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

NCT ID: NCT00314574

Last Updated: 2012-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 850 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2009-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

omalizumab (Xolair)

Intervention Type: 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.

corticosteroids

Intervention Type: DRUG

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

long-acting beta-agonists

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: 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.

corticosteroids

Intervention Type: DRUG

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

long-acting beta-agonists

Intervention Type: DRUG

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

Interventions

omalizumab (Xolair)

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.

Intervention Type: DRUG

placebo

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.

Intervention Type: DRUG

corticosteroids

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

Intervention Type: DRUG

long-acting beta-agonists

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

Intervention Type: DRUG

Other Intervention Names

Xolair

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karin Rosen, M.D., Ph.D.

Role: STUDY_DIRECTOR

Genentech, Inc.

References

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.

Reference Type: DERIVED

PMID: 34303017 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33465457 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33223095 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33217063 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31760132 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23471469 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21536936 (View on PubMed)

Other Identifiers

Q3662g

Identifier Type: -

Identifier Source: org_study_id