Open-label, Multicenter, Extension Study to Evaluate Long-term Safety and Tolerability of LOU064 in Subjects With CSU

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04109313

Collaborator

(none)

195

Enrollment

Locations

Arm

34.4

Anticipated Duration (Months)

2.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is an open-label, single arm, multicenter, long-term safety and tolerability extension study for CSU patients who completed CLOU064A2201 or other preceding studies with LOU064

Condition or Disease	Intervention/Treatment	Phase
Chronic Spontaneous Urticaria	Drug: LOU064	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

195 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This study consists of 3 periods: Observational Period: for upto 12 weeks Treatment Period: for 52 weeks Treatment free follow up period: for a minimum of 4 weeks to a maximum of 16 weeks Subjects rolling over from CLOU064A2201 will be assigned to one of the periods as follows: Subjects with a UAS7≥16 at Week 12 or Week 16 will directly enter the treatment period. (Subjects with a UAS7<16 at Week 12 of CLOU064A2201 enter the follow-up period of CLOU064A2201) Subjects with a UAS7<16 at Week 16 (i.e., who have not relapsed during the follow-up period of CLOU064A2201) will be assigned to the observational period. After relapse (UAS7≥16 at least once), the observational period can be terminated immediately and subjects may enter the treatment period. Subjects who have never relapsed within 12 weeks will discontinue the study after the observational period.This study consists of 3 periods:Observational Period: for upto 12 weeks Treatment Period: for 52 weeks Treatment free follow up period: for a minimum of 4 weeks to a maximum of 16 weeksSubjects rolling over from CLOU064A2201 will be assigned to one of the periods as follows:Subjects with a UAS7≥16 at Week 12 or Week 16 will directly enter the treatment period. (Subjects with a UAS7<16 at Week 12 of CLOU064A2201 enter the follow-up period of CLOU064A2201) Subjects with a UAS7<16 at Week 16 (i.e., who have not relapsed during the follow-up period of CLOU064A2201) will be assigned to the observational period. After relapse (UAS7≥16 at least once), the observational period can be terminated immediately and subjects may enter the treatment period. Subjects who have never relapsed within 12 weeks will discontinue the study after the observational period.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-label, Multicenter, Extension Study to Evaluate the Long-term Safety and Tolerability of LOU064 in Eligible Subjects With CSU Who Have Participated in Preceding Studies With LOU064

Actual Study Start Date :

Oct 24, 2019

Anticipated Primary Completion Date :

Sep 5, 2022

Anticipated Study Completion Date :

Sep 6, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LOU064 Participants will be asked to take selected dose of LOU064 twice daily for 52 weeks	Drug: LOU064 selected dose of LOU064 taken orally twice a day (morning and evening) from day 1 to week 52 of the Treatment period.

Arm

Intervention/Treatment

Experimental: LOU064

Participants will be asked to take selected dose of LOU064 twice daily for 52 weeks

Drug: LOU064

selected dose of LOU064 taken orally twice a day (morning and evening) from day 1 to week 52 of the Treatment period.

Outcome Measures

Primary Outcome Measures

long-term safety and tolerability of LOU064 [overtime from week 1 to week 68]
To assess the long-term safety and tolerability of LOU064 in patients with CSU who have participated in preceding studies with LOU064. Safety endpoints will include but not be limited to: occurrence of treatment emergent (serious and non-serious) adverse events during the extension study

Secondary Outcome Measures

Change from baseline in Utricaria Activity Score (UAS 7); UAS7≤6; UAS7=0 [Week 4]
To evaluate the efficacy of LOU064 when given without H1-antihistamines in patients with CSU with respect to change from baseline in UAS7, achieving controlled disease (defined by a UAS7≤6), and achieving complete response (defined by a UAS7=0) at Week 4 of treatment
UAS7≤ 6 [over time from week 1 to week 68]
To evaluate the long-term efficacy of LOU064 in patients with CSU who have participated in previous studies with LOU064 with respect to maintaining or achieving controlled disease (defined by a UAS7≤6) over time
Change from baseline in UAS7 [over time from week 1 to week 68]
To evaluate the long-term efficacy of LOU064 in patients with CSU who have participated in preceding studies with LOU064 with respect to change from baseline in UAS7 over time

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Written informed consent must be obtained before any assessment is performed.
Willing and able to complete a daily symptom eDiary for the duration of the study and adhere to the study visit schedules.
Subjects rolling over from CLOU064A2201 must have completed the Week 12 visit (end of treatment period) or the Week 16 visit (end of the follow-up period) and will be allocated to the treatment period or the observational period of CLOU064A2201E1 based on the UAS7 score (of the 7 days prior to the respective visit) as follows:
Subjects rolling over at Week 12 of CLOU064A2201 with a UAS7≥16 will be allocated to the Treatment period (note: subjects with UAS7<16 at Week 12 are not eligible to roll-over into CLOU064A2201E1 but need to enter the follow-up period of CLOU064A2201).
Subjects rolling over at Week 16 of CLOU064A2201 with a UAS7≥16 will be allocated to the Treatment period.
Subjects rolling over at Week 16 of CLOU064A2201 with a UAS7<16 will be allocated to the Observational period.

Exclusion Criteria:

Subjects having a clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria) including urticaria factitia (symptomatic dermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact-urticarial
Other diseases with symptoms of urticaria or angioedema, including but not limited to urticaria vasculitis, urticarial pigmentosa, erythema multiforme, mastocytosis, hereditary urticaria, or acquired/drug-induced urticarial
Any other skin disease associated with chronic itching that might influence in the investigators opinion the study evaluations and results, eg atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis.
History or current diagnosis of ECG abnormalities indicating significant risk of safety for subjects participating in the study such as:
Concomitant clinically significant cardiac arrhythmias, eg sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker
History of familial long QT syndrome or known family history of Torsades de Pointes
Resting heart rate (physical exam or 12 lead ECG) < 60 bpm
Resting QTcF ≥450 msec (male) or ≥460 msec (female) at day 1 of the treatment period or inability to determine the QTcF interval
Use of agents known to prolong the QT interval unless it can be permanently discontinued for the duration of study
Significant bleeding risk or coagulation disorders
Known or suspected history of an ongoing, chronic or recurrent infectious disease including but not limited to opportunistic infections (eg tuberculosis, atypical mycobacterioses, listeriosis or aspergillosis), HIV, Hepatitis B/C

Other protocol defined inclusion exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Litchfield Park	Arizona	United States	85340
2	Novartis Investigative Site	Little Rock	Arkansas	United States	72205
3	Novartis Investigative Site	Mission Viejo	California	United States	92691
4	Novartis Investigative Site	San Diego	California	United States	92123
5	Novartis Investigative Site	Walnut Creek	California	United States	94598
6	Novartis Investigative Site	Pembroke Pines	Florida	United States	33028
7	Novartis Investigative Site	Owensboro	Kentucky	United States	42301
8	Novartis Investigative Site	Ypsilanti	Michigan	United States	48197
9	Novartis Investigative Site	Saint Louis	Missouri	United States	63141
10	Novartis Investigative Site	Grove City	Ohio	United States	43123
11	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1414AIF
12	Novartis Investigative Site	La Plata	Buenos Aires	Argentina	B1902COS
13	Novartis Investigative Site	Ciudad de Mendoza	Mendoza	Argentina	M5500AWD
14	Novartis Investigative Site	Caba		Argentina	1035
15	Novartis Investigative Site	Edegem	Antwerpen	Belgium	2650
16	Novartis Investigative Site	Liege		Belgium	4000
17	Novartis Investigative Site	Edmonton	Alberta	Canada	T5K 1X3
18	Novartis Investigative Site	London	Ontario	Canada	N6H 5L5
19	Novartis Investigative Site	Niagara Falls	Ontario	Canada	L2H 1H5
20	Novartis Investigative Site	Ottawa	Ontario	Canada	K1G 6C6
21	Novartis Investigative Site	Verdun	Quebec	Canada	H4G 3E7
22	Novartis Investigative Site	Quebec		Canada	G1V 4W2
23	Novartis Investigative Site	Prague 8	Czech Republic	Czechia	180 00
24	Novartis Investigative Site	Prague	Prague 1	Czechia	11000
25	Novartis Investigative Site	Tabor		Czechia	390 01
26	Novartis Investigative Site	Arhus C		Denmark	DK 8000
27	Novartis Investigative Site	Copenhagen NV		Denmark	2400
28	Novartis Investigative Site	Lille Cedex		France	59037
29	Novartis Investigative Site	Nantes Cedex 1		France	44093
30	Novartis Investigative Site	Nice Cedex		France	06202
31	Novartis Investigative Site	Oroshaza	Bekes	Hungary	5900
32	Novartis Investigative Site	Budapest		Hungary	1085
33	Novartis Investigative Site	Debrecen		Hungary	4032
34	Novartis Investigative Site	Pecs		Hungary	7632
35	Novartis Investigative Site	Szolnok		Hungary	5000
36	Novartis Investigative Site	Ichinomiya	Aichi	Japan	491-0041
37	Novartis Investigative Site	Funabashi	Chiba	Japan
38	Novartis Investigative Site	Hiroshima City	Hiroshima	Japan	734-8551
39	Novartis Investigative Site	Obihiro	Hokkaido	Japan	080 0013
40	Novartis Investigative Site	Yokohama	Kanagawa	Japan	220-6208
41	Novartis Investigative Site	Yokohama	Kanagawa	Japan	221-0825
42	Novartis Investigative Site	Yokohama	Kanagawa	Japan	240-0013
43	Novartis Investigative Site	Itabashi-ku	Tokyo	Japan	173-8610
44	Novartis Investigative Site	Takaoka	Toyama	Japan	933-0871
45	Novartis Investigative Site	Gdansk		Poland	80 803
46	Novartis Investigative Site	Lodz		Poland	90-265
47	Novartis Investigative Site	Lodz		Poland	90-436
48	Novartis Investigative Site	Rzeszow		Poland	35 055
49	Novartis Investigative Site	Warszawa		Poland	02 777
50	Novartis Investigative Site	Moscow		Russian Federation	123182
51	Novartis Investigative Site	St Petersburg		Russian Federation	194325
52	Novartis Investigative Site	St.-Petersburg		Russian Federation	195112
53	Novartis Investigative Site	Stavropol		Russian Federation	355000
54	Novartis Investigative Site	Kosice	Slovak Republic	Slovakia	040 15
55	Novartis Investigative Site	Nove Zamky		Slovakia	940 34
56	Novartis Investigative Site	Svidnik		Slovakia	08901
57	Novartis Investigative Site	Barcelona	Catalunya	Spain	08003
58	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
59	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
60	Novartis Investigative Site	Alicante	Comunidad Valenciana	Spain	03010
61	Novartis Investigative Site	Madrid		Spain	28006
62	Novartis Investigative Site	Madrid		Spain	28046
63	Novartis Investigative Site	Istanbul	TUR	Turkey	34098
64	Novartis Investigative Site	Denizli		Turkey	20070
65	Novartis Investigative Site	Talas / Kayseri		Turkey	38039
66	Novartis Investigative Site	Leeds		United Kingdom	LS9 7TF
67	Novartis Investigative Site	London		United Kingdom	SE1 9RT
68	Novartis Investigative Site	Oxford		United Kingdom	OX3 7LJ
69	Novartis Investigative Site	Plymouth		United Kingdom	PL6 8DH