Efficacy of Omalizumab in Adults (18-60 Years of Age) With Moderate-Severe, Persistent Allergic Asthma, Despite Receiving Inhaled Corticosteroids and Long Acting Beta-agonists

Phase 4

Completed

Conditions: Allergic Asthma

Interventions: Drug: omalizumab at a dose of 0.016mg/kg/IU/mL
Drug: Placebo

Registration Number: NCT00670930

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: This study aims to investigate the effect of omalizumab on the number of tissue eosinophils and other markers of airway inflammation and remodeling, including thickness of the lamina reticularis, in moderate to severe asthmatics with persistent symptoms and evidence of airway inflammation despite treatment with inhaled corticosteroids and long acting beta-agonists. This study will also investigate the correlation between systemic and pulmonary inflammation, and the correlation between clinical outcomes and changes within the tissue, to assist in the future identification of patients with tissue eosinophilia and their response to treatment, without the need for invasive bronchoscopy.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 36

Inclusion Criteria

Patients 18-75 years of age with moderate to severe persistent allergic asthma receiving a high dose inhaled corticosteroid (≥800µg per day BDP or equivalent) and a regular long acting beta-agonist for at least 3 months prior to screening
With a body weight between 20 and 150kg and a serum total IgE level of 30 to 700 IU/mL
With ≥2% eosinophilia in induced sputum at screening
With post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥60% predicted
With a positive skin prick test (diameter of wheal ≥ 3 mm) or RAST test to at least one perennial aero-allergen (eg. dust mite, cat/dog dander, cockroaches), documented within the past 2 years or demonstrated at Visit 1, to which the patient will be exposed on a regular basis (most days) for the duration of the study.

Exclusion Criteria

Patients who've had an asthma exacerbation during the 4 weeks prior to randomization
Current smokers, stopped smoking within the last 12 months or have a smoking history of >10 pack years
History of severe allergy to food or drugs
Previous treatment with omalizumab
Any patient considered to be unsuitable to bronchoscopy, according to the judgment of the investigator

Other protocol-defined inclusion/exclusion criteria applied.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
omalizumab	omalizumab at a dose of 0.016mg/kg/IU/mL	Omalizumab was supplied as lyophilized, sterile powder in a single use, 5 ml vial that was designed to deliver 150 mg of omalizumab for subcutaneous (SQ) administration upon reconstitution with 1.4 ml sterile water for injection. The dose administered was individualized for each patient based on the patient's body weight and total serum Immunoglobulin E (IgE) level at Visit 1 and the number of injections and injection volume was determined using protocol-specified dosing tables. Omalizumab 75 to 375 mg was administered SQ every 2 or 4 weeks depending on the dose for the 78 weeks duration of double-blinded treatment.
Placebo	Placebo	Omalizumab matching placebo was supplied as lyophilized, sterile powder in a single-use, 5 ml vial that was designed to deliver omalizumab matching placebo for subcutaneous (SQ) administration upon reconstitution with 1.4 ml sterile water for injection. The number of injections and injection volume was individualized for each patient based on the patient's body weight and total serum Immunoglobulin E (IgE) level at Visit 1 and was determined using protocol-specified dosing tables. Placebo was administered SQ every 2 or 4 weeks for the 78 weeks duration of double-blinded treatment.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Total Subepithelial Eosinophils at the End of Week 78 (End of Treatment)	Baseline, at end of week 78	The primary variable of change from baseline in total epithelia eosinophils at end of Week 78 was analyzed on sub-population such as responders and non-responders. Responders are defined as all patients having a Global Evaluation of Treatment Effectiveness (GETE) outcome of excellent or good where as non-responders are with GETE outcome of poor, moderate or worsening. GETE categories are excellent, good, moderate, poor, worsening, and missing as determined by the investigator.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Sub-epithelial Cell Count of Mast Cells Following 78 Weeks Treatment, as Assessed Biopsy Samples	Baseline, at end of week 78	The variable of change from baseline in Sub-epithelial cell count of mast cells at end of Week 78 was analyzed on sub-population such as responders and non-responders. Responders are defined as all patients having a Global Evaluation of Treatment Effectiveness (GETE) outcome of excellent or good where as non-responders are with GETE outcome of poor, moderate or worsening. GETE categories are excellent, good, moderate, poor, worsening, and missing as determined by the investigator.
Change From Baseline in Sub-epithelial CD4+ T-lymphocytes Following 78 Weeks Treatment, as Assessed Biopsy Samples	Baseline, at end of week 78	The variable of change from baseline in Sub-epithelial CD4+ T-lymphocytes at end of Week 78 was analyzed on sub-population such as responders and non-responders. Responders are defined as all patients having a Global Evaluation of Treatment Effectiveness (GETE) outcome of excellent or good where as non-responders are with GETE outcome of poor, moderate or worsening. GETE categories are excellent, good, moderate, poor, worsening, and missing as determined by the investigator.
Change From Baseline in Thickness of the Lamina Reticularis Following 78 Weeks Treatment, as Assessed Biopsy Samples	Baseline, at end of week 78	The variable of change from baseline in thickness of the lamina reticularis at end of Week 78 was analyzed on sub-population such as responders and non-responders. Responders are defined as all patients having a Global Evaluation of Treatment Effectiveness (GETE) outcome of excellent or good where as non-responders are with GETE outcome of poor, moderate or worsening. GETE categories are excellent, good, moderate, poor, worsening, and missing as determined by the investigator.
Number of Participants With Adverse Events, Serious Adverse Events and Death as an Assessment of Safety and Tolerability of 78 Weeks Therapy	78 weeks