A Study to Evaluate the Dosing of AMG 827 for Subjects With Inadequately Controlled Asthma

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01199289
• Collaborator: (none)
• Enrollment: 315
• Locations: 49
• Arms: 4
• Actual Duration (Months): 14.6
• Patients Per Site: 6.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if AMG 827 is effective compared to placebo as measured by change in Asthma Control Questionnaire (ACQ) composite scores.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: AMG 827; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 315 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Determine the Safety and Efficacy of AMG 827 in Subjects With Inadequately Controlled Asthma
• Actual Study Start Date: Oct 4, 2010
• Actual Primary Completion Date: Dec 21, 2011
• Actual Study Completion Date: Dec 21, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants will receive the matching placebo administered as subcutaneous (SC) injections at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Drug: Placebo; SC injection.
Experimental: AMG 827 140 mg Participants will receive AMG 140 mg administered as SC injections at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Drug: AMG 827; SC injection.
Experimental: AMG 827 210 mg Participants will receive AMG 210 mg administered as SC injections at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Drug: AMG 827; SC injection.
Experimental: AMG 827 280 mg Participants will receive AMG 280 mg administered as SC injections at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Drug: AMG 827; SC injection.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Scores to Week 12 [Baseline and Week 12]

   The ACQ is an instrument used in clinical research and practice to evaluate asthma control/impairment. It is a validated composite score that assesses disease control by evaluating 7 questions: night time awakenings, asthma symptoms upon awakening, activity limitation, shortness of breath, wheeze frequency, short-acting bronchodilator use, and forced expiratory volume in 1 second (FEV1). The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/limitation) scale. The total score is obtained by adding the value from each question and dividing by the number of questions. Higher scores indicates worsening of condition and a negative change from baseline indicates improvement.

Secondary Outcome Measures

1. Change From Baseline in Pre- and Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) [Baseline and Week 12]

   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. FEV1 was performed both pre and post-administration of bronchodilator treatment at Baseline and Week 12.

2. Change From Baseline in AM and PM Peak Expiratory Flow Rate (PEFR) to Week 12 [Baseline and Week 12]

3. Change From Baseline in the Frequency of Rescue Short Acting β-Agonist (SABA) Use to Week 12 [Baseline to Week 12]

   Participants recorded SABA use for 1 week prior to randomization (baseline) and the average number of days recorded was subtracted from average days of SABA use across 12 week intervention period.

4. Change From Baseline in Daily Asthma Symptom Score to Week 12 [Baseline and Week 12]

   Participants recorded their daily asthma symptoms in their electronic diaries (Ediary). It included 7 questions: frequency of night time awakening, time awake at night, wheezing, shortness of breath, cough, chest tightness and activity limitation. Daily asthma symptoms score is the sum of 7 individual scores (with the total score ranging from 0-21). Higher scores indicates worsening of condition and a negative change from baseline indicates improvement.

5. Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Score at Week 12 [Baseline and Week 12]

   The AQLQ is the most commonly used asthma specific instrument and includes evaluations of both symptom and 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 (Mitchell EA et al, 1997, Juniper et al, 1994, Christie MJ et al, 1993, Juniper et al, 1993). 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 = mean of the responses to the 32 questions. Higher scores indicate "better quality of life" and a positive change from baseline indicates improved symptoms.

6. Proportion of Asthma Symptom-free Days [Up to Week 12]

   Asthma symptom-free days were defined as a participant having a score of zero in their daily asthma symptom score. Asthma symptom-free days without SABA use were defined as a participant having a score of zero in their daily asthma symptom score and no SABA use. The proportion of asthma symptom-free days was calculated as the number of asthma symptom-free days over the number of days in the double-blind treatment period (12 weeks).

7. Time to Maximum Observed Concentration (Tmax) of AMG 827 at Week 8 to 10 [Week 8 (days 60 and 64), and pre-dose on Week 10]

8. Maximum Observed Concentration (Cmax) of AMG 827 at Week 8 to 10 [Week 8 (days 60 and 64), and pre-dose on Week 10]

9. Area Under the Concentration-time Curve During the Dosing Interval (AUCtau) of AMG 827 at Week 8 to 10 [Week 8 (days 60 and 64), and pre-dose on Week 10]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men or women 18 to 65 years of age

• Percent of predicted FEV1 ≥ 50% and ≤ 80%

• At least 12% reversibility over pre-bronchodilator FEV1

• Inhaled corticosteroid (ICS) ≥ 200 and ≤ 1000 µg/day fluticasone powder or equivalent

• Ongoing asthma symptoms with ACQ composite score ≥ 1.5 points

Exclusion Criteria:

• Respiratory infection within 4 weeks of screening visit or 1 week of baseline visit

• History of chronic obstructive pulmonary disease or other chronic pulmonary condition other than asthma

• Any uncontrolled or clinically significant systemic disease (eg, uncontrolled diabetes, liver disease)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Encinitas	California	United States
2	Research Site	Huntington Beach	California	United States
3	Research Site	Los Angeles	California	United States
4	Research Site	San Diego	California	United States
5	Research Site	Stockton	California	United States
6	Research Site	Colorado Springs	Colorado	United States
7	Research Site	Stockbridge	Georgia	United States
8	Research Site	Baltimore	Maryland	United States
9	Research Site	North Dartmouth	Massachusetts	United States
10	Research Site	Saint Louis	Missouri	United States
11	Research Site	Bozeman	Montana	United States
12	Research Site	Bellevue	Nebraska	United States
13	Research Site	Skillman	New Jersey	United States
14	Research Site	Rockville Centre	New York	United States
15	Research Site	High Point	North Carolina	United States
16	Research Site	Cincinnati	Ohio	United States
17	Research Site	Lake Oswego	Oregon	United States
18	Research Site	Medford	Oregon	United States
19	Research Site	Pittsburgh	Pennsylvania	United States
20	Research Site	Dallas	Texas	United States
21	Research Site	El Paso	Texas	United States
22	Research Site	Madison	Wisconsin	United States
23	Research Site	Feldbach		Austria
24	Research Site	Hallein		Austria
25	Research Site	Wien		Austria
26	Research Site	Bruxelles		Belgium
27	Research Site	Leuven		Belgium
28	Research Site	Liege		Belgium
29	Research Site	Calgary	Alberta	Canada
30	Research Site	Ottawa	Ontario	Canada
31	Research Site	Toronto	Ontario	Canada
32	Research Site	Helsinki		Finland
33	Research Site	Jyväskylä		Finland
34	Research Site	Turku		Finland
35	Research Site	Edeleny		Hungary
36	Research Site	Matrahaza		Hungary
37	Research Site	Tatabanya		Hungary
38	Research Site	Torokbalint		Hungary
39	Research Site	Zalaegerszeg - Pozva		Hungary
40	Research Site	Bucheon-si		Korea, Republic of
41	Research Site	Seoul		Korea, Republic of
42	Research Site	Suwon		Korea, Republic of
43	Research Site	Rotterdam		Netherlands
44	Research Site	Bialystok		Poland
45	Research Site	Chodziez		Poland
46	Research Site	Gdansk		Poland
47	Research Site	Wroclaw		Poland
48	Research Site	Moscow		Russian Federation
49	Research Site	Saint Petersburg		Russian Federation

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

• Busse WW, Holgate S, Kerwin E, Chon Y, Feng J, Lin J, Lin SL. Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma. Am J Respir Crit Care Med. 2013 Dec 1;188(11):1294-302. doi: 10.1164/rccm.201212-2318OC.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01199289
• Other Study ID Numbers: 20090203
• First Posted: Sep 10, 2010
• Last Update Posted: Nov 26, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by Amgen: Amgen; chronic inflammatory disease; wheezing
• Additional relevant MeSH terms: Asthma; Brodalumab

Study Results

Participant Flow

Recruitment Details

This study was conducted at 61 centers in Austria, Belgium, Canada, Finland, Hungary, Netherlands, Poland, Russia, South Korea, and the United States; 47 of these sites enrolled participants from 04 October 2010 to 21 December 2011. 315 participants were enrolled, but 10 participants from 1 site were excluded from all analyses due to major issues of Good Clinical Practice (GCP) compliance and are not included in the participant flow.

Pre-assignment Detail

A washout period for specific asthma medications was conducted after informed consent and prior to run-in period. After completing screening and meeting all eligibility criteria, all eligible participants underwent run-in visits for 4 weeks prior to randomization.

Arm/Group Title	Placebo	AMG 827 140 mg	AMG 827 210 mg	AMG 827 280 mg
Arm/Group Description	Participants received the matching placebo administered as a subcutaneous (SC) injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 140 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 872 210 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 280 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.
Period Title: Overall Study
STARTED	77	75	76	77
Participants Who Received Study Treatment	76	74	76	76
COMPLETED	68	68	71	65
NOT COMPLETED	9	7	5	12

Baseline Characteristics

Arm/Group Title	Placebo	AMG 827 140 mg	AMG 827 210 mg	AMG 827 280 mg	Total
Arm/Group Description	Participants received the matching placebo administered as a subcutaneous (SC) injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 140 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 872 210 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 280 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Total of all reporting groups
Overall Participants	76	74	76	76	302
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	46.8 (11.2)	43.6 (11.6)	46.0 (11.2)	46.5 (11.5)	45.7 (11.5)
Sex: Female, Male (Count of Participants)
Female	53 69.7%	42 56.8%	38 50%	46 60.5%	179 59.3%
Male	23 30.3%	32 43.2%	38 50%	30 39.5%	123 40.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 3.9%	8 10.8%	6 7.9%	3 3.9%	20 6.6%
Not Hispanic or Latino	73 96.1%	66 89.2%	70 92.1%	73 96.1%	282 93.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	69 90.8%	55 74.3%	63 82.9%	67 88.2%	254 84.1%
Black or African American	5 6.6%	16 21.6%	6 7.9%	4 5.3%	31 10.3%
Asian	2 2.6%	3 4.1%	2 2.6%	3 3.9%	10 3.3%
American Indian or Alaska Native	0 0%	0 0%	2 2.6%	0 0%	2 0.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Multiple	0 0%	0 0%	2 2.6%	2 2.6%	4 1.3%
Other	0 0%	0 0%	1 1.3%	0 0%	1 0.3%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Scores to Week 12
Description	The ACQ is an instrument used in clinical research and practice to evaluate asthma control/impairment. It is a validated composite score that assesses disease control by evaluating 7 questions: night time awakenings, asthma symptoms upon awakening, activity limitation, shortness of breath, wheeze frequency, short-acting bronchodilator use, and forced expiratory volume in 1 second (FEV1). The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/limitation) scale. The total score is obtained by adding the value from each question and dividing by the number of questions. Higher scores indicates worsening of condition and a negative change from baseline indicates improvement.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study treatment who were not excluded due to GCP violations, and had non-missing baseline and post-baseline data.

Arm/Group Title	Placebo	AMG 827 140 mg	AMG 827 210 mg	AMG 827 280 mg
Arm/Group Description	Participants received the matching placebo administered as a subcutaneous (SC) injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 140 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 872 210 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 280 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.
Measure Participants	76	73	75	74
Mean (Standard Deviation) [Score on a scale]	-0.427 (0.784)	-0.521 (0.796)	-0.512 (0.728)	-0.556 (0.810)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 140 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5838
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.068
	Confidence Interval	(2-Sided) 95%; -0.311 to 0.175
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5391
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.075
	Confidence Interval	(2-Sided) 95%; -0.316 to 0.166
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 280 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3583
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.113
	Confidence Interval	(2-Sided) 95%; -0.355 to 0.129
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Pre- and Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Description	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. FEV1 was performed both pre and post-administration of bronchodilator treatment at Baseline and Week 12.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study treatment who were not excluded due to GCP violations, and had non-missing baseline and post-baseline data.

Arm/Group Title	Placebo	AMG 827 140 mg	AMG 827 210 mg	AMG 827 280 mg
Arm/Group Description	Participants received the matching placebo administered as a subcutaneous (SC) injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 140 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 872 210 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 280 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.
Measure Participants	76	73	75	74
Pre-Bronchodilator	0.075 (0.323)	0.035 (0.307)	0.066 (0.367)	0.058 (0.348)
Post-Bronchodilator	-0.052 (0.275)	-0.019 (0.259)	0.016 (0.227)	-0.032 (0.285)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 140 mg
	Comments	Pre-Bronchodilator
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4076
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.047
	Confidence Interval	(2-Sided) 95%; -0.157 to 0.064
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 210 mg
	Comments	Pre-Bronchodilator
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6915
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.022
	Confidence Interval	(2-Sided) 95%; -0.130 to 0.086
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 280 mg
	Comments	Pre-Bronchodilator
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7271
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.019
	Confidence Interval	(2-Sided) 95%; -0.126 to 0.088
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 140 mg
	Comments	Post-Bronchodilator
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9210
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.005
	Confidence Interval	(2-Sided) 95%; -0.086 to 0.095
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 210 mg
	Comments	Post-Bronchodilator
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1139
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.070
	Confidence Interval	(2-Sided) 95%; -0.017 to 0.157
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 280 mg
	Comments	Post-Bronchodilator
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6426
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.021
	Confidence Interval	(2-Sided) 95%; -0.066 to 0.107
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in AM and PM Peak Expiratory Flow Rate (PEFR) to Week 12
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study treatment who were not excluded due to GCP violations, and had non-missing baseline and post-baseline data.

Arm/Group Title	Placebo	AMG 827 140 mg	AMG 827 210 mg	AMG 827 280 mg
Arm/Group Description	Participants received the matching placebo administered as a subcutaneous (SC) injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 140 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 872 210 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 280 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.
Measure Participants	76	74	76	75
AM	4.26 (39.220)	-14.09 (46.708)	-4.53 (46.468)	-1.95 (44.624)
PM	-0.22 (37.807)	-11.56 (40.277)	-9.16 (45.080)	-7.96 (37.984)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 140 mg
	Comments	AM
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0262
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-16.847
	Confidence Interval	(2-Sided) 95%; -31.686 to -2.009
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 210 mg
	Comments	AM
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3627
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.723
	Confidence Interval	(2-Sided) 95%; -21.239 to 7.793
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 280 mg
	Comments	AM
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4507
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.488
	Confidence Interval	(2-Sided) 95%; -19.791 to 8.814
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 140 mg
	Comments	PM
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1228
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-10.426
	Confidence Interval	(2-Sided) 95%; -23.686 to 2.834
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 210 mg
	Comments	PM
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3092
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-6.738
	Confidence Interval	(2-Sided) 95%; -19.758 to 6.281
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 280 mg
	Comments	PM
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2167
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-8.043
	Confidence Interval	(2-Sided) 95%; -20.831 to 4.744
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in the Frequency of Rescue Short Acting β-Agonist (SABA) Use to Week 12
Description	Participants recorded SABA use for 1 week prior to randomization (baseline) and the average number of days recorded was subtracted from average days of SABA use across 12 week intervention period.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study treatment who were not excluded due to GCP violations, and had non-missing baseline and post-baseline data.

Arm/Group Title	Placebo	AMG 827 140 mg	AMG 827 210 mg	AMG 827 280 mg
Arm/Group Description	Participants received the matching placebo administered as a subcutaneous (SC) injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 140 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 872 210 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 280 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.
Measure Participants	76	74	76	75
Mean (Standard Deviation) [Days]	-0.630 (2.842)	-0.187 (2.971)	-0.727 (2.941)	-0.798 (4.293)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 140 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5157
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.331
	Confidence Interval	(2-Sided) 95%; -0.670 to 1.332
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6434
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.234
	Confidence Interval	(2-Sided) 95%; -1.229 to 0.760
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 280 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6954
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.199
	Confidence Interval	(2-Sided) 95%; -1.196 to 0.799
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Daily Asthma Symptom Score to Week 12
Description	Participants recorded their daily asthma symptoms in their electronic diaries (Ediary). It included 7 questions: frequency of night time awakening, time awake at night, wheezing, shortness of breath, cough, chest tightness and activity limitation. Daily asthma symptoms score is the sum of 7 individual scores (with the total score ranging from 0-21). Higher scores indicates worsening of condition and a negative change from baseline indicates improvement.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study treatment who were not excluded due to GCP violations, and had non-missing baseline and post-baseline data.

Arm/Group Title	Placebo	AMG 827 140 mg	AMG 827 210 mg	AMG 827 280 mg
Arm/Group Description	Participants received the matching placebo administered as a subcutaneous (SC) injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 140 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 872 210 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 280 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.
Measure Participants	76	74	76	75
Mean (Standard Deviation) [Score on a scale]	-1.531 (3.674)	-1.816 (3.250)	-1.629 (2.620)	-1.607 (3.238)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 140 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5577
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.283
	Confidence Interval	(2-Sided) 95%; -1.231 to 0.665
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9366
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.038
	Confidence Interval	(2-Sided) 95%; -0.904 to 0.980
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 280 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7745
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.138
	Confidence Interval	(2-Sided) 95%; -0.808 to 1.084
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Score at Week 12
Description	The AQLQ is the most commonly used asthma specific instrument and includes evaluations of both symptom and 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 (Mitchell EA et al, 1997, Juniper et al, 1994, Christie MJ et al, 1993, Juniper et al, 1993). 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 = mean of the responses to the 32 questions. Higher scores indicate "better quality of life" and a positive change from baseline indicates improved symptoms.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study treatment who were not excluded due to GCP violations, and had non-missing baseline and post-baseline data.

Arm/Group Title	Placebo	AMG 827 140 mg	AMG 827 210 mg	AMG 827 280 mg
Arm/Group Description	Participants received the matching placebo administered as a subcutaneous (SC) injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 140 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 872 210 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 280 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.
Measure Participants	66	65	69	63
Mean (Standard Deviation) [Score on a scale]	0.626 (0.901)	0.596 (0.979)	0.537 (0.710)	0.587 (0.866)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 140 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8524
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.026
	Confidence Interval	(2-Sided) 95%; -0.251 to 0.303
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8139
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.033
	Confidence Interval	(2-Sided) 95%; -0.305 to 0.240
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 280 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9881
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.002
	Confidence Interval	(2-Sided) 95%; -0.281 to 0.276
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Proportion of Asthma Symptom-free Days
Description	Asthma symptom-free days were defined as a participant having a score of zero in their daily asthma symptom score. Asthma symptom-free days without SABA use were defined as a participant having a score of zero in their daily asthma symptom score and no SABA use. The proportion of asthma symptom-free days was calculated as the number of asthma symptom-free days over the number of days in the double-blind treatment period (12 weeks).
Time Frame	Up to Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study treatment who were not excluded due to GCP violations

Arm/Group Title	Placebo	AMG 827 140 mg	AMG 827 210 mg	AMG 827 280 mg
Arm/Group Description	Participants received the matching placebo administered as a subcutaneous (SC) injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 140 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 872 210 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 280 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.
Measure Participants	76	74	76	76
With use of SABA	0.230 (0.299)	0.167 (0.263)	0.198 (0.293)	0.166 (0.267)
Without use of SABA	0.201 (0.294)	0.123 (0.241)	0.181 (0.286)	0.146 (0.256)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 140 mg
	Comments
	Type of Statistical Test	Superiority
	Comments	With use of SABA
Statistical Test of Hypothesis	p-Value	0.1213
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.062
	Confidence Interval	(2-Sided) 95%; -0.141 to 0.017
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 210 mg
	Comments
	Type of Statistical Test	Superiority
	Comments	With use of SABA
Statistical Test of Hypothesis	p-Value	0.6643
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.017
	Confidence Interval	(2-Sided) 95%; -0.095 to 0.061
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 280 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2879
	Comments
	Method	ANCOVA
	Comments	With use of SABA
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.042
	Confidence Interval	(2-Sided) 95%; -0.121 to 0.036
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 140 mg
	Comments
	Type of Statistical Test	Superiority
	Comments	Without use of SABA
Statistical Test of Hypothesis	p-Value	0.0546
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.074
	Confidence Interval	(2-Sided) 95%; -0.150 to 0.001
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 210 mg
	Comments	Without use of SABA
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9078
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.004
	Confidence Interval	(2-Sided) 95%; -0.080 to 0.071
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, AMG 827 280 mg
	Comments	Without use of SABA
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3616
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.035
	Confidence Interval	(2-Sided) 95%; -0.111 to 0.040
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Time to Maximum Observed Concentration (Tmax) of AMG 827 at Week 8 to 10
Time Frame	Week 8 (days 60 and 64), and pre-dose on Week 10

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) analyses set: all participants who received at least one dose of AMG 827 and who had at least 1 PK concentration measurement.

Arm/Group Title	AMG 827 140 mg	AMG 827 210 mg	AMG 827 280 mg
Arm/Group Description	Participants received AMG 827 140 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 872 210 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 280 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.
Measure Participants	33	35	29
Median (Full Range) [Days]	3.1	3.1	3.9

9. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) of AMG 827 at Week 8 to 10
Time Frame	Week 8 (days 60 and 64), and pre-dose on Week 10

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) analyses set: all participants who received at least one dose of AMG 827 and who had at least 1 PK concentration measurement.

Arm/Group Title	AMG 827 140 mg	AMG 827 210 mg	AMG 827 280 mg
Arm/Group Description	Participants received AMG 827 140 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 872 210 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 280 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.
Measure Participants	33	35	29
Mean (Standard Deviation) [µg/mL]	8.11 (6.91)	16.6 (12.4)	29.4 (17.5)

10. Secondary Outcome

Title	Area Under the Concentration-time Curve During the Dosing Interval (AUCtau) of AMG 827 at Week 8 to 10
Time Frame	Week 8 (days 60 and 64), and pre-dose on Week 10

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) analyses set: all participants who received at least one dose of AMG 827 and who had at least 1 PK concentration measurement.

Arm/Group Title	AMG 827 140 mg	AMG 827 210 mg	AMG 827 280 mg
Arm/Group Description	Participants received AMG 827 140 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 872 210 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.	Participants received AMG 827 280 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.
Measure Participants	33	35	29
Mean (Standard Deviation) [µg*day/mL]	68.3 (74.3)	171 (150)	313 (196)

Adverse Events

Time Frame	Day 1 to Week 16
Adverse Event Reporting Description	All-cause mortality is reported for all participants randomized in the study that were not excluded from analysis due to GCP violations. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug that were not excluded from analysis due to GCP violations.
Arm/Group Title	Placebo		AMG 827 140 mg		AMG 827 210 mg		AMG 827 280 mg
Arm/Group Description	Participants received the matching placebo administered as a subcutaneous (SC) injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.		Participants received AMG 827 140 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.		Participants received AMG 872 210 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.		Participants received AMG 827 280 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10.
All Cause Mortality
	Placebo		AMG 827 140 mg		AMG 827 210 mg		AMG 827 280 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/77 (0%)		0/75 (0%)		0/76 (0%)		0/77 (0%)
Serious Adverse Events
	Placebo		AMG 827 140 mg		AMG 827 210 mg		AMG 827 280 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/76 (1.3%)		3/74 (4.1%)		1/76 (1.3%)		2/76 (2.6%)
Infections and infestations
Herpes zoster	0/76 (0%)		1/74 (1.4%)		0/76 (0%)		0/76 (0%)
Meningitis viral	0/76 (0%)		1/74 (1.4%)		0/76 (0%)		0/76 (0%)
Otitis externa	0/76 (0%)		0/74 (0%)		0/76 (0%)		1/76 (1.3%)
Investigations
Alanine aminotransferase increased	0/76 (0%)		1/74 (1.4%)		0/76 (0%)		0/76 (0%)
Metabolism and nutrition disorders
Hypoglycaemia unawareness	0/76 (0%)		0/74 (0%)		0/76 (0%)		1/76 (1.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Degeneration of uterine leiomyoma	0/76 (0%)		1/74 (1.4%)		0/76 (0%)		0/76 (0%)
Nervous system disorders
Sciatica	1/76 (1.3%)		0/74 (0%)		0/76 (0%)		0/76 (0%)
Vascular disorders
Deep vein thrombosis	0/76 (0%)		0/74 (0%)		1/76 (1.3%)		0/76 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		AMG 827 140 mg		AMG 827 210 mg		AMG 827 280 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/76 (31.6%)		28/74 (37.8%)		28/76 (36.8%)		28/76 (36.8%)
General disorders
Injection site erythema	2/76 (2.6%)		5/74 (6.8%)		7/76 (9.2%)		7/76 (9.2%)
Infections and infestations
Nasopharyngitis	5/76 (6.6%)		5/74 (6.8%)		3/76 (3.9%)		3/76 (3.9%)
Oral candidiasis	0/76 (0%)		1/74 (1.4%)		4/76 (5.3%)		3/76 (3.9%)
Sinusitis	4/76 (5.3%)		2/74 (2.7%)		4/76 (5.3%)		0/76 (0%)
Upper respiratory tract infection	6/76 (7.9%)		8/74 (10.8%)		4/76 (5.3%)		8/76 (10.5%)
Respiratory, thoracic and mediastinal disorders
Asthma	11/76 (14.5%)		18/74 (24.3%)		15/76 (19.7%)		14/76 (18.4%)
Skin and subcutaneous tissue disorders
Erythema	1/76 (1.3%)		2/74 (2.7%)		1/76 (1.3%)		4/76 (5.3%)

Limitations/Caveats

10 participants from 1 site were excluded from all analysis due to major GCP violations.

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.