Effect of Omalizumab on Expression of IgE Receptors in Adults With Severe, Inadequately Controlled Allergic Asthma

Phase 4

Completed

Conditions: Asthma

Interventions: Drug: placebo
Drug: Omalizumab

Registration Number: NCT00454051

Lead Sponsor: Novartis Pharmaceuticals

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 31

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Placebo was injected subcutaneously every 2 weeks or every 4 weeks for 16 weeks.
Omalizumab	Omalizumab	Omalizumab was injected subcutaneously every 2 weeks or every 4 weeks for 16 weeks. Dose and dosing interval were determined based on patient body weight and pre-treatment serum IgE level.

Primary Outcome Measures

Name	Time	Method
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	Baseline and Week 16	Blood was drawn from participants at baseline and at Week 16. Basophils and dendritic cells expressing FcεRI were counted and the percentage was calculated. Fluorescence was used to label FcεRI so that they could be visualized. The greater the fluorescence intensity the greater FcεRI expression. The change from baseline is described by the difference (%) between the baseline value, before the first study drug administration, and the value observed at the end of study, expressed as a percent of the baseline value.
Change (%) From Baseline in Mean Fluorescence Intensity of FcεRI After 16 Weeks of Treatment With Omalizumab as Compared With Placebo	Baseline and Week 16	Blood was drawn from participants at baseline and at week 16. Basophils and dendritic cells expressing FcεRI were counted and the percentage was calculated. Fluorescence was used to label FcεRI so that they could be visualized. The greater the fluorescence intensity the greater FcεRI expression. The change from baseline is described by the difference (%) between the baseline value, before the first study drug administration, and the value observed at the end of study, expressed as a percent of the baseline value.

Secondary Outcome Measures

Name	Time	Method
Change (%) From Baseline in Percent of Basophils and Dendritic Cells Expressing FcεRI After 4, 8, 12 and 16 Weeks of Treatment	Baseline, Weeks 4, 8, 12 and 16	Blood was drawn from a sub-group of participants at weeks 4, 8, 12, and 16. Basophils and dendritic cells expressing FcεRI were counted and the percentage was calculated. Fluorescence was used to label FcεRI so that they could be visualized. The change from baseline is described by the difference (%) between the baseline value, before the first study drug administration, and the value observed at the specified time point, expressed as a percent of the baseline value.
Change (%) From Baseline in the Mean Fluorescence Intensity of FcεRI After 4, 8, 12 and 16 Weeks of Treatment	Baseline, Weeks 4, 8, 12, and 16	Blood was drawn from a sub-group of participants at weeks 4, 8, 12, and 16. Basophils and dendritic cells expressing FcεRI were counted and the percentage was calculated. Fluorescence was used to label FcεRI so that they could be visualized. The change from baseline is described by the difference (%) between the baseline value, before the first study drug administration, and the value observed at the specified time point, expressed as a percent of the baseline value.
Change From Baseline in the Number of Days With Asthma Symptoms Per Week	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	Participants maintained a diary to record the number of days with daytime asthma symptoms per week. This analysis compares the mean number of days per week with asthma symptoms during the 4-week screening period prior to randomization with the mean number of days per wek with asthma symptoms in the last 4 weeks of study treatment (Weeks 12 -16).
Change From Baseline in the Number of Puffs of Rescue Medication Per Week	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	Participants maintained a diary to record the daytime number of puffs of rescue Short-acting B2 agonist (SABA) used to treat asthma symptoms per week. This analysis compares the mean number of puffs of rescue medication per week during the 4 week screening period prior to randomization to the mean number of puffs per week during the last 4 weeks on study treatment (Weeks 12 - 16).
Change From Baseline in the Number of Nights With Awakenings Per Week	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	Participants maintained a diary to record the number of nights with awakenings due to asthma symptoms per week. For this analysis, the mean number of nights with awakenings per week during the 4 week screening period prior to randomization was compared with the mean number of nights with awakenings per week during the last 4 weeks of study treatment (Weeks 12 - 16).
Change From Baseline in the Number of Days With Impairment in Daily Activities Per Week	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	Impairment was defined as days with physical activity considered as limited (or "not normal") according to patient's assessment and was recorded in a patient daily diary. For this analysis, the mean number of days with impairment per week during the 4 week screening period prior to randomization was compared with the mean number of days with impairment per week during the last 4 weeks on study treatment (Weeks 12 - 16).
Change From Baseline in the Number of Days With Absence From School or Work Due to Asthma Symptoms	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	Participants maintained a diary to record the number of days with absence from school or work due to asthma symptoms. For this analysis, the number of days with absence from school or work in the four weeks prior to randomization (screening period) were compared with the number of absence days during the last 4 weeks on study treatment (Weeks 12 - 16).
Change From Baseline in the Number of Days With Hospitalizations	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	Participants maintained a diary to record the number of days with hospitalizations during the study. For this analysis, the number of days with hospitalizations during the screening period (4 weeks prior to randomization) was compared with the number of days with hospitalizations during the last 4 weeks on study treatment (Weeks 12 - 16).
Change From Baseline in the Number of Unscheduled Clinic Visits	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	Participants maintained a diary to record the number of unscheduled clinic visits during the study. For this analysis, the number of unscheduled visits during the 4 week screening period prior to randomization is compared with the number of unscheduled visits during the last 4 weeks on treatment (Weeks 12 - 16).
Change From Baseline in the Morning Daily Peak Expiratory Flow (PEF)	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	Peak Expiratory Flow (PEF) was measured every morning using a peak flow meter, and was recorded in the patient diary. For this analysis, the mean morning PEF during the 4-week screening period prior to randomizaton is compared with the mean morning PEF during the last 4 weeks of study treatment (Weeks 12 - 16).
Physician's Overall Assessment of Treatment Effectiveness	After 16 weeks of treatment	The Physician's overall assessment of treatment effectiveness was graded 1-5 as 1 = Excellent asthma control (complete control) 2 = Good asthma control (marked improvement) 3 = Moderate asthma control (discernible, but limited improvement) 4 = Poor asthma control (no appreciable change) 5 = Very poor asthma control (worsening)