- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00314574
A Study of Omalizumab (Xolair) in Subjects With Moderate to Severe Persistent Asthma (EXTRA)
A Phase IIIb Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Xolair in Subjects With Moderate to Severe Persistent Asthma Who Are Inadequately Controlled With High-Dose Inhaled Corticosteroids and Long-Acting Beta-Agonists
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Signed Informed Consent Form and an informed assent, if applicable
- Be between the ages of 12 to 75 years
- Have had a history of moderate to severe asthma for at least one year prior to screening
- Have had treatment with a stable regimen of of salmeterol 50 µg twice a day (BID) or formoterol 12 µg BID for at least 8 weeks prior to screening
- Have had treatment with a stable regimen of high-dose inhaled corticosteroids (ICS) for at least 8 weeks prior to screening
- Have inadequately controlled asthma
- Have had at least one asthma exacerbation requiring systemic corticosteroid rescue in the 12 months prior to the screening visit while receiving treatment with high-dose ICS
- Have less than 10 pack-years smoking history
- Have a positive skin test for or a positive, in vitro response to one relevant perennial aeroallergen documented within the 12 months prior to screening
- If a subject has not had a positive skin test or in vitro reactivity in the 12 months prior to screening, the subject must demonstrate a positive response to at least one relevant perennial aeroallergen in a skin or in vitro test prior to randomization
- Female subjects of childbearing potential must use an effective method of contraception from screening through their duration of participation in the study
- For the collection of additional blood samples for future research (optional), provide signed consent and an informed assent, if applicable.
Exclusion Criteria:
- Have had an asthma exacerbation requiring intubation within 12 months prior to screening
- Have active lung disease other than asthma
- Have had an asthma exacerbation requiring treatment with the addition of systemic (oral or intravenous) corticosteroids or an increase in systemic corticosteroids within 30 days prior to screening
- Require chronic immunosuppressive therapy including cyclosporine, methotrexate, etc.
- Have significant medical illness other than asthma
- Have taken methotrexate, gold salts, cyclosporine, or macrolide antibiotics, within 3 months prior to screening
- Have taken other investigational drugs within 30 days prior to screening
- Have been treated with Xolair within the 12 months prior to screening
- Have a history of drug or alcohol abuse that, in the judgment of the investigator, may put the subject at risk for being unable to participate fully in the study for the duration of the study
- Have elevated serum IgE levels for reasons other than allergy
- Are pregnant or lactating
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Xolair
The subcutaneous dose of Xolair administered in this study was either a minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study. |
Omalizumab (Xolair) was administered by subcutaneous (SC) injection every 2 or 4 weeks.
Xolair was supplied as a sterile, white, preservative-free, lyophilized powder in single-use vials that were reconstituted with Sterile Water for Injection (SWFI), USP.
Other Names:
Minimum dose of 500 µg of fluticasone dry-powder inhaler or its equivalent ex-valve dose twice a day.
50 µg salmeterol twice daily or 12 µg formoterol twice daily.
|
Placebo Comparator: placebo
The subcutaneous dose of placebo administered in this study was either a minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study. |
Minimum dose of 500 µg of fluticasone dry-powder inhaler or its equivalent ex-valve dose twice a day.
50 µg salmeterol twice daily or 12 µg formoterol twice daily.
Placebo was administered by subcutaneous (SC) injection every 2 or 4 weeks.
Placebo contained the same ingredients as the lyophilized formulation of Xolair,excluding omalizumab.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of Asthma Exacerbations Over the 48 Week Treatment Period
Time Frame: 48 weeks
|
A protocol-defined asthma exacerbation was defined as worsening of asthma symptoms requiring treatment with systemic corticosteroids for 3 or more days; for patients receiving long-term oral corticosteroids, an exacerbation was a 20 mg or more increase in average daily dose of oral prednisone (or a similar dose of another systemic corticosteroid).
The rate of protocol-defined asthma exacerbations, normalized by subject-time at risk and computed over the 48 week treatment period in each treatment group.
|
48 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Total Asthma Symptom Scores
Time Frame: Baseline and Week 48
|
Change from baseline to week 48 in Total Asthma Symptom Score (TASS), which included a nocturnal asthma score (0 to 4 scale), morning asthma symptoms (yes or no), and a daytime asthma symptom score (0 to 4 scale, total score range 0 to 9, higher TASS scores represent worse symptoms; breathlessness, tightness in chest, wheezing and cough.
Score achieved by week 48 minus baseline.
|
Baseline and Week 48
|
Change From Baseline in the Number of Puffs Per Day of Beta Agonist Rescue Medication
Time Frame: Baseline and Week 48
|
Change from baseline to week 48 in mean puffs per day of albuterol.
Puffs per day was achieved by week 48 minus baseline.
|
Baseline and Week 48
|
Change From Baseline in Overall Asthma-related Quality of Life
Time Frame: Baseline and Week 48
|
Change from baseline to week 48 in overall asthma-specific health-related quality of life, as measured by the standardized version of the Asthma Quality of Life Questionnaire (AQLQ[S]) score.
The AQLQ(S) consists of 4 domains (activity limitations, symptoms, emotional function, and environmental stimuli), with a total of 32 items; the overall score is the mean of these 32 items on a scale of 1 to 7 (1 = severe impairment, 7 = no impairment).
Overall outcome achieved by mean visit minus baseline.
|
Baseline and Week 48
|
Number of Participants Assessed for Frequency and Severity of Treatment-emergent Adverse Events
Time Frame: Week 48
|
This outcome is represented in the adverse event section of the database.
|
Week 48
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Karin Rosen, M.D., Ph.D., Genentech, Inc.
Publications and helpful links
General Publications
- Szefler SJ, Jerschow E, Yoo B, Janampally P, Pazwash H, Holweg CTJ, Hudes G. Response to Omalizumab in Black and White Patients with Allergic Asthma. J Allergy Clin Immunol Pract. 2021 Nov;9(11):4021-4028. doi: 10.1016/j.jaip.2021.07.013. Epub 2021 Jul 22.
- Chen M, Choo E, Yoo B, Raut P, Haselkorn T, Pazwash H, Holweg CTJ, Hudes G. No difference in omalizumab efficacy in patients with asthma by number of asthma-related and allergic comorbidities. Ann Allergy Asthma Immunol. 2021 Jun;126(6):666-673. doi: 10.1016/j.anai.2021.01.015. Epub 2021 Jan 17.
- Busse WW, Szefler SJ, Haselkorn T, Iqbal A, Ortiz B, Lanier BQ, Chipps BE. Possible Protective Effect of Omalizumab on Lung Function Decline in Patients Experiencing Asthma Exacerbations. J Allergy Clin Immunol Pract. 2021 Mar;9(3):1201-1211. doi: 10.1016/j.jaip.2020.10.027. Epub 2020 Oct 24.
- Chen M, Shepard K 2nd, Yang M, Raut P, Pazwash H, Holweg CTJ, Choo E. Overlap of allergic, eosinophilic and type 2 inflammatory subtypes in moderate-to-severe asthma. Clin Exp Allergy. 2021 Apr;51(4):546-555. doi: 10.1111/cea.13790. Epub 2021 Jan 7.
- Busse WW, Humbert M, Haselkorn T, Ortiz B, Trzaskoma BL, Stephenson P, Garcia Conde L, Kianifard F, Holgate ST. Effect of omalizumab on lung function and eosinophil levels in adolescents with moderate-to-severe allergic asthma. Ann Allergy Asthma Immunol. 2020 Feb;124(2):190-196. doi: 10.1016/j.anai.2019.11.016. Epub 2019 Nov 22.
- Hanania NA, Wenzel S, Rosen K, Hsieh HJ, Mosesova S, Choy DF, Lal P, Arron JR, Harris JM, Busse W. Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study. Am J Respir Crit Care Med. 2013 Apr 15;187(8):804-11. doi: 10.1164/rccm.201208-1414OC.
- Hanania NA, Alpan O, Hamilos DL, Condemi JJ, Reyes-Rivera I, Zhu J, Rosen KE, Eisner MD, Wong DA, Busse W. Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann Intern Med. 2011 May 3;154(9):573-82. doi: 10.7326/0003-4819-154-9-201105030-00002. Erratum In: Ann Intern Med. 2019 Oct 1;171(7):528.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Q3662g
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Asthma
-
Vanderbilt University Medical CenterNot yet recruitingAsthma in Children | Asthma Attack | Asthma Acute | Acute Asthma Exacerbation | Asthma; StatusUnited States
-
University of California, San FranciscoCompletedAsthma in Children | Asthma Attack | Asthma Acute | Asthma ChronicUnited States
-
SingHealth PolyclinicsNot yet recruitingAsthma | Asthma in Children | Asthma Attack | Asthma Acute | Asthma Chronic
-
Johann Wolfgang Goethe University HospitalCompleted
-
Universita di VeronaCompleted
-
Parc de Salut MarActive, not recruitingAsthma in Children | Persistent Asthma | Asthma ExacerbationSpain
-
Forest LaboratoriesCompleted
-
Brunel UniversityKarolinska InstitutetUnknown
-
Value Outcomes Ltd.AstraZenecaCompletedAsthma, Bronchial | Bronchial Asthma | Asthma Chronic | Asthma; EosinophilicCzechia
Clinical Trials on omalizumab (Xolair)
-
Beth Israel Deaconess Medical CenterNovartisWithdrawnAutism Spectrum Disorder | AtopyUnited States
-
National Jewish HealthNovartisWithdrawnPulmonary Disease, Chronic ObstructiveUnited States
-
Massachusetts General HospitalGenentech, Inc.CompletedNasal Polyps | Chronic RhinosinusitisUnited States
-
University of Mississippi Medical CenterNovartisCompleted
-
Boston Children's HospitalStanford UniversityCompleted
-
IRCCS Policlinico S. MatteoCompletedInterstitial Cystitis | Painful Bladder SyndromeItaly
-
University Hospital Inselspital, BerneNovartis; University of Bern; Adverse Drug Reactions, Advice and Consulting ADR-ACCompletedChronic Idiopathic Urticaria | Chronic Urticaria | Chronic Spontaneous UrticariaSwitzerland
-
Johns Hopkins UniversityNational Institute of Allergy and Infectious Diseases (NIAID)Completed
-
Genentech, Inc.Completed
-
University of North Carolina, Chapel HillGenentech, Inc.; National Institutes of Health (NIH)TerminatedAsthma | AllergyUnited States