Study to Evaluate Efficacy and Safety of Benralizumab in Reducing Oral Corticosteroid Use in Adult Patients With Severe Asthma (PONENTE)

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Biological: Benralizumab

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).

• Study Type: Interventional
• Enrollment (Actual): 598
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1121ABE
    • Research Site
  • Caba, Argentina, C1012AAR
    • Research Site
  • Cap. Fed, Argentina, 1280
    • Research Site
  • Ciudad Autónoma de Bs. As., Argentina, 1426
    • Research Site
  • Ciudad Autónoma de Buenos Aire, Argentina, C1440BRR
    • Research Site
  • Florencio Varela, Argentina, 1888
    • Research Site
  • Mar del Plata, Argentina, 7600
    • Research Site
  • Mendoza, Argentina, M5500GIP
    • Research Site
  • Monte Grande, Argentina, 1842
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  • Ranelagh, Argentina, 1886
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  • Rosario, Argentina, 2000
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  • Rosario, Argentina, S2000DEJ
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• Belgium
  • Bruxelles, Belgium, 1200
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  • Erpent, Belgium, 5101
    • Research Site
  • Gent, Belgium, 9000
    • Research Site
• Brazil
  • Botucatu, Brazil, 18618-970
    • Research Site
  • Londrina, Brazil, 86057-970
    • Research Site
  • Maringa, Brazil, 87015-000
    • Research Site
  • Porto Alegre, Brazil, 90610-000
    • Research Site
  • Porto Alegre, Brazil, 91350-200
    • Research Site
  • Salvador, Brazil, 40060-330
    • Research Site
  • Santo Andre, Brazil, 09080-110
    • Research Site
  • Santo Andre, Brazil, 09060-650
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  • Sorocaba, Brazil, 18040-425
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  • Uberlandia, Brazil, 38411-186
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• Canada
  • Quebec, Canada, G1V 4W2
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  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Research Site
  • CA
    • Vancouver, CA, Canada, V5Z 4E1
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  • Ontario
    • Ajax, Ontario, Canada, L1S 2J5
      • Research Site
    • Mississauga, Ontario, Canada, L5A 3V4
      • Research Site
    • Ottawa, Ontario, Canada, K1H 1E4
      • Research Site
    • Toronto, Ontario, Canada, M4V 1R2
      • Research Site
• Colombia
  • Barranquilla, Colombia, 080020
    • Research Site
  • Bogota, Colombia, 110221
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  • Cali, Colombia, 76001000
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  • Cartagena, Colombia, 130013
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  • Floridablanca, Colombia, 681004
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  • Manizales, Colombia, 17001
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  • Medellin, Colombia, 5001000
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• Denmark
  • Herlev, Denmark, 2730
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  • Hvidovre, Denmark, 2650
    • Research Site
  • Vejle, Denmark, 7100
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  • Ålborg, Denmark, 9000
    • Research Site
• France
  • ANGERS Cedex 9, France, 49933
    • Research Site
  • Besancon Cedex, France, 25030
    • Research Site
  • Colmar Cedex, France, 68024
    • Research Site
  • Marseille, France, 13300
    • Research Site
  • NICE Cedex 01, France, 06001
    • Research Site
  • Orléans, France, 45067
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  • Reims, France, 51092
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  • Suresnes Cedex, France, 92151
    • Research Site
  • Tours, France, 37000
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• Germany
  • Bamberg, Germany, 96049
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  • Berlin, Germany, 12203
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  • Berlin, Germany, 13187
    • Research Site
  • Darmstadt, Germany, 64283
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  • Frankfurt, Germany, 60596
    • Research Site
  • Großhansdorf, Germany, 22927
    • Research Site
  • Heidelberg, Germany, 69126
    • Research Site
  • Köln, Germany, 51069
    • Research Site
  • Leipzig, Germany, 04207
    • Research Site
  • Lübeck, Germany, 23552
    • Research Site
  • Magdeburg, Germany, 39120
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  • München, Germany, 81675
    • Research Site
• Italy
  • Firenze, Italy, 50134
    • Research Site
  • Milano, Italy, 20162
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Palermo, Italy, 90129
    • Research Site
  • Pisa, Italy, 56100
    • Research Site
  • Roma, Italy, 00185
    • Research Site
  • Sassari, Italy, 07100
    • Research Site
  • Tradate, Italy, 21049
    • Research Site
• Mexico
  • Del. Cuauhtemoc, Mexico, 06700
    • Research Site
  • Durango, Mexico, 43080
    • Research Site
  • Guadalajara, Mexico, 44130
    • Research Site
  • Guadalajara, Mexico, 44100
    • Research Site
  • Mérida, Mexico, 97070
    • Research Site
  • Veracruz, Mexico, 91910
    • Research Site
  • Villahermosa, Mexico, 86035
    • Research Site
• Poland
  • Białystok, Poland, 15-044
    • Research Site
  • Białystok, Poland, 15-430
    • Research Site
  • Gdańsk, Poland, 80-214
    • Research Site
  • Kraków, Poland, 31-011
    • Research Site
  • Lubin, Poland, 59-300
    • Research Site
  • Ostrowiec Świętokrzyski, Poland, 27-400
    • Research Site
  • Poznań, Poland, 60-693
    • Research Site
  • Poznań, Poland, 60-823
    • Research Site
  • Rzeszów, Poland, 35-051
    • Research Site
  • Sosnowiec, Poland, 41-200
    • Research Site
  • Tarnów, Poland, 33-100
    • Research Site
  • Wieluń, Poland, 98-300
    • Research Site
  • Wrocław, Poland, 50-449
    • Research Site
• Russian Federation
  • Izhevsk, Russian Federation, 426061
    • Research Site
  • Kirov, Russian Federation, 610014
    • Research Site
  • Moscow, Russian Federation, 115478
    • Research Site
  • Omsk, Russian Federation, 644043
    • Research Site
  • Omsk, Russian Federation, 644112
    • Research Site
  • Saint Petersburg, Russian Federation, 194354
    • Research Site
  • Saint Petersburg, Russian Federation, 195257
    • Research Site
  • Ulyanovsk, Russian Federation, 432009
    • Research Site
• Spain
  • Cádiz, Spain, 11009
    • Research Site
  • Marbella (Málaga), Spain, 29603
    • Research Site
  • Mérida, Spain, 06800
    • Research Site
  • Ourense, Spain, 32005
    • Research Site
  • Sant Joan Despí (Barcelona), Spain, 08970
    • Research Site
  • Santiago De Compostela-Coruña, Spain, 15706
    • Research Site
  • Zaragoza, Spain, 50009
    • Research Site
• Sweden
  • Lund, Sweden, 221 85
    • Research Site
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Research Site
  • Kaohsiung Hsien, Taiwan, 83301
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Taichung, Taiwan, 40447
    • Research Site
  • Taipei, Taiwan, 235
    • Research Site
  • Taipei, Taiwan, 10449
    • Research Site
  • Taipei City, Taiwan, 110
    • Research Site
  • Yunlin, Taiwan, 640
    • Research Site
• United Kingdom
  • Bradford, United Kingdom, BND9 6RJ
    • Research Site
  • Cambridge, United Kingdom, CB2 0QQ
    • Research Site
  • London, United Kingdom, SE1 9RT
    • Research Site
  • London, United Kingdom, SW3 6HP
    • Research Site
  • Nottingham, United Kingdom, NG5 1PB
    • Research Site
• United States
  • Arizona
    • Flagstaff, Arizona, United States, 86001
      • Research Site
  • California
    • Los Angeles, California, United States, 90025
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
  • Delaware
    • Newark, Delaware, United States, 19713
      • Research Site
  • Florida
    • Tampa, Florida, United States, 33607
      • Research Site
    • Winter Park, Florida, United States, 32789-4681
      • Research Site
  • Georgia
    • Albany, Georgia, United States, 31707
      • Research Site
    • Atlanta, Georgia, United States, 30322
      • Research Site
    • Savannah, Georgia, United States, 31405
      • Research Site
  • Illinois
    • Normal, Illinois, United States, 61761
      • Research Site
  • Kentucky
    • Georgetown, Kentucky, United States, 40324
      • Research Site
    • Lakeside Park, Kentucky, United States, 41017
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Research Site
    • Saint Paul, Minnesota, United States, 55101
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63156
      • Research Site
  • New York
    • New York, New York, United States, 10016
      • Research Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Research Site
    • Greenville, North Carolina, United States, 27834
      • Research Site
    • Wilmington, North Carolina, United States, 28401
      • Research Site
    • Winston-Salem, North Carolina, United States, 27104
      • Research Site
  • Pennsylvania
    • DuBois, Pennsylvania, United States, 15801
      • Research Site
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 128 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Benralizumab; Benralizumab subcutaneous injection	Biological: Benralizumab; Benralizumab subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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)	Change from baseline in average daily OCS dose (mg) from start of OCS reduction to end of the OCS reduction phase	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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 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	from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days.
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	from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days.
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	from main study baseline to the end of the long term follow up substudy, an average of approximate 922 days.

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• 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. Erratum In: Lancet Respir Med. 2021 Dec;9(12):e114.
• 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.

Helpful Links

• CSP
• Statistical Analysis Plan (SAP)
• CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Actual): April 16, 2021
• Study Completion (Actual): March 24, 2022

Study Registration Dates

• First Submitted: May 14, 2018
• First Submitted That Met QC Criteria: June 4, 2018
• First Posted (Actual): June 15, 2018

Study Record Updates

• Last Update Posted (Actual): June 6, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Asthma; Severe Asthma; Oral Corticosteroids
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Asthmatic Agents; Respiratory System Agents; Benralizumab
• Other Study ID Numbers: D3250C00065

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes