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

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

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.

Study Overview

• Status: Terminated
• Conditions: Asthma
• Intervention / Treatment: Biological: Placebo; Biological: Brodalumab

• Study Type: Interventional
• Enrollment (Actual): 421
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • New Lambton, New South Wales, Australia, 2305
      • Research Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Research Site
• Canada
  • Alberta
    • Sherwood Park, Alberta, Canada, T8H 0N2
      • Research Site
  • British Columbia
    • Kelowna, British Columbia, Canada, V1W 1V3
      • Research Site
    • Surrey, British Columbia, Canada, V3T 0G9
      • Research Site
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Research Site
    • Vancouver, British Columbia, Canada, V6J 1S3
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  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Research Site
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Research Site
    • Newmarket, Ontario, Canada, L3Y 5G8
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    • Sarnia, Ontario, Canada, N7T 4X3
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    • Toronto, Ontario, Canada, M5T 3A9
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    • Toronto, Ontario, Canada, M9V 4B4
      • Research Site
  • Quebec
    • Trois Rivieres, Quebec, Canada, G8T 7A1
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• France
  • Le Kremlin Bicetre, France, 94270
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  • Marseille, France, 13015
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  • Montpellier cedex 05, France, 34295
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  • Pessac Cedex, France, 33604
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  • Saint Herblain, France, 44805
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  • Strasbourg cedex, France, 67091
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  • Tours Cedex 9, France, 37044
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• Germany
  • Berlin, Germany, 10717
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  • Berlin, Germany, 12099
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  • Bonn, Germany, 53119
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  • Cottbus, Germany, 03050
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  • Frankfurt am Main, Germany, 60596
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  • Hamburg, Germany, 22299
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  • Hannover, Germany, 30173
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  • Mainz, Germany, 55131
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  • Radebeul, Germany, 01445
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  • Rüdersdorf, Germany, 15562
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• Greece
  • Alexandroupoli, Greece, 68100
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  • Athens, Greece, 11527
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  • Athens, Greece, 11528
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  • Athens, Greece, 10676
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  • Athens, Greece, 15125
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  • Chaidari, Athens, Greece, 12462
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  • Heraklion - Crete, Greece, 71110
    • Research Site
  • Thessaloniki, Greece, 57010
    • Research Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site
  • New Territories, Hong Kong
    • Research Site
• Ireland
  • Cork, Ireland
    • Research Site
  • Dublin, Ireland
    • Research Site
  • Dublin, Ireland, 24
    • Research Site
  • Dublin, Ireland, 15
    • Research Site
• Italy
  • Catania, Italy, 95123
    • Research Site
  • Ferrara, Italy, 44121
    • Research Site
  • Genova, Italy, 16132
    • Research Site
  • Modena, Italy, 41124
    • Research Site
  • Padova, Italy, 35128
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  • Pavia, Italy, 27100
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  • Pisa, Italy, 56124
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  • Tradate (VA), Italy, 21049
    • Research Site
• Korea, Republic of
  • Bucheon-si, Gyeonggi-do, Korea, Republic of, 420-767
    • Research Site
  • Incheon, Korea, Republic of, 405-760
    • Research Site
  • Seoul, Korea, Republic of, 142-703
    • Research Site
  • Wonju-si, Gangwon-do, Korea, Republic of, 220-710
    • Research Site
• New Zealand
  • Christchurch, New Zealand, 8140
    • Research Site
  • Dunedin, New Zealand, 9058
    • Research Site
  • Remuera, New Zealand, 1051
    • Research Site
• Poland
  • Bialystok, Poland, 15-044
    • Research Site
  • Bialystok, Poland, 15-010
    • Research Site
  • Gdynia, Poland, 81-338
    • Research Site
  • Katowice, Poland, 40-954
    • Research Site
  • Krakow, Poland, 31-011
    • Research Site
  • Krakow, Poland, 31-637
    • Research Site
  • Krakow, Poland, 31-024
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  • Lublin, Poland, 59-300
    • Research Site
  • Skierniewice, Poland, 96-100
    • Research Site
  • Tarnow, Poland, 33-100
    • Research Site
  • Warszawa, Poland, 04-141
    • Research Site
  • Warszawa, Poland, 02-097
    • Research Site
  • Warszawa, Poland, 01-868
    • Research Site
  • Warszawa, Poland, 02-201
    • Research Site
  • Zgierz, Poland, 95-100
    • Research Site
• Puerto Rico
  • San Juan, Puerto Rico, 00917
    • Research Site
• Russian Federation
  • Moscow, Russian Federation, 119991
    • Research Site
  • Moscow, Russian Federation, 115280
    • Research Site
  • Moscow, Russian Federation, 123182
    • Research Site
  • Moscow, Russian Federation, 127018
    • Research Site
  • Moscow, Russian Federation, 105077
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  • Moscow, Russian Federation, 115446
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  • Saint Petersburg, Russian Federation, 197022
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  • Saint Petersburg, Russian Federation, 193231
    • Research Site
  • Saint-Petersburg, Russian Federation, 195271
    • Research Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Research Site
  • Taipei, Taiwan, 112
    • Research Site
  • Taipei, Taiwan, 22050
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Research Site
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Research Site
    • Phoenix, Arizona, United States, 85006
      • Research Site
    • Scottsdale, Arizona, United States, 85251
      • Research Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Research Site
  • California
    • Bakersfield, California, United States, 93301
      • Research Site
    • Encinitas, California, United States, 92024
      • Research Site
    • Los Angeles, California, United States, 90025
      • Research Site
    • Los Angeles, California, United States, 90048
      • Research Site
    • Newport Beach, California, United States, 92663
      • Research Site
    • North Hollywood, California, United States, 91606
      • Research Site
    • Orange, California, United States, 92868
      • Research Site
    • Palmdale, California, United States, 93551
      • Research Site
    • Rolling Hills Estates, California, United States, 90274
      • Research Site
    • San Diego, California, United States, 92108
      • Research Site
    • San Diego, California, United States, 92103
      • Research Site
    • San Jose, California, United States, 95117
      • Research Site
    • Santa Monica, California, United States, 90404
      • Research Site
    • Stockton, California, United States, 95207
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  • Colorado
    • Colorado Springs, Colorado, United States, 80907
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  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Research Site
  • Florida
    • Aventura, Florida, United States, 33180
      • Research Site
    • Hialeah, Florida, United States, 33012
      • Research Site
    • Jacksonville, Florida, United States, 32256
      • Research Site
    • Lynn Haven, Florida, United States, 32444
      • Research Site
    • Miami, Florida, United States, 33173
      • Research Site
    • Orlando, Florida, United States, 32806
      • Research Site
    • Port Orange, Florida, United States, 32127
      • Research Site
    • Tallahassee, Florida, United States, 32308
      • Research Site
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Research Site
    • Lawrenceville, Georgia, United States, 30046
      • Research Site
  • Idaho
    • Eagle, Idaho, United States, 83616
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
    • Chicago, Illinois, United States, 60616
      • Research Site
    • Normal, Illinois, United States, 61761
      • Research Site
    • Peoria, Illinois, United States, 61603
      • Research Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Research Site
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Research Site
    • Baltimore, Maryland, United States, 21236
      • Research Site
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Research Site
  • Minnesota
    • Plymouth, Minnesota, United States, 55441
      • Research Site
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
      • Research Site
  • New Jersey
    • Ocean City, New Jersey, United States, 07712
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Research Site
  • New York
    • Rochester, New York, United States, 14618
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Research Site
    • High Point, North Carolina, United States, 27262
      • Research Site
    • Winston-Salem, North Carolina, United States, 27103
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Research Site
    • Dublin, Ohio, United States, 43016
      • Research Site
    • Middleburg Heights, Ohio, United States, 44130
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Research Site
  • Oregon
    • Lake Oswego, Oregon, United States, 97035
      • Research Site
    • Medford, Oregon, United States, 97504
      • Research Site
    • Portland, Oregon, United States, 97202
      • Research Site
  • Pennsylvania
    • Upland, Pennsylvania, United States, 19013
      • Research Site
  • South Carolina
    • Rock Hill, South Carolina, United States, 29732
      • Research Site
    • Spartanburg, South Carolina, United States, 29303
      • Research Site
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Research Site
    • Nashville, Tennessee, United States, 37203-1424
      • Research Site
    • Nashville, Tennessee, United States, 37214
      • Research Site
  • Texas
    • Arlington, Texas, United States, 76018
      • Research Site
    • Dallas, Texas, United States, 75231
      • Research Site
    • El Paso, Texas, United States, 79903
      • Research Site
    • McKinney, Texas, United States, 75069
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
    • San Antonio, Texas, United States, 78258
      • Research Site
  • Utah
    • Clinton, Utah, United States, 84015
      • Research Site
  • Washington
    • Bellingham, Washington, United States, 98225
      • Research Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Score at Week 24	The ACQ is a validated instrument used in clinical research and practice to evaluate asthma control/impairment. The ACQ assesses disease control by evaluating 7 questions: night time awakenings, asthma symptoms upon wakening, activity limitation, shortness of breath, wheeze frequency, short-acting bronchodilator use, and FEV1. All seven items are scored on a 7-point scale, with 0 indicating good control and 6 indicating poor control; the total score is the mean of the seven items and ranges from 0 (totally-controlled) to 6 (extremely poorly controlled). A negative change from baseline indicates improvement. A change of 0.50 points is considered clinically meaningful and a total score of < 1.0 indicates good asthma control.	Baseline and week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Asthma Exacerbation Rate	The asthma exacerbation event rate is defined as the number of events per subject-year during the 24 week treatment period. An asthma exacerbation was defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study; distinct asthma exacerbations were defined as events with start dates more than 10 days apart from each other.	Baseline to week 24
Change From Baseline in ACQ Composite Score at Week 24 in ICS+LABA Subpopulation	The ACQ is a validated instrument used in clinical research and practice to evaluate asthma control/impairment. The ACQ assesses disease control by evaluating 7 questions: night time awakenings, asthma symptoms upon wakening, activity limitation, shortness of breath, wheeze frequency, short-acting bronchodilator use, and FEV1. All seven items are scored on a 7-point scale, with 0 indicating good control and 6 indicating poor control; the total score is the mean of the seven items and ranges from 0 (totally-controlled) to 6 (extremely poorly controlled). A negative change from baseline indicates improvement. A change of 0.50 points is considered clinically meaningful and a total score of < 1.0 indicates good asthma control.	Baseline and week 24
Asthma Exacerbation Rate in ICS+LABA Subpopulation	The asthma exacerbation event rate is defined as the number of events per subject-year during the 24 week treatment period. An asthma exacerbation was defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study; distinct asthma exacerbations were defined as events with start dates more than 10 days apart from each other.	Baseline to week 24
Change From Baseline in Daily Asthma Symptom Score (7-day Average Score)	The Asthma Symptom Diary (ASD) consists of 23 questions answered on a handheld device, including 10 asthma symptom-related items (5 answered in the morning and 5 in the evening). The morning diary comprises questions on 4 asthma-related symptoms (wheezing, shortness of breath, cough, chest tightness), rated on a 5-point severity scale from 0 (no symptom) to 4 (very severe symptoms), and 1 question on nocturnal awakenings, rated from 0 (did not wake up) to 4 (unable to sleep due to asthma). The evening diary has questions on the same 4 asthma-related symptoms and 1 question on limitations of activities, rated from 0 (not at all) to 4 (extremely). The ASD daily score is computed by averaging the responses to the 10 symptom-related items, and the mean 7-day ASD score is calculated by averaging the 7 daily scores, with the final score ranging from 0 (minimal symptoms) to 4 (very severe symptoms).	Baseline and week 24
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1)		Baseline and week 24
Change From Baseline in Daily Rescue Short-acting Beta-agonist Use	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).	Baseline and week 24
Time to First Asthma Exacerbation	An asthma exacerbation is defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study. Median time to first asthma exacerbation could not be estimated, the percentage of participants with an asthma exacerbation is reported.	From first dose of study drug to week 24
Number of Participants Who Experienced an Asthma Exacerbation	An asthma exacerbation is defined as an asthma worsening that requires systemic corticosteroids for at least 3 days during the study.	Baseline to week 24
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Overall Score	The AQLQ is an asthma-specific instrument that includes evaluations of both symptoms and health-related quality of life measures. The 32-item instrument measures 4 domains affected by asthma including activity limitations, emotional function, exposure to environmental stimuli, and symptoms. Participants were asked to recall their experiences during the last 2 weeks and to respond to each question on a 7-point scale (7=no impairment, 1=severe impairment). The overall score was calculated as mean of the responses to the 32 questions and ranges from 1 (severe impairment) to 7 (no impairment). A positive change from baseline indicates improvement.	Baseline and week 24
Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR)	Peak expiratory flow rate was measured by the participant twice daily at approximately the same time each day (eg, within 1 hour of waking and immediately before bedtime) using a peak flow meter.	Baseline and week 24
Change From Baseline in Variation of Peak Flow	Peak flow was measured by the participant twice daily at approximately the same time each day (eg, within 1 hour of waking and immediately before bedtime) using a peak flow meter. The variation of peak flow is defined as the absolute value of the difference between the A.M. and P.M. peak flow in one day for an individual participant.	Baseline and week 24
Proportion of Asthma Symptom-free Days in 4-weeks Intervals Over the Treatment Period	Asthma symptom-free days is defined as days that a participant had a score of zero in their daily asthma symptom diary score. The ASD consists of 23 questions answered on a handheld device, including 10 asthma symptom-related items (5 answered in the morning and 5 in the evening). The morning diary comprises questions on 4 asthma-related symptoms (wheezing, shortness of breath, cough, chest tightness), rated on a 5-point severity scale from 0 (no symptom) to 4 (very severe symptoms), and 1 question on nocturnal awakenings, rated from 0 (did not wake up) to 4 (unable to sleep due to asthma). The evening diary has questions on the same 4 asthma-related symptoms and 1 question on limitations of activities, rated from 0 (not at all) to 4 (extremely). The daily score is the average of the responses to the 10 items.	Baseline (the 4 weeks prior to first dose) and 4-week intervals up to week 24
Serum Brodalumab Concentration	Serum brodalumab concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) = 0.0500 µg/mL; values below the LLOQ were set to zero.	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Adverse events were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. The investigator assessed whether the adverse event was possibly related to the investigational product. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: fatal;; life threatening;; requires in-patient hospitalization or prolongation of existing hospitalization;; results in persistent or significant disability/incapacity;; congenital anomaly/birth defect;; other medically important serious event.	From first dose of study drug up to the end of study, 28 weeks

Collaborators and Investigators

• Sponsor: Amgen
• Collaborators: AstraZeneca; Kyowa Kirin Co., Ltd.

Publications and helpful links

General Publications

• Globe G, Wiklund I, Mattera M, Zhang H, Revicki DA. Evaluating minimal important differences and responder definitions for the asthma symptom diary in patients with moderate to severe asthma. J Patient Rep Outcomes. 2019 Apr 3;3(1):22. doi: 10.1186/s41687-019-0109-2.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2013
• Primary Completion (Actual): May 15, 2015
• Study Completion (Actual): May 15, 2015

Study Registration Dates

• First Submitted: May 22, 2013
• First Submitted That Met QC Criteria: July 16, 2013
• First Posted (Estimate): July 18, 2013

Study Record Updates

• Last Update Posted (Actual): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 8, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Inadequately controlled asthma, brodalumab, AMG 827
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Dermatologic Agents; Brodalumab
• Other Study ID Numbers: 20120141; 2012-003351-11 (EudraCT Number)