A Phase III Study of Efficacy and Safety of Ligelizumab in the Treatment of CSU in Adolescents and Adults Inadequately Controlled With H1-antihistamines.

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03580356
• Collaborator: (none)
• Enrollment: 1,079
• Locations: 183
• Arms: 4
• Actual Duration (Months): 43.8
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study was to establish efficacy and safety of ligelizumab in adolescent and adult subjects with CSU who remained symptomatic despite standard of care treatment by demonstrating better efficacy over omalizumab and over placebo.

The study population consisted of 1,079 male and female subjects aged ≥ 12 years who were diagnosed with CSU and who remained symptomatic despite the use of H1-antihistamines.

This was a multi-center, randomized, double-blind, active- and placebo-controlled, parallel-group study. There was a screening period of up to 28 days, a 52 week double-blind treatment period, and a 12 week post-treatment follow-up period.

Condition or Disease	Intervention/Treatment	Phase
Chronic Spontaneous Urticaria	Biological: Ligelizumab; Biological: Omalizumab; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1079 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a Phase III multi-center, randomized, double-blind, active- and placebo-controlled, parallel-group study. There is a screening period of up to 28 days, a 52 week double-blind treatment period, and a 12 week post-treatment follow-up period.This is a Phase III multi-center, randomized, double-blind, active- and placebo-controlled, parallel-group study. There is a screening period of up to 28 days, a 52 week double-blind treatment period, and a 12 week post-treatment follow-up period.
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Patients, investigator staff and personnel performing the study assessments will remain blinded to the identity of the treatment from the time of randomization until final database lock. The study drug must be prepared by an independent unblinded pharmacist (or authorized delegate) and administered by an independent unblinded study drug administrator. Neither the unblinded pharmacist nor the unblinded study drug administrator will be involved in any assessments.
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Double-blind, Active and Placebo-controlled Study to Investigate the Efficacy and Safety of Ligelizumab (QGE031) in the Treatment of Chronic Spontaneous Urticaria (CSU) in Adolescents and Adults Inadequately Controlled With H1-antihistamines
• Actual Study Start Date: Oct 20, 2018
• Actual Primary Completion Date: Jun 22, 2021
• Actual Study Completion Date: Jun 14, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ligelizumab Dose A Ligelizumab Dose A q4w	Biological: Ligelizumab; Liquid in vial
Experimental: Ligelizumab Dose B Ligelizumab Dose B q4w	Biological: Ligelizumab; Liquid in vial
Active Comparator: Omalizumab 300 mg Omalizumab 300 mg q4w	Biological: Omalizumab; Lyophilized powder for solution in vial
Placebo Comparator: Placebo Placebo q4w from randomization to week 20. Ligelizumab Dose B from week 24 to week 48.	Other: Placebo; Liquid in vial

Outcome Measures

Primary Outcome Measures

1. Absolute change from baseline in UAS7 at Week 12 [Week 12]

   The Urticaria Activity Score (UAS) is the sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). The HSS has a scale of 0 (none) to 3 (intense/severe). A weekly score (HSS7) is derived by adding up the average daily scores of the preceding 7 days. The ISS also has a scale of 0 (none) to 3 (severe/difficult to tolerate). A weekly score (ISS7) is derived by adding up the average daily scores of the preceding 7 days. The UAS7 is the sum of the HSS7 score and the ISS7 score, and has a possible range in score of 0-42. Complete hives response is defined as HSS7 (average daily HSS over the preceding 7 days) = 0. Complete itch response is defined as ISS7 (average daily ISS over the preceding 7 days) = 0. Complete UAS7 response is defined as UAS7=0.

Secondary Outcome Measures

1. Complete absence of hives and itch at Week 12 [Week 12]

   Assessed as percentage of subjects achieving UAS7 = 0

2. Improvement of severity of itch [Week 12]

   Assessed as absolute change from baseline in ISS7 score at Week 12

3. No impact on subject's quality of life at Week 12 [Week 12]

   Assessed as percentage of subjects achieving DLQI = 0-1

4. Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12 [Weekly to Week 12]

   To assess the cumulative period of time that treated subjects are angioedema occurrence-free

5. Occurrence of treatment emergent adverse events and serious adverse events during the study [52 weeks]

   Treatment emergent adverse events and serious adverse events are those which occur at any time only after treatment has started

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study. The subject's', parent'ssubject's, parent's or legal guardian's signed written informed consent and child's assent, if appropriate, must be obtained before any assessment is performed. Of note, if the subject reaches age of consent (age as per local law) during the study, they will also need to sign the corresponding study Informed Consent Form (ICF) at the next study visit.

• Male and female subjects ≥ 12 years of age at the time of screening.

• CSU diagnosis for ≥ 6 months.

• Diagnosis of CSU refractory to H1-AH at approved doses at the time of randomization, as defined by all of the following:

• The presence of itch and hives for ≥ 6 consecutive weeks at any time prior to Visit 1 (Day - 28 to Day -14) despite current use of non-sedating H1-AH

• UAS7 score (range 0-42) ≥ 16 and HSS7 (range 0-21) ≥ 8 during the 7 days prior to randomization (Visit 110, Day 1)

• Subjects must be on H1-AH at only approved doses for treatment of CSU starting at Visit 1 (Day -28 to Day -14)

• Willing and able to complete a daily symptom eDiary for the duration of the study and adhere to the study visit schedules.

Key Exclusion Criteria:

• History of hypersensitivity to any of the study drugs or their excipients or to drugs of similar chemical classes (i.e. to murine, chimeric or human antibodies).

• Subjects having a clearly defined cause of their chronic urticaria, other than CSU. This includes, but is not limited to, the following: symptomatic dermographism (urticaria factitia), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic- or contact-urticaria.

• Diseases, other than chronic urticaria, with urticarial or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor deficiency).

• Subjects with evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic organism according to local guidelines. All subjects will be screened at Visit 1. If stool testing is positive for pathogenic organism, the subject will not be randomized and will not be allowed to rescreen.

• Any other skin disease associated with chronic itching that might influence in the investigators opinion the study evaluations and results (e.g. atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.).

• Prior exposure to ligelizumab or omalizumab.

• Any H2 antihistamine, LTRA (montelukast or zafirlukast) or H1 antihistamines use at greater than approved doses after Visit 1.

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	72209
4	Novartis Investigative Site	Fresno	California	United States	93720
5	Novartis Investigative Site	Los Angeles	California	United States	90025
6	Novartis Investigative Site	Redwood City	California	United States	94063
7	Novartis Investigative Site	San Jose	California	United States	95117
8	Novartis Investigative Site	Sarasota	Florida	United States	34233
9	Novartis Investigative Site	Tampa	Florida	United States	33609
10	Novartis Investigative Site	Eagle	Idaho	United States	83616
11	Novartis Investigative Site	Normal	Illinois	United States	61761
12	Novartis Investigative Site	Baltimore	Maryland	United States	21204
13	Novartis Investigative Site	Wheaton	Maryland	United States	20902
14	Novartis Investigative Site	White Marsh	Maryland	United States	21162
15	Novartis Investigative Site	Rochester	Minnesota	United States	55905
16	Novartis Investigative Site	Saint Louis	Missouri	United States	63141
17	Novartis Investigative Site	Missoula	Montana	United States	59808
18	Novartis Investigative Site	Papillion	Nebraska	United States	68046
19	Novartis Investigative Site	New York	New York	United States	10029
20	Novartis Investigative Site	Toledo	Ohio	United States	43617
21	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73120
22	Novartis Investigative Site	Clackamas	Oregon	United States	97015
23	Novartis Investigative Site	Blue Bell	Pennsylvania	United States	19422
24	Novartis Investigative Site	Pittsburgh	Pennsylvania	United States	15241
25	Novartis Investigative Site	North Charleston	South Carolina	United States	29420
26	Novartis Investigative Site	Bellaire	Texas	United States	77401
27	Novartis Investigative Site	El Paso	Texas	United States	79903
28	Novartis Investigative Site	Fort Worth	Texas	United States	76132
29	Novartis Investigative Site	San Antonio	Texas	United States	78229
30	Novartis Investigative Site	San Antonio	Texas	United States	78230
31	Novartis Investigative Site	Waco	Texas	United States	76712
32	Novartis Investigative Site	Murray	Utah	United States	84107
33	Novartis Investigative Site	Bellingham	Washington	United States	98225
34	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1181ACH
35	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1414AIF
36	Novartis Investigative Site	Ciudad de Mendoza	Mendoza	Argentina	M5500AWD
37	Novartis Investigative Site	Santa Fe	Rosario	Argentina	S2000DBS
38	Novartis Investigative Site	Rosario	Santa Fe	Argentina	S2000BRH
39	Novartis Investigative Site	Rosario	Santa Fe	Argentina	S2000JKR
40	Novartis Investigative Site	Buenos Aires		Argentina	C1425DKG
41	Novartis Investigative Site	Caba		Argentina	1035
42	Novartis Investigative Site	Salta		Argentina	4400
43	Novartis Investigative Site	Adelaide	South Australia	Australia	5000
44	Novartis Investigative Site	East Melbourne	Victoria	Australia	3002
45	Novartis Investigative Site	Parkville	Victoria	Australia	3002
46	Novartis Investigative Site	Jette	Brussel	Belgium	1090
47	Novartis Investigative Site	Bruxelles		Belgium	1070
48	Novartis Investigative Site	Bruxelles		Belgium	1200
49	Novartis Investigative Site	Gent		Belgium	9000
50	Novartis Investigative Site	Leuven		Belgium	3000
51	Novartis Investigative Site	Loverval		Belgium	6280
52	Novartis Investigative Site	Salvador	BA	Brazil	40110-060
53	Novartis Investigative Site	Rio de Janeiro	RJ	Brazil	21941-913
54	Novartis Investigative Site	Alphaville Barueri	Sao Paulo	Brazil	06454010
55	Novartis Investigative Site	Sao Jose do Rio Preto	SP	Brazil	15090 000
56	Novartis Investigative Site	Sao Paulo	SP	Brazil	05437 010
57	Novartis Investigative Site	Vitacura	Santiago	Chile	7640881
58	Novartis Investigative Site	Osorno		Chile
59	Novartis Investigative Site	Santiago		Chile	8420383
60	Novartis Investigative Site	Tallinn		Estonia	10138
61	Novartis Investigative Site	Tartu		Estonia	51014
62	Novartis Investigative Site	Helsinki		Finland	00180
63	Novartis Investigative Site	Clermont Ferrand		France	63003
64	Novartis Investigative Site	La Tronche		France	38700
65	Novartis Investigative Site	Nice Cedex		France	06202
66	Novartis Investigative Site	Paris		France	75970
67	Novartis Investigative Site	Rouen		France	76031
68	Novartis Investigative Site	Bad Bentheim		Germany	48455
69	Novartis Investigative Site	Dresden		Germany	01307
70	Novartis Investigative Site	Duesseldorf		Germany	40225
71	Novartis Investigative Site	Frankfurt		Germany	60590
72	Novartis Investigative Site	Gera		Germany	07548
73	Novartis Investigative Site	Gottingen		Germany	37075
74	Novartis Investigative Site	Halle		Germany	06097
75	Novartis Investigative Site	Hamburg		Germany	22303
76	Novartis Investigative Site	Hamburg		Germany	22391
77	Novartis Investigative Site	Hannover		Germany	30625
78	Novartis Investigative Site	Heidelberg		Germany	69120
79	Novartis Investigative Site	Leipzig		Germany	04103
80	Novartis Investigative Site	Muenchen		Germany	80377
81	Novartis Investigative Site	Osnabrueck		Germany	49074
82	Novartis Investigative Site	Quedlinburg		Germany	06484
83	Novartis Investigative Site	Simmern		Germany	55469
84	Novartis Investigative Site	Stade		Germany	21682
85	Novartis Investigative Site	Stuttgart		Germany	70178
86	Novartis Investigative Site	Tübingen		Germany	72076
87	Novartis Investigative Site	New Delhi	Delhi	India	110 060
88	Novartis Investigative Site	Bangalore	Karnataka	India	560004
89	Novartis Investigative Site	Mangalore	Karnataka	India	575002
90	Novartis Investigative Site	Nashik	Maharashtra	India	422 101
91	Novartis Investigative Site	Bikaner	Rajasthan	India	334001
92	Novartis Investigative Site	Afula		Israel	1834111
93	Novartis Investigative Site	Haifa		Israel	3339419
94	Novartis Investigative Site	Jerusalem		Israel	9112001
95	Novartis Investigative Site	Kfar Saba		Israel	4428164
96	Novartis Investigative Site	Ramat Gan		Israel	52621
97	Novartis Investigative Site	Rehovot		Israel	76100
98	Novartis Investigative Site	Cagliari	CA	Italy	09042
99	Novartis Investigative Site	Catania	CT	Italy	95125
100	Novartis Investigative Site	Firenze	FI	Italy	50122
101	Novartis Investigative Site	Firenze	FI	Italy	50134
102	Novartis Investigative Site	Rozzano	MI	Italy	20089
103	Novartis Investigative Site	Modena	MO	Italy	41100
104	Novartis Investigative Site	Siena	SI	Italy	53100
105	Novartis Investigative Site	Nagoya	Aichi	Japan	454-0012
106	Novartis Investigative Site	Chikushino	Fukuoka	Japan	818 0083
107	Novartis Investigative Site	Hiroshima City	Hiroshima	Japan	734-8551
108	Novartis Investigative Site	Amagasaki city	Hyogo	Japan	660 8550
109	Novartis Investigative Site	Kobe-shi	Hyogo	Japan	650-0017
110	Novartis Investigative Site	Kawasaki	Kanagawa	Japan	211-0063
111	Novartis Investigative Site	Yokohama	Kanagawa	Japan	220-6208
112	Novartis Investigative Site	Yokohama	Kanagawa	Japan	221-0825
113	Novartis Investigative Site	Kamimashi-gun	Kumamoto	Japan	861-3106
114	Novartis Investigative Site	Sakai	Osaka	Japan	593-8324
115	Novartis Investigative Site	Izumo-city	Shimane	Japan	693 8501
116	Novartis Investigative Site	Itabashi-ku	Tokyo	Japan	173-8610
117	Novartis Investigative Site	Machida-city	Tokyo	Japan	194-0013
118	Novartis Investigative Site	Setagaya-ku	Tokyo	Japan	158-0097
119	Novartis Investigative Site	Shinagawa ku	Tokyo	Japan	141 8625
120	Novartis Investigative Site	Fukuoka		Japan	819 0167
121	Novartis Investigative Site	Ashrafieh		Lebanon	166830
122	Novartis Investigative Site	Beirut		Lebanon	166378
123	Novartis Investigative Site	Saida		Lebanon	652
124	Novartis Investigative Site	Guadalajara	Jalisco	Mexico	44130
125	Novartis Investigative Site	Villahermosa	Tabasco	Mexico	86035
126	Novartis Investigative Site	Breda	CK	Netherlands	4818 CK
127	Novartis Investigative Site	Bergen op Zoom		Netherlands	4624 VT
128	Novartis Investigative Site	Rotterdam		Netherlands	3015 CE
129	Novartis Investigative Site	Utrecht		Netherlands	3584CX
130	Novartis Investigative Site	Lipa City	Batangas	Philippines	4217
131	Novartis Investigative Site	Taguig City	Metro Manila	Philippines	1634
132	Novartis Investigative Site	Makati City		Philippines	1220
133	Novartis Investigative Site	Pasig City		Philippines	1605
134	Novartis Investigative Site	Quezon City		Philippines	1102
135	Novartis Investigative Site	Bydgoszcz		Poland	85-094
136	Novartis Investigative Site	Gdansk		Poland	80-402
137	Novartis Investigative Site	Krosno		Poland	38-400
138	Novartis Investigative Site	Lodz		Poland	90-153
139	Novartis Investigative Site	Lodz		Poland	90-436
140	Novartis Investigative Site	Ossy		Poland	42 624
141	Novartis Investigative Site	Sopot		Poland	81 756
142	Novartis Investigative Site	Warszawa		Poland	02-507
143	Novartis Investigative Site	Bucharest	District 2	Romania	020762
144	Novartis Investigative Site	Brasov		Romania	500283
145	Novartis Investigative Site	Cluj Napoca		Romania	400162
146	Novartis Investigative Site	Craiova		Romania	200642
147	Novartis Investigative Site	Iasi		Romania	700381
148	Novartis Investigative Site	Chelyabinsk		Russian Federation	454048
149	Novartis Investigative Site	Kazan		Russian Federation	420012
150	Novartis Investigative Site	Moscow		Russian Federation	115478
151	Novartis Investigative Site	Saint Petersburg		Russian Federation	191123
152	Novartis Investigative Site	St Petersburg		Russian Federation	194223
153	Novartis Investigative Site	St.-Petersburg		Russian Federation	195112
154	Novartis Investigative Site	Stavropol		Russian Federation	355000
155	Novartis Investigative Site	Levice	Slovak Republic	Slovakia	934 01
156	Novartis Investigative Site	Kezmarok		Slovakia	060 01
157	Novartis Investigative Site	Komarno		Slovakia	945 01
158	Novartis Investigative Site	Nove Zamky		Slovakia	940 34
159	Novartis Investigative Site	Povazska Bystrica		Slovakia	017 26
160	Novartis Investigative Site	Svidnik		Slovakia	08901
161	Novartis Investigative Site	Topolcany		Slovakia	95501
162	Novartis Investigative Site	Zilina		Slovakia	010 01
163	Novartis Investigative Site	Cordoba	Andalucia	Spain	14004
164	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
165	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46014
166	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46015
167	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46026
168	Novartis Investigative Site	Alcorcon	Madrid	Spain	28922
169	Novartis Investigative Site	Fuenlabrada	Madrid	Spain	28942
170	Novartis Investigative Site	Pozuelo de Alarcon	Madrid	Spain	28223
171	Novartis Investigative Site	Pamplona	Navarra	Spain	31008
172	Novartis Investigative Site	La Laguna	Santa Cruz De Tenerife	Spain	38320
173	Novartis Investigative Site	Granada		Spain	18012
174	Novartis Investigative Site	Madrid		Spain	28041
175	Novartis Investigative Site	Taichung		Taiwan	40705
176	Novartis Investigative Site	Taipei		Taiwan	10002
177	Novartis Investigative Site	Tao Yuan		Taiwan	333
178	Novartis Investigative Site	Sfax	Tunusia	Tunisia	3029
179	Novartis Investigative Site	Sousse		Tunisia	4000
180	Novartis Investigative Site	Tunis		Tunisia	1007
181	Novartis Investigative Site	London		United Kingdom	SE1 7EH
182	Novartis Investigative Site	Hanoi		Vietnam	100000
183	Novartis Investigative Site	Ho Chi Minh		Vietnam	7000

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03580356
• Other Study ID Numbers: CQGE031C2303; 2018-000840-24
• First Posted: Jul 9, 2018
• Last Update Posted: Aug 9, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Anti-IgE, CSU (Chronic Spontaneous Urticaria), hives severity score, itch severity score, urticaria activity score
• Additional relevant MeSH terms: Urticaria; Chronic Urticaria; Omalizumab

Study Results

No Results Posted as of Aug 9, 2022