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

NCT ID: NCT02075255

Last Updated: 2018-06-08

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-04-28

Study Completion Date

2016-08-08

Brief Summary

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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.

Detailed Description

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Conditions

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Asthma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Benralizumab Arm A

Benralizumab administered subcutaneously every 4 weeks

Group Type EXPERIMENTAL

Benralizumab

Intervention Type BIOLOGICAL

Benralizumab administered subcutaneously every 4 weeks

Benralizumab Arm B

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.

Group Type EXPERIMENTAL

Benralizumab

Intervention Type BIOLOGICAL

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.

Placebo

Placebo administered subcutaneously every 4 weeks

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

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

Interventions

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Benralizumab

Benralizumab administered subcutaneously every 4 weeks

Intervention Type BIOLOGICAL

Placebo

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

Intervention Type BIOLOGICAL

Benralizumab

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.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Provision of informed consent prior to any study specific procedures.
2. Female and male aged from 18 to 75 years, inclusively.
3. History of physician-diagnosed asthma requiring treatment with medium dose ICS and LABA.
4. Elevated level of peripheral blood eosinophil
5. Documented treatment with high-dose ICS and LABA for at least 6 months prior to Visit 1
6. 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.
7. 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.
8. Morning pre-bronchodilator (Pre-BD) FEV1 of \<80% predicted
9. 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.

If patients do not demonstrate airway reversibility at either Visit 1 or Visit 2 and this is needed to qualify the patient for randomization, the site should reiterate the need to withhold short- and long-acting bronchodilators prior to Visit 3 in an effort to meet this inclusion criterion.
10. At least 1 documented asthma exacerbation in the previous 12 months prior to the date informed consent is obtained
11. Optimized OCS dose reached at least 2 weeks prior to randomization
12. 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)
13. At least 70% compliance with OCS use
14. At least 70% compliance with usual asthma controller ICS-LABA
15. Minimum 70% (i.e. 10 of 14 days) compliance with asthma daily diary (morning and evening diary)

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. 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
3. 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
4. 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
5. History of life-threatening asthma
6. Asthma control reached at an OCS dose of ≤5mg during run-in/OCS optimization phase
7. Qualifies for 3 consecutive dose reductions at Visits 2-4 and continues to meet OCS dose reduction criteria at Visit 5
8. 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.
9. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.5 times the upper limit of normal (ULN) confirmed during screening period
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Parameswaran Nair, MD,PhD,FRCP,FRCPC

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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Los Angeles, California, United States

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Centennial, Colorado, United States

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Denver, Colorado, United States

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Hialeah, Florida, United States

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Hialeah, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Iowa City, Iowa, United States

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Fort Mitchell, Kentucky, United States

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Rochester, Minnesota, United States

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The Bronx, New York, United States

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Durham, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Middleburg Heights, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Mt. Pleasant, South Carolina, United States

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Madison, Wisconsin, United States

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Buenos Aires, , Argentina

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CABA, , Argentina

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Florida, , Argentina

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Mendoza, , Argentina

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Kozloduy, , Bulgaria

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Pazardzhik, , Bulgaria

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Petrich, , Bulgaria

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Rousse, , Bulgaria

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Samokov, , Bulgaria

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Vratsa, , Bulgaria

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Calgary, Alberta, Canada

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Vancouver, British Columbia, Canada

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Hamilton, Ontario, Canada

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Ottawa, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Quillota, , Chile

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Rancagua, , Chile

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Santiago, , Chile

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Talca, , Chile

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Talcahuano, , Chile

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Valparaíso, , Chile

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Brest, , France

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Lyon, , France

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Marseille, , France

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Montpellier, , France

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Strasbourg, , France

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Toulouse, , France

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Bamberg, , Germany

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Berlin, , Germany

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Freiburg im Breisgau, , Germany

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Großhansdorf, , Germany

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Hanover, , Germany

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Leipzig, , Germany

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Mainz, , Germany

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Bydgoszcz, , Poland

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Karczew, , Poland

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Koszalin, , Poland

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Krakow, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Lubin, , Poland

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Szczecin, , Poland

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Tarnów, , Poland

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Trzebnica, , Poland

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Wroclaw, , Poland

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Wroclaw, , Poland

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Suwon, , South Korea

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Málaga, , Spain

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Valencia, , Spain

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Adana, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Bursa, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Dnipropetrovsk, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Kharkiv, , Ukraine

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Kharkiv, , Ukraine

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Kyiv, , Ukraine

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Kyiv, , Ukraine

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Vinnytsia, , Ukraine

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Countries

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United States Argentina Bulgaria Canada Chile France Germany Poland South Korea Spain Turkey (Türkiye) Ukraine

References

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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.

Reference Type BACKGROUND
PMID: 28530840 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35287231 (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)

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.

Reference Type DERIVED
PMID: 30802500 (View on PubMed)

Related Links

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Other Identifiers

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D3250C00020

Identifier Type: -

Identifier Source: org_study_id

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