Back to resultsEffect of Omalizumab on Expression of IgE Receptors in Adults With Severe, Inadequately Controlled Allergic Asthma
Primary Purpose
Asthma
Status
Completed
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Omalizumab
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Asthma focused on measuring Asthma, anti-immunoglobulin E, omalizumab, IgE receptors
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.
Sites / Locations
- Novartis Investigator site
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Omalizumab
Placebo
Arm Description
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.
Placebo was injected subcutaneously every 2 weeks or every 4 weeks for 16 weeks.
Outcomes
Primary Outcome Measures
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
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
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
Change (%) From Baseline in Percent of Basophils and Dendritic Cells Expressing FcεRI 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 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
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
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
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
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
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
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
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
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)
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
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)
Full Information
NCT ID
NCT00454051
First Posted
March 28, 2007
Last Updated
August 2, 2011
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00454051
Brief Title
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
2. Study Status
Record Verification Date
August 2011
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
March 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Asthma, anti-immunoglobulin E, omalizumab, IgE receptors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
31 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Omalizumab
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo was injected subcutaneously every 2 weeks or every 4 weeks for 16 weeks.
Intervention Type
Drug
Intervention Name(s)
Omalizumab
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Placebo was a physiological salt solution, administered according to the same administration scheme to respect the same dosing frequency and injected volume.
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Baseline and Week 16
Title
Change (%) From Baseline in Mean Fluorescence Intensity of FcεRI After 16 Weeks of Treatment With Omalizumab as Compared With Placebo
Description
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.
Time Frame
Baseline and Week 16
Secondary Outcome Measure Information:
Title
Change (%) From Baseline in Percent of Basophils and Dendritic Cells Expressing FcεRI After 4, 8, 12 and 16 Weeks of Treatment
Description
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.
Time Frame
Baseline, Weeks 4, 8, 12 and 16
Title
Change (%) From Baseline in the Mean Fluorescence Intensity of FcεRI After 4, 8, 12 and 16 Weeks of Treatment
Description
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.
Time Frame
Baseline, Weeks 4, 8, 12, and 16
Title
Change From Baseline in the Number of Days With Asthma Symptoms Per Week
Description
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).
Time Frame
Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
Title
Change From Baseline in the Number of Puffs of Rescue Medication Per Week
Description
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).
Time Frame
Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
Title
Change From Baseline in the Number of Nights With Awakenings Per Week
Description
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).
Time Frame
Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
Title
Change From Baseline in the Number of Days With Impairment in Daily Activities Per Week
Description
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).
Time Frame
Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
Title
Change From Baseline in the Number of Days With Absence From School or Work Due to Asthma Symptoms
Description
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).
Time Frame
Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
Title
Change From Baseline in the Number of Days With Hospitalizations
Description
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).
Time Frame
Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
Title
Change From Baseline in the Number of Unscheduled Clinic Visits
Description
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).
Time Frame
Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
Title
Change From Baseline in the Morning Daily Peak Expiratory Flow (PEF)
Description
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).
Time Frame
Baseline (the 4 week screening period prior to randomization) and End of Study (Weeks 12 - 16)
Title
Physician's Overall Assessment of Treatment Effectiveness
Description
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)
Time Frame
After 16 weeks of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Chair
Facility Information:
Facility Name
Novartis Investigator site
City
Rueil-Malmaison
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
20801010
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.
Results Reference
derived
Learn more about this trial
Effect of Omalizumab on Expression of IgE Receptors in Adults With Severe, Inadequately Controlled Allergic Asthma
We'll reach out to this number within 24 hrs