Study of Efficacy and Safety of Xolair® (Omalizumab) in Chinese Patients With Chronic Spontaneous Urticaria

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03328897
• Collaborator: (none)
• Enrollment: 418
• Locations: 27
• Arms: 3
• Actual Duration (Months): 28.9
• Patients Per Site: 15.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study was to demonstrate the efficacy and safety of omalizumab, compared with placebo, as an add-on to H1 antihistamines (H1AH) therapy in adult patients suffering from Chronic Spontaneous Urticaria (CSU) who remained symptomatic despite H1AH therapy.

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

Detailed Description

This was a randomized, multicenteric, double-blinded, placebo-controlled, parallel-group study to evaluate the efficacy and safety of omalizumab as an add-on therapy for the treatment of patients of refractory CSU who remained symptomatic despite approved-dosed H1AH treatment.

The study consisted of three distinct epochs over 24 weeks: Screening epoch (Day -28 to Day -1), Randomized treatment epoch (Day 1 to Week 12) and Post-treatment follow-up epoch (Week 12 to Week 20). Patients were randomized into three treatment groups (omalizumab 300 mg s.c. omalizumab 150 mg s.c. and placebo) in a 2:2:1 ratio, stratified by latent tuberculosis (TB) status at Baseline (Yes/No).

On Day 1, eligible patients were randomly assigned to receive omalizumab (150 mg or 300 mg) or placebo by subcutaneous (s.c.) injection every 4 weeks (on Day 1, Week 4, and Week 8) during the 12-week double-blind randomized-treatment epoch. Patients visited the study center at 4-week intervals. Patients were instructed to stay on the same CSU H1AH treatment at stable dose that they were using during the pre-randomization period during the randomized treatment epoch. They were allowed to use diphenhydramine as rescue medication during all epochs. The last dose of the study drug during the randomized-treatment epoch was administered at Week 8 study visit, however, the last assessment was done at Week 12.

After the completion of the 12-week randomized-treatment epoch, all patients entered an 8-week post-treatment follow-up epoch.

Study Design

• Study Type: Interventional
• Actual Enrollment: 418 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III Study to Evaluate the Efficacy and Safety of Xolair® (Omalizumab) in Chinese Patients With Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite Antihistamine Treatment
• Actual Study Start Date: Apr 26, 2017
• Actual Primary Completion Date: Jul 23, 2019
• Actual Study Completion Date: Sep 24, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Omalizumab 300mg patients received a dose of omalizumab 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)	Drug: Omalizumab; injection of 150mg or 300 mg; Other Names: IGE025
Experimental: Omalizumab 150mg patients received a dose of omalizumab 150 mg which consisted of one injection of omalizumab 150 mg vial and one injection of placebo 150 mg vial every 4 weeks (Day 1, Week 4 and Week 8)	Drug: Omalizumab; injection of 150mg or 300 mg; Other Names: IGE025
Placebo Comparator: Placebo patients received placebo which consisted of two injections of placebo 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)	Drug: Placebo; Injection of placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline of the Itch Severity Score (ISS7) Score After 12 Weeks of Treatment [Baseline, Week 12]

   The severity of the itch was recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). Baseline ISS7 was calculated 7 days prior to the first treatment date. A weekly score (ISS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21, where 0 is the best score and 21 is the worst score. The complete itch response was defined as ISS7 = 0. Itch (Pruritus) Severity Score Scale: 0 = None = Mild (minimal awareness, easily tolerated) = Moderate (definite awareness, bothersome but tolerable) = Severe (difficult to tolerate)

Secondary Outcome Measures

1. Change From Baseline of Urticaria Activity Score (UAS7) After 12 Weeks of Treatment [Baseline, Week 12]

   UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement.

2. Change From Baseline of Number of Hives Score (NHS7) After 12 Weeks of Treatment [Baseline, Week 12]

   Hives Severity Score (HSS), defined by number of hives, were recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). A weekly number of hives score (NHS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21. The complete hives response was defined as NHS7 = 0. Hives Severity Score scale: 0 - None Mild (1-6 hives/12 hours) Moderate (7-12 hives/12 hours) Severe (>12 hives/12 hours)

3. Percentage of Patients With UAS7≤6 at Week 12 [Week 12]

   UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement. Week 12 responders were defined as patients who achieved an absolute UAS7 ≤ 6 at Week 12. A patient with missing data at Week 12 was imputed as a responder if the patient was a responder at Week 10 and Week 11, otherwise as a non-responder.

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

   UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement. Complete responders are defined as participants who achieved UAS7 = 0.

5. Percentage of Patients With ISS7 Minimally Important Difference (MID) at Week 12 [Week 12]

   The severity of the itch was recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). Baseline ISS7 was calculated 7 days prior to the first treatment date. A weekly score (ISS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21, where 0 is the best score and 21 is the worst score. The complete itch response was defined as ISS7 = 0. Itch (Pruritus) Severity Score Scale: 0 = None = Mild (minimal awareness, easily tolerated) = Moderate (definite awareness, bothersome but tolerable) = Severe (difficult to tolerate) The ISS7 MID response was defined as a reduction from Baseline in ISS7 of ≥ 5 points.

6. Change From Baseline of Dermatology Life Quality Index (DLQI) Score After 12 Weeks of Treatment [Week 12]

   Dermatology life quality index (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. An overall score was calculated as well as separate scores for the following domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, treatment. Each domain had 4 response categories ranging from 0 (not at all) to 3 (very much). "Not relevant" is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment.

7. Time to ISS7 MID Response by Week 12 [12 weeks]

   The ISS7 MID response was defined as a reduction from Baseline in ISS7 of ≥ 5 points. Time to ISS7 MID response was the time (in weeks) from the date of the first dose to the date where ISS7 MID response was first achieved during Week 1 to Week 12.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Main Inclusion Criteria:

• Symptomatic CSU patients with CSU diagnosis for at least 6 months.

• Patients must have been on an approved dose of an H1AH for CSU for at least the 3 consecutive days immediately prior to the Day -14 screening visit

• Patients must have documented current use on the day of the initial screening visit

Main Exclusion Criteria

• Clearly defined underlying etiology for chronic urticarias other than CSU (main manifestation being physical urticaria)

• Other skin disease associated with itch Urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary or acquired angioedema, lymphoma, leukemia, or generalized cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Beijing	Beijing	China	100039
2	Novartis Investigative Site	Fuzhou	Fujian	China	350025
3	Novartis Investigative Site	Guangzhou	Guangdong	China	510630
4	Novartis Investigative Site	Nanning	Guangxi	China	530021
5	Novartis Investigative Site	Harbin	Heilongjiang	China	150001
6	Novartis Investigative Site	Wuhan	Hubei	China	430022
7	Novartis Investigative Site	Wuhan	Hubei	China	430030
8	Novartis Investigative Site	Changsha	Hunan	China	410008
9	Novartis Investigative Site	Nanjing	Jiangsu	China	210029
10	Novartis Investigative Site	Suzhou	Jiangsu	China	215006
11	Novartis Investigative Site	Wuxi	Jiangsu	China
12	Novartis Investigative Site	Shenyang	Liaoning	China	110000
13	Novartis Investigative Site	Chengdu	Sichuan	China	610041
14	Novartis Investigative Site	Urumqi	Xinjiang	China	830001
15	Novartis Investigative Site	Hangzhou	Zhejiang	China	310003
16	Novartis Investigative Site	Hangzhou	Zhejiang	China	310006
17	Novartis Investigative Site	Hangzhou	Zhejiang	China	310016
18	Novartis Investigative Site	Beijing		China	100034
19	Novartis Investigative Site	Beijing		China	100050
20	Novartis Investigative Site	Beijing		China	100191
21	Novartis Investigative Site	Chongqing		China	400011
22	Novartis Investigative Site	Chongqing		China	400038
23	Novartis Investigative Site	Guangzhou		China	510000
24	Novartis Investigative Site	Nanjing		China	210042
25	Novartis Investigative Site	Shanghai		China	200025
26	Novartis Investigative Site	Shanghai		China	200040
27	Novartis Investigative Site	Shanghai		China	200433

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Aug 10, 2016
• Statistical Analysis Plan - Nov 11, 2019

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03328897
• Other Study ID Numbers: CIGE025E2305
• First Posted: Nov 1, 2017
• Last Update Posted: Nov 4, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Chronic spontaneous urticaria; ISS7; UAS7; omalizumab; China
• Additional relevant MeSH terms: Urticaria; Chronic Urticaria; Omalizumab

Study Results

Participant Flow

Recruitment Details	Patients were recruited from 27 sites across China.
Pre-assignment Detail	Patients were randomized into three treatment groups (omalizumab 300 mg s.c., omalizumab 150 mg s.c. and placebo) in a 2:2:1 ratio.

Arm/Group Title	Omalizumab 300mg	Omalizumab 150mg	Placebo
Arm/Group Description	patients received a dose of omalizumab 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)	patients received a dose of omalizumab 150 mg which consisted of one injection of omalizumab 150 mg vial and one injection of placebo 150 mg vial every 4 weeks (Day 1, Week 4 and Week 8)	patients received placebo which consisted of two injections of placebo 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)
Period Title: Randomized-treatment Epoch
STARTED	168	167	83
Full Analysis Set (FAS)	167	167	83
COMPLETED	152	162	81
NOT COMPLETED	16	5	2
Period Title: Randomized-treatment Epoch
STARTED	161	163	81
COMPLETED	153	160	79
NOT COMPLETED	8	3	2

Baseline Characteristics

Arm/Group Title	Omalizumab 300mg	Omalizumab 150mg	Placebo	Total
Arm/Group Description	patients received a dose of omalizumab 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)	patients received a dose of omalizumab 150 mg which consisted of one injection of omalizumab 150 mg vial and one injection of placebo 150 mg vial every 4 weeks (Day 1, Week 4 and Week 8)	patients received placebo which consisted of two injections of placebo 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)	Total of all reporting groups
Overall Participants	168	167	83	418
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.4 (12.29)	38.8 (12.18)	42.8 (12.32)	40.2 (12.31)
Sex: Female, Male (Count of Participants)
Female	115 68.5%	108 64.7%	53 63.9%	276 66%
Male	53 31.5%	59 35.3%	30 36.1%	142 34%
Race/Ethnicity, Customized (Count of Participants)
Asian	168 100%	167 100%	83 100%	418 100%
Race/Ethnicity, Customized (Count of Participants)
Chinese	168 100%	167 100%	83 100%	418 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline of the Itch Severity Score (ISS7) Score After 12 Weeks of Treatment
Description	The severity of the itch was recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). Baseline ISS7 was calculated 7 days prior to the first treatment date. A weekly score (ISS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21, where 0 is the best score and 21 is the worst score. The complete itch response was defined as ISS7 = 0. Itch (Pruritus) Severity Score Scale: 0 = None = Mild (minimal awareness, easily tolerated) = Moderate (definite awareness, bothersome but tolerable) = Severe (difficult to tolerate)
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Omalizumab 300mg	Omalizumab 150mg	Placebo
Arm/Group Description	patients received a dose of omalizumab 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)	patients received a dose of omalizumab 150 mg which consisted of one injection of omalizumab 150 mg vial and one injection of placebo 150 mg vial every 4 weeks (Day 1, Week 4 and Week 8)	patients received placebo which consisted of two injections of placebo 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)
Measure Participants	167	167	83
Least Squares Mean (Standard Error) [Score on a scale]	-10.11 (0.430)	-9.66 (0.424)	-5.87 (0.604)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 300mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model with Repeated Measures(MMRM)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.23
	Confidence Interval	(2-Sided) 95%; -5.70 to -2.77
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.746
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 150mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model with Repeated Measures(MMRM)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.79
	Confidence Interval	(2-Sided) 95%; -5.24 to -2.33
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.738
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline of Urticaria Activity Score (UAS7) After 12 Weeks of Treatment
Description	UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Omalizumab 300mg	Omalizumab 150mg	Placebo
Arm/Group Description	patients received a dose of omalizumab 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)	patients received a dose of omalizumab 150 mg which consisted of one injection of omalizumab 150 mg vial and one injection of placebo 150 mg vial every 4 weeks (Day 1, Week 4 and Week 8)	patients received placebo which consisted of two injections of placebo 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)
Measure Participants	167	167	83
Least Squares Mean (Standard Error) [Score on a scale]	-21.82 (0.895)	-20.74 (0.882)	-11.62 (1.258)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 300mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model with Repeated Measures(MMRM)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-10.19
	Confidence Interval	(2-Sided) 95%; -13.25 to -7.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.555
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 150mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model with Repeated Measures(MMRM)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-9.12
	Confidence Interval	(2-Sided) 95%; -12.14 to -6.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.535
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline of Number of Hives Score (NHS7) After 12 Weeks of Treatment
Description	Hives Severity Score (HSS), defined by number of hives, were recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). A weekly number of hives score (NHS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21. The complete hives response was defined as NHS7 = 0. Hives Severity Score scale: 0 - None Mild (1-6 hives/12 hours) Moderate (7-12 hives/12 hours) Severe (>12 hives/12 hours)
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Omalizumab 300mg	Omalizumab 150mg	Placebo
Arm/Group Description	patients received a dose of omalizumab 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)	patients received a dose of omalizumab 150 mg which consisted of one injection of omalizumab 150 mg vial and one injection of placebo 150 mg vial every 4 weeks (Day 1, Week 4 and Week 8)	patients received placebo which consisted of two injections of placebo 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)
Measure Participants	167	167	83
Least Squares Mean (Standard Error) [Score on a scale]	-11.68 (0.492)	-11.11 (0.485)	-5.76 (0.690)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 300mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model with Repeated Measures(MMRM)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-5.92
	Confidence Interval	(2-Sided) 95%; -7.59 to -4.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.853
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 150mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model with Repeated Measures(MMRM)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-5.35
	Confidence Interval	(2-Sided) 95%; -7.00 to -3.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.842
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Patients With UAS7≤6 at Week 12
Description	UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement. Week 12 responders were defined as patients who achieved an absolute UAS7 ≤ 6 at Week 12. A patient with missing data at Week 12 was imputed as a responder if the patient was a responder at Week 10 and Week 11, otherwise as a non-responder.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Omalizumab 300mg	Omalizumab 150mg	Placebo
Arm/Group Description	patients received a dose of omalizumab 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)	patients received a dose of omalizumab 150 mg which consisted of one injection of omalizumab 150 mg vial and one injection of placebo 150 mg vial every 4 weeks (Day 1, Week 4 and Week 8)	patients received placebo which consisted of two injections of placebo 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)
Measure Participants	167	167	83
Count of Participants [Participants]	81 48.2%	79 47.3%	9 10.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 300mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.02
	Confidence Interval	(2-Sided) 95%; 3.27 to 15.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 150mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.03
	Confidence Interval	(2-Sided) 95%; 3.29 to 15.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Complete Responders (UAS7 = 0) at Week 12
Description	UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. A higher urticaria activity score indicates more severe symptoms. A negative change score from baseline indicates improvement. Complete responders are defined as participants who achieved UAS7 = 0.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Omalizumab 300mg	Omalizumab 150mg	Placebo
Arm/Group Description	patients received a dose of omalizumab 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)	patients received a dose of omalizumab 150 mg which consisted of one injection of omalizumab 150 mg vial and one injection of placebo 150 mg vial every 4 weeks (Day 1, Week 4 and Week 8)	patients received placebo which consisted of two injections of placebo 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)
Measure Participants	167	167	83
Count of Participants [Participants]	62 36.9%	39 23.4%	4 4.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 300mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	11.21
	Confidence Interval	(2-Sided) 95%; 3.88 to 32.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 150mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.88
	Confidence Interval	(2-Sided) 95%; 2.01 to 17.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Patients With ISS7 Minimally Important Difference (MID) at Week 12
Description	The severity of the itch was recorded by the patient twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). Baseline ISS7 was calculated 7 days prior to the first treatment date. A weekly score (ISS7) was derived by adding up the average daily scores of the seven days preceding the visit. The possible range of the weekly score was therefore 0 to 21, where 0 is the best score and 21 is the worst score. The complete itch response was defined as ISS7 = 0. Itch (Pruritus) Severity Score Scale: 0 = None = Mild (minimal awareness, easily tolerated) = Moderate (definite awareness, bothersome but tolerable) = Severe (difficult to tolerate) The ISS7 MID response was defined as a reduction from Baseline in ISS7 of ≥ 5 points.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Omalizumab 300mg	Omalizumab 150mg	Placebo
Arm/Group Description	patients received a dose of omalizumab 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)	patients received a dose of omalizumab 150 mg which consisted of one injection of omalizumab 150 mg vial and one injection of placebo 150 mg vial every 4 weeks (Day 1, Week 4 and Week 8)	patients received placebo which consisted of two injections of placebo 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)
Measure Participants	167	167	83
Count of Participants [Participants]	125 74.4%	125 74.9%	49 59%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 300mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.73
	Confidence Interval	(2-Sided) 95%; 1.51 to 4.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 150mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.53
	Confidence Interval	(2-Sided) 95%; 1.41 to 4.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline of Dermatology Life Quality Index (DLQI) Score After 12 Weeks of Treatment
Description	Dermatology life quality index (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. An overall score was calculated as well as separate scores for the following domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, treatment. Each domain had 4 response categories ranging from 0 (not at all) to 3 (very much). "Not relevant" is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Omalizumab 300mg	Omalizumab 150mg	Placebo
Arm/Group Description	patients received a dose of omalizumab 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)	patients received a dose of omalizumab 150 mg which consisted of one injection of omalizumab 150 mg vial and one injection of placebo 150 mg vial every 4 weeks (Day 1, Week 4 and Week 8)	patients received placebo which consisted of two injections of placebo 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)
Measure Participants	167	167	83
Least Squares Mean (Standard Error) [Score on a scale]	-10.4 (0.50)	-9.9 (0.49)	-6.5 (0.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 300mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model with Repeated Measures(MMRM)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.0
	Confidence Interval	(2-Sided) 95%; -5.7 to -2.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.85
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 150mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Model with Repeated Measures(MMRM)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.5
	Confidence Interval	(2-Sided) 95%; -5.1 to -1.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.85
	Estimation Comments

8. Secondary Outcome

Title	Time to ISS7 MID Response by Week 12
Description	The ISS7 MID response was defined as a reduction from Baseline in ISS7 of ≥ 5 points. Time to ISS7 MID response was the time (in weeks) from the date of the first dose to the date where ISS7 MID response was first achieved during Week 1 to Week 12.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Omalizumab 300mg	Omalizumab 150mg	Placebo
Arm/Group Description	patients received a dose of omalizumab 300 mg which consisted of two injections of omalizumab 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)	patients received a dose of omalizumab 150 mg which consisted of one injection of omalizumab 150 mg vial and one injection of placebo 150 mg vial every 4 weeks (Day 1, Week 4 and Week 8)	patients received placebo which consisted of two injections of placebo 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)
Measure Participants	167	167	83
First Response: >0 to <=4 weeks	114 67.9%	109 65.3%	42 50.6%
First Response: >4 to <=8 weeks	18 10.7%	25 15%	10 12%
First Response: >8 to <=12 weeks	10 6%	10 6%	7 8.4%
No response	25 14.9%	23 13.8%	24 28.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 300mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.71
	Confidence Interval	(2-Sided) 95%; 1.25 to 2.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Omalizumab 150mg, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.66
	Confidence Interval	(2-Sided) 95%; 1.22 to 2.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse events were collected from first dose of study treatment until end of study treatment (Day 1 to week 12) plus 8 weeks post-treatment follow-up epoch (week 12 to week 20).
Arm/Group Title	Omalizumab 300 mg		Omalizumab 150 mg		Placebo
Arm/Group Description	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 12 week treatment period.		Participants received omalizumab 150 mg subcutaneously every 4 weeks during the 12 week treatment period.		patients received placebo which consisted of two injections of placebo 150 mg vials every 4 weeks (Day 1, Week 4 and Week 8)
All Cause Mortality
	Omalizumab 300 mg		Omalizumab 150 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/167 (0%)		0/167 (0%)		0/83 (0%)
Serious Adverse Events
	Omalizumab 300 mg		Omalizumab 150 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/167 (3%)		5/167 (3%)		3/83 (3.6%)
Ear and labyrinth disorders
Vertigo positional	1/167 (0.6%)		0/167 (0%)		0/83 (0%)
Infections and infestations
Pelvic inflammatory disease	0/167 (0%)		1/167 (0.6%)		0/83 (0%)
Upper respiratory tract infection	1/167 (0.6%)		0/167 (0%)		0/83 (0%)
Injury, poisoning and procedural complications
Lumbar vertebral fracture	0/167 (0%)		0/167 (0%)		1/83 (1.2%)
Meniscus injury	0/167 (0%)		0/167 (0%)		1/83 (1.2%)
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy	0/167 (0%)		1/167 (0.6%)		0/83 (0%)
Pregnancy	1/167 (0.6%)		1/167 (0.6%)		0/83 (0%)
Reproductive system and breast disorders
Cervical dysplasia	0/167 (0%)		1/167 (0.6%)		0/83 (0%)
Rectocele	0/167 (0%)		1/167 (0.6%)		0/83 (0%)
Skin and subcutaneous tissue disorders
Urticaria chronic	1/167 (0.6%)		0/167 (0%)		0/83 (0%)
Vascular disorders
Embolism venous	0/167 (0%)		0/167 (0%)		1/83 (1.2%)
Hypertension	1/167 (0.6%)		1/167 (0.6%)		0/83 (0%)
Other (Not Including Serious) Adverse Events
	Omalizumab 300 mg		Omalizumab 150 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	84/167 (50.3%)		79/167 (47.3%)		43/83 (51.8%)
Gastrointestinal disorders
Abdominal discomfort	0/167 (0%)		4/167 (2.4%)		2/83 (2.4%)
Diarrhoea	2/167 (1.2%)		4/167 (2.4%)		1/83 (1.2%)
General disorders
Pyrexia	5/167 (3%)		4/167 (2.4%)		1/83 (1.2%)
Hepatobiliary disorders
Hepatic function abnormal	0/167 (0%)		2/167 (1.2%)		3/83 (3.6%)
Infections and infestations
Herpes zoster	1/167 (0.6%)		4/167 (2.4%)		0/83 (0%)
Influenza	7/167 (4.2%)		7/167 (4.2%)		1/83 (1.2%)
Nasopharyngitis	7/167 (4.2%)		8/167 (4.8%)		7/83 (8.4%)
Pharyngitis	1/167 (0.6%)		4/167 (2.4%)		3/83 (3.6%)
Upper respiratory tract infection	36/167 (21.6%)		25/167 (15%)		12/83 (14.5%)
Urinary tract infection	4/167 (2.4%)		1/167 (0.6%)		2/83 (2.4%)
Investigations
Alanine aminotransferase increased	1/167 (0.6%)		6/167 (3.6%)		1/83 (1.2%)
Blood creatine phosphokinase increased	1/167 (0.6%)		5/167 (3%)		0/83 (0%)
Blood glucose increased	2/167 (1.2%)		0/167 (0%)		2/83 (2.4%)
Blood uric acid increased	5/167 (3%)		5/167 (3%)		4/83 (4.8%)
Lymphocyte count increased	0/167 (0%)		0/167 (0%)		2/83 (2.4%)
Platelet count decreased	0/167 (0%)		2/167 (1.2%)		2/83 (2.4%)
Red blood cells urine positive	0/167 (0%)		2/167 (1.2%)		2/83 (2.4%)
Metabolism and nutrition disorders
Hyperuricaemia	4/167 (2.4%)		3/167 (1.8%)		1/83 (1.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	6/167 (3.6%)		4/167 (2.4%)		0/83 (0%)
Back pain	1/167 (0.6%)		1/167 (0.6%)		2/83 (2.4%)
Nervous system disorders
Dizziness	1/167 (0.6%)		2/167 (1.2%)		2/83 (2.4%)
Headache	4/167 (2.4%)		4/167 (2.4%)		0/83 (0%)
Hypoaesthesia	2/167 (1.2%)		0/167 (0%)		2/83 (2.4%)
Respiratory, thoracic and mediastinal disorders
Cough	11/167 (6.6%)		3/167 (1.8%)		2/83 (2.4%)
Dry throat	0/167 (0%)		0/167 (0%)		2/83 (2.4%)
Oropharyngeal pain	4/167 (2.4%)		1/167 (0.6%)		3/83 (3.6%)
Rhinorrhoea	4/167 (2.4%)		2/167 (1.2%)		1/83 (1.2%)
Skin and subcutaneous tissue disorders
Dermatitis	2/167 (1.2%)		1/167 (0.6%)		3/83 (3.6%)
Eczema	5/167 (3%)		4/167 (2.4%)		1/83 (1.2%)
Vascular disorders
Hypertension	4/167 (2.4%)		2/167 (1.2%)		0/83 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.