Dose-finding Study of QGE031 as add-on Therapy to Evaluate Efficacy and Safety in Patients With CSU

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02477332
• Collaborator: (none)
• Enrollment: 382
• Locations: 82
• Arms: 6
• Actual Duration (Months): 22.9
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a placebo and active-controlled phase 2b dose-finding study to evaluate efficacy and safety of QGE031 monthly subcutaneous injections as add-on therapy in patients with Chronic Spontaneous Urticaria.

Condition or Disease	Intervention/Treatment	Phase
Chronic Spontaneous Urticaria	Biological: QGE031; Biological: Omalizumab; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 382 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Double-blind, Placebo, and Active-controlled Phase 2b Dose-finding Study of QGE031 as add-on Therapy to Investigate the Efficacy and Safety in Patients With Chronic Spontaneous Urticaria (CSU)
• Actual Study Start Date: Jul 15, 2015
• Actual Primary Completion Date: Nov 2, 2016
• Actual Study Completion Date: Jun 12, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: QGE031 24 mg s.c. q4w ligelizumab 24 mg injection subcutaneous every 4 weeks	Biological: QGE031
Experimental: QGE031 72 mg s.c. q4w ligelizumab 72 mg injection subcutaneous every 4 weeks	Biological: QGE031
Experimental: QGE031 240 mg s.c. q4w ligelizumab 240 mg injection subcutaneous every 4 weeks	Biological: QGE031
Active Comparator: Omalizumab 300 mg s.c. q4w omalizumab 300 mg injection subcutaneous every 4 weeks	Biological: Omalizumab
Placebo Comparator: Placebo s.c. q4w placebo injection subcutaneous every 4 weeks	Other: Placebo
Experimental: QGE031 120 mg s.c. s.d. ligelizumab 120 mg injection subcutaneous single dose	Biological: QGE031

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Complete Hives Response (HSS7=0) [Week 12]

   The primary objective was to establish the dose-response relationship of ligelizumab (24, 72 and 240 mg every 4 weeks) with respect to achievement of complete hives response (HSS7=0) at Week 12 and select an appropriate dose (or range of doses) which is likely to be superior to omalizumab at the highest approved dose (300 mg every 4 weeks). Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the preceding 7 days, with a possible range of 0 - 21. Hives Severity Score scale: 0 - None - Mild (1-6 hives/12 hours) - Moderate (7-12 hives/12 hours) - Severe (>12 hives/12 hours) To confirm an overall dose-response signal based on MCP-Mod, and to estimate the minimal ligelizumab dose that shows a relevant superior effect over omalizumab, based on the selected dose response model, the lowest ligelizumab dose that provides a response rate 15% higher than the response of omalizumab 300 mg.

Secondary Outcome Measures

1. Complete Hives Response (HSS7=0) Rate at Week 12 Measured Over 7 Days [Week 12]

   Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Complete hives response defined as HSS7 = 0. Hives Severity Score scale: 0 - None - Mild (1-6 hives/12 hours) - Moderate (7-12 hives/12 hours) - Severe (>12 hives/12 hours)

2. Change From Baseline in Hives Severity Score (HSS7) at Week 12 Measured Over 7 Days [Week 12]

   Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None - Mild (1-6 hives/12 hours) - Moderate (7-12 hives/12 hours) - Severe (>12 hives/12 hours)

3. HSS7=0 Response: at Week 20 Measured Over 7 Days [Week 20]

   Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Complete hives response defined as HSS7 = 0. Hives Severity Score scale: 0 - None - Mild (1-6 hives/12 hours) - Moderate (7-12 hives/12 hours) - Severe (>12 hives/12 hours)

4. Change From Baseline in Hives Severity Score (HSS7) at Week 20 Measured Over 7 Days [Week 20]

   Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None - Mild (1-6 hives/12 hours) - Moderate (7-12 hives/12 hours) - Severe (>12 hives/12 hours)

5. Change From Baseline in Itch Severity Score (ISS7) at Week 12 Measured Over 7 Days [Week 12]

   Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None - Mild (minimal awareness, easily tolerated) - Moderate (definite awareness, bothersome but tolerable) - Severe (difficult to tolerate)

6. Change From Baseline in Itch Severity Score (ISS7) at Week 20 Measured Over 7 Days [Week 20]

   Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None - Mild (minimal awareness, easily tolerated) - Moderate (definite awareness, bothersome but tolerable) - Severe (difficult to tolerate)

7. Change From Baseline in Urticaria Activity Score (UAS7) at Week 12 Measured Over 7 Days [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.

8. Change From Baseline in Urticaria Activity Score (UAS7) at Week 20 Measured Over 7 Days [Week 20]

   UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42.

9. Complete Urticaria Activity Score Response (UAS7=0) Rate at Week 12 Measured Over 7 Days [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. Complete urticaria activity response is defined as UAS7 = 0.

10. UAS7=0 Response: at Week 20 Measured Over 7 Days [Week 20]

    UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. Complete urticaria activity response is defined as UAS7 = 0.

11. Complete Itch Response (ISS7=0) Rate at Week 12 Measured Over 7 Days [Week 12]

    Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Complete itch response defined as ISS7 = 0. Itch Severity Score scale: 0 - None - Mild (minimal awareness, easily tolerated) - Moderate (definite awareness, bothersome but tolerable) - Severe (difficult to tolerate)

12. ISS7=0 Response: at Week 20 Measured Over 7 Days [Week 20]

    Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Complete itch response defined as ISS7 = 0. Itch Severity Score scale: 0 - None - Mild (minimal awareness, easily tolerated) - Moderate (definite awareness, bothersome but tolerable) - Severe (difficult to tolerate)

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of chronic spontaneous urticaria for at least 6 months

• Diagnosis of chronic spontaneous urticaria refractory to standard of care at time of randomization

Exclusion Criteria:

• Clearly defined underlying etiology for chronic urticaria other than chronic spontaneous urticaria

• Evidence of parasitic infection

• Any other skin disease with chronic itching

• Previous treatment with omalizumab or QGE031

• Contraindications to or hypersensitivity to fexofenadine, loratadine, cetirizine, or epinephrine

• History of anaphylaxis

• History or current diagnosis of ECG abnormalities indicating significant risk of safety for patients participating in the study

• History of hypersensitivity to any of the study drugs or its components of similar chemical classes

• Pregnant or nursing (lactating) women

Other protocol defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Birmingham	Alabama	United States	35209
2	Novartis Investigative Site	Scottsdale	Arizona	United States	85251
3	Novartis Investigative Site	Little Rock	Arkansas	United States	72205
4	Novartis Investigative Site	Huntington Beach	California	United States	92647
5	Novartis Investigative Site	Mission Viejo	California	United States	92691
6	Novartis Investigative Site	Sarasota	Florida	United States	34233
7	Novartis Investigative Site	Evansville	Indiana	United States	47713
8	Novartis Investigative Site	Louisville	Kentucky	United States	40291
9	Novartis Investigative Site	Owensboro	Kentucky	United States	42301
10	Novartis Investigative Site	Waldorf	Maryland	United States	20602
11	Novartis Investigative Site	Minneapolis	Minnesota	United States	55402
12	Novartis Investigative Site	Rochester	Minnesota	United States	55905
13	Novartis Investigative Site	Saint Louis	Missouri	United States	63141
14	Novartis Investigative Site	Bronx	New York	United States	10461
15	Novartis Investigative Site	Forest Hills	New York	United States	11375
16	Novartis Investigative Site	Asheville	North Carolina	United States	28801
17	Novartis Investigative Site	Cincinnati	Ohio	United States	45231
18	Novartis Investigative Site	Toledo	Ohio	United States	43617
19	Novartis Investigative Site	Lake Oswego	Oregon	United States	97035
20	Novartis Investigative Site	Providence	Rhode Island	United States	02906
21	Novartis Investigative Site	Dallas	Texas	United States	75230
22	Novartis Investigative Site	Fort Worth	Texas	United States	76132
23	Novartis Investigative Site	Katy	Texas	United States	77450
24	Novartis Investigative Site	South Burlington	Vermont	United States	05403
25	Novartis Investigative Site	Spokane	Washington	United States	99204
26	Novartis Investigative Site	Campbelltown	New South Wales	Australia	2560
27	Novartis Investigative Site	Sydney	New South Wales	Australia	2010
28	Novartis Investigative Site	Woolloongabba	Queensland	Australia	4102
29	Novartis Investigative Site	Adelaide	South Australia	Australia	5000
30	Novartis Investigative Site	East Melbourne	Victoria	Australia	3002
31	Novartis Investigative Site	Toronto	Ontario	Canada	M4V 1R2
32	Novartis Investigative Site	Waterloo	Ontario	Canada	N2J 1C4
33	Novartis Investigative Site	Quebec		Canada	G1V 4W2
34	Novartis Investigative Site	Muenchen	Bayern	Germany	80802
35	Novartis Investigative Site	Berlin		Germany	10117
36	Novartis Investigative Site	Dresden		Germany	01307
37	Novartis Investigative Site	Freiburg		Germany	79106
38	Novartis Investigative Site	Hannover		Germany	30625
39	Novartis Investigative Site	Mainz		Germany	55131
40	Novartis Investigative Site	Muenster		Germany	48149
41	Novartis Investigative Site	Athens	GR	Greece	115 27
42	Novartis Investigative Site	Athens		Greece	11527
43	Novartis Investigative Site	Haidari Athens		Greece	12462
44	Novartis Investigative Site	Hiroshima city	Hiroshima	Japan	734-8551
45	Novartis Investigative Site	Obihiro-city	Hokkaido	Japan	080-0013
46	Novartis Investigative Site	Kobe-shi	Hyogo	Japan	650-0017
47	Novartis Investigative Site	Yokohama-city	Kanagawa	Japan	221-0825
48	Novartis Investigative Site	Kamimashi-gun	Kumamoto	Japan	861-3101
49	Novartis Investigative Site	Kyoto-city	Kyoto	Japan	602-8566
50	Novartis Investigative Site	Sakai	Osaka	Japan	593-8324
51	Novartis Investigative Site	Saitama-city	Saitama	Japan	330-0854
52	Novartis Investigative Site	Machida-city	Tokyo	Japan	194-0013
53	Novartis Investigative Site	Ota-ku	Tokyo	Japan	143-0023
54	Novartis Investigative Site	Shinagawa-ku	Tokyo	Japan	141 8625
55	Novartis Investigative Site	Kazan	Tatarstan Republic	Russian Federation	420012
56	Novartis Investigative Site	Chelyabinsk		Russian Federation	454092
57	Novartis Investigative Site	Moscow		Russian Federation	107076
58	Novartis Investigative Site	Moscow		Russian Federation	115478
59	Novartis Investigative Site	Smolensk		Russian Federation	214019
60	Novartis Investigative Site	St Petersburg		Russian Federation	194223
61	Novartis Investigative Site	St.-Petersburg		Russian Federation	195112
62	Novartis Investigative Site	Cordoba	Andalucia	Spain	14004
63	Novartis Investigative Site	Malaga	Andalucia	Spain	29009
64	Novartis Investigative Site	Sevilla	Andalucia	Spain	41009
65	Novartis Investigative Site	Sant Joan Despi	Barcelona	Spain	08970
66	Novartis Investigative Site	Barcelona	Cataluna	Spain	08003
67	Novartis Investigative Site	Barcelona	Cataluna	Spain	08035
68	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
69	Novartis Investigative Site	Alicante	Comunidad Valenciana	Spain	03010
70	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46015
71	Novartis Investigative Site	La Coruna	Galicia	Spain	15006
72	Novartis Investigative Site	Alcorcon	Madrid	Spain	28922
73	Novartis Investigative Site	Pozuelo de Alarcon	Madrid	Spain	28223
74	Novartis Investigative Site	Barcelona		Spain	08041
75	Novartis Investigative Site	Madrid		Spain	28040
76	Novartis Investigative Site	Madrid		Spain	28041
77	Novartis Investigative Site	Taichung		Taiwan	407
78	Novartis Investigative Site	Taipei		Taiwan	10002
79	Novartis Investigative Site	Tao-Yuan		Taiwan	333
80	Novartis Investigative Site	Yeovil	Somerset	United Kingdom	BA21 4AT
81	Novartis Investigative Site	Leeds		United Kingdom	LS9 7TF
82	Novartis Investigative Site	London		United Kingdom	SE1 9RT

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicatrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02477332
• Other Study ID Numbers: CQGE031C2201; 2014-005559-16
• First Posted: Jun 22, 2015
• Last Update Posted: Jan 5, 2021
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: QGE031; ligelizumab; omalizumab; chronic; spontaneous; urticaria; adults; CSU
• Additional relevant MeSH terms: Urticaria; Chronic Urticaria; Omalizumab

Study Results

Participant Flow

Recruitment Details	574 subjects screened; 382 subjects randomized; 338 (88.5%) subjects completed treatment epoch; 349 (91.4%) subjects entered follow-up phase and 320 (83.8%) completed the follow-up epoch

Arm/Group Title	QGE031 24 mg s.c. q4w	QGE031 72 mg s.c. q4w	QGE031 240 mg s.c. q4w	Omalizumab 300 mg s.c. q4w	Placebo s.c. q4w	QGE031 120 mg s.c. s.d.
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks	ligelizumab 72 mg injection subcutaneous every 4 weeks	ligelizumab 240 mg injection subcutaneous every 4 weeks	omalizumab 300 mg injection subcutaneous every 4 weeks	placebo injection subcutaneous every 4 weeks	ligelizumab 120 mg injection subcutaneous single dose
Period Title: Overall Study
STARTED	43	84	85	85	43	42
COMPLETED	40	77	73	72	39	37
NOT COMPLETED	3	7	12	13	4	5

Baseline Characteristics

Arm/Group Title	QGE031 24 mg s.c. q4w	QGE031 72 mg s.c. q4w	QGE031 240 mg s.c. q4w	Omalizumab 300 mg s.c. q4w	Placebo s.c. q4w	QGE031 120 mg s.c. s.d.	Total
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks	ligelizumab 72 mg injection subcutaneous every 4 weeks	ligelizumab 240 mg injection subcutaneous every 4 weeks	omalizumab 300 mg injection subcutaneous every 4 weeks	placebo injection subcutaneous every 4 weeks	ligelizumab 120 mg injection subcutaneous single dose	Total of all reporting groups
Overall Participants	43	84	85	85	43	42	382
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	39 90.7%	77 91.7%	85 100%	81 95.3%	41 95.3%	37 88.1%	360 94.2%
>=65 years	4 9.3%	7 8.3%	0 0%	4 4.7%	2 4.7%	5 11.9%	22 5.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.1 (14.36)	44.3 (12.38)	42.9 (10.51)	41.8 (13.06)	45.4 (11.22)	42.4 (14.54)	43.3 (12.49)
Sex: Female, Male (Count of Participants)
Female	31 72.1%	61 72.6%	67 78.8%	66 77.6%	31 72.1%	30 71.4%	286 74.9%
Male	12 27.9%	23 27.4%	18 21.2%	19 22.4%	12 27.9%	12 28.6%	96 25.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Complete Hives Response (HSS7=0)
Description	The primary objective was to establish the dose-response relationship of ligelizumab (24, 72 and 240 mg every 4 weeks) with respect to achievement of complete hives response (HSS7=0) at Week 12 and select an appropriate dose (or range of doses) which is likely to be superior to omalizumab at the highest approved dose (300 mg every 4 weeks). Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the preceding 7 days, with a possible range of 0 - 21. Hives Severity Score scale: 0 - None - Mild (1-6 hives/12 hours) - Moderate (7-12 hives/12 hours) - Severe (>12 hives/12 hours) To confirm an overall dose-response signal based on MCP-Mod, and to estimate the minimal ligelizumab dose that shows a relevant superior effect over omalizumab, based on the selected dose response model, the lowest ligelizumab dose that provides a response rate 15% higher than the response of omalizumab 300 mg.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients, removing misrandomized patients provided that study drug was not administered.

Arm/Group Title	QGE031 24 mg s.c. q4w	QGE031 72 mg s.c. q4w	QGE031 240 mg s.c. q4w	Omalizumab 300 mg s.c. q4w	Placebo s.c. q4w	QGE031 120 mg s.c. s.d.
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks	ligelizumab 72 mg injection subcutaneous every 4 weeks	ligelizumab 240 mg injection subcutaneous every 4 weeks	omalizumab 300 mg injection subcutaneous every 4 weeks	placebo injection subcutaneous every 4 weeks	ligelizumab 120 mg injection subcutaneous single dose
Measure Participants	43	84	85	85	43	42
Number (95% Confidence Interval) [Percentage of participants]	30.2 70.2%	51.2 61%	42.4 49.9%	25.9 30.5%	0 0%	19.0 45.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	QGE031 24 mg s.c. q4w, QGE031 72 mg s.c. q4w, QGE031 240 mg s.c. q4w, Omalizumab 300 mg s.c. q4w
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments
	Method	Regression, Logistic
	Comments	Target dose was based on this estimated dose response. The 60% CI included the 20 - 80th percentile of target dose estimated in the bootstrap samples.
Method of Estimation	Estimation Parameter	Estimated target dose
	Estimated Value	32.5
	Confidence Interval	(2-Sided) 60%; 27.5 to 42.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Min dose with effect size >15%

2. Secondary Outcome

Title	Complete Hives Response (HSS7=0) Rate at Week 12 Measured Over 7 Days
Description	Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Complete hives response defined as HSS7 = 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	Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients, removing misrandomized patients provided that study drug was not administered. As per protocol and SAP, for the efficacy endpoints at Week 12 or Week 20, only the QGE031 24, 72 & 240 mg, omalizumab 300 mg and placebo arms were analyzed for efficacy comparison between treatment groups.

Arm/Group Title	QGE031 24 mg s.c. q4w	QGE031 72 mg s.c. q4w	QGE031 240 mg s.c. q4w	Omalizumab 300 mg s.c. q4w	Placebo
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks	ligelizumab 72 mg injection subcutaneous every 4 weeks	ligelizumab 240 mg injection subcutaneous every 4 weeks	omalizumab 300 mg injection subcutaneous every 4 weeks	placebo injection subcutaneous every 4 week
Measure Participants	43	84	85	85	43
Number [Particpants]	13	43	36	22	0

3. Secondary Outcome

Title	Change From Baseline in Hives Severity Score (HSS7) at Week 12 Measured Over 7 Days
Description	Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. 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	Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients, removing misrandomized patients provided that study drug was not administered. As per protocol and SAP, for the efficacy endpoints at Week 12 or Week 20, only the QGE031 24, 72 & 240 mg, omalizumab 300 mg and placebo arms were analyzed for efficacy comparison between treatment groups.

Arm/Group Title	QGE031 24 mg s.c. q4w	QGE031 72 mg s.c. q4w	QGE031 240 mg s.c. q4w	Omalizumab 300 mg s.c. q4w	Placebo
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks	ligelizumab 72 mg injection subcutaneous every 4 weeks	ligelizumab 240 mg injection subcutaneous every 4 weeks	omalizumab 300 mg injection subcutaneous every 4 weeks	placebo injection subcutaneous every 4 week
Measure Participants	40	81	78	77	41
Median (95% Confidence Interval) [Score on a scale]	-9.75	-15.50	-13.50	-11.00	-6.50

4. Secondary Outcome

Title	HSS7=0 Response: at Week 20 Measured Over 7 Days
Description	Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Complete hives response defined as HSS7 = 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	Week 20

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients, removing misrandomized patients provided that study drug was not administered. As per protocol and SAP, for the efficacy endpoints at Week 12 or Week 20, only the QGE031 24, 72 & 240 mg, omalizumab 300 mg and placebo arms were analyzed for efficacy comparison between treatment groups.

Arm/Group Title	QGE031 24 mg s.c. q4w	QGE031 72 mg s.c. q4w	QGE031 240 mg s.c. q4w	Omalizumab 300 mg s.c. q4w	Placebo
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks	ligelizumab 72 mg injection subcutaneous every 4 weeks	ligelizumab 240 mg injection subcutaneous every 4 weeks	omalizumab 300 mg injection subcutaneous every 4 weeks	placebo injection subcutaneous every 4 week
Measure Participants	43	84	85	85	43
Number [Participants]	11 25.6%	43 51.2%	38 44.7%	29 34.1%	4 9.3%

5. Secondary Outcome

Title	Change From Baseline in Hives Severity Score (HSS7) at Week 20 Measured Over 7 Days
Description	Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. 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	Week 20

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients, removing misrandomized patients provided that study drug was not administered. As per protocol and SAP, for the efficacy endpoints at Week 12 or Week 20, only the QGE031 24, 72 & 240 mg, omalizumab 300 mg and placebo arms were analyzed for efficacy comparison between treatment groups.

Arm/Group Title	QGE031 24 mg s.c. q4w	QGE031 72 mg s.c. q4w	QGE031 240 mg s.c. q4w	Omalizumab 300 mg s.c. q4w	Placebo
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks	ligelizumab 72 mg injection subcutaneous every 4 weeks	ligelizumab 240 mg injection subcutaneous every 4 weeks	omalizumab 300 mg injection subcutaneous every 4 weeks	placebo injection subcutaneous every 4 week
Measure Participants	39	78	74	73	40
Median (95% Confidence Interval) [Score on a scale]	-9.00	-16.50	-14.00	-11.00	-7.50

6. Secondary Outcome

Title	Change From Baseline in Itch Severity Score (ISS7) at Week 12 Measured Over 7 Days
Description	Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None - Mild (minimal awareness, easily tolerated) - Moderate (definite awareness, bothersome but tolerable) - Severe (difficult to tolerate)
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients, removing misrandomized patients provided that study drug was not administered. As per protocol and SAP, for the efficacy endpoints at Week 12 or Week 20, only the QGE031 24, 72 & 240 mg, omalizumab 300 mg and placebo arms were analyzed for efficacy comparison between treatment groups.

Arm/Group Title	QGE031 24 mg s.c. q4w	QGE031 72 mg s.c. q4w	QGE031 240 mg s.c. q4w	Omalizumab 300 mg s.c. q4w	Placebo
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks	ligelizumab 72 mg injection subcutaneous every 4 weeks	ligelizumab 240 mg injection subcutaneous every 4 weeks	omalizumab 300 mg injection subcutaneous every 4 weeks	placebo injection subcutaneous every 4 week
Measure Participants	40	81	78	77	41
Median (95% Confidence Interval) [Score on a scale]	-7.50	-9.50	-9.00	-8.00	-5.50

7. Secondary Outcome

Title	Change From Baseline in Itch Severity Score (ISS7) at Week 20 Measured Over 7 Days
Description	Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None - Mild (minimal awareness, easily tolerated) - Moderate (definite awareness, bothersome but tolerable) - Severe (difficult to tolerate)
Time Frame	Week 20

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients, removing misrandomized patients provided that study drug was not administered. As per protocol and SAP, for the efficacy endpoints at Week 12 or Week 20, only the QGE031 24, 72 & 240 mg, omalizumab 300 mg and placebo arms were analyzed for efficacy comparison between treatment groups.

Arm/Group Title	QGE031 24 mg s.c. q4w	QGE031 72 mg s.c. q4w	QGE031 240 mg s.c. q4w	Omalizumab 300 mg s.c. q4w	Placebo
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks	ligelizumab 72 mg injection subcutaneous every 4 weeks	ligelizumab 240 mg injection subcutaneous every 4 weeks	omalizumab 300 mg injection subcutaneous every 4 weeks
Measure Participants	39	78	74	73	40
Median (95% Confidence Interval) [Score on a scale]	-7.00	-10.25	-10.00	-8.83	-5.00

8. Secondary Outcome

Title	Change From Baseline in Urticaria Activity Score (UAS7) at Week 12 Measured Over 7 Days
Description	UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients, removing misrandomized patients provided that study drug was not administered. As per protocol and SAP, for the efficacy endpoints at Week 12 or Week 20, only the QGE031 24, 72 & 240 mg, omalizumab 300 mg and placebo arms were analyzed for efficacy comparison between treatment groups.

Arm/Group Title	QGE031 24 mg s.c. q4w	QGE031 72 mg s.c. q4w	QGE031 240 mg s.c. q4w	Omalizumab 300 mg s.c. q4w	Placebo
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks	ligelizumab 72 mg injection subcutaneous every 4 weeks	ligelizumab 240 mg injection subcutaneous every 4 weeks	omalizumab 300 mg injection subcutaneous every 4 weeks	placebo injection subcutaneous every 4 week
Measure Participants	40	81	78	77	41
Median (95% Confidence Interval) [Score on a scale]	-19.50	-26.50	-21.75	-19.00	-12.00

9. Secondary Outcome

Title	Change From Baseline in Urticaria Activity Score (UAS7) at Week 20 Measured Over 7 Days
Description	UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42.
Time Frame	Week 20

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients, removing misrandomized patients provided that study drug was not administered. As per protocol and SAP, for the efficacy endpoints at Week 12 or Week 20, only the QGE031 24, 72 & 240 mg, omalizumab 300 mg and placebo arms were analyzed for efficacy comparison between treatment groups.

Arm/Group Title	QGE031 24 mg s.c. q4w	QGE031 72 mg s.c. q4w	QGE031 240 mg s.c. q4w	Omalizumab 300 mg s.c. q4w	Placebo
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks	ligelizumab 72 mg injection subcutaneous every 4 weeks	ligelizumab 240 mg injection subcutaneous every 4 weeks	omalizumab 300 mg injection subcutaneous every 4 weeks	placebo injection subcutaneous every 4 week
Measure Participants	39	78	74	73	40
Median (95% Confidence Interval) [Score on a scale]	-16.00	-27.00	-22.92	-18.50	-13.00

10. Secondary Outcome

Title	Complete Urticaria Activity Score Response (UAS7=0) Rate at Week 12 Measured Over 7 Days
Description	UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. Complete urticaria activity response is defined as UAS7 = 0.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients, removing misrandomized patients provided that study drug was not administered. As per protocol and SAP, for the efficacy endpoints at Week 12 or Week 20, only the QGE031 24, 72 & 240 mg, omalizumab 300 mg and placebo arms were analyzed for efficacy comparison between treatment groups.

Arm/Group Title	QGE031 24 mg s.c. q4w	QGE031 72 mg s.c. q4w	QGE031 240 mg s.c. q4w	Omalizumab 300 mg s.c. q4w	Placebo
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks	ligelizumab 72 mg injection subcutaneous every 4 weeks	ligelizumab 240 mg injection subcutaneous every 4 weeks	omalizumab 300 mg injection subcutaneous every 4 weeks	placebo injection subcutaneous every 4 week
Measure Participants	43	84	85	85	43
Number [Participants]	13 30.2%	37 44%	34 40%	22 25.9%	0 0%

11. Secondary Outcome

Title	UAS7=0 Response: at Week 20 Measured Over 7 Days
Description	UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. Complete urticaria activity response is defined as UAS7 = 0.
Time Frame	Week 20

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients, removing misrandomized patients provided that study drug was not administered. As per protocol and SAP, for the efficacy endpoints at Week 12 or Week 20, only the QGE031 24, 72 & 240 mg, omalizumab 300 mg and placebo arms were analyzed for efficacy comparison between treatment groups.

Arm/Group Title	QGE031 24 mg s.c. q4w	QGE031 72 mg s.c. q4w	QGE031 240 mg s.c. q4w	Omalizumab 300 mg s.c. q4w	Placebo
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks	ligelizumab 72 mg injection subcutaneous every 4 weeks	ligelizumab 240 mg injection subcutaneous every 4 weeks	omalizumab 300 mg injection subcutaneous every 4 weeks	placebo injection subcutaneous every 4 week
Measure Participants	43	84	85	85	43
Number [participants]	8 18.6%	33 39.3%	34 40%	26 30.6%	2 4.7%

12. Secondary Outcome

Title	Complete Itch Response (ISS7=0) Rate at Week 12 Measured Over 7 Days
Description	Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Complete itch response defined as ISS7 = 0. Itch Severity Score scale: 0 - None - Mild (minimal awareness, easily tolerated) - Moderate (definite awareness, bothersome but tolerable) - Severe (difficult to tolerate)
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients, removing misrandomized patients provided that study drug was not administered. As per protocol and SAP, for the efficacy endpoints at Week 12 or Week 20, only the QGE031 24, 72 & 240 mg, omalizumab 300 mg and placebo arms were analyzed for efficacy comparison between treatment groups.

Arm/Group Title	QGE031 24 mg s.c. q4w	QGE031 72 mg s.c. q4w	QGE031 240 mg s.c. q4w	Omalizumab 300 mg s.c. q4w	Placebo
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks	ligelizumab 72 mg injection subcutaneous every 4 weeks	ligelizumab 240 mg injection subcutaneous every 4 weeks	omalizumab 300 mg injection subcutaneous every 4 weeks	placebo injection subcutaneous every 4 week
Measure Participants	43	84	85	85	43
Number [participants]	17 39.5%	40 47.6%	36 42.4%	25 29.4%	2 4.7%

13. Secondary Outcome

Title	ISS7=0 Response: at Week 20 Measured Over 7 Days
Description	Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Complete itch response defined as ISS7 = 0. Itch Severity Score scale: 0 - None - Mild (minimal awareness, easily tolerated) - Moderate (definite awareness, bothersome but tolerable) - Severe (difficult to tolerate)
Time Frame	Week 20

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomized patients, removing misrandomized patients provided that study drug was not administered. As per protocol and SAP, for the efficacy endpoints at Week 12 or Week 20, only the QGE031 24, 72 & 240 mg, omalizumab 300 mg and placebo arms were analyzed for efficacy comparison between treatment groups.

Arm/Group Title	QGE031 24 mg s.c. q4w	QGE031 72 mg s.c. q4w	QGE031 240 mg s.c. q4w	Omalizumab 300 mg s.c. q4w	Placebo
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks	ligelizumab 72 mg injection subcutaneous every 4 weeks	ligelizumab 240 mg injection subcutaneous every 4 weeks	omalizumab 300 mg injection subcutaneous every 4 weeks	placebo injection subcutaneous every 4 week
Measure Participants	43	84	85	85	43
Number [participants]	8 18.6%	35 41.7%	36 42.4%	28 32.9%	3 7%

Adverse Events

Time Frame	Through study completion, an average of 44 weeks.
Arm/Group Title	QGE031 24 mg s.c. q4w		QGE031 72 mg s.c. q4w		QGE031 240 mg s.c. q4w		Omalizumab 300 mg s.c. q4w		Placebo s.c. q4w		QGE031 120 mg s.c. s.d.
Arm/Group Description	ligelizumab 24 mg injection subcutaneous every 4 weeks		ligelizumab 72 mg injection subcutaneous every 4 weeks		ligelizumab 240 mg injection subcutaneous every 4 weeks		omalizumab 300 mg injection subcutaneous every 4 weeks		placebo injection subcutaneous every 4 weeks		ligelizumab 120 mg injection subcutaneous single dose
All Cause Mortality
	QGE031 24 mg s.c. q4w		QGE031 72 mg s.c. q4w		QGE031 240 mg s.c. q4w		Omalizumab 300 mg s.c. q4w		Placebo s.c. q4w		QGE031 120 mg s.c. s.d.
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/43 (0%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		0/43 (0%)		0/42 (0%)
Serious Adverse Events
	QGE031 24 mg s.c. q4w		QGE031 72 mg s.c. q4w		QGE031 240 mg s.c. q4w		Omalizumab 300 mg s.c. q4w		Placebo s.c. q4w		QGE031 120 mg s.c. s.d.
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/43 (7%)		2/84 (2.4%)		2/85 (2.4%)		3/85 (3.5%)		4/43 (9.3%)		4/42 (9.5%)
Cardiac disorders
Angina pectoris	0/43 (0%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		1/43 (2.3%)		0/42 (0%)
Gastrointestinal disorders
Abdominal distension	0/43 (0%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		1/43 (2.3%)		0/42 (0%)
Abdominal pain	0/43 (0%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		1/43 (2.3%)		0/42 (0%)
Colon dysplasia	0/43 (0%)		0/84 (0%)		1/85 (1.2%)		0/85 (0%)		0/43 (0%)		0/42 (0%)
Diverticular perforation	1/43 (2.3%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		0/43 (0%)		0/42 (0%)
Inguinal hernia	0/43 (0%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		0/43 (0%)		1/42 (2.4%)
Large intestine polyp	0/43 (0%)		0/84 (0%)		1/85 (1.2%)		0/85 (0%)		0/43 (0%)		0/42 (0%)
Subileus	0/43 (0%)		0/84 (0%)		0/85 (0%)		1/85 (1.2%)		0/43 (0%)		0/42 (0%)
General disorders
Chest pain	0/43 (0%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		1/43 (2.3%)		0/42 (0%)
Hepatobiliary disorders
Cholelithiasis	0/43 (0%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		1/43 (2.3%)		0/42 (0%)
Hepatic cyst	0/43 (0%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		1/43 (2.3%)		0/42 (0%)
Hepatitis acute	1/43 (2.3%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		0/43 (0%)		0/42 (0%)
Infections and infestations
Diverticulitis	1/43 (2.3%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		0/43 (0%)		0/42 (0%)
Pilonidal cyst	0/43 (0%)		0/84 (0%)		1/85 (1.2%)		0/85 (0%)		0/43 (0%)		0/42 (0%)
Pneumonia	1/43 (2.3%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		0/43 (0%)		1/42 (2.4%)
Injury, poisoning and procedural complications
Fractured coccyx	0/43 (0%)		1/84 (1.2%)		0/85 (0%)		0/85 (0%)		0/43 (0%)		0/42 (0%)
Radius fracture	0/43 (0%)		0/84 (0%)		0/85 (0%)		1/85 (1.2%)		0/43 (0%)		0/42 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/43 (0%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		1/43 (2.3%)		0/42 (0%)
Sjogren's syndrome	1/43 (2.3%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		0/43 (0%)		0/42 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign lung neoplasm	0/43 (0%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		0/43 (0%)		1/42 (2.4%)
Breast cancer	0/43 (0%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		0/43 (0%)		1/42 (2.4%)
Breast neoplasm	0/43 (0%)		1/84 (1.2%)		0/85 (0%)		0/85 (0%)		0/43 (0%)		0/42 (0%)
Haemangioma of liver	0/43 (0%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		1/43 (2.3%)		0/42 (0%)
Papillary thyroid cancer	0/43 (0%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		1/43 (2.3%)		0/42 (0%)
Skin and subcutaneous tissue disorders
Angioedema	1/43 (2.3%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		0/43 (0%)		0/42 (0%)
Prurigo	0/43 (0%)		0/84 (0%)		0/85 (0%)		1/85 (1.2%)		0/43 (0%)		0/42 (0%)
Urticaria	1/43 (2.3%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		0/43 (0%)		0/42 (0%)
Other (Not Including Serious) Adverse Events
	QGE031 24 mg s.c. q4w		QGE031 72 mg s.c. q4w		QGE031 240 mg s.c. q4w		Omalizumab 300 mg s.c. q4w		Placebo s.c. q4w		QGE031 120 mg s.c. s.d.
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/43 (55.8%)		45/84 (53.6%)		46/85 (54.1%)		44/85 (51.8%)		30/43 (69.8%)		28/42 (66.7%)
Gastrointestinal disorders
Diarrhoea	2/43 (4.7%)		4/84 (4.8%)		5/85 (5.9%)		6/85 (7.1%)		2/43 (4.7%)		2/42 (4.8%)
Gastritis	0/43 (0%)		0/84 (0%)		0/85 (0%)		0/85 (0%)		0/43 (0%)		3/42 (7.1%)
Nausea	1/43 (2.3%)		1/84 (1.2%)		2/85 (2.4%)		5/85 (5.9%)		2/43 (4.7%)		1/42 (2.4%)
General disorders
Injection site erythema	0/43 (0%)		2/84 (2.4%)		5/85 (5.9%)		0/85 (0%)		0/43 (0%)		1/42 (2.4%)
Injection site reaction	0/43 (0%)		3/84 (3.6%)		6/85 (7.1%)		0/85 (0%)		1/43 (2.3%)		0/42 (0%)
Infections and infestations
Bronchitis	1/43 (2.3%)		1/84 (1.2%)		0/85 (0%)		5/85 (5.9%)		1/43 (2.3%)		0/42 (0%)
Influenza	1/43 (2.3%)		4/84 (4.8%)		4/85 (4.7%)		5/85 (5.9%)		1/43 (2.3%)		1/42 (2.4%)
Upper respiratory tract infection	7/43 (16.3%)		7/84 (8.3%)		10/85 (11.8%)		10/85 (11.8%)		6/43 (14%)		9/42 (21.4%)
Urinary tract infection	0/43 (0%)		5/84 (6%)		4/85 (4.7%)		5/85 (5.9%)		0/43 (0%)		2/42 (4.8%)
Viral upper respiratory tract infection	7/43 (16.3%)		13/84 (15.5%)		17/85 (20%)		17/85 (20%)		13/43 (30.2%)		10/42 (23.8%)
Investigations
Blood creatinine increased	1/43 (2.3%)		3/84 (3.6%)		3/85 (3.5%)		2/85 (2.4%)		4/43 (9.3%)		1/42 (2.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/43 (2.3%)		6/84 (7.1%)		1/85 (1.2%)		2/85 (2.4%)		1/43 (2.3%)		1/42 (2.4%)
Back pain	0/43 (0%)		1/84 (1.2%)		0/85 (0%)		1/85 (1.2%)		1/43 (2.3%)		3/42 (7.1%)
Nervous system disorders
Dizziness	2/43 (4.7%)		5/84 (6%)		2/85 (2.4%)		2/85 (2.4%)		4/43 (9.3%)		0/42 (0%)
Headache	7/43 (16.3%)		9/84 (10.7%)		7/85 (8.2%)		12/85 (14.1%)		7/43 (16.3%)		1/42 (2.4%)
Skin and subcutaneous tissue disorders
Eczema	1/43 (2.3%)		5/84 (6%)		4/85 (4.7%)		2/85 (2.4%)		1/43 (2.3%)		3/42 (7.1%)
Urticaria	1/43 (2.3%)		9/84 (10.7%)		3/85 (3.5%)		4/85 (4.7%)		5/43 (11.6%)		7/42 (16.7%)
Vascular disorders
Hypertension	1/43 (2.3%)		5/84 (6%)		2/85 (2.4%)		2/85 (2.4%)		3/43 (7%)		3/42 (7.1%)

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.