Clinical trial NCT00314574: A Study of Omalizumab (Xolair) in Subjects With Moderate to Severe Persistent Asthma (EXTRA)
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Persistent Asthma
EXTRA
Xolair
Difficult Breathing
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2006-04-14
Enrollment: 850
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, double-blind, placebo-controlled study of the efficacy, safety, and tolerability of subcutaneously administered Xolair as add-on therapy for the treatment of subjects aged 12-75 years old diagnosed with moderate to severe asthma who are inadequately controlled with high-dose inhaled corticosteroids (ICS)+ long-acting beta-agonists (LABA) with or without additional controller therapy.


Eligibility criteria: 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

Primary outcomes:
measure: Rate of Asthma Exacerbations Over the 48 Week Treatment Period
timeFrame: 48 weeks
Secondary outcomes:
measure: Change From Baseline in Total Asthma Symptom Scores
timeFrame: Baseline and Week 48
measure: Change From Baseline in the Number of Puffs Per Day of Beta Agonist Rescue Medication
timeFrame: Baseline and Week 48
measure: Change From Baseline in Overall Asthma-related Quality of Life
timeFrame: Baseline and Week 48
measure: Number of Participants Assessed for Frequency and Severity of Treatment-emergent Adverse Events
timeFrame: Week 48
Other outcomes:
Locations:
Study officials:
affiliation: Genentech, Inc.
name: Karin Rosen, M.D., Ph.D.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.