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

Phase 1

• Conditions: Asthma; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2013-002523-42-ES
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-03-11
• Last Update Posted: 8 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

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 > o = 12% and > o = 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 108
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

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 < o = 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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<br>compared with week 0, while maintaining asthma control;Secondary Objective: To assess the effect of 2 dosing regimens of benralizumab on:<br>-OCS dose in adult patients with uncontrolled asthma<br>-parameters associated with asthma exacerbations<br>-pulmonary function<br>-asthma symptoms and other asthma control metrics;Primary end point(s): Percentage reduction in final OCS dose compared with baseline (Visit 6), while maintaining asthma control;Timepoint(s) of evaluation of this end point: Week 28