Therapeutic Utility of Xolair in Patients Undergoing Aspirin Desensitization

A Placebo Controlled, Double-Blind Investigation of the Therapeutic Utility of Xolair (Omalizumab) for Attenuating Aspirin Induced Bronchospasm in Patients With Aspirin Exacerbated Respiratory Disease (AERD) Undergoing Aspirin Desentization

This is a 24 week double-blind study in which subjects will be randomized 2:1 to receive Xolair (Omalizumab) or placebo. 14 subjects will receive Xolair and 7 will receive placebo. Xolair injections will occur every 2-4 weeks. Aspirin desensitization will occur several weeks later. One month after desensitization, the final visit will occur in the GCRC.

We hypothesize that administration of Xolair, a monoclonal anti-IgE antibody, prior to the aspirin desensitization will reduce severity of aspirin-induced reaction.

Study Overview

• Status: Completed
• Conditions: Aspirin Sensitivity
• Intervention / Treatment: Drug: placebo; Drug: Omalizumab

Detailed Description

This is a 24 week double-blind study consisting of up to 11 office visits for people 18 years of age with aspirin exacerbated respiratory disease (AERD). 21 subjects will participate and will be randomized 2:1 to receive Xolair (Omalizumab) or placebo. 14 subjects will receive Xolair and 7 will receive placebo. Xolair is a FDA approved medication for the treatment of moderate to severe allergic asthma. Injections will occur every 2-4 weeks, for 16 weeks. The dosage will be based upon IgE and body weight. Aspirin desensitization will occur 1-3 weeks later. One month after desensitization, the final visit will occur in the GCRC.

Properly selected patients with aspirin exacerbated respiratory disease (AERD) experience benefit in the course of their disease with aspirin desensitization treatment; however, AERD patients are at risk for potentially serious asthmatic reaction when undergoing aspirin desensitization. For this reason, this procedure is currently performed in a monitored setting. We hypothesize that administration of Xolair, a monoclonal anti-IgE antibody, prior to the aspirin desensitization will reduce severity of aspirin-induced respiratory reaction, and that ultimately, use of Xolair will permit this procedure to be performed safely in outpatient settings. This protocol also entails obtaining blood and urine samples to assess the influence of Xolair, compared with placebo. As aspirin induced reaction occurs via heightened release of leukotrienes combined with greater end organ responsiveness to these mediators, we also will be quantifying the impact of prior administration of Xolair, compared with placebo, on the elevation of urinary LTE4 in association with aspirin challenge and with aspirin provoked reaction.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 years.
• Fulfill diagnostic criteria for AERD (described below), and be a candidate for aspirin desensitization chronic asthma - frequently moderate-severe or severe patients will have history compatible with variable airflow obstruction. chronic rhinosinusitis - usually requiring previous sinus surgery procedure(s). sinusitis will have been confirmed by imaging studies presently and/or in the past.

history of adverse reaction to aspirin and/or aspirin-like drugs (e.g., ibuprofen, naproxen, etc.) compatible with AERD.

• Candidate for Xolair [Omalizumab] Moderate-severe persistent asthma IgE = 30-700 IU/ml IgE mediated (allergic) potential to inhalant allergen(s) by cutaneous or in vitro testing.

Exclusion Criteria:

• Women of childbearing potential not using appropriate contraception method(s)
• Women currently breastfeeding
• Women who desire to become pregnant during the time of participation in this study
• Men who desire to get someone pregnant during participation in this study
• Known sensitivity to Xolair [Omalizumab].
• IgE level < 30 IU/ml, or > 700 IU/ml.
• No evidence of atopy by immediate hypersensitivity skin testing
• Use of any other investigational agent in the last 30 days
• Age < 18 years.
• Current tobacco habituation.
• Presence of emphysema
• Ethanolism or drug abuse within last 12 months.
• Presence of significant medical condition including malignancy, neurologic, kidney, gastrointestinal, liver or cardiovascular disease
• extensive travel commitments during the study that would interfere with study measurements or clinic visits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Group; Subjects randomized to placebo	Drug: placebo; Subjects randomized to Placebo prior to aspirin desensitization
Active Comparator: Omalizumab Group; Subjects randomized to omalizumab	Drug: Omalizumab; Subjects randomized to Omalizumab prior to aspirin desensitization; Other Names: Xolair

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Without Respiratory Reaction During Aspirin Desensitization	Lack of Respiratory reaction during aspirin desensitization, including Spirometry (FEV1) testing, to assess the efficacy of Xolair on attenuating aspirin induced bronchospasm in patients with AERD.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurements of Urinary LTE4 in Association With Respiratory Reaction During Aspirin Desensitization	Measurements of urinary LTE4 in association with aspirin desensitization, comparing subjects randomized to placebo with subjects randomized to omalizumab, with study drug administered for 16 weeks. Measurements were compared for respiratory reaction in placebo subjects who exhibited either upper or lower airway reaction and after 100 mg aspirin challenge dose in omalizumab subjects who were non-reactors. For this analysis, the two omalizumab subjects who had respiratory reaction were not included.	Approximately 24 weeks

Collaborators and Investigators

• Sponsor: David Lang
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: David M. Lang, M.D., The Cleveland Clinic, Department of Allergy and Immunology

Publications and helpful links

General Publications

• Lang DM, Aronica MA, Maierson ES, Wang XF, Vasas DC, Hazen SL. Omalizumab can inhibit respiratory reaction during aspirin desensitization. Ann Allergy Asthma Immunol. 2018 Jul;121(1):98-104. doi: 10.1016/j.anai.2018.05.007. Epub 2018 May 16.

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: November 7, 2007
• First Submitted That Met QC Criteria: November 8, 2007
• First Posted (Estimate): November 9, 2007

Study Record Updates

• Last Update Posted (Actual): November 3, 2020
• Last Update Submitted That Met QC Criteria: October 12, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Omalizumab
• Other Study ID Numbers: IRB 05-066; Q3637s (Other Grant/Funding Number: Genentech)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No