treatment, time, stratification factors, treatment by time and baseline value of age, gender, pooled race group, height and PM PEFR.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	5.920
	Confidence Interval	(2-Sided) 95%; -4.515 to 16.354
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference = Brodalumab - Placebo

12. Secondary Outcome

Title	Change From Baseline in Variation of Peak Flow
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set with available data

Arm/Group Title	Placebo	Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Measure Participants	121	115
Least Squares Mean (Standard Error) [L/min]	-0.872 (2.135)	-4.892 (2.169)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Brodalumab 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0871
	Comments
	Method	Mixed-effect model
	Comments	Model includes treatment, time, stratification factors, treatment by time and baseline value of age, gender, race group, height and PEFR variation.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-4.021
	Confidence Interval	(2-Sided) 95%; -8.627 to 0.586
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference = Brodalumab - Placebo

13. Secondary Outcome

Title	Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set with available data during each 4-week interval

Arm/Group Title	Placebo	Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Measure Participants	204	205
Baseline	0.071 (0.179)	0.041 (0.125)
Week 4	0.122 (0.239)	0.083 (0.195)
Week 8	0.174 (0.302)	0.132 (0.268)
Week 12	0.191 (0.319)	0.164 (0.298)
Week 16	0.211 (0.328)	0.194 (0.335)
Week 20	0.222 (0.346)	0.203 (0.339)
Week 24	0.237 (0.371)	0.204 (0.342)

14. Secondary Outcome

Title	Serum Brodalumab Concentration
Description	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

Outcome Measure Data

Analysis Population Description

Participants who received brodalumab with available concentration data at each time point.

Arm/Group Title	Brodalumab 210 mg
Arm/Group Description	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.
Measure Participants	196
Day 1 predose	0 (0)
Week 1 predose	8.48 (5.55)
Week 2 predose	16.8 (9.85)
Week 2 day 3	24.9 (15.8)
Week 4 predose	14.5 (9.28)
Week 8 predose	11.1 (9.03)
Week 12 predose	10.6 (9.86)
Week 16 predose	8.93 (9.06)
Week 22 predose	8.94 (9.32)
Week 22 day 3	18.0 (15.4)
Week 22 day 7	14.8 (13.3)
Week 22 day 10	12.5 (12.2)
Week 22 day 14	9.06 (9.78)

15. Other Pre-specified Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	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

Outcome Measure Data

Analysis Population Description

Randomized participants who received at least 1 dose of study drug.

Arm/Group Title	Placebo	Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.	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.
Measure Participants	207	208
Any treatment-emergent adverse event	134 64.7%	156 75%
TEAE ≥ 2	97 46.9%	103 49.5%
Serious adverse events	8 3.9%	7 3.4%
TEAE leading to discontinuation of study drug	9 4.3%	13 6.3%
Life-threatening adverse events	2 1%	1 0.5%
Fatal adverse events	1 0.5%	0 0%
Treatment-related treatment-emergent adverse events	27 13%	44 21.2%
Treatment-related TEAE ≥ 2	17 8.2%	14 6.7%
Treatment-related serious adverse events	4 1.9%	0 0%
Treatment-related TEAE leading to discontinuation of study drug	5 2.4%	8 3.8%
Treatment-related life-threatening adverse events	1 0.5%	0 0%
Treatment related fatal adverse events	0 0%	0 0%

Adverse Events

Time Frame	From first dose of study drug until the end of study, week 28.
Arm/Group Title	Placebo		Brodalumab 210 mg
Arm/Group Description	Participants received placebo subcutaneous injections on day 1 and weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.		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.
All Cause Mortality
	Placebo		Brodalumab 210 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Brodalumab 210 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/207 (3.9%)		7/208 (3.4%)
Blood and lymphatic system disorders
Microcytic anaemia	0/207 (0%)		1/208 (0.5%)
Cardiac disorders
Atrial fibrillation	0/207 (0%)		1/208 (0.5%)
Cardiac arrest	1/207 (0.5%)		0/208 (0%)
Infections and infestations
Appendicitis	1/207 (0.5%)		1/208 (0.5%)
Pneumonia	1/207 (0.5%)		1/208 (0.5%)
Injury, poisoning and procedural complications
Pneumothorax traumatic	1/207 (0.5%)		0/208 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile duct adenocarcinoma	1/207 (0.5%)		0/208 (0%)
Uterine leiomyoma	1/207 (0.5%)		0/208 (0%)
Nervous system disorders
Paraesthesia	0/207 (0%)		1/208 (0.5%)
Psychiatric disorders
Depression	1/207 (0.5%)		0/208 (0%)
Suicidal behaviour	1/207 (0.5%)		0/208 (0%)
Suicidal ideation	1/207 (0.5%)		0/208 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/207 (0.5%)		0/208 (0%)
Asthma	0/207 (0%)		1/208 (0.5%)
Status asthmaticus	1/207 (0.5%)		1/208 (0.5%)
Other (Not Including Serious) Adverse Events
	Placebo		Brodalumab 210 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	104/207 (50.2%)		129/208 (62%)
Gastrointestinal disorders
Nausea	3/207 (1.4%)		6/208 (2.9%)
General disorders
Fatigue	5/207 (2.4%)		2/208 (1%)
Injection site erythema	3/207 (1.4%)		6/208 (2.9%)
Infections and infestations
Bronchitis	14/207 (6.8%)		13/208 (6.3%)
Influenza	1/207 (0.5%)		8/208 (3.8%)
Nasopharyngitis	19/207 (9.2%)		24/208 (11.5%)
Sinusitis	10/207 (4.8%)		5/208 (2.4%)
Upper respiratory tract infection	19/207 (9.2%)		24/208 (11.5%)
Viral upper respiratory tract infection	6/207 (2.9%)		4/208 (1.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/207 (1%)		8/208 (3.8%)
Back pain	5/207 (2.4%)		6/208 (2.9%)
Nervous system disorders
Headache	11/207 (5.3%)		8/208 (3.8%)
Respiratory, thoracic and mediastinal disorders
Asthma	63/207 (30.4%)		72/208 (34.6%)
Cough	6/207 (2.9%)		11/208 (5.3%)
Dyspnoea	3/207 (1.4%)		7/208 (3.4%)
Rhinitis allergic	5/207 (2.4%)		3/208 (1.4%)
Wheezing	1/207 (0.5%)		8/208 (3.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.