A Study to Evaluate the Efficacy, Response Duration and Safety of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite Antihistamine Treatment (H1)

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01292473
• Collaborator: (none)
• Enrollment: 323
• Locations: 61
• Arms: 4
• Duration (Months): 15
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The study is a global Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of omalizumab administered subcutaneously as an add-on therapy for the treatment of adolescent and adult patients aged 12-75 who have been diagnosed with refractory CIU and who remain symptomatic despite standard-dosed H1 antihistamine treatment.

Condition or Disease	Intervention/Treatment	Phase
Chronic Idiopathic Urticaria	Drug: Placebo; Drug: Omalizumab	Phase 3

Detailed Description

The trial incorporated a Type I error control plan, as follows:

The testing of the primary endpoint was conducted in the following hierarchical order. A p-value that is less than 0.05 can only be claimed statistically significant if statistical significance has been claimed at the previous stage.

• Stage 1: Omalizumab 300-mg group vs. placebo

• Stage 2: Omalizumab 150-mg group vs. placebo

• Stage 3: Omalizumab 75-mg group vs. placebo

A hierarchical analysis of the secondary endpoints was performed for each dose found to be significant in the primary endpoint. A p-value that is less than 0.05 can only be claimed statistically significant if statistical significance has been claimed at the previous stage.

• Stage 1: Change from baseline in Urticaria Activity Score (UAS7) at Week 12

• Stage 2: Change from baseline in the weekly number of hives score at Week 12

• Stage 3: Time to weekly itch severity score Minimally Important Difference (MID) response at Week 12

• Stage 4: Proportion of patients with UAS7 ≤ 6 at Week 12

• Stage 5: Proportion of weekly itch severity score MID Responders at Week 12

• Stage 6: Change from baseline in weekly size of the largest hive score at Week 12

• Stage 7: Change from baseline in overall Dermatology Life Quality Index (DLQI) score at Week 12

• Stage 8: Proportion of angioedema-free days from Week 4 to Week 12

Study Design

• Study Type: Interventional
• Actual Enrollment: 323 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicenter, Randomized, Double-blind, Dose-ranging, Placebo-controlled Study to Evaluate the Efficacy, Response Duration and Safety of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria Who Remain Symptomatic Despite Antihistamine Treatment (H1)
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Placebo Placebo subcutaneously (sc) every 4 weeks	Drug: Placebo; Placebo was supplied lyophilized in vials.; Drug: Omalizumab; Omalizumab was supplied lyophilized in vials.; Other Names: Xolair
Experimental: Omalizumab 75 mg Omalizumab 75 mg sc every 4 weeks	Drug: Omalizumab; Omalizumab was supplied lyophilized in vials.; Other Names: Xolair
Experimental: Omalizumab 150 mg Omalizumab 150 mg sc every 4 weeks	Drug: Omalizumab; Omalizumab was supplied lyophilized in vials.; Other Names: Xolair
Experimental: Omalizumab 300 mg Omalizumab 300 mg sc every 4 weeks.	Drug: Omalizumab; Omalizumab was supplied lyophilized in vials.; Other Names: Xolair

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Weekly Itch Severity Score at Week 12 [Baseline, Week 12]

   The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score indicates improvement.

Secondary Outcome Measures

1. Change From Baseline in the Weekly Urticaria Activity Score (UAS7) at Week 12 [Baseline, Week 12]

   The urticaria activity score (UAS) is a composite of scores on a scale of 0 (none) to 3 (intense/severe) for 1) the number of wheals (hives); and 2) the intensity of the itch, measured twice daily (morning and evening). Daily UAS is the average of morning and evening scores (ranging from 0-6) and the UAS7 is the sum of the daily UAS over 7 days (ranging from 0-42). Baseline UAS7 is calculated using data from the 7 days prior to the first treatment date. A higher UAS indicates more urticaria activity. A negative change score indicates improvement.

2. Change From Baseline in the Weekly Number of Hives Score at Week 12 [Baseline, Week 12]

   The weekly hives score is the sum of the daily hives scores over 7 days and ranges from 0 to 21. The number of hives is measured twice daily (morning and evening) on a scale of 0 (none) to 3 (> 12 hives per 12 hours). The daily hives score is the average of the morning and evening scores. The Baseline score is the sum of the daily hives scores over the 7 days prior to the first treatment. A higher score indicates more hives. A negative change score indicates improvement.

3. Time to Minimally Important Difference (MID) Response in the Weekly Itch Severity Score by Week 12 [by Week 12]

   The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score indicates improvement. The MID response for weekly itch severity score was defined as a reduction from baseline in weekly itch severity score of 5 points or more. The time to weekly itch severity score MID response was defined as the time (in weeks) from Day 1 to the study week when weekly itch severity score MID response was first achieved.

4. Percentage of Participants With a UAS7 Less Than or Equal to 6 at Week 12 [Week 12]

   The urticaria activity score (UAS) is a composite of scores on a scale of 0 (none) to 3 (intense/severe) for 1) the number of wheals (hives); and 2) the intensity of the itch, measured twice daily (morning and evening). Daily UAS is the average of morning and evening scores (ranging from 0-6) and the UAS7 is the sum of the daily UAS over 7 days (ranging from 0-42). Baseline UAS7 is calculated using data from the 7 days prior to the first treatment date. A higher UAS indicates more urticaria activity. A negative change score indicates improvement.

5. Percentage of Weekly Itch Severity Score MID Responders at Week 12 [Baseline, Week 12]

   The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score indicates improvement. The MID response for weekly itch severity score was defined as a reduction from baseline in weekly itch severity score of 5 points or more. This outcome measure shows the percentage of participants classified as MID Responders at Week 12, meaning their weekly itch severity scores at Week 12 were at least 5 points lower than at Baseline.

6. Change From Baseline in the Weekly Size of the Largest Hive Score at Week 12 [Baseline, Week 12]

   The size of the largest hive is assessed twice daily (morning and evening) on a scale of 0 (none) to 3 (> 2.5 cm). The daily score is the average of the morning and evening scores. The weekly size of the largest hive score is the sum of the daily scores over 7 days, and ranges from 0 to 21. The Baseline weekly size of the largest hive score is the sum of daily scores over the 7 days prior to the first treatment. A higher score indicates larger hives. A negative change score indicates a reduction in hive size.

7. Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) at Week 12 [Baseline, Week 12]

   The dermatology life quality index (DLQI) is a 10-item dermatology-specific health-related quality of life measure. Participants rate their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives on a scale of 0 (Not at all) to 3 (Very much). The overall DLQI is the sum of the responses to the 10 items and ranges from 0 to 30. A lower score indicates a better quality of life. A negative change score indicates improvement.

8. Percentage of Angioedema-free Days From Week 4 to Week 12 [Week 4 to Week 12]

   The percentage of angioedema-free days from Weeks 4 to 12 was defined as the number of days a patient reported as angioedema-free in the daily diary divided by the total number of days with a non-missing diary entry, starting at the Week 4 visit and ending the day prior to the Week 12 visit.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) CIU/CSU refractory to H1 antihistamines at the time of randomization.

Exclusion Criteria:

• Treatment with an investigational agent within 30 days prior to screening.

• Weight < 20 kg (44 lbs).

• Clearly defined underlying etiology for chronic urticarias other than CIU.

• Evidence of parasitic infection.

• Atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or other skin disease associated with itch.

• Previous treatment with omalizumab within a year prior to screening.

• Routine doses of the following medications within 30 days prior to screening: Systemic or cutaneous (topical) corticosteroids (prescription or over the counter), hydroxychloroquine, methotrexate, cyclosporine, or cyclophosphamide.

• Intravenous (IV) immunoglobulin G (IVIG), or plasmapheresis within 30 days prior to screening.

• Regular (daily/every other day) doxepin (oral) use within 6 weeks prior to screening.

• Any H2 antihistamine use within 7 days prior to screening.

• Any leukotriene receptor antagonist (LTRA) (montelukast or zafirlukast) within 7 days prior to screening.

• Any H1 antihistamines at greater than approved doses within 3 days prior to screening.

• Patients with current malignancy, history of malignancy, or currently under work-up for suspected malignancy except non-melanoma skin cancer that has been treated or excised and is considered resolved.

• Hypersensitivity to omalizumab or any component of the formulation.

• History of anaphylactic shock.

• Presence of clinically significant cardiovascular, neurological, psychiatric, metabolic, or other pathological conditions that could interfere with the interpretation of the study results and or compromise the safety of the patients.

• Evidence of current drug or alcohol abuse.

• Nursing women or women of childbearing potential, unless they meet the following definition of post-menopausal: 12 months of natural amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels > 40 milli-international units per milliliter (mIU/mL) or 6 weeks post surgical bilateral oophorectomy (with or without hysterectomy) or hysterectomy or are using one or more of the following acceptable methods of contraception: surgical sterilization, hormonal contraception, and double-barrier methods.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		La Jolla	California	United States	92037
2		Los Angeles	California	United States	90045
3		Redwood City	California	United States	94063
4		Walnut Creek	California	United States	94598
5		Denver	Colorado	United States	80206
6		Miami	Florida	United States	33173
7		Savannah	Georgia	United States	31405
8		Woodstock	Georgia	United States	30188
9		Shiloh	Illinois	United States	62269
10		Indianapolis	Indiana	United States	46256
11		Overland Park	Kansas	United States	66210
12		Baltimore	Maryland	United States	21237
13		Wheaton	Maryland	United States	20902
14		Ypsilanti	Michigan	United States	48197
15		Omaha	Nebraska	United States	68130
16		Omaha	Nebraska	United States	68131
17		Brick	New Jersey	United States	08724
18		Bayside	New York	United States	11361
19		Bronx	New York	United States	10461
20		Brooklyn	New York	United States	11203
21		North Syracuse	New York	United States	13212
22		Rochester	New York	United States	14642
23		Rockville Centre	New York	United States	11570
24		Asheville	North Carolina	United States	28801
25		Canton	Ohio	United States	44718
26		Cincinnati	Ohio	United States	45231
27		Philadelphia	Pennsylvania	United States	19140
28		Pittsburgh	Pennsylvania	United States	15213
29		Pittsburgh	Pennsylvania	United States	15241
30		Providence	Rhode Island	United States	02906
31		El Paso	Texas	United States	79903
32		Sandy	Utah	United States	84070
33		Seattle	Washington	United States	98105
34		Spokane	Washington	United States	99204
35		Madison	Wisconsin	United States	53715
36		Milwaukee	Wisconsin	United States	53226
37		Arhus		Denmark	8000
38		Copenhagen		Denmark	2900
39		Montpellier		France	34295
40		Nice Cedex 3		France	06200
41		Paris		France	75475
42		Bonn		Germany	53127
43		Hannover		Germany	30449
44		Leipzig		Germany	D-'04103
45		Mainz		Germany	55131
46		Muenster		Germany	48149
47		München		Germany	80802
48		Genova		Italy	16132
49		Milano		Italy	20122
50		Milano		Italy	20132
51		Gdansk		Poland	80-211
52		Krakow		Poland	31-913
53		Lodz		Poland	90-265
54		Warszawa		Poland	02-256
55		Wroclaw		Poland	54-239
56		Barcelona		Spain	08003
57		Madrid		Spain	28041
58		Ankara		Turkey	06100
59		Istanbul		Turkey	34372
60		Izmir		Turkey	35100
61		Kayseri		Turkey	38039

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Karin E Rosén, MD, PhD, Genentech, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT01292473
• Other Study ID Numbers: Q4882g
• First Posted: Feb 9, 2011
• Last Update Posted: Oct 11, 2013
• Last Verified: Oct 1, 2013

• Additional relevant MeSH terms: Urticaria; Chronic Urticaria; Omalizumab

Study Results

Participant Flow

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Placebo subcutaneously (sc) every 4 weeks.	Omalizumab 75 mg sc every 4 weeks.	Omalizumab 150 mg sc every 4 weeks.	Omalizumab 300 mg sc every 4 weeks.
Period Title: Overall Study
STARTED	79	82	83	79
COMPLETED	74	75	74	67
NOT COMPLETED	5	7	9	12

Baseline Characteristics

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg	Total
Arm/Group Description	Placebo administered subcutaneously (sc) every 4 weeks.	Omalizumab 75 mg sc every 4 weeks.	Omalizumab 150 mg sc every 4 weeks.	Omalizumab 300 mg sc every 4 weeks.	Total of all reporting groups
Overall Participants	79	82	82	79	322
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	43.1 (12.5)	39.7 (15.0)	43.0 (13.2)	44.3 (13.7)	42.5 (13.7)
Sex: Female, Male (Count of Participants)
Female	55 69.6%	61 74.4%	65 79.3%	63 79.7%	244 75.8%
Male	24 30.4%	21 25.6%	17 20.7%	16 20.3%	78 24.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Weekly Itch Severity Score at Week 12
Description	The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score indicates improvement.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least one dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Placebo administered subcutaneously (sc) every 4 weeks	Omalizumab 75 mg sc every 4 weeks	Omalizumab 150 mg sc every 4 weeks.	Omalizumab 300 mg sc every 4 weeks.
Measure Participants	79	82	82	79
Mean (Standard Deviation) [Units on a scale]	-5.14 (5.58)	-5.87 (6.45)	-8.14 (6.44)	-9.77 (5.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 75 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4637
	Comments	Refer to the Type-I error control plan.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline weekly itch severity score (< 13 vs ≥ 13) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.69
	Confidence Interval	(2-Sided) 95%; -2.54 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 150 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments	Refer to the Type-I error control plan.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline weekly itch severity score (< 13 vs ≥ 13) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-3.04
	Confidence Interval	(2-Sided) 95%; -4.85 to -1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 300 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 300 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Refer to the Type-I error control plan.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline weekly itch severity score (< 13 vs ≥ 13) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-4.81
	Confidence Interval	(2-Sided) 95%; -6.49 to -3.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in the Weekly Urticaria Activity Score (UAS7) at Week 12
Description	The urticaria activity score (UAS) is a composite of scores on a scale of 0 (none) to 3 (intense/severe) for 1) the number of wheals (hives); and 2) the intensity of the itch, measured twice daily (morning and evening). Daily UAS is the average of morning and evening scores (ranging from 0-6) and the UAS7 is the sum of the daily UAS over 7 days (ranging from 0-42). Baseline UAS7 is calculated using data from the 7 days prior to the first treatment date. A higher UAS indicates more urticaria activity. A negative change score indicates improvement.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least one dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Placebo administered subcutaneously (sc) every 4 weeks.	Omalizumab 75 mg sc every 4 weeks.	Omalizumab 150 mg sc every 4 weeks.	Omalizumab 300 mg sc every 4 weeks.
Measure Participants	79	82	82	79
Mean (Standard Deviation) [Units on a scale]	-10.36 (11.61)	-13.08 (12.67)	-17.89 (13.23)	-21.74 (12.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 75 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1575
	Comments	Refer to the Type-I error control plan. The p-value was not evaluated for statistical significance in accordance with the Type I error control plan provided in the Detailed Description.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline UAS7 (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-2.73
	Confidence Interval	(2-Sided) 95%; -6.53 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 150 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	Refer to the Type-I error control plan.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline UAS7 (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-7.69
	Confidence Interval	() 95%; -11.49 to -3.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 300 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 300 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Refer to the Type-I error control plan.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline UAS7 (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-12.40
	Confidence Interval	(2-Sided) 95%; -16.13 to -8.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in the Weekly Number of Hives Score at Week 12
Description	The weekly hives score is the sum of the daily hives scores over 7 days and ranges from 0 to 21. The number of hives is measured twice daily (morning and evening) on a scale of 0 (none) to 3 (> 12 hives per 12 hours). The daily hives score is the average of the morning and evening scores. The Baseline score is the sum of the daily hives scores over the 7 days prior to the first treatment. A higher score indicates more hives. A negative change score indicates improvement.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least one dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Placebo administered subcutaneously (sc) every 4 weeks	Omalizumab 75 mg sc every 4 weeks	Omalizumab 150 mg sc every 4 weeks	Omalizumab 300 mg sc every 4 weeks
Measure Participants	79	82	82	79
Mean (Standard Deviation) [Units on a scale]	-5.22 (6.56)	-7.21 (6.96)	-9.75 (7.28)	-11.97 (7.58)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 75 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0603
	Comments	Refer to the Type-I error control plan. The p-value was not evaluated for statistical significance in accordance with the Type I error control plan provided in the Detailed Description.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline weekly number of hives (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-2.01
	Confidence Interval	(2-Sided) 95%; -4.11 to 0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 150 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Refer to the Type-I error control plan.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline weekly number of hives (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-4.51
	Confidence Interval	(2-Sided) 95%; -6.65 to -2.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 300 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 300 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Refer to the Type-I error control plan.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline weekly number of hives (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-7.09
	Confidence Interval	(2-Sided) 95%; -9.26 to -4.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Time to Minimally Important Difference (MID) Response in the Weekly Itch Severity Score by Week 12
Description	The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score indicates improvement. The MID response for weekly itch severity score was defined as a reduction from baseline in weekly itch severity score of 5 points or more. The time to weekly itch severity score MID response was defined as the time (in weeks) from Day 1 to the study week when weekly itch severity score MID response was first achieved.
Time Frame	by Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least one dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Placebo administered subcutaneously (sc) every 4 weeks	Omalizumab 75 mg sc every 4 weeks	Omalizumab 150 mg sc every 4 weeks	Omalizumab 300 mg sc every 4 weeks
Measure Participants	79	82	82	79
Median (95% Confidence Interval) [Weeks]	4.0	2.0	2.0	1.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis is that there is no difference between Placebo and Omalizumab 75 mg.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0478
	Comments	Refer to the Type-I error control plan. The p-value was not evaluated for statistical significance in accordance with the Type I error control plan provided in the Detailed Description.
	Method	Cox proportional hazards model
	Comments	Covariates included in the analysis were baseline weekly itch severity score (< 13 vs ≥ 13) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95%; 1.00 to 2.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 150 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0101
	Comments	Refer to the Type-I error control plan.
	Method	Cox proportional hazards model
	Comments	Covariates included in the analysis were baseline weekly itch severity score (< 13 vs ≥ 13) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.59
	Confidence Interval	(2-Sided) 95%; 1.12 to 2.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 300 mg
	Comments	The null hypothesis is that there is no difference between placebo and omalizumab 300 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Refer to the Type-I error control plan.
	Method	Cox proportional hazards model
	Comments	Covariates included in the analysis were baseline weekly itch severity score (< 13 vs ≥ 13) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.12
	Confidence Interval	(2-Sided) 95%; 1.48 to 3.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants With a UAS7 Less Than or Equal to 6 at Week 12
Description	The urticaria activity score (UAS) is a composite of scores on a scale of 0 (none) to 3 (intense/severe) for 1) the number of wheals (hives); and 2) the intensity of the itch, measured twice daily (morning and evening). Daily UAS is the average of morning and evening scores (ranging from 0-6) and the UAS7 is the sum of the daily UAS over 7 days (ranging from 0-42). Baseline UAS7 is calculated using data from the 7 days prior to the first treatment date. A higher UAS indicates more urticaria activity. A negative change score indicates improvement.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least one dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Placebo administered subcutaneously (sc) every 4 weeks	Omalizumab 75 mg sc every 4 weeks	Omalizumab 150 mg sc every 4 weeks	Omalizumab 300 mg sc every 4 weeks
Measure Participants	79	82	82	79
Number [Percentage of participants]	19.0 24.1%	26.8 32.7%	42.7 52.1%	65.8 83.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 75 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3419
	Comments	Refer to the Type-I error control plan. The p-value was not evaluated for statistical significance in accordance with the Type I error control plan provided in the Detailed Description.
	Method	Cochran-Mantel-Haenszel
	Comments	Covariates included in the analysis were baseline UAS7 (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 150 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments	Refer to the Type-I error control plan.
	Method	Cochran-Mantel-Haenszel
	Comments	Covariates included in the analysis were baseline UAS7 (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 300 mg
	Comments	The null hypothesis is that there is no difference between placebo and omalizumab 300 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Refer to the Type-I error control plan.
	Method	Cochran-Mantel-Haenszel
	Comments	Covariates included in the analysis were baseline UAS7 (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).

6. Secondary Outcome

Title	Percentage of Weekly Itch Severity Score MID Responders at Week 12
Description	The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score indicates improvement. The MID response for weekly itch severity score was defined as a reduction from baseline in weekly itch severity score of 5 points or more. This outcome measure shows the percentage of participants classified as MID Responders at Week 12, meaning their weekly itch severity scores at Week 12 were at least 5 points lower than at Baseline.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least one dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Placebo administered subcutaneously (sc) every 4 weeks	Omalizumab 75 mg sc every 4 weeks	Omalizumab 150 mg sc every 4 weeks	Omalizumab 300 mg sc every 4 weeks
Measure Participants	79	82	82	79
Number [Percentage of participants]	48.1 60.9%	56.1 68.4%	69.5 84.8%	78.5 99.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 75 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4366
	Comments	Refer to the Type-I error control plan. The p-value was not evaluated for statistical significance in accordance with the Type I error control plan provided in the Detailed Description.
	Method	Cochran-Mantel-Haenszel
	Comments	Covariates included in the analysis were baseline weekly itch severity score (< 13 vs ≥ 13) and baseline weight (< 80 kg vs ≥ 80 kg).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 150 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0045
	Comments	Refer to the Type-I error control plan.
	Method	Cochran-Mantel-Haenszel
	Comments	Covariates included in the analysis were baseline weekly itch severity score (< 13 vs ≥ 13) and baseline weight (< 80 kg vs ≥ 80 kg).

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 300 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 300 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Refer to the Type-I error control plan.
	Method	Cochran-Mantel-Haenszel
	Comments	Covariates included in the analysis were baseline weekly itch severity score (< 13 vs ≥ 13) and baseline weight (< 80 kg vs ≥ 80 kg).

7. Secondary Outcome

Title	Change From Baseline in the Weekly Size of the Largest Hive Score at Week 12
Description	The size of the largest hive is assessed twice daily (morning and evening) on a scale of 0 (none) to 3 (> 2.5 cm). The daily score is the average of the morning and evening scores. The weekly size of the largest hive score is the sum of the daily scores over 7 days, and ranges from 0 to 21. The Baseline weekly size of the largest hive score is the sum of daily scores over the 7 days prior to the first treatment. A higher score indicates larger hives. A negative change score indicates a reduction in hive size.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least one dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Placebo administered subcutaneously (sc) every 4 weeks	Omalizumab 75 mg sc every 4 weeks	Omalizumab 150 mg sc every 4 weeks	Omalizumab 300 mg sc every 4 weeks
Measure Participants	79	82	82	79
Mean (Standard Deviation) [Units on a scale]	-4.04 (5.55)	-6.52 (6.33)	-7.84 (6.75)	-11.00 (7.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 75 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0082
	Comments	Refer to the Type-I error control plan. The p-value was not evaluated for statistical significance in accordance with the Type I error control plan provided in the Detailed Description.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline weekly size of largest hive score (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-2.48
	Confidence Interval	(2-Sided) 95%; -4.32 to -0.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 150 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Refer to the Type-I error control plan.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline weekly size of largest hive score (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-3.76
	Confidence Interval	(2-Sided) 95%; -5.61 to -1.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 300 mg
	Comments	The null hypothesis is that there is no difference between the placebo and the omalizumab 300 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Refer to the Type-I error control plan.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline weekly size of largest hive score (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-7.15
	Confidence Interval	(2-Sided) 95%; -9.03 to -5.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) at Week 12
Description	The dermatology life quality index (DLQI) is a 10-item dermatology-specific health-related quality of life measure. Participants rate their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives on a scale of 0 (Not at all) to 3 (Very much). The overall DLQI is the sum of the responses to the 10 items and ranges from 0 to 30. A lower score indicates a better quality of life. A negative change score indicates improvement.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least one dose of study drug and who had a DLQI score at Week 12.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Placebo administered subcutaneously (sc) every 4 weeks	Omalizumab 75 mg sc every 4 weeks	Omalizumab 150 mg sc every 4 weeks	Omalizumab 300 mg sc every 4 weeks
Measure Participants	69	68	70	73
Mean (Standard Deviation) [Units on a scale]	-6.09 (7.47)	-7.50 (7.16)	-8.29 (6.31)	-10.15 (6.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 75 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1207
	Comments	Refer to the Type-I error control plan. The p-value was not evaluated for statistical significance in accordance with the Type I error control plan provided in the Detailed Description.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline overall DLQI score (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-1.68
	Confidence Interval	(2-Sided) 95%; -3.82 to 0.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 150 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0215
	Comments	Refer to the Type-I error control plan.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline overall DLQI score (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-2.51
	Confidence Interval	(2-Sided) 95%; -4.64 to -0.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 300 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 300 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments	Refer to the Type-I error control plan.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline overall DLQI score (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-3.79
	Confidence Interval	(2-Sided) 95%; -5.85 to -1.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Angioedema-free Days From Week 4 to Week 12
Description	The percentage of angioedema-free days from Weeks 4 to 12 was defined as the number of days a patient reported as angioedema-free in the daily diary divided by the total number of days with a non-missing diary entry, starting at the Week 4 visit and ending the day prior to the Week 12 visit.
Time Frame	Week 4 to Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least one dose of study drug. Patients who withdrew before the Week 4 visit or who had missing responses for more than 40% of the daily diary entries between the Week 4 visit and the Week 12 visit were not included in the analysis.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Placebo administered subcutaneously (sc) every 4 weeks	Omalizumab 75 mg sc every 4 weeks	Omalizumab 150 mg sc every 4 weeks	Omalizumab 300 mg sc every 4 weeks
Measure Participants	70	71	74	74
Mean (Standard Deviation) [Percentage of days]	89.2 (19.0)	93.5 (14.9)	91.6 (17.4)	95.5 (14.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 75 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1361
	Comments	Refer to the Type-I error control plan. The p-value was not evaluated for statistical significance in accordance with the Type I error control plan provided in the Detailed Description.
	Method	Stratified Wilcoxon
	Comments	Stratification variables included in the analysis were presence of angioedema at baseline (yes vs no) and baseline weight (< 80 kg vs ≥ 80 kg).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 150 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0905
	Comments	Refer to the Type-I error control plan.
	Method	Stratified Wilcoxon
	Comments	Stratification variables included in the analysis were presence of angioedema at baseline (yes vs no) and baseline weight (< 80 kg vs ≥ 80 kg).

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 300 mg
	Comments	The null hypothesis is that there is no difference between the placebo and omalizumab 300 mg.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Refer to the Type-I error control plan.
	Method	Stratified Wilcoxon
	Comments	Stratification variables included in the analysis were presence of angioedema at baseline (yes vs no) and baseline weight (< 80 kg vs ≥ 80 kg).

Adverse Events

Time Frame	Adverse events were collected from the date of first treatment through the end of the study (up to 28 weeks).
Adverse Event Reporting Description	Safety evaluable set: All randomized participants who received at least one dose of study drug. Data are presented according to the doses actually received - one subject randomized to the 150 mg group withdrew before dosing, and six subjects randomized to the 75 mg group actually received 150 mg.
Arm/Group Title	Placebo		Omalizumab 75 mg		Omalizumab 150 mg		Omalizumab 300 mg
Arm/Group Description	Placebo administered subcutaneously (sc) every 4 weeks.		Omalizumab 75 mg sc every 4 weeks.		Omalizumab 150 mg sc every 4 weeks.		Omalizumab 300 mg sc every 4 weeks.
All Cause Mortality
	Placebo		Omalizumab 75 mg		Omalizumab 150 mg		Omalizumab 300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Omalizumab 75 mg		Omalizumab 150 mg		Omalizumab 300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/79 (2.5%)		1/76 (1.3%)		1/88 (1.1%)		5/79 (6.3%)
Gastrointestinal disorders
Haemorrhoids	1/79 (1.3%)		0/76 (0%)		0/88 (0%)		0/79 (0%)
Melaena	0/79 (0%)		0/76 (0%)		0/88 (0%)		1/79 (1.3%)
Renal and urinary disorders
Nephrolithiasis	0/79 (0%)		0/76 (0%)		0/88 (0%)		1/79 (1.3%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/79 (1.3%)		0/76 (0%)		0/88 (0%)		0/79 (0%)
Skin and subcutaneous tissue disorders
Angioedema	0/79 (0%)		1/76 (1.3%)		1/88 (1.1%)		0/79 (0%)
Malignant melanoma in situ	0/79 (0%)		0/76 (0%)		0/88 (0%)		1/79 (1.3%)
Idiopathic urticaria	0/79 (0%)		0/76 (0%)		1/88 (1.1%)		1/79 (1.3%)
Urticaria	0/79 (0%)		0/76 (0%)		1/88 (1.1%)		0/79 (0%)
Surgical and medical procedures
Tonsillectomy	0/79 (0%)		0/76 (0%)		0/88 (0%)		1/79 (1.3%)
Other (Not Including Serious) Adverse Events
	Placebo		Omalizumab 75 mg		Omalizumab 150 mg		Omalizumab 300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/79 (44.3%)		30/76 (39.5%)		42/88 (47.7%)		35/79 (44.3%)
Gastrointestinal disorders
Diarrhoea	4/79 (5.1%)		2/76 (2.6%)		4/88 (4.5%)		3/79 (3.8%)
Infections and infestations
Nasopharyngitis	15/79 (19%)		13/76 (17.1%)		15/88 (17%)		12/79 (15.2%)
Upper respiratory tract infection	7/79 (8.9%)		0/76 (0%)		2/88 (2.3%)		6/79 (7.6%)
Influenza	4/79 (5.1%)		5/76 (6.6%)		3/88 (3.4%)		2/79 (2.5%)
Sinusitis	2/79 (2.5%)		3/76 (3.9%)		2/88 (2.3%)		6/79 (7.6%)
Bronchitis	2/79 (2.5%)		4/76 (5.3%)		0/88 (0%)		3/79 (3.8%)
Urinary tract infection	1/79 (1.3%)		4/76 (5.3%)		3/88 (3.4%)		0/79 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/79 (5.1%)		1/76 (1.3%)		2/88 (2.3%)		4/79 (5.1%)
Nervous system disorders
Headache	7/79 (8.9%)		4/76 (5.3%)		18/88 (20.5%)		9/79 (11.4%)
Respiratory, thoracic and mediastinal disorders
Cough	3/79 (3.8%)		4/76 (5.3%)		2/88 (2.3%)		2/79 (2.5%)
Skin and subcutaneous tissue disorders
Idiopathic urticaria	3/79 (3.8%)		8/76 (10.5%)		6/88 (6.8%)		4/79 (5.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.