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

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

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

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Omalizumab; Drug: Inhaled corticosteroids (ICS); Drug: Long-acting beta 2-adrenergic agonist (LABA); Drug: Short-acting beta 2-adrenergic agonist (SABA)

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil
    • Novartis Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Mean Change From Baseline to Week 20 in the Overall Asthma Quality of Life Questionnaire (AQLQ)	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.	Baseline and Week 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With an Increase of More Than 1.5 in AQLQ Overall Score at 20 Weeks	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.	Baseline and Week 20
Percentage of Participants With an Increase of More Than 0.5 in AQLQ Overall Score at 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.	Baseline and Week 20
The Mean Change From Baseline to the End of Study in AQLQ Domain Score	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.	Baseline and Week 20
Number of Asthma Exacerbation Episodes Per Participant	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.	From Baseline through 20 weeks
Percentage of Participants Using Rescue Medication	When necessary, patients were allowed to take rescue medication using inhaled salbutamol or terbutaline for symptoms of intercurrent bronchospasm.	From Baseline through 20 Weeks
Free Days With no Rescue Medication	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.	From Baseline through 20 weeks (140 days)
Mean Number of Puffs of Rescue Medication Taken Per Day	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.	From Baseline through 20 Weeks
Physician's Global Assessment of Treatment Effectiveness	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	20 Weeks
Patient's Global Assessment of Treatment Effectiveness	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	20 Weeks

Collaborators and Investigators

• Sponsor: Novartis

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (ACTUAL): April 1, 2010
• Study Completion (ACTUAL): April 1, 2010

Study Registration Dates

• First Submitted: December 4, 2007
• First Submitted That Met QC Criteria: December 4, 2007
• First Posted (ESTIMATE): December 5, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): June 30, 2011
• Last Update Submitted That Met QC Criteria: June 28, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: Asthma, anti-immunoglobulin E, omalizumab
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Sympathomimetics; Adrenergic Agonists; Omalizumab; Adrenergic Agents; Terbutaline
• Other Study ID Numbers: CIGE025ABR01