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
Condition: Asthma
MeSH terms: Asthma
Intervention: Benralizumab; Placebo; Benralizumab
Intervention description: Benralizumab administered subcutaneously every 4 weeks; Placebo subcutaneously on study week 0 until study week 24 inclusive.; 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 MeSH terms: Benralizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 220.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive Lung Diseases, OCS, Oral Corticosteroids

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.
    

Eligibility 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
             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