Clinical trial NCT00454051: Effect of Omalizumab on Expression of IgE Receptors in Adults With Severe, Inadequately Controlled Allergic Asthma
Official title: Double Blind Placebo Controlled Study to Assess the Expression of IgE on Basophils and Dendritic Cells During Omalizumab Treatment.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Keywords: Asthma, anti-immunoglobulin E, omalizumab, IgE receptors
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-03-29
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the expression of IgE high affinity receptors (the part of the cell associated with allergic response) in patients suffering from uncontrolled severe asthma despite long term treatment with high dose of inhaled corticosteroid and long acting Beta-2 agonist.

Detailed description: Double blind placebo controlled study to assess the expression of IgE on blood basophils and dendritic cells in patients with uncontrolled, severe, persistent allergic asthma after a 16-week Omalizumab treatment.

Eligibility criteria: Inclusion Criteria:

* Adults aged \>= 18 years.
* Patients with severe persistent allergic asthma with the following characteristics:
* FEV1 (Forced Expiratory Volume in One Second) \<80% of predicted.
* Frequent daily symptoms (\>=4 days/week on average) or nocturnal awakening (\>=1/week on average).
* Multiple severe asthma exacerbations: either \>=2 severe asthma exacerbations having required an unscheduled medical intervention with systemic corticosteroid in the past year, or hospitalization (including emergency room treatment) for an asthma exacerbation in the past year.
* Despite a high dose inhaled corticosteroid \>1000 mg beclomethasone dipropionate or equivalent and a inhaled long-acting B2-agonist.
* With an allergy to a perennial allergen demonstrated with convincing criteria, i.e. positive prick skin test or in vitro reactivity to a perennial aeroallergen (RAST).
* Total serum IgE level \>= 30 to \<=700 IU/ml and suitable serum total IgE level and weight according to Xolair dosing tablets.

Exclusion Criteria:

* Age \< 18 years.
* Smoking history \> 20 pack years.
* Patients who have had an asthma exacerbation during the 4 weeks prior to randomization
* History of food or drug related severe anaphylactoid or anaphylactic reaction
* Elevated serum IgE levels for reasons other than allergy (e.g. parasite infections, hyperimmunoglobulin E syndrome, Wiskott-Aldrich Syndrome or allergic bronchopulmonary aspergillosis).
* Patients with active cancer, suspicion of cancer or any history of cancer.
* Pregnant women.
* Known hypersensitivity to omalizumab or to one of its components.
* Patients already treated with omalizumab (indeed a previous treatment with omalizumab could have modified the FceRI expression).
* Patients who had participated in a clinical trial in the past 3 months.

Primary outcomes:
measure: Change (%) From Baseline in FcεRI (High-affinity IgE Receptor) Expression on Blood Basophils and Dendritic Cells After 16 Weeks of Treatment With Omalizumab as Compared With Placebo
timeFrame: Baseline and Week 16
measure: Change (%) From Baseline in Mean Fluorescence Intensity of FcεRI After 16 Weeks of Treatment With Omalizumab as Compared With Placebo
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Change (%) From Baseline in Percent of Basophils and Dendritic Cells Expressing FcεRI After 4, 8, 12 and 16 Weeks of Treatment
timeFrame: Baseline, Weeks 4, 8, 12 and 16
measure: Change (%) From Baseline in the Mean Fluorescence Intensity of FcεRI After 4, 8, 12 and 16 Weeks of Treatment
timeFrame: Baseline, Weeks 4, 8, 12, and 16
measure: Change From Baseline in the Number of Days With Asthma Symptoms Per Week
timeFrame: Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
measure: Change From Baseline in the Number of Puffs of Rescue Medication Per Week
timeFrame: Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
measure: Change From Baseline in the Number of Nights With Awakenings Per Week
timeFrame: Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
measure: Change From Baseline in the Number of Days With Impairment in Daily Activities Per Week
timeFrame: Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
measure: Change From Baseline in the Number of Days With Absence From School or Work Due to Asthma Symptoms
timeFrame: Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
measure: Change From Baseline in the Number of Days With Hospitalizations
timeFrame: Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
measure: Change From Baseline in the Number of Unscheduled Clinic Visits
timeFrame: Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
measure: Change From Baseline in the Morning Daily Peak Expiratory Flow (PEF)
timeFrame: Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
measure: Physician's Overall Assessment of Treatment Effectiveness
timeFrame: After 16 weeks of treatment
Other outcomes:
Locations:
city: Rueil-Malmaison
country: France
facility: Novartis Investigator site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_CHAIR
References:
citation: Chanez P, Contin-Bordes C, Garcia G, Verkindre C, Didier A, De Blay F, de Lara MT, Blanco P, Moreau JF, Robinson P, Bourdeix I, Trunet P, Le Gros V, Humbert M, Molimard M. Omalizumab-induced decrease of FcxiRI expression in patients with severe allergic asthma. Respir Med. 2010 Nov;104(11):1608-17. doi: 10.1016/j.rmed.2010.07.011. Epub 2010 Aug 30.