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

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01287117
• Collaborator: (none)
• Enrollment: 319
• Locations: 66
• Arms: 4
• Duration (Months): 20
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.2

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-dose H1 antihistamine treatment.

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

Detailed Description

Type I Error Rate Control Plan

Primary Outcome Measure

In order to maintain an overall type I error rate of 0.05 (2-sided) across the 3 omalizumab dose levels, the testing of the primary Outcome Measure was conducted in the following hierarchical order. A p-value < 0.05 is only considered statistically significant if statistical significance was 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

Secondary Outcome Measures

A hierarchical analysis of the following secondary Outcome Measures was performed for each dose found to be significant in the primary Outcome Measure. A p-value < 0.05 is only considered statistically significant if statistical significance was claimed at the previous stage.

• Stage 1: Change from baseline to Week 12 in the urticaria activity score over 7 days (UAS7)

• Stage 2: Change from Baseline to Week 12 in the weekly number of hives score

• Stage 3: Time to minimally important difference (MID) response in the weekly itch severity score by Week 12

• Stage 4: Percentage of participants with a UAS7 score ≤ 6 at Week 12

• Stage 5: Percentage of weekly itch severity score MID responders at Week 12

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

• Stage 7: Change from Baseline in the overall dermatology life quality index (DLQI) score at Week 12

• Stage 8: Change from Baseline in the overall dermatology life quality index (DLQI) score at Week 12

• Stage 9: Percentage of complete responders (UAS7 = 0) at Week 12

Study Design

• Study Type: Interventional
• Actual Enrollment: 319 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Efficacy and Safety of Xolair® (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite Antihistamine Treatment (H1)
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Drug: Placebo; Placebo was supplied as a lyophilized, sterile powder in a single-use vial without study drug.
Experimental: Omalizumab 75 mg Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.	Drug: Omalizumab; Omalizumab was supplied as a lyophilized, sterile powder in a single-use vial.; Other Names: Xolair
Experimental: Omalizumab 150 mg Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.	Drug: Omalizumab; Omalizumab was supplied as a lyophilized, sterile powder in a single-use vial.; Other Names: Xolair
Experimental: Omalizumab 300 mg Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.	Drug: Omalizumab; Omalizumab was supplied as a lyophilized, sterile powder in a single-use vial.; Other Names: Xolair

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 12 in the Weekly Itch Severity Score [Baseline to 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 to Week 12 in the Urticaria Activity Score Over 7 Days (UAS7) [Baseline to Week 12]

   The UAS7 is the sum of the daily urticarial activity scores over 7 days and ranges from 0 to 42. The daily urticarial activity score is the average of the morning and evening urticarial activity scores and ranges from 0 to 6. The urticarial activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticarial activity scores over the 7 days prior to the first treatment. A higher urticarial activity score indicates more urticaria activity. A negative change score indicates improvement.

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

   The time to the MID response is the number of weeks from the start of treatment (Baseline) until the time point at which the first MID response occurs. The MID response is defined as a reduction ≥ 5 points from Baseline in the weekly itch severity score.

4. Percentage of Participants With a UAS7 Score ≤ 6 at Week 12 [Week 12]

   The UAS7 is the sum of the daily urticarial activity scores over 7 days and ranges from 0 to 42. The daily urticarial activity score is the average of the morning and evening urticarial activity scores and ranges from 0 to 6. The urticarial activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticarial activity scores over the 7 days prior to the first treatment. A higher urticarial activity score indicates more urticaria activity.

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

   The percentage of participants with an itch severity score at 12 Weeks at least 5 points lower than at Baseline.

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

   The weekly size of the largest hive score is the sum of the daily size of the largest hive scores over 7 days and ranges from 0 to 21. The daily size of the largest hive score is assessed twice daily (morning and evening) on a scale of 0 (none) to 3 (> 2.5 cm). The daily size of the largest hive score is the average of the morning and evening scores. The Baseline weekly size of the largest hive score is calculated 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) Score at Week 12 [Baseline to Week 12]

   The DLQI is a 10-item dermatology-specific health-related quality of life measure. Patients rated 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 for which a patient responded "No" to the angioedema question 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.

9. Percentage of Complete Responders (UAS7 = 0) at Week 12 [Week 12]

   A complete responder was defined as a participant with a UAS7 score = 0 at Week 12.

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) 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 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		Birmingham	Alabama	United States	35209
2		Huntington Beach	California	United States	92647
3		Long Beach	California	United States	90808
4		Los Angeles	California	United States	90027
5		Palmdale	California	United States	93551
6		Sacramento	California	United States	95817
7		San Jose	California	United States	95117-1840
8		Studio City	California	United States	91607
9		Centennial	Colorado	United States	80112
10		Washington	District of Columbia	United States	20037
11		Coral Gables	Florida	United States	33134
12		Sarasota	Florida	United States	34233
13		Tallahassee	Florida	United States	32308
14		Columbus	Georgia	United States	31904
15		Springfield	Illinois	United States	62703
16		Indianapolis	Indiana	United States	46208
17		Baltimore	Massachusetts	United States	21224
18		Boston	Massachusetts	United States	02114
19		Burlington	Massachusetts	United States	01805
20		St Louis	Missouri	United States	63141
21		Edison	New Jersey	United States	08820
22		Skillman	New Jersey	United States	08558
23		Bronx	New York	United States	10465
24		Staten Island	New York	United States	10304
25		Durham	North Carolina	United States	27710
26		Columbus	Ohio	United States	43235
27		Toledo	Ohio	United States	43623
28		Tulsa	Oklahoma	United States	74136
29		Portland	Oregon	United States	97210
30		Pittsburgh	Pennsylvania	United States	15212
31		Upland	Pennsylvania	United States	19013
32		Charleston	South Carolina	United States	29406
33		Fort Worth	Texas	United States	76123
34		Houston	Texas	United States	77054
35		Waco	Texas	United States	76712
36		Salt Lake City	Utah	United States	84107
37		Sandy	Utah	United States	84070
38		Springfield	Virginia	United States	22152
39		Lacrosse	Wisconsin	United States	54601
40		Madison	Wisconsin	United States	53792
41		København		Denmark	2400
42		Odense		Denmark	5000
43		Bordeaux		France	33000
44		Marseille		France	13385
45		Reims		France	51092
46		Berlin		Germany	10117
47		Berlin		Germany	10249
48		Berlin		Germany	D-13585
49		Dresden		Germany	D-01062
50		Freiburg		Germany	79098
51		Heidelberg		Germany	69115
52		Muenchen		Germany	80337
53		Muenster		Germany	48149
54		Perugia		Italy	06159
55		Roma		Italy	00167
56		Terni		Italy	05100
57		Krakow		Poland	31-531
58		Lodz		Poland	90-153
59		Lublin		Poland	20-718
60		Wroclaw		Poland	51-124
61		Barcelona		Spain	08003
62		Barcelona		Spain	08041
63		Pamplona		Spain	31003
64		Ankara		Turkey	06500
65		Bursa		Turkey	16059
66		Istanbul		Turkey	35100

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Clinical Trials, Genentech, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT01287117
• Other Study ID Numbers: Q4881g; GA00887
• First Posted: Feb 1, 2011
• Last Update Posted: Nov 27, 2013
• Last Verified: Nov 1, 2013

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

Study Results

Participant Flow

Pre-assignment Detail	Randomized population: All randomized participants regardless of whether they received any study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Period Title: Overall Study
STARTED	80	78	80	81
Received Treatment	80	77	80	81
COMPLETED	65	64	64	69
NOT COMPLETED	15	14	16	12

Baseline Characteristics

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg	Total
Arm/Group Description	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.	Total of all reporting groups
Overall Participants	80	77	80	81	318
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.4 (15.6)	40.7 (15.2)	41.1 (14.0)	42.4 (13.2)	41.2 (14.5)
Sex: Female, Male (Count of Participants)
Female	52 65%	55 71.4%	64 80%	60 74.1%	231 72.6%
Male	28 35%	22 28.6%	16 20%	21 25.9%	87 27.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 12 in the Weekly Itch Severity Score
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 to Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Measure Participants	80	77	80	81
Mean (Standard Deviation) [Units on a scale]	-3.63 (5.22)	-6.46 (6.14)	-6.66 (6.28)	-9.40 (5.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 75 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments	A multiplicity type I error control plan was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided).
	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	-2.96
	Confidence Interval	(2-Sided) 95%; -4.71 to -1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 150 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments	A multiplicity type I error control plan was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided).
	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	-2.95
	Confidence Interval	(2-Sided) 95%; -4.72 to -1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 300 mg
	Comments	The null hypothesis was that there was 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	A multiplicity type I error control plan was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided).
	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	-5.80
	Confidence Interval	(2-Sided) 95%; -7.49 to -4.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Week 12 in the Urticaria Activity Score Over 7 Days (UAS7)
Description	The UAS7 is the sum of the daily urticarial activity scores over 7 days and ranges from 0 to 42. The daily urticarial activity score is the average of the morning and evening urticarial activity scores and ranges from 0 to 6. The urticarial activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticarial activity scores over the 7 days prior to the first treatment. A higher urticarial activity score indicates more urticaria activity. A negative change score indicates improvement.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Measure Participants	80	77	80	81
Mean (Standard Deviation) [Units on a scale]	-8.01 (11.47)	-13.82 (13.26)	-14.44 (12.95)	-20.75 (12.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 75 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0035
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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	-5.75
	Confidence Interval	(2-Sided) 95%; -9.59 to -1.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 150 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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	-6.54
	Confidence Interval	(2-Sided) 95%; -10.33 to -2.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 300 mg
	Comments	The null hypothesis was that there was 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	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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	-12.80
	Confidence Interval	(2-Sided) 95%; -16.44 to -9.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline to Week 12 in the Weekly Number of Hives Score
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 to Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Measure Participants	80	77	80	81
Mean (Standard Deviation) [Units on a scale]	-4.37 (6.60)	-7.36 (7.52)	-7.78 (7.08)	-11.35 (7.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 75 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0149
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline weekly number of hives score (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-2.75
	Confidence Interval	(2-Sided) 95%; -4.95 to -0.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 150 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0017
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline weekly number of hives score (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-3.44
	Confidence Interval	(2-Sided) 95%; -5.57 to -1.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 300 mg
	Comments	The null hypothesis was that there was 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	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	Method	ANCOVA
	Comments	Covariates included in the analysis were baseline weekly number of hives score (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-6.93
	Confidence Interval	(2-Sided) 95%; -9.10 to -4.76
	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 time to the MID response is the number of weeks from the start of treatment (Baseline) until the time point at which the first MID response occurs. The MID response is defined as a reduction ≥ 5 points from Baseline in the weekly itch severity score.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Measure Participants	57	57	66	76
Median (95% Confidence Interval) [Weeks]	4.0	3.0	2.0	1.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 75 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0879
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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	1.39
	Confidence Interval	(2-Sided) 95%; 0.95 to 2.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 150 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0301
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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	1.49
	Confidence Interval	(2-Sided) 95%; 1.04 to 2.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 300 mg
	Comments	The null hypothesis was that there was 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	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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	2.34
	Confidence Interval	(2-Sided) 95%; 1.63 to 3.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants With a UAS7 Score ≤ 6 at Week 12
Description	The UAS7 is the sum of the daily urticarial activity scores over 7 days and ranges from 0 to 42. The daily urticarial activity score is the average of the morning and evening urticarial activity scores and ranges from 0 to 6. The urticarial activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticarial activity scores over the 7 days prior to the first treatment. A higher urticarial activity score indicates more urticaria activity.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Measure Participants	80	77	80	81
Number [Percentage of participants]	11.3 14.1%	26.0 33.8%	40.0 50%	51.9 64.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 75 mg groups. The p-value was not evaluated for statistical significance in accordance with the type I error rate control plan.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0148
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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 was that there was no difference between the placebo and the omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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 was that there was 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	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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 percentage of participants with an itch severity score at 12 Weeks at least 5 points lower than at Baseline.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Measure Participants	80	77	80	81
Number [Percentage of participants]	36.3 45.4%	55.8 72.5%	56.3 70.4%	75.3 93%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 75 mg groups. The p-value was not evaluated for statistical significance in accordance with the type I error rate control plan.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0118
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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 was that there was no difference between the placebo and the omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0226
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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 was that there was 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	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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 to Week 12 in the Weekly Size of the Largest Hive Score
Description	The weekly size of the largest hive score is the sum of the daily size of the largest hive scores over 7 days and ranges from 0 to 21. The daily size of the largest hive score is assessed twice daily (morning and evening) on a scale of 0 (none) to 3 (> 2.5 cm). The daily size of the largest hive score is the average of the morning and evening scores. The Baseline weekly size of the largest hive score is calculated 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 to Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Measure Participants	80	77	80	81
Mean (Standard Deviation) [Units on a scale]	-3.93 (5.44)	-6.20 (6.29)	-6.96 (6.68)	-9.79 (6.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 75 mg groups. The p-value was not evaluated for statistical significance in accordance with the type I error rate control plan.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0124
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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	-2.34
	Confidence Interval	(2-Sided) 95%; -4.17 to -0.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 150 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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	-3.16
	Confidence Interval	(2-Sided) 95%; -5.05 to -1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 300 mg
	Comments	The null hypothesis was that there was 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	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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	-5.73
	Confidence Interval	(2-Sided) 95%; -7.59 to -3.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12
Description	The DLQI is a 10-item dermatology-specific health-related quality of life measure. Patients rated 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 to Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Measure Participants	62	66	63	72
Mean (Standard Deviation) [Units on a scale]	-6.13 (6.25)	-6.33 (6.08)	-8.00 (7.24)	-10.29 (7.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 75 mg groups. The p-value was not evaluated for statistical significance in accordance with the type I error rate control plan.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7956
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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	0.26
	Confidence Interval	(2-Sided) 95%; -1.76 to 2.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 150 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 150 mg groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2286
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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	-1.31
	Confidence Interval	(2-Sided) 95%; -3.46 to 0.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 300 mg
	Comments	The null hypothesis was that there was 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	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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	-4.08
	Confidence Interval	(2-Sided) 95%; -5.96 to -2.20
	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 for which a patient responded "No" to the angioedema question 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 1 dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Measure Participants	66	69	70	74
Mean (Standard Deviation) [Percentage]	88.2 (19.4)	86.5 (28.4)	89.6 (20.6)	96.1 (11.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 75 mg groups. The p-value was not evaluated for statistical significance in accordance with the type I error rate control plan.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4867
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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 was that there was no difference between the placebo and the omalizumab 150 mg groups. The p-value was not evaluated for statistical significance in accordance with the type I error rate control plan.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1747
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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 was that there was 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	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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).

10. Secondary Outcome

Title	Percentage of Complete Responders (UAS7 = 0) at Week 12
Description	A complete responder was defined as a participant with a UAS7 score = 0 at Week 12.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Arm/Group Title	Placebo	Omalizumab 75 mg	Omalizumab 150 mg	Omalizumab 300 mg
Arm/Group Description	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Measure Participants	80	77	80	81
Number [Percentage of participants]	8.8 11%	11.7 15.2%	15.0 18.8%	35.8 44.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Omalizumab 75 mg
	Comments	The null hypothesis was that there was no difference between the placebo and the omalizumab 75 mg groups. The p-value was not evaluated for statistical significance in accordance with the type I error rate control plan.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4580
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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 was that there was no difference between the placebo and the omalizumab 150 mg groups. The p-value was not evaluated for statistical significance in accordance with the type I error rate control plan.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2087
	Comments	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	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 was that there was 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	A pre-specified hierarchical order of testing was employed to adjust for the comparison of multiple omalizumab groups to the placebo group in order to maintain an overall type I error rate of 0.05 (2-sided) within each dose.
	Method	Cochran-Mantel-Haenszel
	Comments	Covariates included in the analysis were baseline UAS7 (< median vs ≥ median) and baseline weight (< 80 kg vs ≥ 80 kg).

Adverse Events

Time Frame	Adverse events were reported starting with the first dose of study drug through the end of the study (up to 40 weeks).
Adverse Event Reporting Description	Safety population: All randomized participants who received at least 1 dose of study drug.
Arm/Group Title	Placebo		Omalizumab 75 mg		Omalizumab 150 mg		Omalizumab 300 mg
Arm/Group Description	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.		Participants received omalizumab 75 mg subcutaneously every 4 weeks during the 24 week treatment period.		Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 24 week treatment period.		Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
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	5/80 (6.3%)		2/70 (2.9%)		5/87 (5.7%)		2/81 (2.5%)
Cardiac disorders
Angina unstable	0/80 (0%)		0/70 (0%)		1/87 (1.1%)		0/81 (0%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	0/80 (0%)		1/70 (1.4%)		0/87 (0%)		0/81 (0%)
Immune system disorders
Anaphylactic reaction	0/80 (0%)		0/70 (0%)		0/87 (0%)		1/81 (1.2%)
Infections and infestations
Appendicitis	0/80 (0%)		0/70 (0%)		1/87 (1.1%)		0/81 (0%)
Injury, poisoning and procedural complications
Radius fracture	1/80 (1.3%)		0/70 (0%)		0/87 (0%)		0/81 (0%)
Metabolism and nutrition disorders
Type 2 diabetes mellitus	1/80 (1.3%)		0/70 (0%)		0/87 (0%)		0/81 (0%)
Shock hypoglycaemic	0/80 (0%)		0/70 (0%)		0/87 (0%)		1/81 (1.2%)
Musculoskeletal and connective tissue disorders
Pain in extremity	0/80 (0%)		0/70 (0%)		1/87 (1.1%)		0/81 (0%)
Reproductive system and breast disorders
Cervical dysplasia	1/80 (1.3%)		0/70 (0%)		0/87 (0%)		0/81 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/80 (1.3%)		0/70 (0%)		0/87 (0%)		0/81 (0%)
Skin and subcutaneous tissue disorders
Urticaria	0/80 (0%)		1/70 (1.4%)		1/87 (1.1%)		0/81 (0%)
Idiopathic urticaria	1/80 (1.3%)		0/70 (0%)		0/87 (0%)		0/81 (0%)
Angioedema	0/80 (0%)		0/70 (0%)		1/87 (1.1%)		0/81 (0%)
Surgical and medical procedures
Abortion induced	0/80 (0%)		0/70 (0%)		1/87 (1.1%)		0/81 (0%)
Vascular disorders
Hypertension	0/80 (0%)		0/70 (0%)		1/87 (1.1%)		0/81 (0%)
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	38/80 (47.5%)		37/70 (52.9%)		46/87 (52.9%)		40/81 (49.4%)
Infections and infestations
Nasopharyngitis	17/80 (21.3%)		5/70 (7.1%)		14/87 (16.1%)		10/81 (12.3%)
Sinusitis	5/80 (6.3%)		6/70 (8.6%)		7/87 (8%)		5/81 (6.2%)
Upper respiratory tract infection	3/80 (3.8%)		6/70 (8.6%)		4/87 (4.6%)		4/81 (4.9%)
Bronchitis	6/80 (7.5%)		5/70 (7.1%)		2/87 (2.3%)		2/81 (2.5%)
Urinary tract infection	3/80 (3.8%)		3/70 (4.3%)		7/87 (8%)		2/81 (2.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/80 (0%)		3/70 (4.3%)		5/87 (5.7%)		4/81 (4.9%)
Nervous system disorders
Headache	4/80 (5%)		5/70 (7.1%)		12/87 (13.8%)		7/81 (8.6%)
Respiratory, thoracic and mediastinal disorders
Asthma	4/80 (5%)		1/70 (1.4%)		4/87 (4.6%)		2/81 (2.5%)
Oropharyngeal pain	4/80 (5%)		2/70 (2.9%)		5/87 (5.7%)		0/81 (0%)
Cough	3/80 (3.8%)		4/70 (5.7%)		3/87 (3.4%)		0/81 (0%)
Skin and subcutaneous tissue disorders
Idiopathic urticaria	4/80 (5%)		10/70 (14.3%)		7/87 (8%)		11/81 (13.6%)
Urticaria	8/80 (10%)		8/70 (11.4%)		7/87 (8%)		5/81 (6.2%)

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.