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

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ClinicalTrials.gov Identifier: NCT03557307

Recruitment Status : Completed

First Posted : June 15, 2018

Results First Posted : June 28, 2022

Last Update Posted : June 28, 2022

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

AstraZeneca

Tracking Information

First Submitted Date ^ICMJE

May 14, 2018

First Posted Date ^ICMJE

June 15, 2018

Results First Submitted Date ^ICMJE

February 7, 2022

Results First Posted Date ^ICMJE

June 28, 2022

Last Update Posted Date

June 28, 2022

Actual Study Start Date ^ICMJE

August 1, 2018

Actual Primary Completion Date

April 16, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Patients Who Achieve 100% Reduction in Daily OCS Dose [ 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.) ]
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 [ 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.) ]
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

Original Primary Outcome Measures ^ICMJE

Patients who achieve 100% reduction in daily OCS dose [ Time Frame: Visit 3 to End of OCS Reduction Phase (up to 38 weeks) ]
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 [ Time Frame: Visit 3 to End of OCS Reduction Phase (up to 38 weeks) ]
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

Change History

Current Secondary Outcome Measures ^ICMJE

Patients Who Achieve a Daily OCS of ≤5mg [ 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.) ]
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 [ 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.) ]
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) [ 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.) ]
Change from baseline in average daily OCS dose (mg) from start of OCS reduction to end of the OCS reduction phase

Original Secondary Outcome Measures ^ICMJE

Patients who achieve a daily OCS of ≤5mg [ Time Frame: Visit 3 to End of OCS Reduction Phase (up to 38 weeks) ]
Patients who achieve a daily OCS dose of ≤5 mg 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 [ Time Frame: Visit 3 to End of OCS Reduction Phase (up to 38 weeks) ]
Patients who achieve a ≥90%, ≥75%, and ≥50% reduction in average daily OCS dose, sustained over at least 4 weeks without worsening of asthma
Change from baseline in average daily OCS dose (mg) [ Time Frame: Visit 3 to End of OCS Reduction Phase (up to 38 weeks) ]
Change from baseline in average daily OCS dose (mg) from start of OCS reduction to end of the OCS reduction phase

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

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).

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 3

Study Design ^ICMJE

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:

Open label

Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

Asthma

Intervention ^ICMJE

Biological: Benralizumab

Benralizumab subcutaneous injection

Study Arms ^ICMJE

Experimental: Benralizumab

Benralizumab subcutaneous injection

Intervention: Biological: Benralizumab

Publications *

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Actual Enrollment ^ICMJE

598

Original Estimated Enrollment ^ICMJE

600

Actual Study Completion Date ^ICMJE

March 24, 2022

Actual Primary Completion Date

April 16, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Peripheral blood eosinophil count of ≥150 cells/μL assessed by central lab at Visit 1 or ≥ 300 cells/μL in the past 12 months
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.
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.
Patient should be on a stable OCS dose for at least 4 weeks prior to Visit 1.
Non-smokers, current smokers or former smokers with a smoking history of < or =20 pack-years at Visit 1

Exclusion Criteria:

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
Known history of allergy or reaction to the study drug formulation
History of anaphylaxis to any biologic therapy
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
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)
A history of known immunodeficiency disorder including history of a positive human immunodeficiency virus (HIV) test
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥3 times the upper limit of normal (ULN) confirmed at Visit 1.
Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained
Coincident primary adrenal failure (Addison's disease) or irreversible secondary hypoadrenalism due to another independent cause (e.g. pituitary tumour or its treatment)
Co-existent inflammatory conditions for which chronic OCS doses are part of their maintenance treatment such as Giant Cell Arteritis, Polymyalgia Rheumatica
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
Current night-shift workers

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years to 130 Years (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

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

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT03557307

Other Study ID Numbers ^ICMJE

D3250C00065

Has Data Monitoring Committee

Not Provided

U.S. FDA-regulated Product

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

IPD Sharing Statement ^ICMJE

Plan to Share IPD:	Yes
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.
Supporting Materials:	Study Protocol
Supporting Materials:	Statistical Analysis Plan (SAP)
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.
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.
URL:	https://astrazenecagroup-dt.pharmacm.com/DT/Home