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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02075255
First received: February 14, 2014
Last updated: August 21, 2014
Last verified: August 2014
  Purpose

The purpose of this trial is to confirm if benralizumab can reduce OCS dependence (after dose optimisation) in patients who are uncontrolled on high-dose ICS-LABA, and chronically dependent on OCS as part of their regular asthma controller regimen.


Condition Intervention Phase
Asthma
Biological: Benralizumab
Biological: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase 3 Efficacy and Safety Study of Benralizumab (MEDI-563) to Reduce Oral Corticosteroid Use in Patients With Uncontrolled Asthma on High Dose Inhaled Corticosteroid Plus Long-acting β2 Agonist and Chronic Oral Corticosteroid Therapy (ZONDA)

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • The effect of 2 dosing regimens of benralizumab on percentage reduction of Oral Corticosteroid dose in the terms of percentage reduction in final Oral Corticosteroid dose compared with week 0, while maintaining asthma control [ Time Frame: Starting from week 0 following the first administration of study drug through study week 28. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The effect of 2 dosing regimens of benralizumab on Oral Corticosteroid dose in the terms of proportion of patients with ≥50% reduction in average daily Oral Corticosteroid dose at week 28 compared with dose at week 0 while maintaining asthma control [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on Oral Corticosteroid dose in the terms of proportion of patients with average final Oral Corticosteroid dose ≤5.0 mg daily at week 28, while maintaining asthma control. [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on Oral Corticosteroid dose in the terms of proportion of patients with ≤5.0 mg reduction on daily Oral Corticosteroid dose at week 28 compared with dose at week 0, while maintaining asthma control. [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on parameters associated with asthma exacerbations in the terms of proportion of patients with ≥1 asthma exacerbation after randomization [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on parameters associated with asthma exacerbations in the terms of time to the first asthma exacerbation after randomization [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on parameters associated with asthma exacerbations in the terms of annual rate of asthma exacerbations that are associated with an emergency room visit or a hospitalization after randomization [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on pulmonary function in the terms of change from week 0 in prebronchodilator Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on pulmonary function in the terms of change from week 0 in prebronchodilator Inspiratory Capacity (IC). [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on pulmonary function in the terms of change from week 0 in Expiratory Reserve Volume (ERV). [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on pulmonary function in the terms of change from week 0 in Inspiratory Reserve Volume (IRV). [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on pulmonary function in the terms of change from week 0 in Inspiratory Vital Capacity (VCIN). [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on pulmonary function in the terms of change from week 0 in Expiratory Vital Capacity (VCEX). [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on pulmonary function in the terms of change from week 0 in Maximum Vital Capacity (VCMAX). [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on asthma symptoms and other asthma control metrics in the terms of change from week 0 in asthma symptom score (total, daytime, and night time). [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on asthma symptoms and other asthma control metrics in the terms of change from week 0 in rescue medication use. [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on asthma symptoms and other asthma control metrics in the terms of change from week 0 in home lung function (morning and evening Peak Expiratory Flow (PEF)). [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on asthma symptoms and other asthma control metrics in the terms of change from week 0 in the number of nights with awakening due to asthma requiring rescue medication. [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on asthma symptoms and other asthma control metrics in the terms of change from week 0 in Asthma Control Questionnaire 6 (ACQ-6). [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on asthma related health-related quality of life in the terms of change from week 0 in Standardised Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12). [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The pharmacokinetics (PK) of 2 dosing regimens of benralizumab in the terms of PK parameters [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The immunogenicity of 2 dosing regimens of benralizumab in the terms of Anti-drug antibodies (ADA) presence or absence [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The safety and tolerability of 2 dosing regimens of benralizumab in the terms of Adverse Event (AE)/Serious Adverse Event (SAE) [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: Yes ]
  • The safety and tolerability of 2 dosing regimens of benralizumab in the terms of laboratory variables [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: Yes ]
  • The safety and tolerability of 2 dosing regimens of benralizumab in the terms of electrocardiogram (ECG) evaluation [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: Yes ]
  • The safety and tolerability of 2 dosing regimens of benralizumab in the terms of physical examination results [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: Yes ]
  • The impact of 2 dosing regimens of benralizumab on blood eosinophil count. [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The impact of 2 dosing regimens of benralizumab on blood eosinophil levels (subset of patients) in the terms of assessment of eosinophil progenitor cells [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The impact of 2 dosing regimens of benralizumab on sputum differential cell count (subset of patients) in the terms of sputum cell differential count [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The impact of 2 dosing regimens of benralizumab on biomarkers (subset of patients) in the terms of quantification of sputum cytokines and biomarkers [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The impact of 2 dosing regimens of benralizumab on sputum differential cell count (subset of patients) in the terms of assessment of eosinophil progenitor cells [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The effect of 2 dosing regimens of benralizumab on blood biomarkers in the terms of quantification of serum biomarkers. [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The impact of 2 dosing regimens of benralizumab on lung function as assessed thru body plethysmography (subset of patients) in the terms of Total Lung Capacity (TLC) [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The impact of 2 dosing regimens of benralizumab on lung function as assessed thru body plethysmography (subset of patients) in the terms of Residual Volume (RV) [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The impact of 2 dosing regimens of benralizumab on lung function as assessed thru body plethysmography (subset of patients) in the terms of Vital Capacity (VC) [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The impact of 2 dosing regimens of benralizumab on lung function as assessed thru body plethysmography (subset of patients) in the terms of Inspiratory Capacity (IC) [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]
  • The impact of 2 dosing regimens of benralizumab on lung function as assessed thru body plethysmography (subset of patients) in the terms of Functional Residual Capacity (FRC) [ Time Frame: From week 0 to week 28 in study treatment phase ] [ Designated as safety issue: No ]

Estimated Enrollment: 240
Study Start Date: April 2014
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Benralizumab Arm A
Benralizumab administered subcutaneously every 4 weeks
Biological: Benralizumab
Benralizumab administered subcutaneously every 4 weeks
Experimental: 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.
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.
Placebo Comparator: Placebo
Placebo administered subcutaneously every 4 weeks
Biological: Placebo
Placebo subcutaneously on study week 0 until study week 24 inclusive.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 a 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 prednisone or prednisolone therapy for at least 6 continuous months directly preceding Visit 1, and on a stable dose for at least one month prior to Visit 1
  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. Either documented post bronchodilator (post-BD) reversibility of ≥ 12% and ≥ 200 mL in FEV1 or PC20 FEV1
  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 period
  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)
  16. No documented asthma exacerbations during the screening/dose optimization period

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, haematological, 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, haematology, clinical chemistry, or urinalysis during screening/run-in 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 dexamethasone as the maintenance oral steroid controller for asthma symptoms
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02075255

Contacts
Contact: Clinical Trial Transparency ClinicalTrialTransparency@astrazeneca.com
Contact: Clinical Study Information +1 800-236-9933 information.center@astrazeneca.com

  Show 53 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Parameswaran Nair, MD,PhD,FRCP,FRCPC St Joseph's Healthcare Hamilton Firestone Institute for Respiratory Health 50 Charlton Avenue East Hamilton
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02075255     History of Changes
Other Study ID Numbers: D3250C00020
Study First Received: February 14, 2014
Last Updated: August 21, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Canada: Health Canada
Chile: Instituto de Salud Pública de Chile
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Germany: Paul-Ehrlich-Institut
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
France: National Agency for Medicine and Health Products

Keywords provided by AstraZeneca:
Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive Lung Diseases, OCS, Oral Corticosteroids

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014