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

Asthma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01902290
• Other study ID #: 20120141
• Secondary ID: 2012-003351-11
• Status: Terminated
• Phase: Phase 2
• Start date: May 22, 2013
• Est. completion date: May 15, 2015

Study information

• Verified date: September 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 421
• Est. completion date: May 15, 2015
• Est. primary completion date: May 15, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma

Intervention

Biological:
• Placebo
Placebo administered subcutaneously
• Brodalumab
Brodalumab administered subcutaneously

Locations

Country	Name	City	State
Australia	Research Site	Nedlands	Western Australia
Australia	Research Site	New Lambton	New South Wales
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Kelowna	British Columbia
Canada	Research Site	Newmarket	Ontario
Canada	Research Site	Sarnia	Ontario
Canada	Research Site	Sherwood Park	Alberta
Canada	Research Site	Surrey	British Columbia
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Trois Rivieres	Quebec
Canada	Research Site	Vancouver	British Columbia
Canada	Research Site	Vancouver	British Columbia
France	Research Site	Le Kremlin Bicetre
France	Research Site	Marseille
France	Research Site	Montpellier cedex 05
France	Research Site	Pessac Cedex
France	Research Site	Saint Herblain
France	Research Site	Strasbourg cedex
France	Research Site	Tours Cedex 9
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Bonn
Germany	Research Site	Cottbus
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Mainz
Germany	Research Site	Radebeul
Germany	Research Site	Rüdersdorf
Greece	Research Site	Alexandroupoli
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Chaidari, Athens
Greece	Research Site	Heraklion - Crete
Greece	Research Site	Thessaloniki
Hong Kong	Research Site	Hong Kong
Hong Kong	Research Site	New Territories
Ireland	Research Site	Cork
Ireland	Research Site	Dublin
Ireland	Research Site	Dublin
Ireland	Research Site	Dublin
Italy	Research Site	Catania
Italy	Research Site	Ferrara
Italy	Research Site	Genova
Italy	Research Site	Modena
Italy	Research Site	Padova
Italy	Research Site	Pavia
Italy	Research Site	Pisa
Italy	Research Site	Tradate (VA)
Korea, Republic of	Research Site	Bucheon-si, Gyeonggi-do
Korea, Republic of	Research Site	Incheon
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Wonju-si, Gangwon-do
New Zealand	Research Site	Christchurch
New Zealand	Research Site	Dunedin
New Zealand	Research Site	Remuera
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Gdynia
Poland	Research Site	Katowice
Poland	Research Site	Krakow
Poland	Research Site	Krakow
Poland	Research Site	Krakow
Poland	Research Site	Lublin
Poland	Research Site	Skierniewice
Poland	Research Site	Tarnow
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Zgierz
Puerto Rico	Research Site	San Juan
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Arlington	Texas
United States	Research Site	Aventura	Florida
United States	Research Site	Bakersfield	California
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baltimore	Maryland
United States	Research Site	Bellevue	Nebraska
United States	Research Site	Bellingham	Washington
United States	Research Site	Birmingham	Alabama
United States	Research Site	Bristol	Tennessee
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Clinton	Utah
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Dallas	Texas
United States	Research Site	Decatur	Georgia
United States	Research Site	Dublin	Ohio
United States	Research Site	Eagle	Idaho
United States	Research Site	El Paso	Texas
United States	Research Site	Encinitas	California
United States	Research Site	Glendale	Arizona
United States	Research Site	Hialeah	Florida
United States	Research Site	High Point	North Carolina
United States	Research Site	Iowa City	Iowa
United States	Research Site	Jackson	Mississippi
United States	Research Site	Jacksonville	Florida
United States	Research Site	Lake Oswego	Oregon
United States	Research Site	Lawrenceville	Georgia
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Lynn Haven	Florida
United States	Research Site	McKinney	Texas
United States	Research Site	Medford	Oregon
United States	Research Site	Miami	Florida
United States	Research Site	Middleburg Heights	Ohio
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Nashville	Tennessee
United States	Research Site	Nashville	Tennessee
United States	Research Site	Newport Beach	California
United States	Research Site	Normal	Illinois
United States	Research Site	North Dartmouth	Massachusetts
United States	Research Site	North Hollywood	California
United States	Research Site	Ocean City	New Jersey
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Orange	California
United States	Research Site	Orlando	Florida
United States	Research Site	Paducah	Kentucky
United States	Research Site	Palmdale	California
United States	Research Site	Peoria	Illinois
United States	Research Site	Phoenix	Arizona
United States	Research Site	Plymouth	Minnesota
United States	Research Site	Port Orange	Florida
United States	Research Site	Portland	Oregon
United States	Research Site	Rochester	New York
United States	Research Site	Rock Hill	South Carolina
United States	Research Site	Rolling Hills Estates	California
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	San Diego	California
United States	Research Site	San Jose	California
United States	Research Site	Santa Monica	California
United States	Research Site	Scottsdale	Arizona
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Stockton	California
United States	Research Site	Tallahassee	Florida
United States	Research Site	Upland	Pennsylvania
United States	Research Site	Waterbury	Connecticut
United States	Research Site	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Amgen	AstraZeneca, Kyowa Kirin Co., Ltd.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Greece,  Hong Kong,  Ireland,  Italy,  Korea, Republic of,  New Zealand,  Poland,  Puerto Rico,  Russian Federation,  Taiwan, 

References & Publications (1)

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. — View Citation

Outcome

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

External Links

•   AmgenTrials clinical trials website