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

NCT ID: NCT03557307

Last Updated: 2023-06-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 598 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-01
• Study Completion Date: 2022-03-24

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).

Conditions

Asthma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Benralizumab

Benralizumab subcutaneous injection

Group Type: EXPERIMENTAL

Benralizumab

Intervention Type: BIOLOGICAL

Benralizumab subcutaneous injection

Interventions

Benralizumab

Benralizumab subcutaneous injection

Intervention Type: BIOLOGICAL

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

12. Current night-shift workers

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Flagstaff, Arizona, United States

Research Site

Los Angeles, California, United States

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Aurora, Colorado, United States

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Newark, Delaware, United States

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Tampa, Florida, United States

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Winter Park, Florida, United States

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Albany, Georgia, United States

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Atlanta, Georgia, United States

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Savannah, Georgia, United States

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Normal, Illinois, United States

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Georgetown, Kentucky, United States

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Lakeside Park, Kentucky, United States

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Ann Arbor, Michigan, United States

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Minneapolis, Minnesota, United States

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Saint Paul, Minnesota, United States

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St Louis, Missouri, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Greenville, North Carolina, United States

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Wilmington, North Carolina, United States

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Winston-Salem, North Carolina, United States

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DuBois, Pennsylvania, United States

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North Charleston, South Carolina, United States

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Buenos Aires, , Argentina

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CABA, , Argentina

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Cap. Fed, , Argentina

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Ciudad Autónoma de Bs. As., , Argentina

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Ciudad Autónoma de Buenos Aire, , Argentina

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Mar del Plata, , Argentina

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Mendoza, , Argentina

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Monte Grande, , Argentina

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Ranelagh, , Argentina

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Rosario, , Argentina

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Rosario, , Argentina

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San Juan Bautista, , Argentina

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Brussels, , Belgium

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Erpent, , Belgium

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Ghent, , Belgium

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Botucatu, , Brazil

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Londrina, , Brazil

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Maringá, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Salvador, , Brazil

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Santo André, , Brazil

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Santo André, , Brazil

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Sorocaba, , Brazil

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Uberlândia, , Brazil

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Vancouver, British Columbia, Canada

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Vancouver, CA, Canada

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Ajax, Ontario, Canada

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Mississauga, Ontario, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Québec, Quebec, Canada

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Barranquilla, , Colombia

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Bogotá, , Colombia

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Cali, , Colombia

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Cartagena, , Colombia

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Floridablanca, , Colombia

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Manizales, , Colombia

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Medellín, , Colombia

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Aalborg, , Denmark

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Herlev, , Denmark

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Hvidovre, , Denmark

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Vejle, , Denmark

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Angers, , France

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Besançon, , France

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Colmar, , France

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Marseille, , France

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Nice, , France

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Orléans, , France

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Reims, , France

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Suresnes, , France

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Tours, , France

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Bamberg, , Germany

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Berlin, , Germany

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Berlin, , Germany

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Cologne, , Germany

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Darmstadt, , Germany

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Frankfurt, , Germany

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Großhansdorf, , Germany

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Heidelberg, , Germany

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Leipzig, , Germany

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Lübeck, , Germany

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Magdeburg, , Germany

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München, , Germany

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Florence, , Italy

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Milan, , Italy

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Napoli, , Italy

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Palermo, , Italy

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Pisa, , Italy

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Roma, , Italy

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Sassari, , Italy

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Tradate, , Italy

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Del. Cuauhtemoc, , Mexico

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Durango, , Mexico

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Guadalajara, , Mexico

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Guadalajara, , Mexico

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Mérida, , Mexico

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Veracruz, , Mexico

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Villahermosa, , Mexico

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Bialystok, , Poland

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Bialystok, , Poland

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Gdansk, , Poland

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Krakow, , Poland

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Lubin, , Poland

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Ostrowiec Świętokrzyski, , Poland

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Poznan, , Poland

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Poznan, , Poland

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Rzeszów, , Poland

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Sosnowiec, , Poland

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Tarnów, , Poland

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Wieluń, , Poland

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Wroclaw, , Poland

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Izhevsk, , Russia

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Kirov, , Russia

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Moscow, , Russia

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Omsk, , Russia

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Omsk, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Ulyanovsk, , Russia

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Cadiz, , Spain

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Marbella (Málaga), , Spain

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Mérida, , Spain

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Ourense, , Spain

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Sant Joan Despí (Barcelona), , Spain

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Santiago de Compostela-Coruña, , Spain

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Zaragoza, , Spain

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Lund, , Sweden

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Kaohsiung City, , Taiwan

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Kaohsiung Hsien, , Taiwan

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Taichung, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Yunlin, , Taiwan

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Bradford, , United Kingdom

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Cambridge, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Nottingham, , United Kingdom

Countries

United States; Argentina; Belgium; Brazil; Canada; Colombia; Denmark; France; Germany; Italy; Mexico; Poland; Russia; Spain; Sweden; Taiwan; United Kingdom

References

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, Faison S, Padilla K, Martin UJ, Garcia Gil E; PONENTE Study Group. Adrenal function recovery after durable oral corticosteroid sparing with benralizumab in the PONENTE study. Eur Respir J. 2022 Dec 22;60(6):2103226. doi: 10.1183/13993003.03226-2021. Print 2022 Dec.

Reference Type: DERIVED

PMID: 35896216 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34619104 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31579676 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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CSP

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Statistical Analysis Plan (SAP)

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CSR Synopsis

Other Identifiers

D3250C00065

Identifier Type: -

Identifier Source: org_study_id