Clinical trial NCT02049294: Study of the Steroid Sparing Effect of Xolair (Omalizumab) in Patients With Persistent Eosinophilic Bronchitis
Official title: Randomized Double Blind Placebo Controlled Trial of the Steroid Sparing Effect of Xolair (Omalizumab) in Patients With Persistent Eosinophilic Bronchitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Steroid and/or Prednisone Dependent Asthma
Eosinophilic Bronchitis
Keywords: Prednisone
Eosinophils
Immunoglobin E (IgE)
Asthma
Bronchitis
Inflammation
Allergy
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2014-01-30
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients with change in absolute % count of sputum eosinophil week 0 to week 12, and week 12 to week 32
timeFrame: From Week 0 to Week 12 and Week 12 to week 32
measure: Magnitude of the reduction in the dose of corticosteroid from week 12 to week 32.
timeFrame: From Week 12 to Week 32
Secondary outcomes:
measure: change in % sputum eosinophil
timeFrame: From Week 0 to Week 32
measure: Blood eosinophils
timeFrame: From Week 0 to week 32
measure: Forced Expired Volume in 1 second (FEV1)
timeFrame: From Week 0 to Week 32
measure: Ratio of Forced Expired Volume in 1 second to Forced Vital Capacity (FEV1/VC)
timeFrame: From Week 0 to Week 32
measure: Provocative concentration causing a 20% drop in FEV1 (PC20)
timeFrame: From Week 0 to Week 32
measure: Asthma Control Questionnaire
timeFrame: From Week 0 to Week 32
measure: Fraction of exhaled nitric oxide (FeNO)
timeFrame: From Week 0 to Week 32
Other outcomes:
measure: • Sputum eosinophilopoietic cytokines, chemokines, immunoglobulin levels, expression variation of constitutive immunoglobulin receptors.
timeFrame: From Week 0 to Week 12 and Week 12 to week 32
measure: IgE antagonism and its effect on TSLP with respect to in situ eosinophilopoeisis and local eosinophil activity
timeFrame: From Week 0 to Week 12 and Week 12 to week 32
Locations:
city: Calgary
country: Canada
facility: Richard Leigh
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Laval
country: Canada
facility: University of Laval
state: Quebec
city: Montreal
country: Canada
facility: University of Montreal
state: Quebec
Study officials:
affiliation: McMaster University
name: Parameswaran Nair, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Laval
name: Louis-Philippe Boulet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Université de Montréal
name: Catherine Lemiere, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: Richard Leigh, MB
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Delbert Dorscheid, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mukherjee M, Kjarsgaard M, Radford K, Huang C, Leigh R, Dorscheid DR, Lemiere C, Boulet LP, Waserman S, Martin J, Nair P. Omalizumab in patients with severe asthma and persistent sputum eosinophilia. Allergy Asthma Clin Immunol. 2019 Apr 3;15:21. doi: 10.1186/s13223-019-0337-2. eCollection 2019.