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

Novartis Pharmaceuticals36 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Allergic Asthma

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (16)

Novartis Investigative Site

Denver, Colorado, United States

Novartis Investigative Site

St Louis, Missouri, United States

Novartis Investigative Site

Durham, North Carolina, United States

Novartis Investigative Site

Philadelphia, Pennsylvania, United States

Novartis Investigative Site

Philadelphia, Pennsylvania, United States

Novartis Investigative Site

Galveston, Texas, United States

Novartis Investigative Site

Calgary, Alberta, Canada

Novartis Investigative Site

Montreal, Quebec, Canada

Novartis Investigative Site

Québec, Quebec, Canada

Novartis Investigative Site

Montpellier, France

...and 6 more locations

Outcomes

Primary Outcomes

Change From Baseline in Total Subepithelial Eosinophils at the End of Week 78 (End of Treatment)

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.

Time frame: Baseline, at end of week 78

Secondary Outcomes

Change From Baseline in Sub-epithelial Cell Count of Mast Cells Following 78 Weeks Treatment, as Assessed Biopsy Samples

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.

Time frame: Baseline, at end of week 78

Change From Baseline in Sub-epithelial CD4+ T-lymphocytes Following 78 Weeks Treatment, as Assessed Biopsy Samples

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.

Time frame: Baseline, at end of week 78

Change From Baseline in Thickness of the Lamina Reticularis Following 78 Weeks Treatment, as Assessed Biopsy Samples

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.

Time frame: Baseline, at end of week 78

Number of Participants With Adverse Events, Serious Adverse Events and Death as an Assessment of Safety and Tolerability of 78 Weeks Therapy

Time frame: 78 weeks