Therapeutic Utility of Xolair in Patients Undergoing Aspirin Desensitization

• Sponsor: David Lang (Other)
• Overall Status: Completed
• CT.gov ID: NCT00555971
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 16
• Location: 1
• Arms: 2
• Duration (Months): 117.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Aspirin Sensitivity	Drug: Omalizumab; Drug: placebo	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: Feb 1, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants Without Respiratory Reaction During Aspirin Desensitization [24 weeks]

   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.

Secondary Outcome Measures

1. Measurements of Urinary LTE4 in Association With Respiratory Reaction During Aspirin Desensitization [Approximately 24 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Cleveland Clinic	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• David Lang
• Genentech, Inc.

Investigators

• Principal Investigator: David M. Lang, M.D., The Cleveland Clinic, Department of Allergy and Immunology

Study Documents (Full-Text)

• Study Protocol - Jan 16, 2013

More Information

Publications

None provided.

• Responsible Party: David Lang, Chairman, Allergy and Immunology, The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT00555971
• Other Study ID Numbers: IRB 05-066; Q3637s
• First Posted: Nov 9, 2007
• Last Update Posted: Nov 3, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Hypersensitivity; Omalizumab

Study Results

Participant Flow

Recruitment Details	Patients seen for evaluation and management for suspected AERD
Pre-assignment Detail	16 subjects signed consent but only 13 were randomized 2 were screen fails and 1 lost to follow up

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Subjects with aspirin exacerbated respiratory disease enrolled and randomized to either omalizumab or placebo (2:1) in a blinded fashion, administered for 16 weeks. The study is double-blind. placebo: aspirin desensitization will be carried out for all subjects with aspirin exacerbated respiratory disease who participate in the study, with subjects randomized 2:1 to receive either omalizumab or placebo, which will allow us to evaluate the study hypothesis	Subjects with aspirin exacerbated respiratory disease enrolled and randomized to either omalizumab or placebo (2:1) in a blinded fashion, administered for 16 weeks. The study is double-blind. Omalizumab: aspirin desensitization will be carried out for all subjects with aspirin exacerbated respiratory disease who participate in the study, with subjects randomized 2:1 to receive either omalizumab or placebo, which will allow us to evaluate the study hypothesis
Period Title: Overall Study
STARTED	5	8
COMPLETED	4	7
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Placebo	Omalizumab	Total
Arm/Group Description	Subjects with aspirin exacerbated respiratory disease enrolled and randomized to either omalizumab or placebo (2:1) in a blinded fashion, administered for 16 weeks. The study is double-blind. placebo: aspirin desensitization will be carried out for all subjects with aspirin exacerbated respiratory disease who participate in the study, with subjects randomized 2:1 to receive either omalizumab or placebo, which will allow us to evaluate the study hypothesis	Subjects with aspirin exacerbated respiratory disease enrolled and randomized to either omalizumab or placebo (2:1) in a blinded fashion, administered for 16 weeks. The study is double-blind. Omalizumab: aspirin desensitization will be carried out for all subjects with aspirin exacerbated respiratory disease who participate in the study, with subjects randomized 2:1 to receive either omalizumab or placebo, which will allow us to evaluate the study hypothesis	Total of all reporting groups
Overall Participants	4	7	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.8 (7.2)	45.7 (11.9)	44.3 (11.1)
Sex: Female, Male (Count of Participants)
Female	4 100%	4 57.1%	8 72.7%
Male	0 0%	3 42.9%	3 27.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 14.3%	1 9.1%
White	4 100%	6 85.7%	10 90.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
FEV1 Percent predicted (Percent predicted) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percent predicted]	90.0 (18.5)	92.6 (14.4)	91.6 (16.8)
IgE IU/ml (IU/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [IU/ml]	64.6 (36.6)	120.5 (76.7)	100.3 (73.9)

Outcome Measures

1. Primary Outcome

Title	Number of Participants Without Respiratory Reaction During Aspirin Desensitization
Description	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.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Subjects with aspirin exacerbated respiratory disease enrolled and randomized to either omalizumab or placebo (2:1) in a blinded fashion, administered for 16 weeks. The study is double-blind. placebo: aspirin desensitization will be carried out for all subjects with aspirin exacerbated respiratory disease who participate in the study, with subjects randomized 2:1 to receive either omalizumab or placebo, which will allow us to evaluate the study hypothesis	Subjects with aspirin exacerbated respiratory disease enrolled and randomized to either omalizumab or placebo (2:1) in a blinded fashion, administered for 16 weeks. The study is double-blind. Omalizumab: aspirin desensitization will be carried out for all subjects with aspirin exacerbated respiratory disease who participate in the study, with subjects randomized 2:1 to receive either omalizumab or placebo, which will allow us to evaluate the study hypothesis
Measure Participants	4	7
Count of Participants [Participants]	0 0%	5 71.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab
	Comments
	Type of Statistical Test	Equivalence
	Comments	This was a statistical analysis to address the null hypothesis that there was no difference between treatment and placebo groups.
Statistical Test of Hypothesis	p-Value	0.036
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Measurements of Urinary LTE4 in Association With Respiratory Reaction During Aspirin Desensitization
Description	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.
Time Frame	Approximately 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Subjects with aspirin exacerbated respiratory disease enrolled and randomized to either omalizumab or placebo (2:1) in a blinded fashion, administered for 16 weeks. The study is double-blind. placebo: aspirin desensitization will be carried out for all subjects with aspirin exacerbated respiratory disease who participate in the study, with subjects randomized 2:1 to receive either omalizumab or placebo, which will allow us to evaluate the study hypothesis	Subjects with aspirin exacerbated respiratory disease enrolled and randomized to either omalizumab or placebo (2:1) in a blinded fashion, administered for 16 weeks. The study is double-blind. Omalizumab: aspirin desensitization will be carried out for all subjects with aspirin exacerbated respiratory disease who participate in the study, with subjects randomized 2:1 to receive either omalizumab or placebo, which will allow us to evaluate the study hypothesis
Measure Participants	4	5
Mean (Standard Error) [pg/mg creatinine units]	17489 (7102)	1852 (280)

Adverse Events

Time Frame	Entire study until last randomized subject completed participation, approximately 24 weeks
Arm/Group Title	Placebo		Omalizumab
Arm/Group Description	Subjects with aspirin exacerbated respiratory disease enrolled and randomized to either omalizumab or placebo (2:1) in a blinded fashion, administered for 16 weeks. The study is double-blind. placebo: aspirin desensitization will be carried out for all subjects with aspirin exacerbated respiratory disease who participate in the study, with subjects randomized 2:1 to receive either omalizumab or placebo, which will allow us to evaluate the study hypothesis		Subjects with aspirin exacerbated respiratory disease enrolled and randomized to either omalizumab or placebo (2:1) in a blinded fashion, administered for 16 weeks. The study is double-blind. Omalizumab: aspirin desensitization will be carried out for all subjects with aspirin exacerbated respiratory disease who participate in the study, with subjects randomized 2:1 to receive either omalizumab or placebo, which will allow us to evaluate the study hypothesis
All Cause Mortality
	Placebo		Omalizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/7 (0%)
Serious Adverse Events
	Placebo		Omalizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Omalizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		0/7 (0%)
Gastrointestinal disorders
Aspirin intolerance	1/4 (25%)	1	0/7 (0%)	0

Limitations/Caveats

Findings cannot be generalized to patients with aspirin exacerbated respiratory disease receiving omalizumab for less than 16 weeks, or to those who do not fulfill label criteria for omalizumab.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.