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

Asthma Clinical Trial

Official title:

Double Blind Placebo Controlled Study to Assess the Expression of IgE on Basophils and Dendritic Cells During Omalizumab Treatment.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00454051
• Other study ID #: CIGE025AFR02
• Status: Completed
• Phase: Phase 4
• First received: March 28, 2007
• Last updated: August 2, 2011
• Start date: December 2006
• Est. completion date: March 2008

Study information

• Verified date: August 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: March 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Omalizumab
Omalizumab was supplied as a sterile, freeze dried preparation, to be reconstituted to deliver 150mg of omalizumab. Each vial was reconstituted with 1.4ml of sterile water for injection. The appropriate dose and dosing frequency of omalizumab were determined by baseline total IgE and body weight. A dosing table was used following the European Summary of Product Characteristics (SmPC) of omalizumab.
• placebo
Placebo was a physiological salt solution, administered according to the same administration scheme to respect the same dosing frequency and injected volume.

Locations

Country	Name	City	State
France	Novartis Investigator site	Rueil-Malmaison

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change (%) From Baseline in FceRI (High-affinity IgE Receptor) Expression on Blood Basophils and Dendritic Cells After 16 Weeks of Treatment With Omalizumab as Compared With Placebo	Blood was drawn from participants at baseline and at Week 16. Basophils and dendritic cells expressing FceRI were counted and the percentage was calculated. Fluorescence was used to label FceRI so that they could be visualized. The greater the fluorescence intensity the greater FceRI 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.	Baseline and Week 16	No
Primary	Change (%) From Baseline in Mean Fluorescence Intensity of FceRI After 16 Weeks of Treatment With Omalizumab as Compared With Placebo	Blood was drawn from participants at baseline and at week 16. Basophils and dendritic cells expressing FceRI were counted and the percentage was calculated. Fluorescence was used to label FceRI so that they could be visualized. The greater the fluorescence intensity the greater FceRI 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.	Baseline and Week 16	No
Secondary	Change (%) From Baseline in Percent of Basophils and Dendritic Cells Expressing FceRI After 4, 8, 12 and 16 Weeks of Treatment	Blood was drawn from a sub-group of participants at weeks 4, 8, 12, and 16. Basophils and dendritic cells expressing FceRI were counted and the percentage was calculated. Fluorescence was used to label FceRI 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.	Baseline, Weeks 4, 8, 12 and 16	No
Secondary	Change (%) From Baseline in the Mean Fluorescence Intensity of FceRI After 4, 8, 12 and 16 Weeks of Treatment	Blood was drawn from a sub-group of participants at weeks 4, 8, 12, and 16. Basophils and dendritic cells expressing FceRI were counted and the percentage was calculated. Fluorescence was used to label FceRI 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.	Baseline, Weeks 4, 8, 12, and 16	No
Secondary	Change From Baseline in the Number of Days With Asthma Symptoms Per Week	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).	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	No
Secondary	Change From Baseline in the Number of Puffs of Rescue Medication Per Week	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).	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	No
Secondary	Change From Baseline in the Number of Nights With Awakenings Per Week	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).	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	No
Secondary	Change From Baseline in the Number of Days With Impairment in Daily Activities Per Week	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).	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	No
Secondary	Change From Baseline in the Number of Days With Absence From School or Work Due to Asthma Symptoms	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).	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	No
Secondary	Change From Baseline in the Number of Days With Hospitalizations	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).	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	No
Secondary	Change From Baseline in the Number of Unscheduled Clinic Visits	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).	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	No
Secondary	Change From Baseline in the Morning Daily Peak Expiratory Flow (PEF)	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).	Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)	No
Secondary	Physician's Overall Assessment of Treatment Effectiveness	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)	After 16 weeks of treatment	No