Treatment of Idiopathic Angioedema With Xolair as Add-on Therapy

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Completed
• CT.gov ID: NCT02966314
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 12
• Location: 1
• Arms: 2
• Actual Duration (Months): 33.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The overall hospitalizations for a diagnosis of angioedema doubled from the year 2000 to 2009. Although some of the cases represented hereditary angioedema or ace-inhibitor induced angioedema, the majority of episodes were idiopathic. Idiopathic Angioedema (IAE) can be life- threatening especially when affecting tissues within the respiratory tract. No clear guidelines exist for management of this important condition for clinicians. Current therapies typically include avoidance of potential triggers and use of medications either for prophylaxis or for acute events, such as antihistamines, corticosteroids, and epinephrine. There remains a critical need for therapeutic options to provide more effective prophylaxis.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Angioedema	Drug: Omalizumab; Drug: Placebos	Phase 4

Detailed Description

This study is a randomized, double-blind, placebo-controlled, parallel group trial which will study the effects of omalizumab on patients with 2 or more episodes of Idiopathic Angioedema (IAE) in the past 6 months, despite current therapy. This study has three periods; screening, treatment, and follow-up. Subjects in the screening period will be consented and screened for eligibility criteria. 40 qualified individuals will enter the treatment period. Individuals will be randomized to either monthly subcutaneous administration of omalizumab 300mg (20 subjects) versus monthly placebo injection (20 subjects) in addition to their previously prescribed management plan for a total of 6 months. Individuals will then enter a follow-up period of 4 months. Study visits will occur monthly during the treatment period for update of clinical status and administration of omalizumab/placebo injection. After, the treatment period individuals will be seen twice for follow-up period. The entire study will consist of 10 study visits and will last approx. 10 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: A Phase IV, Randomized, Double-Blind, Placebo-Controlled Exploratory Study of Xolair (Omalizumab) for Treatment of Idiopathic Angioedema in Patients Who Remain Symptomatic Despite Current Therapy
• Actual Study Start Date: Mar 30, 2017
• Actual Primary Completion Date: Jan 6, 2020
• Actual Study Completion Date: Jan 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection.	Drug: Placebos; Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.
Active Comparator: Omalizumab Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP.	Drug: Omalizumab; Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.; Other Names: Xolair

Outcome Measures

Primary Outcome Measures

1. Mean 7-day Angioedema Activity Score (AAS7) [baseline to end of treatment period at 6 months]

   The AAS7 Score is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity.

2. Presence of a 7-day Angioedema Activity Score (AAS7) Greater Than 0 Across All Treatment Visits [across all visits during treatment period (up to 6 months)]

   The AAS7 Score is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity.

Secondary Outcome Measures

1. Mean Angioedema Quality of Life (AE-QoL) Questionnaire [baseline to end of treatment period at 6 months]

   The AE-QoL Questionnaire is a 17-item survey, the total possible range of scores is transformed to a scale of 1-100 where higher score indicate increased impairment.

2. Mean Angioedema Quality of Life (AE-QoL) Questionnaire Across All Treatment Visits [across all visits during treatment period (up to 6 months)]

   The AE-QoL Questionnaire is a 17-item survey, the total possible range of scores is transformed to a scale of 1-100 where higher score indicate increased impairment.

3. Mean Visual Analog Scale [baseline to end of treatment period at 6 months]

   The effect of treatment compared to placebo on the change in IAE severity from baseline to the end of the treatment period as recorded on a 0-100 visual analog scale. Lower numbers indicate increased severity.

4. Presence of Visual Analog Scale Less Than 100 Across All Treatment Visits [across all visits during treatment period (up to 6 months)]

   The effect of treatment compared to placebo on the change in IAE severity from baseline to the end of the treatment period as recorded on a 0-100 visual analog scale. Lower numbers indicate increased severity.

5. Mean Number of IAE Events [baseline to end of treatment period at 6 months]

   baseline measure is the mean number of IAE events 6 months prior to study

6. Number of IAE Events Across All Treatment Visits [across all visits during treatment period (up to 6 months)]

7. Change in Duration of IAE Episodes [baseline to end of treatment period at 6 months]

   Duration of IAE Episodes is participant reported for the 6 months prior to study (baseline) and again at the 6 month time point for the time on study.

8. Number of Participants Who Visited Urgent Care or Emergency Room [baseline, end of treatment period at 6 months, follow up at 9 months]

   Count of participants who visited urgent care or the emergency room is participant reported. The baseline measure is for the 6 months prior to study, at the 6 month time point for the time on study, and the 9 month time point for the previous 3 months on study.

9. Number of Participants Who Used Rescue Medication or Corticosteroids [baseline, end of treatment period at 6 months, follow up at 9 months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Adults or adolescents who are 18 years or older at the time of screening with physician diagnosis of idiopathic angioedema

• Minimum of two episodes of idiopathic angioedema in the past 6 months at the time of screening

• Management of idiopathic angioedema with a stable controller treatment plan for the prior 6 months

• Complement profile (C1 Esterase inhibitor panel) within normal reference values

• If a woman is of child-bearing potential, she must agree to a reliable form of birth control including: abstinence, oral contraceptives (birth control pills), Depo-provera, an intrauterine device (IUD), or double-barrier contraception (partner using condom and participant using diaphragm, contraceptive sponge or cervical cap, and spermicidal)

Exclusion Criteria:

• Diagnosis of Hereditary Angioedema (HAE), Acquired Angioedema, or Ace-inhibitor associated angioedema, which are forms of angioedema with known mechanisms and alternate treatment options

• Chronic Urticaria (itching and/or hives) with or without Angioedema which are known mast cell mediated processes previously shown to be responsive to the use of omalizumab

• Previous usage of omalizumab in the last 3 months which can affect the patient-related outcomes and biomarker assessments if not "washed out" of the system

• Patients, who in the judgment of the investigator, have a history or condition that might compromise patient safety or compliance, interfere with evaluations, or preclude completion of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UW Madison	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• University of Wisconsin, Madison
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Sameer Mathur, MD/PhD, UW Madison
• Principal Investigator: Ravi Viswanathan, MD, UW Madison

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 22, 2018

More Information

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT02966314
• Other Study ID Numbers: 2016-0645; SMPH/MEDICINE/MEDICINE*A; A534220; Protocol Version 5/22/2018
• First Posted: Nov 17, 2016
• Last Update Posted: Nov 22, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Wisconsin, Madison: Angioedema; Idiopathic Angioedema; IAE
• Additional relevant MeSH terms: Angioedema; Omalizumab

Study Results

Participant Flow

Recruitment Details	Participants were screened and enrolled at the University of Wisconsin-Madison Allergy and Asthma Clinical Research Unit from March 2017 to April 2019.
Pre-assignment Detail	Two participants were screened and enrolled but not randomized to an arm to start the study.

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. Placebos: Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.	Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP. Omalizumab: Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.
Period Title: Overall Study
STARTED	5	5
COMPLETED	4	5
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Placebo	Omalizumab	Total
Arm/Group Description	Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. Placebos: Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.	Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP. Omalizumab: Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.	Total of all reporting groups
Overall Participants	5	5	10
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 60%	4 80%	7 70%
>=65 years	2 40%	1 20%	3 30%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	53	53.8	53.4
Sex: Female, Male (Count of Participants)
Female	2 40%	2 40%	4 40%
Male	3 60%	3 60%	6 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	5 100%	5 100%	10 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
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%	0 0%	0 0%
White	5 100%	5 100%	10 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%	5 100%	10 100%
Height (centimeters) [Mean (Full Range) ]
Mean (Full Range) [centimeters]	171.18	180.86	176.02
Weight (kg) [Mean (Full Range) ]
Mean (Full Range) [kg]	93.4	91.2	92.3
Number of IAE Episodes in past 6 months (IAE Episodes) [Mean (Full Range) ]
Mean (Full Range) [IAE Episodes]	15.2	10.6	12.9
Duration of IAE Episodes (hours) [Mean (Full Range) ]
Mean (Full Range) [hours]	14.3	21.1	17.7
Number of Urgent Care / Emergency Department Visits in past 6 months (visits) [Mean (Full Range) ]
Mean (Full Range) [visits]	0.6	0.2	0.4

Outcome Measures

1. Primary Outcome

Title	Mean 7-day Angioedema Activity Score (AAS7)
Description	The AAS7 Score is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity.
Time Frame	baseline to end of treatment period at 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. Placebos: Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.	Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP. Omalizumab: Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.
Measure Participants	5	5
baseline	2.8	1.6
6 months	0.69	0.20

2. Primary Outcome

Title	Presence of a 7-day Angioedema Activity Score (AAS7) Greater Than 0 Across All Treatment Visits
Description	The AAS7 Score is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity.
Time Frame	across all visits during treatment period (up to 6 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. Placebos: Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.	Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP. Omalizumab: Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.
Measure Participants	5	5
Measure participant visits	103	120
Count of Units [participant visits]	38	4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Regression, Logistic
	Comments	Accounting for repeated measures
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	18.7
	Confidence Interval	(2-Sided) 95%; 2.77 to 126.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Mean Angioedema Quality of Life (AE-QoL) Questionnaire
Description	The AE-QoL Questionnaire is a 17-item survey, the total possible range of scores is transformed to a scale of 1-100 where higher score indicate increased impairment.
Time Frame	baseline to end of treatment period at 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. Placebos: Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.	Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP. Omalizumab: Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.
Measure Participants	5	5
baseline	28.25	21.47
6 months	19.12	8.53

4. Secondary Outcome

Title	Mean Angioedema Quality of Life (AE-QoL) Questionnaire Across All Treatment Visits
Description	The AE-QoL Questionnaire is a 17-item survey, the total possible range of scores is transformed to a scale of 1-100 where higher score indicate increased impairment.
Time Frame	across all visits during treatment period (up to 6 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. Placebos: Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.	Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP. Omalizumab: Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.
Measure Participants	5	5
Measure participant visits	28	30
Mean (Standard Deviation) [score on a scale]	19.0 (12.9)	8.5 (10.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	9.43
	Confidence Interval	(2-Sided) 95%; 1.24 to 17.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Mean Visual Analog Scale
Description	The effect of treatment compared to placebo on the change in IAE severity from baseline to the end of the treatment period as recorded on a 0-100 visual analog scale. Lower numbers indicate increased severity.
Time Frame	baseline to end of treatment period at 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. Placebos: Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.	Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP. Omalizumab: Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.
Measure Participants	5	5
baseline	91	84
6 months	88.75	97

6. Secondary Outcome

Title	Presence of Visual Analog Scale Less Than 100 Across All Treatment Visits
Description	The effect of treatment compared to placebo on the change in IAE severity from baseline to the end of the treatment period as recorded on a 0-100 visual analog scale. Lower numbers indicate increased severity.
Time Frame	across all visits during treatment period (up to 6 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. Placebos: Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.	Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP. Omalizumab: Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.
Measure Participants	5	5
Measure participant visits	28	30
Count of Units [participant visits]	17	4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Regression, Logistic
	Comments	Accounting for repeated measures
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	32.8
	Confidence Interval	(2-Sided) 95%; 1.49 to 720.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Mean Number of IAE Events
Description	baseline measure is the mean number of IAE events 6 months prior to study
Time Frame	baseline to end of treatment period at 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. Placebos: Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.	Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP. Omalizumab: Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.
Measure Participants	5	5
baseline	1	0.4
6 months	0.5	0.2

8. Secondary Outcome

Title	Number of IAE Events Across All Treatment Visits
Time Frame	across all visits during treatment period (up to 6 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. Placebos: Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.	Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP. Omalizumab: Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.
Measure Participants	5	5
Measure participant visits	28	30
Mean (Standard Deviation) [count of events]	1.8 (2.3)	0.2 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Regression, Linear
	Comments	Accounting for multiple measures, using poisson distribution with natural log link
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	6.9
	Confidence Interval	(2-Sided) 95%; 1.9 to 25.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change in Duration of IAE Episodes
Description	Duration of IAE Episodes is participant reported for the 6 months prior to study (baseline) and again at the 6 month time point for the time on study.
Time Frame	baseline to end of treatment period at 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. Placebos: Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.	Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP. Omalizumab: Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.
Measure Participants	5	5
baseline	14.3	21.1
6 months	3.25	0.5

10. Secondary Outcome

Title	Number of Participants Who Visited Urgent Care or Emergency Room
Description	Count of participants who visited urgent care or the emergency room is participant reported. The baseline measure is for the 6 months prior to study, at the 6 month time point for the time on study, and the 9 month time point for the previous 3 months on study.
Time Frame	baseline, end of treatment period at 6 months, follow up at 9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. Placebos: Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.	Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP. Omalizumab: Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.
Measure Participants	5	5
baseline	1 20%	1 20%
6 months	0 0%	0 0%
9 months	0 0%	0 0%

11. Secondary Outcome

Title	Number of Participants Who Used Rescue Medication or Corticosteroids
Time Frame	baseline, end of treatment period at 6 months, follow up at 9 months

Outcome Measure Data

Analysis Population Description

data was not collected

Arm/Group Title	Placebo	Omalizumab
Arm/Group Description	Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. Placebos: Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.	Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP. Omalizumab: Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.
Measure Participants	0	0

Adverse Events

Time Frame	up to 9 months
Arm/Group Title	Placebo		Omalizumab
Arm/Group Description	Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. Placebos: Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.		Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP. Omalizumab: Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.
All Cause Mortality
	Placebo		Omalizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Serious Adverse Events
	Placebo		Omalizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Omalizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		1/5 (20%)
Injury, poisoning and procedural complications
Delayed Injection Site Reaction	0/5 (0%)	0	1/5 (20%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.