Clinical trial NCT03557307: Study to Evaluate Efficacy and Safety of Benralizumab in Reducing Oral Corticosteroid Use in Adult Patients With Severe Asthma
Official title: PONENTE: A Multicenter, Open-label, Phase 3b Efficacy and Safety Study of Benralizumab 30 mg Administered Subcutaneously to Reduce Oral Corticosteroid Use in Adult Patients With Severe Eosinophilic Asthma on High Dose Inhaled Corticosteroid Plus Long-acting β2 Agonist and Chronic Oral Corticosteroid Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Severe Asthma
Oral Corticosteroids
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-06-15
Enrollment: 598
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Open label
Primary purpose: TREATMENT

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).

Eligibility criteria: 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 exclusion criteria specified in the main study or allogeneic bone marrow transplant, Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection
12. Current night-shift workers

Primary outcomes:
measure: Patients Who Achieve 100% Reduction in Daily OCS Dose
timeFrame: 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.)
measure: Patients Who Achieve 100% Reduction or a Daily OCS Dose of <=5mg
timeFrame: 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.)
Secondary outcomes:
measure: Patients Who Achieve a Daily OCS of ≤5mg
timeFrame: 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.)
measure: Patients Who Achieve a ≥90%, ≥75%, and ≥50% Reduction in Daily OCS Dose
timeFrame: 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.)
measure: Change From Baseline in Average Daily OCS Dose (mg)
timeFrame: 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.)
Other outcomes:
measure: 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
timeFrame: from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days.
measure: Patients Who Achieve a Daily OCS Dose of ≤5 mg at the End of the Long Term Follow up Substudy
timeFrame: from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days.
measure: 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
timeFrame: from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days.
measure: Change in Daily OCS Dose (mg) From Main Study Baseline to the End of the Long Term Follow up Substudy
timeFrame: from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days.
Locations:
city: Flagstaff
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facility: Research Site
state: Arizona
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state: California
city: Aurora
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state: Colorado
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state: Delaware
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state: Florida
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state: Georgia
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state: North Carolina
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state: North Carolina
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city: Buenos Aires
country: Argentina
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city: Caba
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city: Cap. Fed
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city: Ciudad Autónoma de Buenos Aire
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city: Rosario
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city: Rosario
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city: Bruxelles
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city: Erpent
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city: Gent
country: Belgium
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city: Botucatu
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city: Herlev
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city: Vejle
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city: Ålborg
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city: ANGERS Cedex 9
country: France
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city: Besancon Cedex
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city: Marseille
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city: Berlin
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city: Heidelberg
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city: Del. Cuauhtemoc
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city: Guadalajara
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city: Mérida
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city: Veracruz
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city: Villahermosa
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city: Białystok
country: Poland
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city: Białystok
country: Poland
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city: Gdańsk
country: Poland
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city: Kraków
country: Poland
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city: Lubin
country: Poland
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city: Ostrowiec Świętokrzyski
country: Poland
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city: Poznań
country: Poland
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city: Poznań
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city: Rzeszów
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city: Sosnowiec
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city: Tarnów
country: Poland
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city: Wieluń
country: Poland
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city: Wrocław
country: Poland
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city: Izhevsk
country: Russian Federation
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city: Kirov
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Omsk
country: Russian Federation
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city: Omsk
country: Russian Federation
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city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
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city: Ulyanovsk
country: Russian Federation
facility: Research Site
city: Cádiz
country: Spain
facility: Research Site
city: Marbella (Málaga)
country: Spain
facility: Research Site
city: Mérida
country: Spain
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city: Ourense
country: Spain
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city: Sant Joan Despí (Barcelona)
country: Spain
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city: Santiago De Compostela-Coruña
country: Spain
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city: Zaragoza
country: Spain
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city: Lund
country: Sweden
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city: Kaohsiung Hsien
country: Taiwan
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city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
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city: Taichung
country: Taiwan
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city: Taipei City
country: Taiwan
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city: Taipei
country: Taiwan
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city: Taipei
country: Taiwan
facility: Research Site
city: Yunlin
country: Taiwan
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city: Bradford
country: United Kingdom
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city: Cambridge
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
Study officials:
References:
citation: Menzies-Gow A, Gurnell M, Heaney LG, Corren J, Bel EH, Maspero J, Harrison T, Jackson DJ, Price D, Lugogo N, Kreindler J, Burden A, de Giorgio-Miller A, Padilla K, Martin UJ, Garcia Gil E. Oral corticosteroid elimination via a personalised reduction algorithm in adults with severe, eosinophilic asthma treated with benralizumab (PONENTE): a multicentre, open-label, single-arm study. Lancet Respir Med. 2022 Jan;10(1):47-58. doi: 10.1016/S2213-2600(21)00352-0. Epub 2021 Oct 4.
citation: Menzies-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.