Asthma
Conditions
Keywords
Asthma, Severe Asthma, Oral Corticosteroids
Brief summary
This is a study designed to evaluate efficacy and safety of Benralizumab in reducing the Oral Corticosteroid (OCS) use in adult patients with severe asthma who are receiving OCS with or without additional asthma controller medications.
Detailed description
This is an open-label, multicenter study designed to evaluate efficacy and safety of reducing daily oral corticosteroid (OCS) use after initiation of 30 mg dose of benralizumab administered subcutaneously (SC) in patients with severe eosinophilic asthma receiving high-dose inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) and OCS with or without additional asthma controller(s).
Interventions
BIOLOGICALBenralizumab
Benralizumab subcutaneous injection
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
1. Peripheral blood eosinophil count of ≥150 cells/μL assessed by central lab at Visit 1 or ≥ 300 cells/μL in the past 12 months 2. History of physician diagnosed asthma requiring continuous treatment with high dose ICS (high-dose ICS is budesonide/formoterol HFA ≥640/18 per day or equivalent, fluticasone propionate DPI \> 500/day or equivalent, or authorized generics for these products) plus LABA for at least 6 months prior to Visit 1. The ICS and LABA can be contained within a combination product or given by separate inhalers. The ICS can also be given via nebulized solution for inhalation. 3. Chronic oral corticosteroid therapy equivalent to a daily dose of at least 5 mg of prednisone, for at least 3 continuous months directly preceding Visit 1. 4. Patient should be on a stable OCS dose for at least 4 weeks prior to Visit 1. 5. Non-smokers, current smokers or former smokers with a smoking history of \< or =20 pack-years at Visit 1
Exclusion criteria
1. 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 2. Known history of allergy or reaction to the study drug formulation 3. History of anaphylaxis to any biologic therapy 4. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy 5. Asthma exacerbation requiring use of systemic corticosteroids, or an increase in maintenance dose of OCS, or acute upper/lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to Visit 2 (first benralizumab dose) 6. A history of known immunodeficiency disorder including history of a positive human immunodeficiency virus (HIV) test 7. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥3 times the upper limit of normal (ULN) confirmed at Visit 1. 8. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained 9. Coincident primary adrenal failure (Addison's disease) or irreversible secondary hypoadrenalism due to another independent cause (e.g. pituitary tumour or its treatment) 10. Co-existent inflammatory conditions for which chronic OCS doses are part of their maintenance treatment such as Giant Cell Arteritis, Polymyalgia Rheumatica 11. Exclusion from genetic research may be for any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patients Who Achieve 100% Reduction in Daily OCS Dose | Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.) | Patients who achieve 100% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma |
| Patients Who Achieve 100% Reduction or a Daily OCS Dose of <=5mg | Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.) | Patients who achieve 100% reduction or a daily OCS dose of \<=5mg, if reason for no further OCS reduction is Adrenal Insufficiency, that are sustained over at least 4 weeks without worsening of asthma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients Who Achieve a Daily OCS of ≤5mg | Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.) | Patients who achieve a daily OCS dose of ≤5 mg (regardless of reason for no further OCS reduction), that are sustained over at least 4 weeks without worsening of asthma |
| Patients Who Achieve a ≥90%, ≥75%, and ≥50% Reduction in Daily OCS Dose | Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.) | Patients who achieve a ≥90%, ≥75%, and ≥50% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma |
| Change From Baseline in Average Daily OCS Dose (mg) | Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.) | Change from baseline in average daily OCS dose (mg) from start of OCS reduction to end of the OCS reduction phase |
Other
| Measure | Time frame | Description |
|---|---|---|
| Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days. | Patients who achieve a ≥90%, ≥75%, and ≥50% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma |
| Patients Who Achieve a Daily OCS Dose of ≤5 mg at the End of the Long Term Follow up Substudy | from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days. | Patients who achieve a daily OCS dose of ≤5 mg (regardless of reason for no further OCS reduction), that are sustained over at least 4 weeks without worsening of asthma |
| Change in Daily OCS Dose (mg) From Main Study Baseline to the End of the Long Term Follow up Substudy | from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days. | Change in average daily OCS dose (mg) from main study baseline to the end of the long term follow up substudy |
| Patients Who Achieve 100% Reduction in Daily OCS Dose From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days. | Patients who achieve 100% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma |
Countries
Argentina, Belgium, Brazil, Canada, Colombia, Denmark, France, Germany, Italy, Mexico, Poland, Russia, Spain, Sweden, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
705 participants provided informed consent and were assigned a unique enrollment number prior to screening. Of the 705 patients screened, 598 (84.8%) were eligible to receive Benralizumab 30 mg and entered the study. All 598 (100%) patients received the study drug. 195 of the 538 patients who completed the main study treatment enrolled into PONENTE Long Term Follow Up Substudy.
Pre-assignment details
In PONENTE, at the first visit, ie, the enrollment visit 1, patients were assigned an enrollment number and then evaluated regarding the protocol mandated inclusion and exclusion criteria. After screening and evaluation, only those eligible to receive Benralizumab 30 mg were assigned treatment and entered a 4 week induction phase on a stable dose of oral corticosteroids (OCS). In Substudy, patients were treated according to healthcare provider discretion with no IP provided by sponsor.
Participants by arm
| Arm | Count |
|---|---|
| Benra 30 mg For main study (period 1 (OCS reduction period) and period 2 (maintenance period)): Benralizumab 30 mg administered subcutaneously every 4 weeks. For substudy (period 3 (long term follow up substudy), asthma treatment as per healthcare provider discretion, including Benralizumab 30 mg administered subcutaneously every 4-8 weeks or other biologics. | 598 |
| Total | 598 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 1: To End of OCS Reduction Phase | Adverse Event | 7 |
| Period 1: To End of OCS Reduction Phase | Death | 2 |
| Period 1: To End of OCS Reduction Phase | Failure to meet inclusion/exclusion criteria | 2 |
| Period 1: To End of OCS Reduction Phase | Lost to Follow-up | 5 |
| Period 1: To End of OCS Reduction Phase | other | 3 |
| Period 1: To End of OCS Reduction Phase | Protocol Violation | 6 |
| Period 1: To End of OCS Reduction Phase | Withdrawal by Subject | 10 |
| Period 2: Maintenance Phase | Adverse Event | 4 |
| Period 2: Maintenance Phase | Death | 3 |
| Period 2: Maintenance Phase | Lost to Follow-up | 2 |
| Period 2: Maintenance Phase | other | 3 |
| Period 2: Maintenance Phase | Pregnancy | 2 |
| Period 2: Maintenance Phase | Protocol Violation | 11 |
| Period 2: Maintenance Phase | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Benra 30 mg |
|---|---|
| Age, Continuous | 53.3 years STANDARD_DEVIATION 13.59 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 46 Participants |
| Race/Ethnicity, Customized Asian | 29 Participants |
| Race/Ethnicity, Customized Black or African American | 26 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Other | 12 Participants |
| Race/Ethnicity, Customized White | 475 Participants |
| Sex: Female, Male Female | 383 Participants |
| Sex: Female, Male Male | 215 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 598 | 0 / 195 | 0 / 78 | 0 / 69 |
| other Total, other adverse events | 181 / 598 | 0 / 195 | 0 / 78 | 0 / 69 |
| serious Total, serious adverse events | 89 / 598 | 0 / 195 | 0 / 78 | 0 / 69 |
Outcome results
Primary
Patients Who Achieve 100% Reduction in Daily OCS Dose
Patients who achieve 100% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma
Time frame: Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)
Population: Full analysis set - All enrolled patients who received at least one dose of benralizumab are included in the FAS, irrespective of their protocol adherence and continued participation in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Benra 30 mg | Patients Who Achieve 100% Reduction in Daily OCS Dose | 376 Participants |
95% CI: [58.86, 66.76]Clopper-Pearson Exact CI
Primary
Patients Who Achieve 100% Reduction or a Daily OCS Dose of <=5mg
Patients who achieve 100% reduction or a daily OCS dose of \<=5mg, if reason for no further OCS reduction is Adrenal Insufficiency, that are sustained over at least 4 weeks without worsening of asthma
Time frame: Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)
Population: All enrolled patients who received at least one dose of benralizumab are included in the FAS, irrespective of their protocol adherence and continued participation in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Benra 30 mg | Patients Who Achieve 100% Reduction or a Daily OCS Dose of <=5mg | 490 Participants |
95% CI: [78.62, 84.94]Clopper-Pearson Exact CI
Secondary
Change From Baseline in Average Daily OCS Dose (mg)
Change from baseline in average daily OCS dose (mg) from start of OCS reduction to end of the OCS reduction phase
Time frame: Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)
Population: Full analysis set - All enrolled patients who received at least one dose of benralizumab are included in the FAS, irrespective of their protocol adherence and continued participation in the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Benra 30 mg | Change From Baseline in Average Daily OCS Dose (mg) | -8.50 mg |
95% CI: [-79.9, -73.94]Clopper-Pearson Exact CI
Secondary
Patients Who Achieve a ≥90%, ≥75%, and ≥50% Reduction in Daily OCS Dose
Patients who achieve a ≥90%, ≥75%, and ≥50% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma
Time frame: Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)
Population: Full analysis set - All enrolled patients who received at least one dose of benralizumab are included in the FAS, irrespective of their protocol adherence and continued participation in the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Benra 30 mg | Patients Who Achieve a ≥90%, ≥75%, and ≥50% Reduction in Daily OCS Dose | ≥90% reduction | 383 Participants |
| Benra 30 mg | Patients Who Achieve a ≥90%, ≥75%, and ≥50% Reduction in Daily OCS Dose | ≥75% reduction | 412 Participants |
| Benra 30 mg | Patients Who Achieve a ≥90%, ≥75%, and ≥50% Reduction in Daily OCS Dose | ≥50% reduction | 489 Participants |
95% CI: [60.06, 67.9]Clopper-Pearson Exact CI
95% CI: [65.02, 72.59]Clopper-Pearson Exact CI
95% CI: [78.44, 84.79]Clopper-Pearson Exact CI
Secondary
Patients Who Achieve a Daily OCS of ≤5mg
Patients who achieve a daily OCS dose of ≤5 mg (regardless of reason for no further OCS reduction), that are sustained over at least 4 weeks without worsening of asthma
Time frame: Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)
Population: Full analysis set - All enrolled patients who received at least one dose of benralizumab are included in the FAS, irrespective of their protocol adherence and continued participation in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Benra 30 mg | Patients Who Achieve a Daily OCS of ≤5mg | 547 Participants |
95% CI: [88.94, 93.58]Clopper-Pearson Exact CI
Other Pre-specified
Change in Daily OCS Dose (mg) From Main Study Baseline to the End of the Long Term Follow up Substudy
Change in average daily OCS dose (mg) from main study baseline to the end of the long term follow up substudy
Time frame: from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days.
Population: Long Term Follow Up analysis set - All patients who enrolled in Long Term Follow Up substudy
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Benra 30 mg | Change in Daily OCS Dose (mg) From Main Study Baseline to the End of the Long Term Follow up Substudy | -10.01 mg |
| >=50% Any Biologic | Change in Daily OCS Dose (mg) From Main Study Baseline to the End of the Long Term Follow up Substudy | -10.28 mg |
| >=50% Benra | Change in Daily OCS Dose (mg) From Main Study Baseline to the End of the Long Term Follow up Substudy | -10.8 mg |
Other Pre-specified
Patients Who Achieve 100% Reduction in Daily OCS Dose From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy
Patients who achieve 100% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma
Time frame: from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days.
Population: Long term follow up analysis set - All patients who enrolled in Long Term Follow Up substudy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Benra 30 mg | Patients Who Achieve 100% Reduction in Daily OCS Dose From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | 138 Participants |
| >=50% Any Biologic | Patients Who Achieve 100% Reduction in Daily OCS Dose From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | 60 Participants |
| >=50% Benra | Patients Who Achieve 100% Reduction in Daily OCS Dose From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | 54 Participants |
Other Pre-specified
Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy
Patients who achieve a ≥90%, ≥75%, and ≥50% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma
Time frame: from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days.
Population: Long Term Follow Up analysis set - All patients who enrolled in Long Term Follow Up substudy
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Benra 30 mg | Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | >=90% reduction | 141 Participants |
| Benra 30 mg | Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | >=75% reduction | 151 Participants |
| Benra 30 mg | Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | >=50% reduction | 172 Participants |
| Benra 30 mg | Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | >0% reduction | 175 Participants |
| >=50% Any Biologic | Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | >0% reduction | 72 Participants |
| >=50% Any Biologic | Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | >=90% reduction | 61 Participants |
| >=50% Any Biologic | Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | >=50% reduction | 71 Participants |
| >=50% Any Biologic | Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | >=75% reduction | 64 Participants |
| >=50% Benra | Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | >0% reduction | 65 Participants |
| >=50% Benra | Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | >=75% reduction | 58 Participants |
| >=50% Benra | Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | >=50% reduction | 64 Participants |
| >=50% Benra | Patients Who Achieve ≥90%, ≥75%, ≥50% or >0% OCS Reduction From Main Study Baseline OCS Dose to the End of the Long Term Follow up Substudy | >=90% reduction | 55 Participants |
Other Pre-specified
Patients Who Achieve a Daily OCS Dose of ≤5 mg at the End of the Long Term Follow up Substudy
Patients who achieve a daily OCS dose of ≤5 mg (regardless of reason for no further OCS reduction), that are sustained over at least 4 weeks without worsening of asthma
Time frame: from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days.
Population: Long Term Follow Up analysis set - All patients who enrolled in Long Term Follow Up substudy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Benra 30 mg | Patients Who Achieve a Daily OCS Dose of ≤5 mg at the End of the Long Term Follow up Substudy | 177 Participants |
| >=50% Any Biologic | Patients Who Achieve a Daily OCS Dose of ≤5 mg at the End of the Long Term Follow up Substudy | 72 Participants |
| >=50% Benra | Patients Who Achieve a Daily OCS Dose of ≤5 mg at the End of the Long Term Follow up Substudy | 65 Participants |