AsthmaPhase 3NCT02075255
Efficacy and Safety Study of Benralizumab to Reduce OCS Use in Patients With Uncontrolled Asthma on High Dose Inhaled Corticosteroid Plus LABA and Chronic OCS Therapy
A Phase 3 study testing Benralizumab in people with Asthma, run by AstraZeneca at 87 sites in 12 countries.
Trial summary
The purpose of this trial is to confirm if benralizumab can reduce the use of maintenance OCS in systemic corticosteroid dependent patients with severe refractory asthma with elevated eosinophils. Read more about this study
- Who is it for?
- Ages 18 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
- 220 participants
- Where
- 87 sitesin 12 countries
- Study dates
- 28 Apr 2014to 8 Aug 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed consent prior to any study specific procedures.
- Female and male aged from 18 to 75 years, inclusively.
- History of physician-diagnosed asthma requiring treatment with medium dose ICS and LABA.
- Elevated level of peripheral blood eosinophil
- Documented treatment with high-dose ICS and LABA for at least 6 months prior to Visit 1
- Chronic oral corticosteroid therapy for at least 6 continuous months directly preceding Visit 1. Subjects must be on doses equivalent to 7.5 - 40 mg/day of prednisolone/prednisone at Visit 1 and be on a stable dose for at least 2 weeks prior to randomization. Patients must agree to switch to study required prednisone/prednisolone as their oral corticosteroid for the duration of the study.
Show all 18Show fewer
- Patients with documented failures of OCS reduction within 6 months prior to Visit 1 will not be required to proceed through the dose optimization phase during run-in.
- Morning pre-bronchodilator (Pre-BD) FEV1 of <80% predicted
- Evidence of asthma as documented by either:
- Airway reversibility (FEV1 ≥12% and 200 mL) demonstrated at Visit 1, Visit 2, or Visit 3 using the Maximum Post-bronchodilator Procedure OR Documented reversibility in the previous 24 months prior to Visit 1 OR Airway hyperresponsiveness (PC20 FEV1 methacholine concentration ≤8mg/mL) documented in the previous 12 months prior to planned date of randomization OR Airflow variability in clinic FEV1 ≥20% between 2 consecutive clinic visits documented in the 12 months prior to the planned date of randomization (FEV1 recorded during an exacerbation should not be considered for this criterion).
- All patients must have reversibility testing performed before randomization to establish a baseline characteristic.
- If patients do not demonstrate airway reversibility at either Visit 1 or Visit 2 and this is needed to qualify the patient for randomization, the site should reiterate the need to withhold short- and long-acting bronchodilators prior to Visit 3 in an effort to meet this inclusion criterion.
- At least 1 documented asthma exacerbation in the previous 12 months prior to the date informed consent is obtained
- Optimized OCS dose reached at least 2 weeks prior to randomization
- Additional asthma controller medication must not have been initiated during run in/optimization period (not applicable for management of exacerbations during screening/ run in optimization phase)
- At least 70% compliance with OCS use
- At least 70% compliance with usual asthma controller ICS-LABA
- Minimum 70% (i.e. 10 of 14 days) compliance with asthma daily diary (morning and evening diary)
Who cannot join
- Clinically important pulmonary disease other than asthma or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts.
- Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, 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
Show all 12Show fewer
- Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during run-in/optimization 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
- History of life-threatening asthma
- Asthma control reached at an OCS dose of ≤5mg during run-in/OCS optimization phase
- Qualifies for 3 consecutive dose reductions at Visits 2-4 and continues to meet OCS dose reduction criteria at Visit 5
- Receipt of oral corticosteroids, other than prednisone or prednisolone, as the maintenance oral steroid controller for asthma symptoms from Visit 1 and throughout the study.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.5 times the upper limit of normal (ULN) confirmed during screening period
Trial locations and contacts
87 sites in 12 countries.
87 sites in 12 countries
United States20 sites
Research Site
Centennial, Colorado, 80112
Research Site
Cincinnati, Ohio, 45231
Research Site
Denver, Colorado, 80206
Research Site
Durham, North Carolina, 27704
Research Site
Fort Mitchell, Kentucky, 41017
Research Site
Hialeah, Florida, 33010
Research Site
Hialeah, Florida, 33013
Research Site
Iowa City, Iowa, 52242
Research Site
Los Angeles, California, 90025
Research Site
Madison, Wisconsin, 53792
Research Site
Miami, Florida, 33015
Research Site
Middleburg Heights, Ohio, 44130
Research Site
Mt. Pleasant, South Carolina, 29464
Research Site
Oklahoma City, Oklahoma, 73112
Research Site
Orlando, Florida, 32825
Research Site
Philadelphia, Pennsylvania, 19140
Research Site
Pittsburgh, Pennsylvania, 15213
Research Site
Rochester, Minnesota, 55905
Research Site
The Bronx, New York, 10461
Research Site
Winston-Salem, North Carolina, 27103
Poland12 sites
Research Site
Bydgoszcz, 85-231
Research Site
Karczew, 05-480
Research Site
Koszalin, 75-679
Research Site
Krakow, 31-011
Research Site
Krakow, 31-159
Research Site
Lodz, 90-141
Research Site
Lubin, 59-300
Research Site
Szczecin, 70-111
Research Site
Tarnów, 33-100
Research Site
Trzebnica, 55-100
Research Site
Wroclaw, 53-201
Research Site
Wroclaw, 53-301
Germany7 sites
Research Site
Bamberg, 96049
Research Site
Berlin, 10119
Research Site
Freiburg im Breisgau, 79106
Research Site
Großhansdorf, 20927
Research Site
Hanover, 30625
Research Site
Leipzig, 04207
Research Site
Mainz, 55131
Ukraine7 sites
Research Site
Dnipropetrovsk, 49007
Research Site
Ivano-Frankivsk, 76012
Research Site
Kharkiv, 61035
Research Site
Kharkiv, 61039
Research Site
Kyiv, 03680
Research Site
Kyiv, 04201
Research Site
Vinnytsia, 21029
Bulgaria6 sites
Research Site
Kozloduy, 3320
Research Site
Pazardzhik, 4400
Research Site
Petrich, 2850
Research Site
Rousse, 7002
Research Site
Samokov, 2000
Research Site
Vratsa, 3000
Canada6 sites
Research Site
Calgary, Alberta, T2N 4Z6
Research Site
Hamilton, Ontario, L8N 4A6
Research Site
Montreal, Quebec, H4A 3J1
Research Site
Ottawa, Ontario, K1G 6C6
Research Site
Québec, Quebec, G1V 4G5
Research Site
Vancouver, British Columbia, V6Z 1Y6
Chile6 sites
Research Site
Quillota
Research Site
Rancagua, 2820000
Research Site
Santiago, 8380453
Research Site
Talca, 3465584
Research Site
Talcahuano, 4270918
Research Site
Valparaíso, 2341131
France6 sites
Research Site
Brest, 29609
Research Site
Lyon, 69317
Research Site
Marseille, 13015
Research Site
Montpellier, 34295
Research Site
Strasbourg, 67091
Research Site
Toulouse, 31059
South Korea6 sites
Research Site
Seoul, 02559
Research Site
Seoul, 03080
Research Site
Seoul, 03722
Research Site
Seoul, 06591
Research Site
Seoul, 135-710
Research Site
Suwon, 16499
Turkey (Türkiye)5 sites
Research Site
Adana, 01330
Research Site
Ankara, 06230
Research Site
Bursa
Research Site
Istanbul, 34098
Research Site
Istanbul, 34844
Argentina4 sites
Research Site
Buenos Aires, C1414AIF
Research Site
CABA, 1426
Research Site
Florida, 1638
Research Site
Mendoza, 5500
About this study
Official title: A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase 3 Efficacy and Safety Study of Benralizumab (MEDI-563) to Reduce Oral Corticosteroid Use in Patients With Uncontrolled Asthma on High Dose Inhaled Corticosteroid Plus Long-acting β2 Agonist and Chronic Oral Corticosteroid Therapy (ZONDA)
The purpose of this trial is to confirm if benralizumab can reduce the use of maintenance OCS in systemic corticosteroid dependent patients with severe refractory asthma with elevated eosinophils.
- Conditions
- Asthma
- Being tested
- Benralizumab, Placebo
- Keywords
- Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive Lung Diseases, OCS, Oral Corticosteroids
- 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 administered subcutaneously every 4 weeks
PlaceboBiological
Placebo subcutaneously on study week 0 until study week 24 inclusive.
BenralizumabBiological
Benralizumab administered subcutaneously every 4 weeks for the first 3 dose and then every 8 weeks; matching placebo subcutaneously at the 4 week interim to maintain the blind.
| Study group | Role | What they receive |
|---|---|---|
| Benralizumab Arm A | Experimental | Benralizumab administered subcutaneously every 4 weeks Receives: Biological: Benralizumab |
| Benralizumab Arm B | Experimental | Benralizumab administered subcutaneously every 4 weeks for the first 3 dose and then every 8 weeks; matching placebo subcutaneously at the 4 week interim to maintain the blind. Receives: Biological: Benralizumab |
| Placebo | Placebo comparator | Placebo administered subcutaneously every 4 weeks Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control
Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. The percentage reduction from baseline is defined as: {(Baseline dose-final dose)/baseline dose}*100%. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.
Measured: Week 28
Secondary outcomes (33)
Number and Percentage of Patients in Different Categories of Percent Reduction From Baseline in Final OCS Dose While Maintaining Asthma Control
Number and percentage of patients in different categories of percent reduction from baseline in final OCS dose.
Measured: Week 28
Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control for Patients With Baseline Eosinophils >=300/uL
Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. The percentage reduction from baseline is defined as: {(Baseline dose-final dose)/baseline dose}*100%. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.
Measured: Week 28
The Percentage of Patients With ≥50% Reduction in Average Daily OCS Dose at Visit 14 Compared With Baseline Dose at Visit 6, While Maintaining Asthma Control
Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. The percentage reduction from baseline is defined as: {(Baseline dose-final dose)/baseline dose}*100%. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.
Measured: Week 28
The Proportion of Eligible Patients With ≥100% Reduction in Average Daily OCS Dose at Visit 14 Compared With Baseline Dose at Visit 6, While Maintaining Asthma Control
Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. The percentage reduction from baseline is defined as: {(Baseline dose-final dose)/baseline dose}*100%. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.
Measured: Week 28
The Proportion of Patients With ≤5.0 mg Reduction on Daily OCS Dose at Visit 14 Compared With Baseline Dose at Visit 6, While Maintaining Asthma Control.
Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.
Measured: Week 28
The Proportion of Patients With Average Final OCS Dose ≤5.0 mg Daily at Visit 14, While Maintaining Asthma Control
Final OCS dose is the dose at Week 28. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.
Measured: Week 28
Number and Percentage of Patients With ≥1 Asthma Exacerbation
Number and percentage of patients with at least one post randomisation asthma exacerbation.
Measured: Immediately following the randomisation through Study Week 28
Time to the First Asthma Exacerbation
Time to the first occurrence of asthma exacerbation post randomisation
Measured: The time from randomisation to the date of first asthma exacerbation over 28 weeks
Time to the First Asthma Exacerbation Requiring Hospitalization or ER Visit
Time to the first exacerbation requiring hospitalization or ER visit post randomisation
Measured: The time from randomisation to the date of first asthma exacerbation associated with hospitalization or ER over 28 weeks.
The Annualized Rate of Asthma Exacerbation
The annualized exacerbation rate is based on unadjudicated exacerbation reported by the investigator adjusted by the time of follow-up.
Measured: The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up
The Annualized Rate of Asthma Exacerbations That Are Associated With an Emergency Room Visit or a Hospitalization
The annualized exacerbation rate is based on unadjudicated exacerbation reported by the investigator that are associated with an emergency room visit or a hospitalization adjusted by the time of follow-up.
Measured: The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up
Number of Days in Hospital Due to Asthma
Number of days in hospital due to asthma, if none, 0 day is considered
Measured: The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up
Change From Baseline to Week 28 in Pre-bronchodilator FEV1
Baseline is defined as the last non-missing value prior to the first dose of study treatment. Change from baseline to Week 28 in two treatment groups is compared to placebo group.
Measured: Change from baseline at week 28
Change From Baseline to Week 28 in Asthma Symptom Scores (Total)
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 -14 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: Change from baseline at week 28
Change From Baseline to Week 28 in Asthma Symptom Scores (Daytime)
Asthma symptoms during 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). Lower score (0) is indicating better asthma symptom, while higher score (3) is indicating worse asthma symptom. Baseline is defined as the average of data collected from the evening of study day -14 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: Change from baseline at week 28
Change From Baseline to Week 28 in Asthma Symptom Scores (Nighttime)
Asthma symptoms during night time 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). Lower score (0) is indicating better asthma symptom, while higher score (3) is indicating worse asthma symptom. Baseline is defined as the average of data collected from the evening of study day -14 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: Change from baseline at week 28
Change From Baseline to Week 28 in Rescue Medication Use
Baseline is defined as the average of data collected from the evening of study day -14 to the morning of study day 1. Each timepoint 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 will be considered as missing. The number of inhalations (puffs) per day will be calculated as follows: Number of night inhaler puffs + 2 x [number of night nebulizer times] + number of day inhaler puffs + 2 x [number of day nebulizer times].
Measured: Change from baseline at week 28
Change From Baseline to Week 28 in Home Lung Function (Morning Peak Expiratory Flow)
Morning peak expiratory flow change from baseline to week 28. Baseline is defined as the average of data collected from the evening of study day -14 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data.
Measured: Change from baseline at week 28
Change From Baseline to Week 28 in Home Lung Function (Evening Peak Expiratory Flow)
Evening peak expiratory flow change from baseline to week 28. Baseline is defined as the average of data collected from the evening of study day -14 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data
Measured: Change from baseline at week 28
Change From Baseline to Week 28 in the Proportion of Nights With Awakening Due to Asthma Requiring Rescue Medication
Baseline is defined as the proportion of nights from the evening of study day -14 to the morning of study day 1.Each timepoint is calculated as bi-weekly proportions based on daily diary data. If more than 50% of data are missing in a 14 day period then this will be considered as missing.Proportion of nights with noctural awakenings is defined as the number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data.
Measured: Change from baseline at week 28
Change From Baseline to Week 28 in ACQ-6
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: Change from baseline at week 28
ACQ-6 Responders (Improvement) at Week 28
Improvement is defined as ACQ-6 (End of treatment - baseline) <= -0.5. No change is defined as ACQ-6 (End of treatment - baseline) >-0.5 and <0.5. Deterioration is defined as ACQ-6 (End of treatment - baseline) >= 0.5. ACQ-6 score is defined as the average of the first 6 items of the ACQ questionnaire on symptoms, activity limitations and rescue medication.Scores range from 0 (totally controlled) to 6 (severely uncontrolled). Baseline is defined as the last non-missing value prior to randomisation. End of treatment is defined as week 28. Patients with missing or non-evaluable ACQ-6 at week 28 are considered non-responder.
Measured: Week 28
Change From Baseline at Week 28 in AQLQ(S)+12 (Overall)
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: Change from baseline at week 28
AQLQ(s)+12 Responders (Improvement) at Week 28
AQLQ(S)+12 overall score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. Improvement is defined as AQLQ(S)+12 (End of treatment - baseline)>=0.5. No change is defined as AQLQ(S)+12 (End of treatment - baseline) >-0.5 and <0.5. Deterioration is defined as AQLQ(S)+12 (End of treatment - baseline) <= -0.5. Baseline is defined as the last AQLQ(S)+12 score prior to randomisation. End of treatment is defined as week 28. Patients with missing or non-evaluable score at week 28 are considered as non-responder.
Measured: Week 28
Extent of Exposure
Duration of exposure from first dose date to last dose date.
Measured: From first dose to Week 24
Serum Concentration of Benralizumab
Pre-dose serum concentrations at each visit
Measured: Pre-first dose to Week 36
Anti-drug Antibody Response
Number and percentage of patients in different ADA response categories
Measured: From baseline to follow-up Week 36
Percent Change From Baseline in Blood Eosinophil Counts
Percent change from baseline in blood eosinophil counts at week 28
Measured: Change from baseline at Week 28
Total Lung Capacity
Change from baseline in total lung capacity
Measured: From baseline to Week 28
Residual Volume
Change from baseline in residual volume
Measured: From baseline to Week 28
Vital Capacity
Change from baseline in vital capacity
Measured: From baseline to Week 28
Functional Residual Capacity
Change from baseline in functional residual capacity
Measured: From baseline to Week 28
Inspiratory Capacity
Change from baseline in inspiratory capacity
Measured: From baseline to Week 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2014 (estimated)
- Study start28 Apr 2014
- Primary completion8 Aug 2016
- Study completion8 Aug 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 (4)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
- 220 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Parameswaran Nair, MD,PhD,FRCP,FRCPC, Principal investigator, St Joseph's Healthcare Hamilton Firestone Institute for Respiratory Health 50 Charlton Avenue East Hamilton
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02075255
- Sponsor's protocol ID
- D3250C00020
- Status last verified
- May 2018
- First submitted
- 14 Feb 2014
- Last updated
- 8 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, Barker P, Sproule S, Ponnarambil S, Goldman M; ZONDA Trial Investigators. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017 Jun 22;376(25):2448-2458. doi: 10.1056/NEJMoa1703501. Epub 2017 May 22.
PubMed 28530840Menzies-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 35287231Menzies-Gow A, Corren J, Bel EH, Maspero J, Heaney LG, Gurnell M, Wessman P, Martin UJ, Siddiqui S, Garcia Gil E. Corticosteroid tapering with benralizumab treatment for eosinophilic asthma: PONENTE Trial. ERJ Open Res. 2019 Sep 25;5(3):00009-2019. doi: 10.1183/23120541.00009-2019. eCollection 2019 Jul.
PubMed 31579676Chupp 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 30802500
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase 3 Efficacy and Safety Study of Benralizumab (MEDI-563) to Reduce Oral Corticosteroid Use in Patients With Uncontrolled Asthma on High Dose Inhaled Corticosteroid Plus Long-acting β2 Agonist and Chronic Oral Corticosteroid Therapy (ZONDA)
- ClinicalTrials.gov ID
- NCT02075255
- Acronym / sponsor ID
- D3250C00020
- Conditions
- Asthma
- Keywords
- Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive Lung Diseases, OCS, Oral Corticosteroids
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 220 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 28 Apr 2014 (actual)
- Primary completion
- 8 Aug 2016 (actual)
- Study completion
- 8 Aug 2016 (actual)
- First posted
- 3 Mar 2014 (estimated)
- Results
- Posted 17 Oct 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 trial is to confirm if benralizumab can reduce the use of maintenance OCS in systemic corticosteroid dependent patients with severe refractory asthma with elevated eosinophils.
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 Arm A | Experimental | Biological: BenralizumabBenralizumab administered subcutaneously every 4 weeks |
| Benralizumab Arm B | Experimental | Biological: BenralizumabBenralizumab administered subcutaneously every 4 weeks for the first 3 dose and then every 8 weeks; matching placebo subcutaneously at the 4 week interim to maintain the blind. |
| Placebo | Placebo comparator | Biological: PlaceboPlacebo administered subcutaneously every 4 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Provision of informed consent prior to any study specific procedures.
- Female and male aged from 18 to 75 years, inclusively.
- History of physician-diagnosed asthma requiring treatment with medium dose ICS and LABA.
- Elevated level of peripheral blood eosinophil
- Documented treatment with high-dose ICS and LABA for at least 6 months prior to Visit 1
Key exclusion criteria (12 listed)
- Clinically important pulmonary disease other than asthma or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts.
- Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, 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, hematology, clinical chemistry, or urinalysis during run-in/optimization 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
- History of life-threatening asthma
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 administered subcutaneously every 4 weeks | Biological | Benralizumab Arm A |
| PlaceboPlacebo subcutaneously on study week 0 until study week 24 inclusive. | Biological | Placebo |
| BenralizumabBenralizumab administered subcutaneously every 4 weeks for the first 3 dose and then every 8 weeks; matching placebo subcutaneously at the 4 week interim to maintain the blind. | Biological | Benralizumab Arm B |
Primary outcome
Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control
Time frame: Week 28
Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. The percentage reduction from baseline is defined as: {(Baseline dose-final dose)/baseline dose}*100%. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.
33 secondary outcomes
Number and Percentage of Patients in Different Categories of Percent Reduction From Baseline in Final OCS Dose While Maintaining Asthma Control
Time frame: Week 28
Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control for Patients With Baseline Eosinophils >=300/uL
Time frame: Week 28
The Percentage of Patients With ≥50% Reduction in Average Daily OCS Dose at Visit 14 Compared With Baseline Dose at Visit 6, While Maintaining Asthma Control
Time frame: Week 28
The Proportion of Eligible Patients With ≥100% Reduction in Average Daily OCS Dose at Visit 14 Compared With Baseline Dose at Visit 6, While Maintaining Asthma Control
Time frame: Week 28
The Proportion of Patients With ≤5.0 mg Reduction on Daily OCS Dose at Visit 14 Compared With Baseline Dose at Visit 6, While Maintaining Asthma Control.
Time frame: Week 28
The Proportion of Patients With Average Final OCS Dose ≤5.0 mg Daily at Visit 14, While Maintaining Asthma Control
Time frame: Week 28
Number and Percentage of Patients With ≥1 Asthma Exacerbation
Time frame: Immediately following the randomisation through Study Week 28
Time to the First Asthma Exacerbation
Time frame: The time from randomisation to the date of first asthma exacerbation over 28 weeks
Time to the First Asthma Exacerbation Requiring Hospitalization or ER Visit
Time frame: The time from randomisation to the date of first asthma exacerbation associated with hospitalization or ER over 28 weeks.
The Annualized Rate of Asthma Exacerbation
Time frame: The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up
The Annualized Rate of Asthma Exacerbations That Are Associated With an Emergency Room Visit or a Hospitalization
Time frame: The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up
Number of Days in Hospital Due to Asthma
Time frame: The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up
Change From Baseline to Week 28 in Pre-bronchodilator FEV1
Time frame: Change from baseline at week 28
Change From Baseline to Week 28 in Asthma Symptom Scores (Total)
Time frame: Change from baseline at week 28
Change From Baseline to Week 28 in Asthma Symptom Scores (Daytime)
Time frame: Change from baseline at week 28
Change From Baseline to Week 28 in Asthma Symptom Scores (Nighttime)
Time frame: Change from baseline at week 28
Change From Baseline to Week 28 in Rescue Medication Use
Time frame: Change from baseline at week 28
Change From Baseline to Week 28 in Home Lung Function (Morning Peak Expiratory Flow)
Time frame: Change from baseline at week 28
Change From Baseline to Week 28 in Home Lung Function (Evening Peak Expiratory Flow)
Time frame: Change from baseline at week 28
Change From Baseline to Week 28 in the Proportion of Nights With Awakening Due to Asthma Requiring Rescue Medication
Time frame: Change from baseline at week 28
Change From Baseline to Week 28 in ACQ-6
Time frame: Change from baseline at week 28
ACQ-6 Responders (Improvement) at Week 28
Time frame: Week 28
Change From Baseline at Week 28 in AQLQ(S)+12 (Overall)
Time frame: Change from baseline at week 28
AQLQ(s)+12 Responders (Improvement) at Week 28
Time frame: Week 28
Extent of Exposure
Time frame: From first dose to Week 24
Serum Concentration of Benralizumab
Time frame: Pre-first dose to Week 36
Anti-drug Antibody Response
Time frame: From baseline to follow-up Week 36
Percent Change From Baseline in Blood Eosinophil Counts
Time frame: Change from baseline at Week 28
Total Lung Capacity
Time frame: From baseline to Week 28
Residual Volume
Time frame: From baseline to Week 28
Vital Capacity
Time frame: From baseline to Week 28
Functional Residual Capacity
Time frame: From baseline to Week 28
Inspiratory Capacity
Time frame: From baseline to Week 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28530840Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, Barker P, Sproule S, Ponnarambil S, Goldman M; ZONDA Trial Investigators. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017 Jun 22;376(25):2448-2458. doi: 10.1056/NEJMoa1703501. Epub 2017 May 22.
- 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 31579676Menzies-Gow A, Corren J, Bel EH, Maspero J, Heaney LG, Gurnell M, Wessman P, Martin UJ, Siddiqui S, Garcia Gil E. Corticosteroid tapering with benralizumab treatment for eosinophilic asthma: PONENTE Trial. ERJ Open Res. 2019 Sep 25;5(3):00009-2019. doi: 10.1183/23120541.00009-2019. eCollection 2019 Jul.
- 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.
- CSP redactedLink 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.
Parameswaran Nair, MD,PhD,FRCP,FRCPC principal investigator
St Joseph's Healthcare Hamilton Firestone Institute for Respiratory Health 50 Charlton Avenue East Hamilton
87 sites in 12 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 87 sites in 12 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 18 inclusion and 12 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 8 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 87 sites in United States, Poland, Germany, Ukraine, Bulgaria and 7 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 17 Oct 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?
Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control (time frame: Week 28). 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 NCT02075255, which also lists 4 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 8 Jun 2018.