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: NCT03580369
• Collaborator: (none)
• Enrollment: 1,072
• Locations: 161
• Arms: 4
• Actual Duration (Months): 43.9
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

The study population will consist of approximately 1050 male and female subjects aged ≥ 12 years who have been diagnosed with CSU and who remain symptomatic despite the use of H1-antihistamines. Of these, approximately 1000 adults and 50 adolescents are planned for inclusion in the study.

This is a 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.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 1072 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 17, 2018
• Actual Primary Completion Date: Jul 16, 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 subjects 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'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-antihistamine

• 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-antihistamine 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	Gilbert	Arizona	United States	85234
2	Novartis Investigative Site	Litchfield Park	Arizona	United States	85340
3	Novartis Investigative Site	Scottsdale	Arizona	United States	85258
4	Novartis Investigative Site	Little Rock	Arkansas	United States	72205
5	Novartis Investigative Site	Bakersfield	California	United States	93301
6	Novartis Investigative Site	Huntington Beach	California	United States	92647
7	Novartis Investigative Site	Long Beach	California	United States	90808
8	Novartis Investigative Site	Colorado Springs	Colorado	United States	80907
9	Novartis Investigative Site	Denver	Colorado	United States	80230
10	Novartis Investigative Site	Greenacres City	Florida	United States	33467
11	Novartis Investigative Site	Tallahassee	Florida	United States	32308
12	Novartis Investigative Site	Tampa	Florida	United States	33613
13	Novartis Investigative Site	Boise	Idaho	United States	83706
14	Novartis Investigative Site	Evansville	Indiana	United States	47713
15	Novartis Investigative Site	Indianapolis	Indiana	United States	46256
16	Novartis Investigative Site	Overland Park	Kansas	United States	66211
17	Novartis Investigative Site	Bangor	Maine	United States	04401
18	Novartis Investigative Site	Waldorf	Maryland	United States	20602
19	Novartis Investigative Site	Clarkston	Michigan	United States	48346
20	Novartis Investigative Site	Ypsilanti	Michigan	United States	48197
21	Novartis Investigative Site	Plymouth	Minnesota	United States	55441
22	Novartis Investigative Site	Asheville	North Carolina	United States	28801
23	Novartis Investigative Site	Cincinnati	Ohio	United States	45231
24	Novartis Investigative Site	Tulsa	Oklahoma	United States	74136
25	Novartis Investigative Site	Medford	Oregon	United States	97504
26	Novartis Investigative Site	Dallas	Texas	United States	75230
27	Novartis Investigative Site	Dallas	Texas	United States	75231
28	Novartis Investigative Site	Pflugerville	Texas	United States	78660
29	Novartis Investigative Site	San Antonio	Texas	United States	78251
30	Novartis Investigative Site	South Burlington	Vermont	United States	05403
31	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1056ABJ
32	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1414AIF
33	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires	Argentina	C1425BEA
34	Novartis Investigative Site	La Plata	Buenos Aires	Argentina	B1902COS
35	Novartis Investigative Site	Buenos Aires	Nueve De Julio	Argentina	B6500BWQ
36	Novartis Investigative Site	Bahia Blanca		Argentina	B8000JRB
37	Novartis Investigative Site	Buenos Aires		Argentina	C1125ABE
38	Novartis Investigative Site	Capital Federal		Argentina	C1023AAB
39	Novartis Investigative Site	Innsbruck		Austria	6020
40	Novartis Investigative Site	Wien		Austria	A 1090
41	Novartis Investigative Site	Vitoria	ES	Brazil	29025 023
42	Novartis Investigative Site	Alphaville Barueri	Sao Paulo	Brazil	06454010
43	Novartis Investigative Site	Santo Andre	SP	Brazil	09060 650
44	Novartis Investigative Site	Sao Paulo	SP	Brazil	05403 000
45	Novartis Investigative Site	Pleven		Bulgaria	5800
46	Novartis Investigative Site	Sofia		Bulgaria	1407
47	Novartis Investigative Site	Sofia		Bulgaria	1431
48	Novartis Investigative Site	Sofia		Bulgaria	1606
49	Novartis Investigative Site	Varna		Bulgaria	9000
50	Novartis Investigative Site	Hamilton	Ontario	Canada	L8N 3Z5
51	Novartis Investigative Site	Kingston	Ontario	Canada	K7L 2V7
52	Novartis Investigative Site	Mississauga	Ontario	Canada	L5A 3V4
53	Novartis Investigative Site	Toronto	Ontario	Canada	M3B 3S6
54	Novartis Investigative Site	Waterloo	Ontario	Canada	N2J 1C4
55	Novartis Investigative Site	Montreal	Quebec	Canada	H2V 2K1
56	Novartis Investigative Site	Quebec		Canada	G1V 4W2
57	Novartis Investigative Site	Medellin	Antioquia	Colombia	0050010
58	Novartis Investigative Site	Bogota		Colombia	110221
59	Novartis Investigative Site	Zagreb		Croatia	10000
60	Novartis Investigative Site	Teplice	CZE	Czechia	415 01
61	Novartis Investigative Site	Prague	Prague 1	Czechia	11000
62	Novartis Investigative Site	Olomouc		Czechia	775 20
63	Novartis Investigative Site	Plzen		Czechia	305 99
64	Novartis Investigative Site	Copenhagen NV		Denmark	2400
65	Novartis Investigative Site	Herlev		Denmark	2730
66	Novartis Investigative Site	Bordeaux Cedex		France	33075
67	Novartis Investigative Site	Montpellier cedex 5		France	34295
68	Novartis Investigative Site	Pierre Benite Cedex		France	69495
69	Novartis Investigative Site	Toulouse		France	31400
70	Novartis Investigative Site	Trevenans		France	90400
71	Novartis Investigative Site	Berlin		Germany	13353
72	Novartis Investigative Site	Bochum		Germany	44791
73	Novartis Investigative Site	Bochum		Germany	44793
74	Novartis Investigative Site	Erlangen		Germany	91054
75	Novartis Investigative Site	Essen		Germany	45147
76	Novartis Investigative Site	Freiburg		Germany	79106
77	Novartis Investigative Site	Jena		Germany	07740
78	Novartis Investigative Site	Langenau		Germany	89129
79	Novartis Investigative Site	Mainz		Germany	55131
80	Novartis Investigative Site	Marburg		Germany	35039
81	Novartis Investigative Site	Memmingen		Germany	87700
82	Novartis Investigative Site	Muenchen		Germany	81377
83	Novartis Investigative Site	Oldenburg		Germany	26133
84	Novartis Investigative Site	Athens	GR	Greece	115 27
85	Novartis Investigative Site	Athens		Greece	115 27
86	Novartis Investigative Site	Athens		Greece	12462
87	Novartis Investigative Site	Athens		Greece	161 21
88	Novartis Investigative Site	Guatemala City		Guatemala	01010
89	Novartis Investigative Site	Guatemala City		Guatemala	01015
90	Novartis Investigative Site	Kecskemet	Bacs Kiskun	Hungary	6000
91	Novartis Investigative Site	Szeged	Csongrad	Hungary	6720
92	Novartis Investigative Site	Debrecen		Hungary	4032
93	Novartis Investigative Site	Pecs		Hungary	7623
94	Novartis Investigative Site	Belagavi	Karnataka	India	590010
95	Novartis Investigative Site	Nashik	Maharashtra	India	422 101
96	Novartis Investigative Site	Nashik	Maharashtra	India	422005
97	Novartis Investigative Site	Navi Mumbai	Maharashtra	India	400 706
98	Novartis Investigative Site	New Delhi		India	110029
99	Novartis Investigative Site	Vijayawada		India	520002
100	Novartis Investigative Site	Daegu	Dalseo Gu	Korea, Republic of	42602
101	Novartis Investigative Site	Wonju	Gangwon-Do	Korea, Republic of	26426
102	Novartis Investigative Site	Bundang Gu	Gyeonggi Do	Korea, Republic of	13620
103	Novartis Investigative Site	Hwaseong si	Gyeonggi Do	Korea, Republic of	18450
104	Novartis Investigative Site	Suwon si	Gyeonggi Do	Korea, Republic of	16499
105	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	08308
106	Novartis Investigative Site	Seoul	Seocho Gu	Korea, Republic of	06591
107	Novartis Investigative Site	Incheon		Korea, Republic of	405 760
108	Novartis Investigative Site	Seoul		Korea, Republic of	03080
109	Novartis Investigative Site	Seoul		Korea, Republic of	03722
110	Novartis Investigative Site	Seoul		Korea, Republic of	05505
111	Novartis Investigative Site	Seoul		Korea, Republic of	06973
112	Novartis Investigative Site	Seoul		Korea, Republic of	07061
113	Novartis Investigative Site	Seoul		Korea, Republic of	150-950
114	Novartis Investigative Site	Ipoh	Perak	Malaysia	30450
115	Novartis Investigative Site	Kuala Lumpur	Wilayah Persekutuan	Malaysia	50586
116	Novartis Investigative Site	Penang		Malaysia	10990
117	Novartis Investigative Site	Muscat		Oman	123
118	Novartis Investigative Site	Miraflores	Lima	Peru	15074
119	Novartis Investigative Site	San Borja	Lima	Peru	41
120	Novartis Investigative Site	Ksawerow	POL	Poland	95-054
121	Novartis Investigative Site	Kielce		Poland	25-155
122	Novartis Investigative Site	Krakow		Poland	31-530
123	Novartis Investigative Site	Lublin		Poland	20-080
124	Novartis Investigative Site	Rzeszow		Poland	35 055
125	Novartis Investigative Site	Wroclaw		Poland	50 566
126	Novartis Investigative Site	San Juan		Puerto Rico	00927
127	Novartis Investigative Site	Moscow		Russian Federation	123182
128	Novartis Investigative Site	Rostov on Don		Russian Federation	344022
129	Novartis Investigative Site	Ryazan		Russian Federation	390046
130	Novartis Investigative Site	Saratov		Russian Federation	410012
131	Novartis Investigative Site	Smolensk		Russian Federation	214019
132	Novartis Investigative Site	St Petersburg		Russian Federation	194325
133	Novartis Investigative Site	St. Petersburg		Russian Federation	193231
134	Novartis Investigative Site	Singapore		Singapore	119074
135	Novartis Investigative Site	Singapore		Singapore	169608
136	Novartis Investigative Site	Singapore		Singapore	229899
137	Novartis Investigative Site	Singapore		Singapore	308205
138	Novartis Investigative Site	Cape Town	Western Province	South Africa	7700
139	Novartis Investigative Site	Cape Town		South Africa	7700
140	Novartis Investigative Site	Durban		South Africa	3630
141	Novartis Investigative Site	Malaga	Andalucia	Spain	29009
142	Novartis Investigative Site	Sevilla	Andalucia	Spain	41009
143	Novartis Investigative Site	Hospitalet de Llobregat	Barcelona	Spain	08907
144	Novartis Investigative Site	Barcelona	Catalunya	Spain	08003
145	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
146	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
147	Novartis Investigative Site	Alicante	Comunidad Valenciana	Spain	03010
148	Novartis Investigative Site	Bilbao	Pais Vasco	Spain	48013
149	Novartis Investigative Site	Barcelona		Spain	08041
150	Novartis Investigative Site	Malmo		Sweden	SE-205 02
151	Novartis Investigative Site	Bangkoknoi	Bangkok	Thailand	10700
152	Novartis Investigative Site	Bangkok	Phayathai	Thailand	10400
153	Novartis Investigative Site	Bangkok		Thailand	10400
154	Novartis Investigative Site	Istanbul	Pendik	Turkey	348999
155	Novartis Investigative Site	Istanbul	TUR	Turkey	34098
156	Novartis Investigative Site	Aydin		Turkey	09100
157	Novartis Investigative Site	Denizli		Turkey	20070
158	Novartis Investigative Site	Gaziantep		Turkey	27310
159	Novartis Investigative Site	Izmir		Turkey	35380
160	Novartis Investigative Site	Okmeydani		Turkey	34370
161	Novartis Investigative Site	Samsun		Turkey	55139

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: NCT03580369
• Other Study ID Numbers: CQGE031C2302; 2018-000839-28
• First Posted: Jul 9, 2018
• Last Update Posted: Aug 1, 2022
• Last Verified: Jul 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 urticarial), 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 1, 2022