A Study of Omalizumab (Xolair) in Subjects With Moderate to Severe Persistent Asthma (EXTRA)

NCT00314574 | Completed Phase 3 Results

• 1 other identifier: Q3662g
• Study Type: interventional
• Target: 850
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Asthma

Keywords

Persistent Asthma; EXTRA; Xolair; Difficult Breathing

Outcome Measures

Primary Outcomes (1)

• Rate of Asthma Exacerbations Over the 48 Week Treatment Period

  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 Outcomes (4)

• Change From Baseline in Total Asthma Symptom Scores

  Baseline and Week 48

• Change From Baseline in the Number of Puffs Per Day of Beta Agonist Rescue Medication

  Baseline and Week 48

• Change From Baseline in Overall Asthma-related Quality of Life

  Baseline and Week 48

• Number of Participants Assessed for Frequency and Severity of Treatment-emergent Adverse Events

  Week 48

Study Arms (2)

Xolair

EXPERIMENTAL

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.

Drug: omalizumab (Xolair); Drug: corticosteroids; Drug: long-acting beta-agonists

placebo

PLACEBO COMPARATOR

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.

Drug: placebo; Drug: corticosteroids; Drug: long-acting beta-agonists

Interventions

omalizumab (Xolair) DRUG

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.

Also known as: Xolair

Xolair

placebo DRUG

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.

placebo

corticosteroids DRUG

Minimum dose of 500 µg of fluticasone dry-powder inhaler or its equivalent ex-valve dose twice a day.

Xolair; placebo

long-acting beta-agonists DRUG

50 µg salmeterol twice daily or 12 µg formoterol twice daily.

Xolair; placebo

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Related Publications (7)

• 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.

  PMID: 34303017 DERIVED

• 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.

  PMID: 33465457 DERIVED

• 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.

  PMID: 33223095 DERIVED

• 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.

  PMID: 33217063 DERIVED

• 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.

  PMID: 31760132 DERIVED

• 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.

  PMID: 23471469 DERIVED

• 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.

  PMID: 21536936 DERIVED

MeSH Terms

Conditions

Asthma; Dyspnea

Interventions

Omalizumab; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffman-LaRoche

800-821-8590

Study Officials

• Karin Rosen, M.D., Ph.D.

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2006
• First Posted: April 14, 2006
• Study Start: December 1, 2005
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: February 9, 2012
• Results First Posted: October 13, 2011

Record last verified: 2012-02