Efficacy and Safety Study of Benralizumab to Reduce OCS Use in Patients With Uncontrolled Asthma on High Dose Inhaled Corticosteroid Plus LABA and Chronic OCS Therapy

NCT02075255 | Completed Phase 3 Results

• 1 other identifier: D3250C00020
• Study Type: interventional
• Target: 220
• Locations: 12 countries
• Sites: 87

Brief Summary

The purpose of this trial is to confirm if benralizumab can reduce the use of maintenance OCS in systemic corticosteroid dependent patients with severe refractory asthma with elevated eosinophils.

Conditions

Asthma

Keywords

Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive Lung Diseases, OCS, Oral Corticosteroids

Outcome Measures

Primary Outcomes (1)

• Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control

  Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. The percentage reduction from baseline is defined as: {(Baseline dose-final dose)/baseline dose}\*100%. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.

  Week 28

Secondary Outcomes (33)

• Number and Percentage of Patients in Different Categories of Percent Reduction From Baseline in Final OCS Dose While Maintaining Asthma Control

  Week 28

• Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control for Patients With Baseline Eosinophils >=300/uL

  Week 28

• The Percentage of Patients With ≥50% Reduction in Average Daily OCS Dose at Visit 14 Compared With Baseline Dose at Visit 6, While Maintaining Asthma Control

  Week 28

• The Proportion of Eligible Patients With ≥100% Reduction in Average Daily OCS Dose at Visit 14 Compared With Baseline Dose at Visit 6, While Maintaining Asthma Control

  Week 28

• The Proportion of Patients With ≤5.0 mg Reduction on Daily OCS Dose at Visit 14 Compared With Baseline Dose at Visit 6, While Maintaining Asthma Control.

  Week 28

Study Arms (3)

Benralizumab Arm A

EXPERIMENTAL

Benralizumab administered subcutaneously every 4 weeks

Biological: Benralizumab

Benralizumab Arm B

EXPERIMENTAL

Benralizumab administered subcutaneously every 4 weeks for the first 3 dose and then every 8 weeks; matching placebo subcutaneously at the 4 week interim to maintain the blind.

Biological: Benralizumab

Placebo

PLACEBO COMPARATOR

Placebo administered subcutaneously every 4 weeks

Biological: Placebo

Interventions

Benralizumab BIOLOGICAL

Benralizumab administered subcutaneously every 4 weeks

Benralizumab Arm A

Placebo BIOLOGICAL

Placebo subcutaneously on study week 0 until study week 24 inclusive.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures.
• Female and male aged from 18 to 75 years, inclusively.
• History of physician-diagnosed asthma requiring treatment with medium dose ICS and LABA.
• Elevated level of peripheral blood eosinophil
• Documented treatment with high-dose ICS and LABA for at least 6 months prior to Visit 1
• Chronic oral corticosteroid therapy for at least 6 continuous months directly preceding Visit 1. Subjects must be on doses equivalent to 7.5 - 40 mg/day of prednisolone/prednisone at Visit 1 and be on a stable dose for at least 2 weeks prior to randomization. Patients must agree to switch to study required prednisone/prednisolone as their oral corticosteroid for the duration of the study.
• Patients with documented failures of OCS reduction within 6 months prior to Visit 1 will not be required to proceed through the dose optimization phase during run-in.
• Morning pre-bronchodilator (Pre-BD) FEV1 of \<80% predicted
• Evidence of asthma as documented by either:
• Airway reversibility (FEV1 ≥12% and 200 mL) demonstrated at Visit 1, Visit 2, or Visit 3 using the Maximum Post-bronchodilator Procedure OR Documented reversibility in the previous 24 months prior to Visit 1 OR Airway hyperresponsiveness (PC20 FEV1 methacholine concentration ≤8mg/mL) documented in the previous 12 months prior to planned date of randomization OR Airflow variability in clinic FEV1 ≥20% between 2 consecutive clinic visits documented in the 12 months prior to the planned date of randomization (FEV1 recorded during an exacerbation should not be considered for this criterion).
• All patients must have reversibility testing performed before randomization to establish a baseline characteristic.
• At least 1 documented asthma exacerbation in the previous 12 months prior to the date informed consent is obtained
• Optimized OCS dose reached at least 2 weeks prior to randomization
• Additional asthma controller medication must not have been initiated during run in/optimization period (not applicable for management of exacerbations during screening/ run in optimization phase)
• At least 70% compliance with OCS use

You may not qualify if:

• 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.
• Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could:
• Affect the safety of the patient throughout the study
• Influence the findings of the studies or their interpretations
• Impede the patient's ability to complete the entire duration of study
• Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period
• Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during run-in/optimization period, which in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient's ability to complete entire duration of the study
• History of life-threatening asthma
• Asthma control reached at an OCS dose of ≤5mg during run-in/OCS optimization phase
• Qualifies for 3 consecutive dose reductions at Visits 2-4 and continues to meet OCS dose reduction criteria at Visit 5
• Receipt of oral corticosteroids, other than prednisone or prednisolone, as the maintenance oral steroid controller for asthma symptoms from Visit 1 and throughout the study.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.5 times the upper limit of normal (ULN) confirmed during screening period

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (87)

Research Site

Los Angeles, California, 90025, United States

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Centennial, Colorado, 80112, United States

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Denver, Colorado, 80206, United States

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Hialeah, Florida, 33010, United States

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Hialeah, Florida, 33013, United States

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Miami, Florida, 33015, United States

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Orlando, Florida, 32825, United States

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Iowa City, Iowa, 52242, United States

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Fort Mitchell, Kentucky, 41017, United States

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Rochester, Minnesota, 55905, United States

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The Bronx, New York, 10461, United States

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Durham, North Carolina, 27704, United States

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Winston-Salem, North Carolina, 27103, United States

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Cincinnati, Ohio, 45231, United States

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Middleburg Heights, Ohio, 44130, United States

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Oklahoma City, Oklahoma, 73112, United States

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Philadelphia, Pennsylvania, 19140, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Mt. Pleasant, South Carolina, 29464, United States

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Madison, Wisconsin, 53792, United States

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Buenos Aires, C1414AIF, Argentina

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CABA, 1426, Argentina

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Florida, 1638, Argentina

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Mendoza, 5500, Argentina

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Kozloduy, 3320, Bulgaria

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Pazardzhik, 4400, Bulgaria

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Petrich, 2850, Bulgaria

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Rousse, 7002, Bulgaria

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Samokov, 2000, Bulgaria

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Vratsa, 3000, Bulgaria

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Calgary, Alberta, T2N 4Z6, Canada

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Vancouver, British Columbia, V6Z 1Y6, Canada

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Hamilton, Ontario, L8N 4A6, Canada

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Ottawa, Ontario, K1G 6C6, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Québec, Quebec, G1V 4G5, Canada

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Quillota, Chile

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Rancagua, 2820000, Chile

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Santiago, 8380453, Chile

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Talca, 3465584, Chile

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Talcahuano, 4270918, Chile

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Valparaíso, 2341131, Chile

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Brest, 29609, France

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Lyon, 69317, France

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Marseille, 13015, France

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Montpellier, 34295, France

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Strasbourg, 67091, France

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Toulouse, 31059, France

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Bamberg, 96049, Germany

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Berlin, 10119, Germany

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Freiburg im Breisgau, 79106, Germany

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Großhansdorf, 20927, Germany

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Hanover, 30625, Germany

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Leipzig, 04207, Germany

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Mainz, 55131, Germany

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Bydgoszcz, 85-231, Poland

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Karczew, 05-480, Poland

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Koszalin, 75-679, Poland

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Krakow, 31-011, Poland

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Krakow, 31-159, Poland

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Lodz, 90-141, Poland

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Lubin, 59-300, Poland

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Szczecin, 70-111, Poland

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Tarnów, 33-100, Poland

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Trzebnica, 55-100, Poland

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Wroclaw, 53-201, Poland

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Wroclaw, 53-301, Poland

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Seoul, 02559, South Korea

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Seoul, 06591, South Korea

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Seoul, 135-710, South Korea

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Suwon, 16499, South Korea

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Málaga, 29010, Spain

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Valencia, 46017, Spain

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Adana, 01330, Turkey (Türkiye)

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Ankara, 06230, Turkey (Türkiye)

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Bursa, Turkey (Türkiye)

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Istanbul, 34098, Turkey (Türkiye)

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Istanbul, 34844, Turkey (Türkiye)

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Dnipropetrovsk, 49007, Ukraine

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Ivano-Frankivsk, 76012, Ukraine

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Kharkiv, 61035, Ukraine

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Kharkiv, 61039, Ukraine

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Kyiv, 03680, Ukraine

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Kyiv, 04201, Ukraine

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Vinnytsia, 21029, Ukraine

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Related Publications (4)

• Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, Barker P, Sproule S, Ponnarambil S, Goldman M; ZONDA Trial Investigators. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017 Jun 22;376(25):2448-2458. doi: 10.1056/NEJMoa1703501. Epub 2017 May 22.

  PMID: 28530840 BACKGROUND

• Menzies-Gow A, Hoyte FL, Price DB, Cohen D, Barker P, Kreindler J, Jison M, Brooks CL, Papeleu P, Katial R. Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab. Adv Ther. 2022 May;39(5):2065-2084. doi: 10.1007/s12325-022-02098-1. Epub 2022 Mar 14.

  PMID: 35287231 DERIVED

• 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.

  PMID: 31579676 DERIVED

• Chupp G, Lugogo NL, Kline JN, Ferguson GT, Hirsch I, Goldman M, Zangrilli JG, Trudo F. Rapid onset of effect of benralizumab on morning peak expiratory flow in severe, uncontrolled asthma. Ann Allergy Asthma Immunol. 2019 May;122(5):478-485. doi: 10.1016/j.anai.2019.02.016. Epub 2019 Feb 23.

  PMID: 30802500 DERIVED

Related Links

• CSP redacted

MeSH Terms

Conditions

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Mitchell Goldman, Global Clinical Lead Benralizumab
• Organization: AstraZeneca

Mitchell.Goldman@astrazeneca.com

+1 301 398 0323

Study Officials

• Parameswaran Nair, MD,PhD,FRCP,FRCPC

  St Joseph's Healthcare Hamilton Firestone Institute for Respiratory Health 50 Charlton Avenue East Hamilton

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2014
• First Posted: March 3, 2014
• Study Start: April 28, 2014
• Primary Completion: August 8, 2016
• Study Completion: August 8, 2016
• Last Updated: June 8, 2018
• Results First Posted: October 17, 2017

Record last verified: 2018-05

Locations

BU (6); CA (6); PL (12); UA (7); AR (4); DE (7); TU (5); ES (2); FR (6); US (20); KR (6); CL (6)