Effect of Anti-IgE in Non-Allergic Asthma
Recruitment status was Recruiting
The purpose of this study is to find out if omalizumab is effective in treating non-allergic asthma. The US Food and Drug Administration has approved the use of omalizumab to treat moderate to severe allergic asthma.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||Effect of Anti-IgE in Non-Allergic Asthma|
- Serum IgE levels
- Basophil FceRI surface expression
- -Changes in free serum IgE levels from baseline,
- -Changes in basophil response to non-IgE mediated stimuli from baseline,
- -Changes in basophil response to IgE mediated stimuli from baseline,
- -Changes in the expression of activation-linked markers on basophils,
- -Changes in serum alpha tryptase from baseline,
- -Changes in leukocyte markers
- -Change in daytime and nocturnal asthma symptom scores, -Changes in morning and evening peak expiratory flow (liters/min) from baseline,
- -Need for albuterol rescue medication from baseline,
- -The frequency of asthma exacerbations from baseline, -Change in standardized quality of life scores from baseline, -visual analogue score (VAS) from baseline,
- -all study outcomes between ID positive and ID negative patients
|Study Start Date:||April 2005|
Asthma is a chronic inflammatory disease of the lower airways. The inflammatory process is associated with changes in airway hyperresponsiveness (irritability), and airflow limitations caused by bronchoconstriction, edema, and mucous plugging. Mast cells, basophils, eosinophils, activated T-lymphocytes, macrophages, neutrophils, and airway epithelial cells all play a role in this inflammatory process by releasing mediators directly responsible for local inflammation and by releasing mediators that encourage a further influx of inflammatory cells (Expert Panel Report 2, 1997). These cells and their products eventually produce a state of chronic allergic inflammation leading to increased vascular leakage, mucous secretion, smooth muscle hyperresponsiveness, and nerve activation. Clinically, this process is characterized by intermittent shortness of breath, wheezing, coughing, and chest tightness.
Although most asthmatics are atopic (allergic), non-atopic asthmatics exist and can develop equally severe disease. Non-allergic asthmatics have a trend towards higher than normal levels of the allergic antibody (IgE) though obviously they lack skin test specificity. When examining skin test reactivity and serum IgE as independent variables for asthma risk, there was a stronger association with serum IgE elevation than skin test reactivity. In fact, serum IgE tended to be high in asthmatics regardless of skin test reactivity.
Omalizumab (Xolair®) is a recombinant humanized monoclonal antibody that binds specifically to the (FceRI) binding site on human IgE. The binding of omalizumab inhibits the ability of IgE to bind to basophils or mast cells.
Omalizumab recently received FDA approval for the treatment of moderate to severe persistent allergic asthma in pediatric (12 years of age and above) and adult patients. The addition of omalizumab to standard asthma therapies has been found to reduce asthma exacerbations and decrease both inhaled corticosteroid dose and rescue medication use. (Busse, 2001). In a phase III double blinded placebo controlled trial involving 525 severe allergic asthmatics, omalizumab treated patients had fewer exacerbations during both a steroid stable phase and steroid reduction phase than did placebo controls (Busse, 2001). The median reduction in steroid dose during reduction phase was 75% and 50% in the omalizumab and placebo groups respectively. In a similarly designed steroid reduction study involving 6 to 12 year-old moderate to severe allergic asthmatics, steroid reduction was possible in 100% of treated patient verses 66.7% of placebo treated patients (Milgrom, 2001). Other steroid reduction studies have had similar results (Buhl 2002, Soler 2001). Omalizumab has also been shown to improve quality of life in allergic asthmatics as measured by the Asthma Quality of Life Questionnaire (AQLQ). In adults, AQLQ demonstrated greater improvement at 16, 28 and 52 weeks in omalizumab treated patients than in placebo treated (Finn 2003). Similarly in pediatric populations, AQLQ improvement reached statistical significance in omalizumab treated patients (Lemanske 2002).
Omalizumab has shown itself to be a promising new therapy for the treatment of moderate to severe allergic asthma. It is currently not indicated for patients with non-allergic asthma. The objective of this study will be to define the effects of omalizumab on cell surface FceRI expression and serum IgE of non-allergic asthmatics.
|Contact: Susan L Whaley, MPHemail@example.com|
|United States, Maryland|
|Johns Hopkins Asthma and Allergy Center||Recruiting|
|Baltimore, Maryland, United States, 21224|
|Contact: Susan L Whaley, MPH 410-550-2122 firstname.lastname@example.org|
|Principal Investigator: Peter S Creticos, MD|
|Principal Investigator:||Peter S Creticos, M.D.||Johns Hopkins University|