Eosinophilic Bronchitis, Steroid and/or Prednisone Dependent Asthma
Conditions
Keywords
Prednisone, Eosinophils, Immunoglobin E (IgE), Asthma, Bronchitis, Inflammation, Allergy
Brief summary
The purpose of this study is to investigate whether addition of Omalizumab enables a reduction in the dose of prednisone in patients with asthma and eosinophilic bronchitis. This will be a double-blind placebo-controlled, 3-centre, randomized parallel group trial divided into two sequential study periods. Period 1: After establishing the minimum dose of prednisone to maintain asthma control and maintain sputum eosinophils \<3%, subjects will be randomized to either placebo or Omalizumab for 16 weeks (either once monthly for 4 months or every 2 weeks for 4 months). Period 2: standardised prednisone reduction at intervals of 4-weeks until there is a clinical and eosinophilic exacerbation or bothersome steroid withdrawal effects. If patients have an exacerbation, they will be treated with prednisone. This patient will continue on Omalizumab or placebo during the entire duration of the study but not continue the phase of steroid reduction.
Interventions
BIOLOGICALOmalizumab (Xolair)
DRUGPlacebo
Sponsors
Novartis
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Confirmed asthma within the past 2 years (12% bronchodilator reversibility or PC20 methacholine less than 8 mg/ml) 2. ACQ ≥1.5 and sputum eos ≥3% at the time of randomization 3. On ICS (≥ 1500 mcg fluticasone propionate or equivalent) with or without additional prednisone 4. Total serum IgE ≥30 IU/L and positive allergy skin prick test 5. Age between 18 and 75 years 6. Ability to provide informed consent
Exclusion criteria
1. Current smoker or ex-smokers with greater than 20 pack years 2. Co-morbid diseases which in the investigator's opinion would make the patient unsuitable to participate in the study 3. Currently on Omalizumab or has previously been treated with Omalizumab 4. Currently on other biologic therapies (eg. Prolia) 5. Pregnancy or lactation 6. Post bronchodilator FEV1 less than 50% predicted
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of patients with change in absolute % count of sputum eosinophil week 0 to week 12, and week 12 to week 32 | From Week 0 to Week 12 and Week 12 to week 32 |
| Magnitude of the reduction in the dose of corticosteroid from week 12 to week 32. | From Week 12 to Week 32 |
Secondary
| Measure | Time frame |
|---|---|
| Blood eosinophils | From Week 0 to week 32 |
| Forced Expired Volume in 1 second (FEV1) | From Week 0 to Week 32 |
| Provocative concentration causing a 20% drop in FEV1 (PC20) | From Week 0 to Week 32 |
| Asthma Control Questionnaire | From Week 0 to Week 32 |
| Fraction of exhaled nitric oxide (FeNO) | From Week 0 to Week 32 |
| Ratio of Forced Expired Volume in 1 second to Forced Vital Capacity (FEV1/VC) | From Week 0 to Week 32 |
| change in % sputum eosinophil | From Week 0 to Week 32 |
Other
| Measure | Time frame |
|---|---|
| • Sputum eosinophilopoietic cytokines, chemokines, immunoglobulin levels, expression variation of constitutive immunoglobulin receptors. | From Week 0 to Week 12 and Week 12 to week 32 |
| IgE antagonism and its effect on TSLP with respect to in situ eosinophilopoeisis and local eosinophil activity | From Week 0 to Week 12 and Week 12 to week 32 |
Countries
Canada
Outcome results
None listed