AsthmaPhase 3NCT01928771
Efficacy and Safety Study of Benralizumab Added to High-dose Inhaled Corticosteroid Plus LABA in Patients With Uncontrolled Asthma
A Phase 3 study testing Benralizumab in people with Asthma, run by AstraZeneca at 275 sites in 17 countries.
Trial summary
The purpose of this study is to determine whether Benralizumab reduces the number of asthma exacerbations in patients who remain uncontrolled on high doses of ICS-LABA. Read more about this study
- Who is it for?
- Ages 12 to 75 years
- Conditions the study is for
- Asthma
- What is being tested?
- Benralizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,681 participants
- Where
- 275 sitesin 17 countries
- Study dates
- 19 Sep 2013to 5 Apr 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Written informed consent for study participation must be obtained prior to any study related procedures being performed (local regulations are to be followed in determining the assent/consent requirements for children and parent[s]/guardian[s]) and according to international guidelines and/or applicable European Union guidelines.
- Female and Male aged 12 to 75 years inclusively, at the time of visit 1. For those patients, who are 17 on the day of Visit 1 but will turn 18 after this day, will be considered an adolescent for the purposes of this trial.
- History of physician-diagnosed asthma requiring treatment with medium-to-high dose ICS (>250μg fluticasone dry powder formulation equivalents total daily dose) and a LABA, for at least 12 months prior to Visit 1
- Documented treatment with ICS and LABA for at least 3 months prior to Visit 1 with or without oral corticosteroids and additional asthma controllers.
- For subjects 18 years of age and older, the ICS dose must be >500 mcg/day fluticasone propionate dry powder formulation or equivalent daily.
- For subjects ages 12-17, the ICS dose must be ≥500 mcg /day fluticasone propionate dry powder formulation or equivalent daily.
Who cannot join
- Clinically important pulmonary disease other than asthma (e.g. active lung infection, COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg- Strauss syndrome, hypereosinophilic syndrome)
- Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could:
- Affect the safety of the patient throughout the study
- Influence the findings of the studies or their interpretations
- Impede the patient's ability to complete the entire duration of study
- Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period
- Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in period, which in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient's ability to complete entire duration of the study
Trial locations and contacts
275 sites in 17 countries.
275 sites in 17 countries
United States110 sites
Research Site
Abingdon, Virginia
Research Site
Albany, Georgia
Research Site
Albuquerque, New Mexico
Research Site
Allen, Texas
Research Site
Bakersfield, California
Research Site
Baltimore, Maryland
Research Site
Bellevue, Nebraska
Research Site
Beverly Hills, California
Research Site
Billings, Montana
Research Site
Brandon, Florida
Research Site
Charleston, South Carolina
Research Site
Chattanooga, Tennessee
Research Site
Clearwater, Florida
Research Site
Costa Mesa, California
Research Site
Cutler Bay, Florida
Research Site
Dallas, Texas
Research Site
DeLand, Florida
Research Site
Dickinson, Texas
Research Site
Duncanville, Texas
Research Site
Easley, South Carolina
Research Site
Erie, Pennsylvania
Research Site
Farmington Hills, Michigan
Research Site
Feasterville, Pennsylvania
Research Site
Foley, Alabama
Research Site
Fort Mitchell, Kentucky
Research Site
Gainesville, Florida
Research Site
Gainesville, Georgia
Research Site
Gardner, Massachusetts
Research Site
Georgetown, Texas
Research Site
Germantown, Tennessee
Research Site
Grand Forks, North Dakota
Research Site
Greenfield, Wisconsin
Research Site
Gurnee, Illinois
Research Site
Hartford, Connecticut
Research Site
Hazard, Kentucky
Research Site
Hialeah, Florida
Research Site
Hodges, South Carolina
Research Site
Hollywood, Florida
Research Site
Homestead, Florida
Research Site
Hopewell, Virginia
Research Site
Hopewell Jct, New York
Research Site
Houston, Texas
Research Site
Huntersville, North Carolina
Research Site
Huntington Beach, California
Research Site
Huntington Park, California
Research Site
Huntsville, Alabama
Research Site
Iowa City, Iowa
Research Site
Jackonsville, Florida
Research Site
Las Vegas, Nevada
Research Site
Lawrenceville, Georgia
Research Site
Los Angles, California
Research Site
Louisville, Kentucky
Research Site
Lynn Haven, Florida
Research Site
Marlton, New Jersey
Research Site
McAllen, Texas
Research Site
McKinney, Texas
Research Site
Miami, Florida
Research Site
Mobile, Alabama
Research Site
Morgantown, West Virginia
Research Site
Mt. Pleasant, South Carolina
Research Site
New Haven, Connecticut
Research Site
New York, New York
Research Site
Newport Beach, California
Research Site
Normal, Illinois
Research Site
North Dartmouth, Massachusetts
Research Site
Northfield, New Jersey
Research Site
Oklahoma City, Oklahoma
Research Site
Opelousas, Louisiana
Research Site
Orange, California
Research Site
Oregon, Ohio
Research Site
Orem, Utah
Research Site
Orlando, Florida
Research Site
Pembroke Pines, Florida
Research Site
Pharr, Texas
Research Site
Philadelphia, Pennsylvania
Research Site
Phoenix, Arizona
Research Site
Phoenixville, Pennsylvania
Research Site
Picayune, Mississippi
Research Site
Pittsburgh, Pennsylvania
Research Site
Plano, Texas
Research Site
Port Charlotte, Florida
Research Site
Provo, Utah
Research Site
Quincy, Massachusetts
Research Site
Riverside, California
Research Site
Rochester, Minnesota
Research Site
Rock Hill, South Carolina
Research Site
Saint Paul, Minnesota
Research Site
Salt Lake City, Utah
Research Site
San Jose, California
Research Site
Santa Ana, California
Research Site
Scottsboro, Alabama
Research Site
Sealy, Texas
Research Site
Sebring, Florida
Research Site
Sheffield, Alabama
Research Site
Shelby, North Carolina
Research Site
Sparks, Nevada
Research Site
Splendora, Texas
Research Site
St. Petersburg, Florida
Research Site
Staten Island, New York
Research Site
Tampa, Florida
Research Site
The Bronx, New York
Research Site
Toledo, Ohio
Research Site
Tucson, Arizona
Research Site
Tulsa, Oklahoma
Research Site
Union, New Jersey
Research Site
Vero Beach, Florida
Research Site
Warwick, Rhode Island
Research Site
Winston-Salem, North Carolina
Research Site
Winter Park, Florida
Research Site
Wooster, Ohio
United Kingdom22 sites
Research Site
Birmingham
Research Site
Bradford
Research Site
Cambridge
Research Site
Chertsey
Research Site
Chester
Research Site
Chippenham
Research Site
Cottingham
Research Site
Darlington
Research Site
Glasgow
Research Site
High Heaton/Newcastle Upon Tyn
Research Site
Leeds
Research Site
Liverpool
Research Site
London
Research Site
Maidstone
Research Site
Manchester
Research Site
Nottingham
Research Site
Plymouth
Research Site
Portsmouth
Research Site
Soham
Research Site
Somerset
Research Site
Stevenage
Research Site
Stockton
Russia20 sites
Research Site
Chelyabinsk
Research Site
Ivanovo
Research Site
Izhevsk
Research Site
Kazan'
Research Site
Moscow
Research Site
Nizhny Novgorod
Research Site
Novosibirsk
Research Site
Pyatigorsk
Research Site
Rostov-on-Don
Research Site
Ryazan
Research Site
Saint Petersburg
Research Site
Saratov
Research Site
Smolensk
Research Site
StPetersburg
Research Site
Tomsk
Research Site
Vladikavkaz
Research Site
Vladimir
Research Site
Volgograd
Research Site
Yaroslavl
Research Site
Yekaterinburg
Italy17 sites
Research Site
Bari
Research Site
Bologna
Research Site
Catania
Research Site
Cona
Research Site
Florence
Research Site
Foggia
Research Site
Legnago
Research Site
Milan
Research Site
Naples
Research Site
Palermo
Research Site
Pavia
Research Site
Perugia
Research Site
Pisa
Research Site
Roma
Research Site
San Pietro Vernotico
Research Site
Torino
Research Site
Verona
Poland16 sites
Research Site
Bialystok
Research Site
Dobre Miasto
Research Site
Gdansk
Research Site
Giżycko
Research Site
Grodzisk Mazowiecki
Research Site
Kościan
Research Site
Legnica
Research Site
Lodz
Research Site
Lublin
Research Site
Poznan
Research Site
Proszowice
Research Site
Rzeszów
Research Site
Sosnowiec
Research Site
Wołomin
Research Site
Wroclaw
Research Site
Zgierz
France14 sites
Research Site
Brest
Research Site
Clermont-Ferrand
Research Site
Dijon
Research Site
Le Kremlin-Bicêtre
Research Site
Le Mans
Research Site
Lyon
Research Site
Marseille
Research Site
Montpellier
Research Site
Paris
Research Site
Pau
Research Site
Pringy
Research Site
Saint-Pierre
Research Site
Strasbourg
Research Site
Toulouse
Australia11 sites
Research Site
Bedford Park
Research Site
Box Hill
Research Site
Clayton
Research Site
Concord
Research Site
Frankston
Research Site
Nedlands
Research Site
New Lambton Heights
Research Site
Parkville
Research Site
Prahran
Research Site
Randwick
Research Site
Woolloongabba
Bulgaria11 sites
Research Site
Dupnitsa
Research Site
Pernik
Research Site
Pleven
Research Site
Rousse
Research Site
Samokov
Research Site
Sliven
Research Site
Sofia
Research Site
Stara Zagora
Research Site
Varna
Research Site
Velingrad
Research Site
Yambol
Czechia10 sites
Research Site
Brno
Research Site
Jindřichův Hradec
Research Site
Karlovy Vary
Research Site
Ostrava
Research Site
Pardubice
Research Site
Pilsen
Research Site
Prague
Research Site
Rokycany
Research Site
Strakonice
Research Site
Teplice
South Korea9 sites
Research Site
Anyang-si
Research Site
Bucheon-si
Research Site
Busan
Research Site
Cheongju-si
Research Site
Gwangju
Research Site
Incheon
Research Site
Jeju City
Research Site
Seoul
Research Site
Suwon
Spain9 sites
Research Site
Barcelona
Research Site
Lugo
Research Site
Madrid
Research Site
Málaga
Research Site
Oviedo
Research Site
Palma de Mallorca
Research Site
Sagunto(Valencia)
Research Site
Salamanca
Research Site
Valencia
Turkey (Türkiye)8 sites
Research Site
Adana
Research Site
Ankara
Research Site
Antalya
Research Site
Bursa
Research Site
Istanbul
Research Site
Izmir
Research Site
Kocaeli
Research Site
Mersin
Brazil5 sites
Research Site
Porto Alegre
Research Site
Rio de Janeiro
Research Site
Santo André
Research Site
São Paulo
Research Site
Sorocaba
South Africa5 sites
Research Site
Benoni
Research Site
Cape Town
Research Site
Durban
Research Site
KwaDukuza
Research Site
Mowbray
Mexico3 sites
Research Site
Guadalajara
Research Site
Monterrey
Research Site
Morelia
About this study
Official title: A Multicentre, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase III Efficacy and Safety Study of Benralizumab (MEDI-563) Added to High-dose Inhaled Corticosteroid Plus Long-acting β2 Agonist in Patients With Uncontrolled Asthma
The purpose of this study is to determine whether Benralizumab reduces the number of asthma exacerbations in patients who remain uncontrolled on high doses of ICS-LABA.
- Conditions
- Asthma
- Being tested
- Benralizumab, Placebo
- Keywords
- Asthma,, Bronchial Diseases,, Respiratory Tract Diseases,, Lung Diseases,, Obstructive Lung Diseases
- Medical subject headings
- Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Lung Diseases, Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BenralizumabBiological
Benralizumab subcutaneously on study week 0 until study week 44 inclusive.
PlaceboBiological
Placebo subcutaneously on study week 0 until study week 44 inclusive.
| Study group | Role | What they receive |
|---|---|---|
| Benralizumab 30 mg q.4 weeks | Experimental | Benralizumab administered subcutaneously every 4 weeks Receives: Biological: Benralizumab |
| Benralizumab 30 mg q.8 weeks | Experimental | Benralizumab administered subcutaneously every 8 weeks Receives: Biological: Benralizumab |
| Placebo | Placebo comparator | Placebo administered subcutaneously Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Eosinophils >=300/uL
The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF
Measured: Immediately following the first administration of study drug through Study Week 48.
Secondary outcomes (23)
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Eosinophils < 300/uL
The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF
Measured: Immediately following the first administration of study drug through Study Week 48.
Annual Asthma Exacerbation Rate Resulting Emergency Room Visits and Hospitalizations
The annual exacerbation rate associated with an emergency room visit or a hospitalization (adjudicated)
Measured: Immediately following the first administration of study drug through Study Week 48.
Number of Patients With >=1 Asthma Exacerbations
Measured: Immediately following the first administration of study drug through Study Week 48.
Time to First Asthma Exacerbation
Measured: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils >=300/uL
Measured: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils <300/uL
Measured: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils >=300/uL
Asthma symptoms during night time and daytime are recorded by the patient in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma, or unable to do normal activities due to asthma), and total asthma symptom score is the sum of the daytime and night time score (0 to 6). Lower score (0) is indicating better asthma symptom, while higher score (6) is indicating worse asthma symptom. Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each time point is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.
Measured: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils <300/uL
Asthma symptoms during night time and daytime are recorded by the patient in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma, or unable to do normal activities due to asthma), and total asthma symptom score is the sum of the daytime and night time score (0 to 6). Lower score (0) is indicating better asthma symptom, while higher score (6) is indicating worse asthma symptom. Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each time point is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.
Measured: Immediately following the first administration of study drug through Study Week 48.
Change in Asthma Rescue Medication
Change from baseline to week 48 in number of rescue medication use (puffs/day)
Measured: Immediately following the first administration of study drug through Study Week 48.
Home Lung Function Assessment Based on Morning PEF
Change from baseline to week 48 in home lung function morning peak expiratory flow [PEF]
Measured: Immediately following the first administration of study drug through Study Week 48.
Home Lung Function Assessment Based on Evening PEF
Change from baseline to week 48 in home lung function evening peak expiratory flow [PEF]
Measured: Immediately following the first administration of study drug through Study Week 48.
Proportion of Night Awakening Due to Asthma
Change from baseline to Week 48 on proportion of night awakening due to asthma
Measured: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in ACQ-6 for Baseline Eosinophils >=300/uL
ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses. Mean scores of <=0.75 indicates well-controlled asthma, scores between 0.75 to <=1.5 indicate partly controlled asthma, and >1.5 indicates not well controlled asthma.
Measured: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in ACQ-6 for Baseline Eosinophils <300/uL
ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses. Mean scores of <=0.75 indicates well-controlled asthma, scores between 0.75 to <=1.5 indicate partly controlled asthma, and >1.5 indicates not well controlled asthma.
Measured: Immediately following the first administration of study drug through Study Week 48.
Pharmacokinetics of Benralizumab
Mean PK concentrations at each visit
Measured: Baseline, week 4, week 4 day 6, week 8, week 16, week 24, week 32, week 40, week 48, week 56
Immunogenicity of Benralizumab
Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at >=2 post baseline assessments (with >=16 weeks between the first and the last positive) or positive at last post baseline assessment. Transiently positive is defined as having at least one post baseline ADA positive assessment and not fulfilling the conditions of persistently positive.
Measured: Pre-treatment until end of follow-up
Extend of Exposure
Extend of exposure is defined as duration of treatment in days
Measured: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in AQLQ(S)+12
AQLQ(S)+12 overall score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment). Total or domain score change of >=0.5 are considered clinically meaningful.
Measured: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in EQ-5D-5L VAS
EQ-5D-5L VAS is to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state.
Measured: Immediately following the first administration of study drug through Study Week 48.
Mean Work Productivity Loss Due to Asthma
WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Work productivity loss is derived by sum of percentage of missed work due to asthma and product of percentage of actual working hours times degree of asthma affecting work productivity while working. Percentage of missed work due to asthma is calculated by number of hours missed work due to asthma divided by total number of hours missed work plus number of hours actually worked. The work productivity loss is only applicable to patients who employed, which is only subset of the study population.
Measured: Immediately following the first administration of study drug through Study Week 48.
Mean Productivity Loss Due to Asthma in Classroom
WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Classroom productivity loss is derived by sum of percentage of missed classes due to asthma and product of percentage of actual hours attending classes times degree of asthma affecting classroom productivity. Percentage of missed classes due to asthma is calculated by number of hours missed classes due to asthma divided by total number of hours missed classes plus number of hours actually attending classes. This is only applicable to patients who attending classes
Measured: Immediately following the first administration of study drug through Study Week 48.
Number of Participants That Utilized Health Care Resources
Measured: Immediately following the first administration of study drug through Study Week 48.
Patient and Clinician's Responder Assessment to Treatment
CGIC (Clinical global impression of change), and PGIC (Patient global impression of change) are overall evaluation of response to treatment, conducted separately by investigator and patient using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse). This is additional measures collected after second Amendment, thus not all patients had data to be analyzed.
Measured: Immediately following the first administration of study drug through Study Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2013 (estimated)
- Study start19 Sep 2013
- Primary completion5 Apr 2016
- Study completion5 Apr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 2,681 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Eugene R. Bleecker, MD, Professor of Medicine, Principal investigator, Center for Genomics and Personalized Medicine Research, Medical Center Boulevard, Winston-Salem, North Carolina 27157
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01928771
- Sponsor's protocol ID
- D3250C00017
- Status last verified
- Mar 2017
- First submitted
- 16 Aug 2013
- Last updated
- 3 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Menzies-Gow A, Hoyte FL, Price DB, Cohen D, Barker P, Kreindler J, Jison M, Brooks CL, Papeleu P, Katial R. Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab. Adv Ther. 2022 May;39(5):2065-2084. doi: 10.1007/s12325-022-02098-1. Epub 2022 Mar 14.
PubMed 35287231Lugogo NL, Kreindler JL, Martin UJ, Cook B, Hirsch I, Trudo FJ. Blood eosinophil count group shifts and kinetics in severe eosinophilic asthma. Ann Allergy Asthma Immunol. 2020 Aug;125(2):171-176. doi: 10.1016/j.anai.2020.04.011. Epub 2020 Apr 22.
PubMed 32334141Jackson DJ, Humbert M, Hirsch I, Newbold P, Garcia Gil E. Ability of Serum IgE Concentration to Predict Exacerbation Risk and Benralizumab Efficacy for Patients with Severe Eosinophilic Asthma. Adv Ther. 2020 Feb;37(2):718-729. doi: 10.1007/s12325-019-01191-2. Epub 2019 Dec 14.
PubMed 31836949Chipps BE, Hirsch I, Trudo F, Alacqua M, Zangrilli JG. Benralizumab efficacy for patients with fixed airflow obstruction and severe, uncontrolled eosinophilic asthma. Ann Allergy Asthma Immunol. 2020 Jan;124(1):79-86. doi: 10.1016/j.anai.2019.10.006. Epub 2019 Oct 15.
PubMed 31626906Chupp G, Lugogo NL, Kline JN, Ferguson GT, Hirsch I, Goldman M, Zangrilli JG, Trudo F. Rapid onset of effect of benralizumab on morning peak expiratory flow in severe, uncontrolled asthma. Ann Allergy Asthma Immunol. 2019 May;122(5):478-485. doi: 10.1016/j.anai.2019.02.016. Epub 2019 Feb 23.
PubMed 30802500Bleecker ER, Wechsler ME, FitzGerald JM, Menzies-Gow A, Wu Y, Hirsch I, Goldman M, Newbold P, Zangrilli JG. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur Respir J. 2018 Oct 18;52(4):1800936. doi: 10.1183/13993003.00936-2018. Print 2018 Oct.
PubMed 30139780DuBuske L, Newbold P, Wu Y, Trudo F. Seasonal variability of exacerbations of severe, uncontrolled eosinophilic asthma and clinical benefits of benralizumab. Allergy Asthma Proc. 2018 Sep 4;39(5):345-349. doi: 10.2500/aap.2018.39.4162. Epub 2018 Aug 4.
PubMed 30077185Chipps BE, Newbold P, Hirsch I, Trudo F, Goldman M. Benralizumab efficacy by atopy status and serum immunoglobulin E for patients with severe, uncontrolled asthma. Ann Allergy Asthma Immunol. 2018 May;120(5):504-511.e4. doi: 10.1016/j.anai.2018.01.030. Epub 2018 Feb 1.
PubMed 29409951Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, Sproule S, Gilmartin G, Aurivillius M, Werkstrom V, Goldman M; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016 Oct 29;388(10056):2115-2127. doi: 10.1016/S0140-6736(16)31324-1. Epub 2016 Sep 5.
PubMed 27609408
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase III Efficacy and Safety Study of Benralizumab (MEDI-563) Added to High-dose Inhaled Corticosteroid Plus Long-acting β2 Agonist in Patients With Uncontrolled Asthma
- ClinicalTrials.gov ID
- NCT01928771
- Acronym / sponsor ID
- D3250C00017
- Conditions
- Asthma
- Keywords
- Asthma,, Bronchial Diseases,, Respiratory Tract Diseases,, Lung Diseases,, Obstructive Lung Diseases
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,681 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 19 Sep 2013
- Primary completion
- 5 Apr 2016 (actual)
- Study completion
- 5 Apr 2016 (actual)
- First posted
- 27 Aug 2013 (estimated)
- Results
- Posted 3 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether Benralizumab reduces the number of asthma exacerbations in patients who remain uncontrolled on high doses of ICS-LABA.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Benralizumab 30 mg q.4 weeks | Experimental | Biological: BenralizumabBenralizumab administered subcutaneously every 4 weeks |
| Benralizumab 30 mg q.8 weeks | Experimental | Biological: BenralizumabBenralizumab administered subcutaneously every 8 weeks |
| Placebo | Placebo comparator | Biological: PlaceboPlacebo administered subcutaneously |
Who may qualify
- Ages
- 12 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Written informed consent for study participation must be obtained prior to any study related procedures being performed (local regulations are to be followed in determining the assent/consent requirements for children and parent[s]/guardian[s]) and according to international guidelines and/or applicable European Union guidelines.
- Female and Male aged 12 to 75 years inclusively, at the time of visit 1. For those patients, who are 17 on the day of Visit 1 but will turn 18 after this day, will be considered an adolescent for the purposes of this trial.
- History of physician-diagnosed asthma requiring treatment with medium-to-high dose ICS (>250μg fluticasone dry powder formulation equivalents total daily dose) and a LABA, for at least 12 months prior to Visit 1
- Documented treatment with ICS and LABA for at least 3 months prior to Visit 1 with or without oral corticosteroids and additional asthma controllers.
Key exclusion criteria (7 listed)
- Clinically important pulmonary disease other than asthma (e.g. active lung infection, COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg- Strauss syndrome, hypereosinophilic syndrome)
- Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could:
- Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period
- Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in period, which in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient's ability to complete entire duration of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BenralizumabBenralizumab subcutaneously on study week 0 until study week 44 inclusive. | Biological | Benralizumab 30 mg q.4 weeks, Benralizumab 30 mg q.8 weeks |
| PlaceboPlacebo subcutaneously on study week 0 until study week 44 inclusive. | Biological | Placebo |
Primary outcome
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Eosinophils >=300/uL
Time frame: Immediately following the first administration of study drug through Study Week 48.
The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF
23 secondary outcomes
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Eosinophils < 300/uL
Time frame: Immediately following the first administration of study drug through Study Week 48.
Annual Asthma Exacerbation Rate Resulting Emergency Room Visits and Hospitalizations
Time frame: Immediately following the first administration of study drug through Study Week 48.
Number of Patients With >=1 Asthma Exacerbations
Time frame: Immediately following the first administration of study drug through Study Week 48.
Time to First Asthma Exacerbation
Time frame: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils >=300/uL
Time frame: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils <300/uL
Time frame: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils >=300/uL
Time frame: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils <300/uL
Time frame: Immediately following the first administration of study drug through Study Week 48.
Change in Asthma Rescue Medication
Time frame: Immediately following the first administration of study drug through Study Week 48.
Home Lung Function Assessment Based on Morning PEF
Time frame: Immediately following the first administration of study drug through Study Week 48.
Home Lung Function Assessment Based on Evening PEF
Time frame: Immediately following the first administration of study drug through Study Week 48.
Proportion of Night Awakening Due to Asthma
Time frame: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in ACQ-6 for Baseline Eosinophils >=300/uL
Time frame: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in ACQ-6 for Baseline Eosinophils <300/uL
Time frame: Immediately following the first administration of study drug through Study Week 48.
Pharmacokinetics of Benralizumab
Time frame: Baseline, week 4, week 4 day 6, week 8, week 16, week 24, week 32, week 40, week 48, week 56
Immunogenicity of Benralizumab
Time frame: Pre-treatment until end of follow-up
Extend of Exposure
Time frame: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in AQLQ(S)+12
Time frame: Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in EQ-5D-5L VAS
Time frame: Immediately following the first administration of study drug through Study Week 48.
Mean Work Productivity Loss Due to Asthma
Time frame: Immediately following the first administration of study drug through Study Week 48.
Mean Productivity Loss Due to Asthma in Classroom
Time frame: Immediately following the first administration of study drug through Study Week 48.
Number of Participants That Utilized Health Care Resources
Time frame: Immediately following the first administration of study drug through Study Week 48.
Patient and Clinician's Responder Assessment to Treatment
Time frame: Immediately following the first administration of study drug through Study Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35287231Menzies-Gow A, Hoyte FL, Price DB, Cohen D, Barker P, Kreindler J, Jison M, Brooks CL, Papeleu P, Katial R. Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab. Adv Ther. 2022 May;39(5):2065-2084. doi: 10.1007/s12325-022-02098-1. Epub 2022 Mar 14.
- Derived from this study: PubMed 32334141Lugogo NL, Kreindler JL, Martin UJ, Cook B, Hirsch I, Trudo FJ. Blood eosinophil count group shifts and kinetics in severe eosinophilic asthma. Ann Allergy Asthma Immunol. 2020 Aug;125(2):171-176. doi: 10.1016/j.anai.2020.04.011. Epub 2020 Apr 22.
- Derived from this study: PubMed 31836949Jackson DJ, Humbert M, Hirsch I, Newbold P, Garcia Gil E. Ability of Serum IgE Concentration to Predict Exacerbation Risk and Benralizumab Efficacy for Patients with Severe Eosinophilic Asthma. Adv Ther. 2020 Feb;37(2):718-729. doi: 10.1007/s12325-019-01191-2. Epub 2019 Dec 14.
- Derived from this study: PubMed 31626906Chipps BE, Hirsch I, Trudo F, Alacqua M, Zangrilli JG. Benralizumab efficacy for patients with fixed airflow obstruction and severe, uncontrolled eosinophilic asthma. Ann Allergy Asthma Immunol. 2020 Jan;124(1):79-86. doi: 10.1016/j.anai.2019.10.006. Epub 2019 Oct 15.
- Derived from this study: PubMed 30802500Chupp G, Lugogo NL, Kline JN, Ferguson GT, Hirsch I, Goldman M, Zangrilli JG, Trudo F. Rapid onset of effect of benralizumab on morning peak expiratory flow in severe, uncontrolled asthma. Ann Allergy Asthma Immunol. 2019 May;122(5):478-485. doi: 10.1016/j.anai.2019.02.016. Epub 2019 Feb 23.
- Derived from this study: PubMed 30139780Bleecker ER, Wechsler ME, FitzGerald JM, Menzies-Gow A, Wu Y, Hirsch I, Goldman M, Newbold P, Zangrilli JG. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur Respir J. 2018 Oct 18;52(4):1800936. doi: 10.1183/13993003.00936-2018. Print 2018 Oct.
- Derived from this study: PubMed 30077185DuBuske L, Newbold P, Wu Y, Trudo F. Seasonal variability of exacerbations of severe, uncontrolled eosinophilic asthma and clinical benefits of benralizumab. Allergy Asthma Proc. 2018 Sep 4;39(5):345-349. doi: 10.2500/aap.2018.39.4162. Epub 2018 Aug 4.
- Derived from this study: PubMed 29409951Chipps BE, Newbold P, Hirsch I, Trudo F, Goldman M. Benralizumab efficacy by atopy status and serum immunoglobulin E for patients with severe, uncontrolled asthma. Ann Allergy Asthma Immunol. 2018 May;120(5):504-511.e4. doi: 10.1016/j.anai.2018.01.030. Epub 2018 Feb 1.
- Derived from this study: PubMed 27609408Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, Sproule S, Gilmartin G, Aurivillius M, Werkstrom V, Goldman M; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016 Oct 29;388(10056):2115-2127. doi: 10.1016/S0140-6736(16)31324-1. Epub 2016 Sep 5.
- D3250C00017CSP3redactedLink provided by the sponsor.
Related trials for Asthma
RecruitingPhase 1
Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation
Asthma
RecruitingPhase 1
A Study to Compare the Relative Potency of Salbutamol Administered Via Metered Dose Inhalers (MDI) Containing Propellants HFA-152a to HFA-134a in Mild Asthmatics Aged 18 to 65 Inclusive
Asthma, Mild Asthma
RecruitingPhase 3
A Study Assessing the Effect of Dupilumab on Inducing Clinical Remission in Asthma
Asthma Control
Active, not recruitingPhase 2/3
Local Antibiotic Delivery for Community Acquired Pneumonia
Community Acquired Pneumonia (CAP)
RecruitingPhase 2
A Study to Learn About the Study Medicine Called PF-07275315 in People With Moderate-To-Severe Asthma
Asthma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eugene R. Bleecker, MD, Professor of Medicine principal investigator
Center for Genomics and Personalized Medicine Research, Medical Center Boulevard, Winston-Salem, North Carolina 27157
275 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Benralizumab in people with Asthma, run by AstraZeneca at 275 sites in 17 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 275 sites in United States, United Kingdom, Russia, Italy, Poland and 12 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Eosinophils >=300/uL (time frame: Immediately following the first administration of study drug through Study Week 48.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01928771, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2017.