Omalizumab Use and Asthma-Related Quality of Life in Patients With Severe Persistent Allergic Asthma

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00567476
• Collaborator: (none)
• Enrollment: 116
• Location: 1
• Arms: 2
• Duration (Months): 29
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

This study investigated asthma-related quality of life in Brazilian patients using omalizumab.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Omalizumab; Drug: Inhaled corticosteroids (ICS); Drug: Long-acting beta 2-adrenergic agonist (LABA); Drug: Short-acting beta 2-adrenergic agonist (SABA)	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label, Multicenter Study to Evaluate the Effect of Xolair (Omalizumab) as Add-on Therapy to Inhaled Corticosteroid + Long-Acting Beta Agonist in Fixed or Flexible Dosing Compared to Isolated Inhaled Corticosteroid + Long-Acting Beta Agonist in Fixed or Flexible Dosing in the Asthma-Related Quality of Life in Patients With Severe Persistent Allergic Asthma
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Omalizumab + Conventional Therapy Omalizumab was administered subcutaneously every 2 or 4 weeks over a period of 20 weeks to provide a dose of at least 0.016 mg/kg per UI/ml of immunoglobulin E (IgE). Doses (mg) and dosing frequency were determined by serum total IgE level (IU/mL) and body weight (kg). Also, participants continued using their current formulation of inhaled corticosteroid (ICS) and long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.	Drug: Omalizumab; Omalizumab 150 to 375 mg was administered subcutaneously every 2 or 4 weeks to provide a dose of at least 0.016 mg/kg per UI/ml of IgE.; Other Names: Xolair ; Drug: Inhaled corticosteroids (ICS); Any ICS with proprietary drug and device > 500 mcg of fluticasone or equivalent; Drug: Long-acting beta 2-adrenergic agonist (LABA); Fixed dose of LABA as prescribed prior to study entry; Drug: Short-acting beta 2-adrenergic agonist (SABA); Home use of nebulized Β2-agonist such as salbutamol 5 mg or terbutaline 10 mg for symptoms of intercurrent bronchospasm.; Other Names: salbutamol terbutaline
Active Comparator: Conventional Therapy Participants continued using their current formulation of inhaled corticosteroid (ICS) and a long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.	Drug: Inhaled corticosteroids (ICS); Any ICS with proprietary drug and device > 500 mcg of fluticasone or equivalent; Drug: Long-acting beta 2-adrenergic agonist (LABA); Fixed dose of LABA as prescribed prior to study entry; Drug: Short-acting beta 2-adrenergic agonist (SABA); Home use of nebulized Β2-agonist such as salbutamol 5 mg or terbutaline 10 mg for symptoms of intercurrent bronchospasm.; Other Names: salbutamol terbutaline

Outcome Measures

Primary Outcome Measures

1. The Mean Change From Baseline to Week 20 in the Overall Asthma Quality of Life Questionnaire (AQLQ) [Baseline and Week 20]

   The AQLQ was administered to all patients at Baseline, Week 12 and Week 20. The 32 questions in the AQLQ were divided into four domains; activity limitations, symptoms, emotional function, and environmental stimuli. Individual questions are equally weighted. The overall AQLQ score is the mean of the responses to each of the 32 questions, and ranges from 1 to 7. A score 7.0 indicates that the patient has no impairments due to asthma and a score of 1.0 indicates severe impairment.

Secondary Outcome Measures

1. Percentage of Participants With an Increase of More Than 1.5 in AQLQ Overall Score at 20 Weeks [Baseline and Week 20]

   The AQLQ was administered to all patients at Baseline, Week 12 and Week 20. The 32 questions in the AQLQ were divided into four domains; activity limitations, symptoms, emotional function, and environmental stimuli. Individual questions are equally weighted. The overall AQLQ score is the mean of the responses to each of the 32 questions and ranges from 1 to 7. A score 7.0 indicates that the patient has no impairments due to asthma and score 1.0 indicates severe impairment.

2. Percentage of Participants With an Increase of More Than 0.5 in AQLQ Overall Score at Week 20 [Baseline and Week 20]

   The AQLQ was administered to all patients at Baseline, Week 12 and Week 20. The 32 questions in the AQLQ were divided into four domains; activity limitations, symptoms, emotional function, and environmental stimuli. Individual questions are equally weighted. The overall AQLQ score is the mean of the responses to each of the 32 questions and ranges from 1 to 7. AQLQ of each domain is the mean of the responses to each of the questions within that domain. A score 7.0 indicates that the patient has no impairments due to asthma and score 1.0 indicates severe impairment.

3. The Mean Change From Baseline to the End of Study in AQLQ Domain Score [Baseline and Week 20]

   AQLQ was administered to all patients at Baseline, Week 12 and Week 20, and prior to any clinic visit evaluation and drug administration. The 32 questions in the AQLQ were divided into four domains: activity limitations, symptoms, emotional function, and environmental stimuli. AQLQ domain scores were calculated by adding the responses to each of the questions in the domain and dividing by the number of questions in the domain. Each domain score was between 1 and 7. Score 7.0 meant that the patient had no impairments due to asthma and score 1.0 indicated severe impairment.

4. Number of Asthma Exacerbation Episodes Per Participant [From Baseline through 20 weeks]

   For the purpose of evaluating efficacy, a clinically significant asthma exacerbation was defined as a worsening of asthma symptoms as judged clinically by the investigator, requiring doubling the baseline ICS dose for at least 3 days and/or treatment with rescue systemic (oral or IV) corticosteroids. The initiation of the above corticosteroid regimens marked the start of an asthma exacerbation episode and cessation of the additional corticosteroid regimens marked the end of an exacerbation episode.

5. Percentage of Participants Using Rescue Medication [From Baseline through 20 Weeks]

   When necessary, patients were allowed to take rescue medication using inhaled salbutamol or terbutaline for symptoms of intercurrent bronchospasm.

6. Free Days With no Rescue Medication [From Baseline through 20 weeks (140 days)]

   When necessary, patients were allowed to take rescue medication using inhaled salbutamol or terbutaline for symptoms of intercurrent bronchospasm. Days with no rescue medication intake were the variable of interest for this analysis.

7. Mean Number of Puffs of Rescue Medication Taken Per Day [From Baseline through 20 Weeks]

   When necessary, patients were allowed to take rescue medication using inhaled salbutamol or terbutaline for symptoms of intercurrent bronchospasm. The number of puffs taken during each 24 hour period was recorded in the patient dairy. The total number of puffs over 20 weeks of treatment was divided by the number of treatment days (140 days) to calculate the mean number of puffs per day.

8. Physician's Global Assessment of Treatment Effectiveness [20 Weeks]

   At the end of Week 20 a global evaluation of the treatment effectiveness was performed by the investigator using the following scale: Excellent: complete control of asthma; Good: marked improvement of asthma; Moderate: discernible, but limited improvement in asthma; Poor: no appreciable change in asthma; Worsening of asthma

9. Patient's Global Assessment of Treatment Effectiveness [20 Weeks]

   At the end of Week 20, a global evaluation of the treatment effectiveness was performed by the patient using the following scale: Excellent: complete control of asthma; Good: marked improvement of asthma; Moderate: discernible, but limited improvement in asthma; Poor: no appreciable change in asthma; Worsening of asthma

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• 12 to 75 years-old during screening visit.

• Body weight > 20 kg and < 150 kg.

• Daily or persistent asthma symptoms.

• Night symptoms at least once a week.

• Forced expiratory volume in 1 second (FEV1) > 40% and < 80% of predicted normal value and continuing asthma symptoms.

• FEV1 increased > 12% from baseline within 30 minutes of inhaled (up to 400 mcg) or nebulized (up to 5 mg) salbutamol.

• Subject taking more than 500 mcg/day of fluticasone or equivalent associated to a long-acting β2-agonist.

• Inhaled corticosteroid and long-acting beta-2 adrenergic agonist (LABA) doses that remained fixed during the last 12 weeks prior to screening.

• Medical history of at least two episodes of asthma exacerbation treated with systemic corticoid or at least one severe asthma exacerbation treated with systemic corticoid and hospitalization or emergency room visit in the last 12 months prior to screening.

• Positive skin prick test (diameter of wheal > 3mm) to at least one perennial aeroallergen (dust mite, cat/dog dander, cockroaches), to which the subject was likely to be exposed during the study.

• Subject capable to read and understand asthma related quality of life questionnaire (Juniper's questionnaire).

Exclusion criteria:

• Pregnant, nursing female subjects.

• Female subjects without current acceptable contraceptive method.

• Previous history of allergy or hypersensitivity to omalizumab.

• Subjects with prior treatment with omalizumab.

• Subjects with medical history of psychiatric disorder.

• Subject had been treated with systemic corticosteroid for any reason other than asthma.

• Subject took β2 antagonist medication in the last 3 months prior to screening visit.

• Subject took protocol prohibited medication prior to screening.

• Medical history of food or drug related severe anaphylactoid reactions.

• Medical history of antibiotics allergy. Patients were included if the antibiotics to which they were allergic to were to be avoided for the entire duration of the study.

• Asthma related to non-steroidal anti-inflammatory drug (NSAID).

• Treatment of exacerbation in the 4 weeks prior to randomization.

• Other active lung diseases.

• Medical history of others uncontrolled diseases 3 months prior randomization (eg, infections, coronary heart diseases and metabolic diseases).

• Any history of cancer.

• Abnormal electrocardiogram (ECG), laboratory exams (clinically significant abnormalities), and chest X-ray (CXR).

• Evidence or history of drug or alcohol abuse.

• Airway infection (eg, pneumonia, acute sinusitis) 4 weeks prior to screening visit.

• Smokers or smoking history of > 10 pack-years.

• Subject that had been treated with investigational drugs over the past 30 days or during the course of the trial.

• Subject had elevated IgE levels for reasons other than allergy.

Other protocol-defined inclusion/exclusion criteria applied to the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigator Site	São Paulo		Brazil

Sponsors and Collaborators

• Novartis

Investigators

• Study Chair: Novartis Pharma, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00567476
• Other Study ID Numbers: CIGE025ABR01
• First Posted: Dec 5, 2007
• Last Update Posted: Jun 30, 2011
• Last Verified: Jun 1, 2011

• Keywords provided by , ,: Asthma, anti-immunoglobulin E, omalizumab
• Additional relevant MeSH terms: Asthma; Omalizumab; Terbutaline; Adrenergic Agents; Adrenergic Agonists

Study Results

Participant Flow

Arm/Group Title	Omalizumab + Conventional Therapy	Conventional Therapy
Arm/Group Description	Omalizumab was administered subcutaneously every 2 or 4 weeks over a period of 20 weeks to provide a dose of at least 0.016 mg/kg per UI/ml of immunoglobulin E (IgE). Doses (mg) and dosing frequency were determined by serum total IgE level (IU/mL) and body weight (kg). Also, participants continued using their current formulation of inhaled corticosteroid (ICS) and long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.	Participants continued using their current formulation of inhaled corticosteroid (ICS) and a long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.
Period Title: Overall Study
STARTED	78	38
COMPLETED	70	34
NOT COMPLETED	8	4

Baseline Characteristics

Arm/Group Title	Omalizumab + Conventional Therapy	Conventional Therapy	Total
Arm/Group Description	Omalizumab was administered subcutaneously every 2 or 4 weeks over a period of 20 weeks to provide a dose of at least 0.016 mg/kg per UI/ml of immunoglobulin E (IgE). Doses (mg) and dosing frequency were determined by serum total IgE level (IU/mL) and body weight (kg). Also, participants continued using their current formulation of inhaled corticosteroid (ICS) and long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.	Participants continued using their current formulation of inhaled corticosteroid (ICS) and a long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.	Total of all reporting groups
Overall Participants	78	38	116
Age, Customized (Number) [Number]
> 12 years and < 25 years	4 (13.1) 5.1%	4 (12.8) 10.5%	8 6.9%
≥ 25 and < 35 years	15 19.2%	3 7.9%	18 15.5%
≥ 35 and < 55 years	42 53.8%	23 60.5%	65 56%
≥ 55 and < 65 years	12 15.4%	4 10.5%	16 13.8%
≥ 65 and < 75 years	5 6.4%	4 10.5%	9 7.8%
Sex: Female, Male (Count of Participants)
Female	60 76.9%	29 76.3%	89 76.7%
Male	18 23.1%	9 23.7%	27 23.3%

Outcome Measures

1. Secondary Outcome

Title	Percentage of Participants With an Increase of More Than 1.5 in AQLQ Overall Score at 20 Weeks
Description	The AQLQ was administered to all patients at Baseline, Week 12 and Week 20. The 32 questions in the AQLQ were divided into four domains; activity limitations, symptoms, emotional function, and environmental stimuli. Individual questions are equally weighted. The overall AQLQ score is the mean of the responses to each of the 32 questions and ranges from 1 to 7. A score 7.0 indicates that the patient has no impairments due to asthma and score 1.0 indicates severe impairment.
Time Frame	Baseline and Week 20

Outcome Measure Data

Analysis Population Description

Patients who took at least one dose of double-blind study drug and who had at least one post-baseline safety or efficacy assessment made up the intent-to treat (ITT) population. Last observation carried forward (LOCF) approach was used. Scores of completed AQLQ at Week 12 were used at Week 20 for dropped out patients or for missing values.

Arm/Group Title	Omalizumab + Conventional Therapy	Conventional Therapy
Arm/Group Description	Omalizumab was administered subcutaneously every 2 or 4 weeks over a period of 20 weeks to provide a dose of at least 0.016 mg/kg per UI/ml of immunoglobulin E (IgE). Doses (mg) and dosing frequency were determined by serum total IgE level (IU/mL) and body weight (kg). Also, participants continued using their current formulation of inhaled corticosteroid (ICS) and long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.	Participants continued using their current formulation of inhaled corticosteroid (ICS) and a long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.
Measure Participants	77	36
Number (95% Confidence Interval) [Percentage of participants]	40.3 51.7%	2.8 7.4%

2. Secondary Outcome

Title	Percentage of Participants With an Increase of More Than 0.5 in AQLQ Overall Score at Week 20
Description	The AQLQ was administered to all patients at Baseline, Week 12 and Week 20. The 32 questions in the AQLQ were divided into four domains; activity limitations, symptoms, emotional function, and environmental stimuli. Individual questions are equally weighted. The overall AQLQ score is the mean of the responses to each of the 32 questions and ranges from 1 to 7. AQLQ of each domain is the mean of the responses to each of the questions within that domain. A score 7.0 indicates that the patient has no impairments due to asthma and score 1.0 indicates severe impairment.
Time Frame	Baseline and Week 20

Outcome Measure Data

Analysis Population Description

Patients who took at least one dose of double-blind study drug and who had at least one post-baseline safety or efficacy assessment made up the intent-to treat (ITT) population. Last observation carried forward (LOCF) approach was used. Scores of completed AQLQ at Week 12 were used at Week 20 for dropped out patients or for missing values.

Arm/Group Title	Omalizumab + Conventional Therapy	Conventional Therapy
Arm/Group Description	Omalizumab was administered subcutaneously every 2 or 4 weeks over a period of 20 weeks to provide a dose of at least 0.016 mg/kg per UI/ml of immunoglobulin E (IgE). Doses (mg) and dosing frequency were determined by serum total IgE level (IU/mL) and body weight (kg). Also, participants continued using their current formulation of inhaled corticosteroid (ICS) and long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.	Participants continued using their current formulation of inhaled corticosteroid (ICS) and a long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.
Measure Participants	77	36
Number (95% Confidence Interval) [Percentage of participants]	70.1 89.9%	22.2 58.4%

3. Primary Outcome

Title	The Mean Change From Baseline to Week 20 in the Overall Asthma Quality of Life Questionnaire (AQLQ)
Description	The AQLQ was administered to all patients at Baseline, Week 12 and Week 20. The 32 questions in the AQLQ were divided into four domains; activity limitations, symptoms, emotional function, and environmental stimuli. Individual questions are equally weighted. The overall AQLQ score is the mean of the responses to each of the 32 questions, and ranges from 1 to 7. A score 7.0 indicates that the patient has no impairments due to asthma and a score of 1.0 indicates severe impairment.
Time Frame	Baseline and Week 20

Outcome Measure Data

Analysis Population Description

Patients who took at least one dose of double-blind study drug and who had at least one post-baseline safety or efficacy assessment made up the intent-to treat (ITT) population. Last observation carried forward (LOCF) approach was used. Scores of completed AQLQ at Week 12 were used at Week 20 for dropped out patients or for missing values.

Arm/Group Title	Omalizumab + Conventional Therapy	Conventional Therapy
Arm/Group Description	Omalizumab was administered subcutaneously every 2 or 4 weeks over a period of 20 weeks to provide a dose of at least 0.016 mg/kg per UI/ml of immunoglobulin E (IgE). Doses (mg) and dosing frequency were determined by serum total IgE level (IU/mL) and body weight (kg). Also, participants continued using their current formulation of inhaled corticosteroid (ICS) and long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.	Participants continued using their current formulation of inhaled corticosteroid (ICS) and a long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.
Measure Participants	78	38
Baseline (n=77, 37)	3.1 (1.0)	3.1 (1.1)
At Week 20 (n=78, 36)	4.4 (1.4)	3.0 (1.1)
Change from baseline to week 20 (n=77, 36)	1.2 (0.1)	-0.1 (0.1)

4. Secondary Outcome

Title	The Mean Change From Baseline to the End of Study in AQLQ Domain Score
Description	AQLQ was administered to all patients at Baseline, Week 12 and Week 20, and prior to any clinic visit evaluation and drug administration. The 32 questions in the AQLQ were divided into four domains: activity limitations, symptoms, emotional function, and environmental stimuli. AQLQ domain scores were calculated by adding the responses to each of the questions in the domain and dividing by the number of questions in the domain. Each domain score was between 1 and 7. Score 7.0 meant that the patient had no impairments due to asthma and score 1.0 indicated severe impairment.
Time Frame	Baseline and Week 20

Outcome Measure Data

Analysis Population Description

Patients who took at least one dose of double-blind study drug and who had at least one post-baseline safety or efficacy assessment made up the intent-to treat (ITT) population. Last observation carried forward (LOCF) approach was used. Scores of completed AQLQ at Week 12 were used at Week 20 for dropped out patients or for missing values.

Arm/Group Title	Omalizumab + Conventional Therapy	Conventional Therapy
Arm/Group Description	Omalizumab was administered subcutaneously every 2 or 4 weeks over a period of 20 weeks to provide a dose of at least 0.016 mg/kg per UI/ml of immunoglobulin E (IgE). Doses (mg) and dosing frequency were determined by serum total IgE level (IU/mL) and body weight (kg). Also, participants continued using their current formulation of inhaled corticosteroid (ICS) and long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.	Participants continued using their current formulation of inhaled corticosteroid (ICS) and a long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.
Measure Participants	78	38
Activity limitation score	1.3 (0.1)	-0.2 (0.1)
Symptoms score	1.2 (0.2)	-0.2 (0.2)
Emotional function score	1.3 (0.2)	0.0 (0.1)
Environmental stimuli score	1.2 (0.2)	0.0 (0.2)

5. Secondary Outcome

Title	Number of Asthma Exacerbation Episodes Per Participant
Description	For the purpose of evaluating efficacy, a clinically significant asthma exacerbation was defined as a worsening of asthma symptoms as judged clinically by the investigator, requiring doubling the baseline ICS dose for at least 3 days and/or treatment with rescue systemic (oral or IV) corticosteroids. The initiation of the above corticosteroid regimens marked the start of an asthma exacerbation episode and cessation of the additional corticosteroid regimens marked the end of an exacerbation episode.
Time Frame	From Baseline through 20 weeks

Outcome Measure Data

Analysis Population Description

All randomized patients who took at least one dose of double-blind study medication and who had at least one post-baseline safety or efficacy assessment made up the ITT population.

Arm/Group Title	Omalizumab + Conventional Therapy	Conventional Therapy
Arm/Group Description	Omalizumab was administered subcutaneously every 2 or 4 weeks over a period of 20 weeks to provide a dose of at least 0.016 mg/kg per UI/ml of immunoglobulin E (IgE). Doses (mg) and dosing frequency were determined by serum total IgE level (IU/mL) and body weight (kg). Also, participants continued using their current formulation of inhaled corticosteroid (ICS) and long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.	Participants continued using their current formulation of inhaled corticosteroid (ICS) and a long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.
Measure Participants	78	38
Patients with 1 episode	25 32.1%	12 31.6%
Patients with 2 episodes	5 6.4%	6 15.8%
Patients with 3 episodes	3 3.8%	1 2.6%
Patients with 4 episodes	1 1.3%	1 2.6%
Total number of patients with episodes	34 43.6%	20 52.6%

6. Secondary Outcome

Title	Percentage of Participants Using Rescue Medication
Description	When necessary, patients were allowed to take rescue medication using inhaled salbutamol or terbutaline for symptoms of intercurrent bronchospasm.
Time Frame	From Baseline through 20 Weeks

Outcome Measure Data

Analysis Population Description

All randomized patients who took at least one dose of double-blind study medication and who had at least one post-baseline safety or efficacy assessment made up the intention-to-treat (ITT) population.

Arm/Group Title	Omalizumab + Conventional Therapy	Conventional Therapy
Arm/Group Description	Omalizumab was administered subcutaneously every 2 or 4 weeks over a period of 20 weeks to provide a dose of at least 0.016 mg/kg per UI/ml of immunoglobulin E (IgE). Doses (mg) and dosing frequency were determined by serum total IgE level (IU/mL) and body weight (kg). Also, participants continued using their current formulation of inhaled corticosteroid (ICS) and long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.	Participants continued using their current formulation of inhaled corticosteroid (ICS) and a long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.
Measure Participants	78	38
Number (95% Confidence Interval) [Percentage of participants]	43.6 55.9%	44.7 117.6%

7. Secondary Outcome

Title	Free Days With no Rescue Medication
Description	When necessary, patients were allowed to take rescue medication using inhaled salbutamol or terbutaline for symptoms of intercurrent bronchospasm. Days with no rescue medication intake were the variable of interest for this analysis.
Time Frame	From Baseline through 20 weeks (140 days)

Outcome Measure Data

Analysis Population Description

All randomized patients who took at least one dose of double-blind study medication and who had at least one post-baseline safety or efficacy assessment made up the intention-to-treat (ITT) population.

Arm/Group Title	Omalizumab + Conventional Therapy	Conventional Therapy
Arm/Group Description	Omalizumab was administered subcutaneously every 2 or 4 weeks over a period of 20 weeks to provide a dose of at least 0.016 mg/kg per UI/ml of immunoglobulin E (IgE). Doses (mg) and dosing frequency were determined by serum total IgE level (IU/mL) and body weight (kg). Also, participants continued using their current formulation of inhaled corticosteroid (ICS) and long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.	Participants continued using their current formulation of inhaled corticosteroid (ICS) and a long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.
Measure Participants	78	38
Mean (Standard Deviation) [Days]	73.5 (39.4)	74.9 (35.4)

8. Secondary Outcome

Title	Mean Number of Puffs of Rescue Medication Taken Per Day
Description	When necessary, patients were allowed to take rescue medication using inhaled salbutamol or terbutaline for symptoms of intercurrent bronchospasm. The number of puffs taken during each 24 hour period was recorded in the patient dairy. The total number of puffs over 20 weeks of treatment was divided by the number of treatment days (140 days) to calculate the mean number of puffs per day.
Time Frame	From Baseline through 20 Weeks

Outcome Measure Data

Analysis Population Description

All randomized patients who took at least one dose of double-blind study medication and who had at least one post-baseline safety or efficacy assessment made up the intention-to-treat (ITT) population. Number of patients analyzed includes only those patients requiring rescue medication during the study.

Arm/Group Title	Omalizumab + Conventional Therapy	Conventional Therapy
Arm/Group Description	Omalizumab was administered subcutaneously every 2 or 4 weeks over a period of 20 weeks to provide a dose of at least 0.016 mg/kg per UI/ml of immunoglobulin E (IgE). Doses (mg) and dosing frequency were determined by serum total IgE level (IU/mL) and body weight (kg). Also, participants continued using their current formulation of inhaled corticosteroid (ICS) and long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.	Participants continued using their current formulation of inhaled corticosteroid (ICS) and a long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.
Measure Participants	34	17
Mean (Standard Deviation) [Puffs]	5.5 (4.1)	6.4 (4.7)

9. Secondary Outcome

Title	Physician's Global Assessment of Treatment Effectiveness
Description	At the end of Week 20 a global evaluation of the treatment effectiveness was performed by the investigator using the following scale: Excellent: complete control of asthma; Good: marked improvement of asthma; Moderate: discernible, but limited improvement in asthma; Poor: no appreciable change in asthma; Worsening of asthma
Time Frame	20 Weeks

Outcome Measure Data

Analysis Population Description

All randomized patients who took at least one dose of double-blind study medication and who had at least one post-baseline safety or efficacy assessment made up the intention-to-treat (ITT) population.

Arm/Group Title	Omalizumab + Conventional Therapy	Conventional Therapy
Arm/Group Description	Omalizumab was administered subcutaneously every 2 or 4 weeks over a period of 20 weeks to provide a dose of at least 0.016 mg/kg per UI/ml of immunoglobulin E (IgE). Doses (mg) and dosing frequency were determined by serum total IgE level (IU/mL) and body weight (kg). Also, participants continued using their current formulation of inhaled corticosteroid (ICS) and long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.	Participants continued using their current formulation of inhaled corticosteroid (ICS) and a long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.
Measure Participants	76	37
Excellent	22 28.2%	2 5.3%
Good	35 44.9%	4 10.5%
Moderate	13 16.7%	11 28.9%
Poor	6 7.7%	18 47.4%
Worsening	0 0%	2 5.3%

10. Secondary Outcome

Title	Patient's Global Assessment of Treatment Effectiveness
Description	At the end of Week 20, a global evaluation of the treatment effectiveness was performed by the patient using the following scale: Excellent: complete control of asthma; Good: marked improvement of asthma; Moderate: discernible, but limited improvement in asthma; Poor: no appreciable change in asthma; Worsening of asthma
Time Frame	20 Weeks

Outcome Measure Data

Analysis Population Description

All randomized patients who took at least one dose of double-blind study medication and who had at least one post-baseline safety or efficacy assessment made up the ITT population.

Arm/Group Title	Omalizumab + Conventional Therapy	Conventional Therapy
Arm/Group Description	Omalizumab was administered subcutaneously every 2 or 4 weeks over a period of 20 weeks to provide a dose of at least 0.016 mg/kg per UI/ml of immunoglobulin E (IgE). Doses (mg) and dosing frequency were determined by serum total IgE level (IU/mL) and body weight (kg). Also, participants continued using their current formulation of inhaled corticosteroid (ICS) and long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.	Participants continued using their current formulation of inhaled corticosteroid (ICS) and a long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.
Measure Participants	76	37
Excellent	33 42.3%	3 7.9%
Good	30 38.5%	13 34.2%
Moderate	10 12.8%	10 26.3%
Poor	3 3.8%	9 23.7%
Worsening	0 0%	2 5.3%

Adverse Events

Arm/Group Title	Omalizumab + Conventional Therapy		Conventional Therapy
Arm/Group Description	Omalizumab was administered subcutaneously every 2 or 4 weeks over a period of 20 weeks to provide a dose of at least 0.016 mg/kg per UI/ml of immunoglobulin E (IgE). Doses (mg) and dosing frequency were determined by serum total IgE level (IU/mL) and body weight (kg). Also, participants continued using their current formulation of inhaled corticosteroid (ICS) and long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.		Participants continued using their current formulation of inhaled corticosteroid (ICS) and a long-acting beta 2-adrenergic agonist (LABA). Home use of nebulized beta 2-agonist was allowed for the treatment of symptoms of intercurrent bronchospasm or during an asthma exacerbation if this treatment regimen was already established prior to screening visit.
All Cause Mortality
	Omalizumab + Conventional Therapy		Conventional Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Omalizumab + Conventional Therapy		Conventional Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/78 (3.8%)		0/38 (0%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	1/78 (1.3%)		0/38 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/78 (1.3%)		0/38 (0%)
Pneumothorax	1/78 (1.3%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	Omalizumab + Conventional Therapy		Conventional Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/78 (53.8%)		16/38 (42.1%)
General disorders
Pyrexia	4/78 (5.1%)		0/38 (0%)
Injury, poisoning and procedural complications
Joint sprain	4/78 (5.1%)		0/38 (0%)
Musculoskeletal and connective tissue disorders
Back pain	8/78 (10.3%)		1/38 (2.6%)
Nervous system disorders
Headache	16/78 (20.5%)		4/38 (10.5%)
Psychiatric disorders
Anxiety	4/78 (5.1%)		1/38 (2.6%)
Reproductive system and breast disorders
Dysmenorrhoea	1/78 (1.3%)		2/38 (5.3%)
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis	6/78 (7.7%)		0/38 (0%)
Respiratory tract infection	8/78 (10.3%)		3/38 (7.9%)
Rhinitis	3/78 (3.8%)		4/38 (10.5%)
Rhinitis allergic	1/78 (1.3%)		2/38 (5.3%)
Sinusitis	10/78 (12.8%)		2/38 (5.3%)
Upper respiratory tract infection	5/78 (6.4%)		3/38 (7.9%)
Skin and subcutaneous tissue disorders
Pruritus	5/78 (6.4%)		2/38 (5.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.