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

Asthma Clinical Trial

— PONENTE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03557307
• Other study ID #: D3250C00065
• Status: Completed
• Phase: Phase 3
• Start date: August 1, 2018
• Est. completion date: March 24, 2022

Study information

• Verified date: May 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 598
• Est. completion date: March 24, 2022
• Est. primary completion date: April 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma

Intervention

Biological:
• Benralizumab
Benralizumab subcutaneous injection

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Cap. Fed
Argentina	Research Site	Ciudad Autónoma de Bs. As.
Argentina	Research Site	Ciudad Autónoma de Buenos Aire
Argentina	Research Site	Florencio Varela
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Mendoza
Argentina	Research Site	Monte Grande
Argentina	Research Site	Ranelagh
Argentina	Research Site	Rosario
Argentina	Research Site	Rosario
Belgium	Research Site	Bruxelles
Belgium	Research Site	Erpent
Belgium	Research Site	Gent
Brazil	Research Site	Botucatu
Brazil	Research Site	Londrina
Brazil	Research Site	Maringa
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Salvador
Brazil	Research Site	Santo Andre
Brazil	Research Site	Santo Andre
Brazil	Research Site	Sorocaba
Brazil	Research Site	Uberlandia
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Mississauga	Ontario
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
Canada	Research Site	Vancouver	CA
Colombia	Research Site	Barranquilla
Colombia	Research Site	Bogota
Colombia	Research Site	Cali
Colombia	Research Site	Cartagena
Colombia	Research Site	Floridablanca
Colombia	Research Site	Manizales
Colombia	Research Site	Medellin
Denmark	Research Site	Ålborg
Denmark	Research Site	Herlev
Denmark	Research Site	Hvidovre
Denmark	Research Site	Vejle
France	Research Site	ANGERS Cedex 9
France	Research Site	Besancon Cedex
France	Research Site	Colmar Cedex
France	Research Site	Marseille
France	Research Site	NICE Cedex 01
France	Research Site	Orléans
France	Research Site	Reims
France	Research Site	Suresnes Cedex
France	Research Site	Tours
Germany	Research Site	Bamberg
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Darmstadt
Germany	Research Site	Frankfurt
Germany	Research Site	Großhansdorf
Germany	Research Site	Heidelberg
Germany	Research Site	Köln
Germany	Research Site	Leipzig
Germany	Research Site	Lübeck
Germany	Research Site	Magdeburg
Germany	Research Site	München
Italy	Research Site	Firenze
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Palermo
Italy	Research Site	Pisa
Italy	Research Site	Roma
Italy	Research Site	Sassari
Italy	Research Site	Tradate
Mexico	Research Site	Del. Cuauhtemoc
Mexico	Research Site	Durango
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mérida
Mexico	Research Site	Veracruz
Mexico	Research Site	Villahermosa
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Gdansk
Poland	Research Site	Kraków
Poland	Research Site	Lubin
Poland	Research Site	Ostrowiec Swietokrzyski
Poland	Research Site	Poznan
Poland	Research Site	Poznan
Poland	Research Site	Rzeszów
Poland	Research Site	Sosnowiec
Poland	Research Site	Tarnów
Poland	Research Site	Wielun
Poland	Research Site	Wroclaw
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Kirov
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Ulyanovsk
Spain	Research Site	Cádiz
Spain	Research Site	Marbella (Málaga)
Spain	Research Site	Mérida
Spain	Research Site	Ourense
Spain	Research Site	Sant Joan Despí (Barcelona)
Spain	Research Site	Santiago De Compostela-Coruña
Spain	Research Site	Zaragoza
Sweden	Research Site	Lund
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung Hsien
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Yunlin
United Kingdom	Research Site	Bradford
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Nottingham
United States	Research Site	Albany	Georgia
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Atlanta	Georgia
United States	Research Site	Aurora	Colorado
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	DuBois	Pennsylvania
United States	Research Site	Flagstaff	Arizona
United States	Research Site	Georgetown	Kentucky
United States	Research Site	Greenville	North Carolina
United States	Research Site	Lakeside Park	Kentucky
United States	Research Site	Los Angeles	California
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	New York	New York
United States	Research Site	Newark	Delaware
United States	Research Site	Normal	Illinois
United States	Research Site	North Charleston	South Carolina
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Paul	Minnesota
United States	Research Site	Savannah	Georgia
United States	Research Site	Tampa	Florida
United States	Research Site	Wilmington	North Carolina
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Colombia,  Denmark,  France,  Germany,  Italy,  Mexico,  Poland,  Russian Federation,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.
Other	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.
Other	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.
Other	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.
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	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.)
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	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	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.)
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	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	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.)

External Links

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