Clinical trial NCT04109313: An Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of LOU064 in Subjects With CSU
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 CLOU064A2201
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Spontaneous Urticaria
Keywords: Chronic spontaneous urticaria
BTK Inhibitor
Long term safety
Urticaria activity score
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-09-30
Enrollment: 229
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main objective to assess the long-term safety and tolerability of LOU064 in patients with chronic spontaneous urticaria (CSU) who have participated in study CLOU064A2201 (NCT03926611)

Detailed description: This was an open-label, single-arm, multicenter, long-term safety and tolerability extension study for CSU patients rolling over from study CLOU064A2201 (NCT03926611).

Subjects rolling over from CLOU064A2201 with a weekly Urticaria Activity Score (UAS7)\<16 after the follow-up period at Week 16 were further followed up without receiving LOU064 for up to 12 weeks (observational period). If there was a relapse (UAS7≥16 at least once), the 12-week observational period was terminated, and subjects entered the treatment period. Subjects who never relapsed within 12 weeks completed the study after the observational period without treatment.

Subjects who rolled over from CLOU064A2201 with a UAS7≥16 at Week 12 or Week 16, as well as those subjects who relapsed during the 12-week observational period, were treated with 100 mg LOU064 twice a day (b.i.d.) open-label for 52 weeks. No background medication with a second-generation H1-antihistamine was permitted up to Week 4 of the treatment period. Subjects who completed the treatment period or who discontinued treatment early were followed-up for a minimum duration of 4 weeks. Subjects who had a UAS7≤6 at Week 52 of the treatment period had their follow-up period extended until relapse (UAS7≥16) for up to a total of 16 weeks.

Eligibility criteria: Key Inclusion Criteria:

* Participants must provide written informed consent prior to any assessments.
* Participants must be willing and able to complete a daily symptom eDiary throughout the study and adhere to the study visit schedules.
* Participants transitioning from the CLOU064A2201 trial must have completed either the Week 12 visit (end of treatment period) or the Week 16 visit (end of follow-up period). They will be assigned to either the treatment period or the observational period based on their UAS7 score (average score from the 7 days prior to the respective visit) as follows:

  1. Participants transitioning at Week 12 of CLOU064A2201 with a UAS7 score of ≥16 will be allocated to the treatment period.
  2. Participants transitioning at Week 16 of CLOU064A2201 with a UAS7 score of ≥16 will be allocated to the treatment period.
  3. Participants transitioning at Week 16 of CLOU064A2201 with a UAS7 score of \<16 will be allocated to the observational period.

Key Exclusion Criteria:

* Participants with a clearly defined predominant or sole trigger for their chronic urticaria, such as chronic inducible urticaria (including symptomatic dermographism, cold-induced, heat-induced, solar-induced, pressure-induced, delayed pressure-induced, aquagenic-induced, cholinergic-induced, or contact-induced urticaria).
* Participants with other diseases presenting with urticaria or angioedema symptoms, including but not limited to urticaria vasculitis, urticarial pigmentosa, erythema multiforme, mastocytosis, hereditary urticaria, or acquired/drug-induced urticaria.
* Participants with any other skin disease associated with chronic itching that, in the opinion of the investigator, could affect the study evaluations and results, such as atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or psoriasis.
* Participants with a history or current diagnosis of ECG abnormalities that indicate a significant safety risk for their participation in the study, including:
* Concomitant clinically significant cardiac arrhythmias (e.g., sustained ventricular tachycardia) and clinically significant second or third-degree AV block without a pacemaker.
* History of familiar long QT syndrome or a known family history of Torsades de Pointes.
* Resting heart rate (as determined by physical exam or 12-lead ECG) below 50 bpm.
* Resting QTcF interval ≥450 msec (in males) or ≥460 msec (in females) at day 1 of the treatment period or inability to determine the QTcF interval.
* Use of agents known to prolong the QT interval, unless they can be permanently discontinued for the duration of the study.
* Participants with a significant risk of bleeding or coagulation disorders.
* Participants with a known or suspected history of an ongoing, chronic, or recurrent infectious disease, including but not limited to opportunistic infections (e.g., tuberculosis, atypical mycobacterioses, listeriosis, or aspergillosis), HIV, or Hepatitis B/C.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (AEs)
timeFrame: From first dose of treatment up to 28 days after last dose, assessed up to 56 weeks
Secondary outcomes:
measure: Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4 of the Treatment Period
timeFrame: Baseline, Week 4 of treatment period
measure: Percentage of Participants With Well-controlled Disease (UAS7≤6) at Week 4 of the Treatment Period
timeFrame: Week 4 of the treatment period
measure: Percentage of Participants With Complete Response (UAS7=0) at Week 4 of the Treatment Period
timeFrame: Week 4 of the treatment period
measure: Percentage of Participants With Well-controlled Disease (UAS7≤ 6) Overtime
timeFrame: From baseline until Week 52 of the treatment period
measure: Change From Baseline in UAS7 Overtime
timeFrame: From baseline until Week 52 of the treatment period
Other outcomes:
Locations:
city: Litchfield Park
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Little Rock
country: United States
facility: Novartis Investigative Site
state: Arkansas
city: Mission Viejo
country: United States
facility: Novartis Investigative Site
state: California
city: San Diego
country: United States
facility: Novartis Investigative Site
state: California
city: Walnut Creek
country: United States
facility: Novartis Investigative Site
state: California
city: Pembroke Pines
country: United States
facility: Novartis Investigative Site
state: Florida
city: Owensboro
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Ypsilanti
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Grove City
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: La Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Ciudad de Mendoza
country: Argentina
facility: Novartis Investigative Site
state: Mendoza
city: Caba
country: Argentina
facility: Novartis Investigative Site
city: Edegem
country: Belgium
facility: Novartis Investigative Site
state: Antwerpen
city: Liege
country: Belgium
facility: Novartis Investigative Site
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Niagara Falls
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Verdun
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Prague 8
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Prague
country: Czechia
facility: Novartis Investigative Site
state: Prague 1
city: Tabor
country: Czechia
facility: Novartis Investigative Site
city: Arhus C
country: Denmark
facility: Novartis Investigative Site
city: Copenhagen NV
country: Denmark
facility: Novartis Investigative Site
city: Lille Cedex
country: France
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Nice Cedex
country: France
facility: Novartis Investigative Site
city: Oroshaza
country: Hungary
facility: Novartis Investigative Site
state: Bekes
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Pecs
country: Hungary
facility: Novartis Investigative Site
city: Szolnok
country: Hungary
facility: Novartis Investigative Site
city: Ichinomiya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Funabashi
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Hiroshima City
country: Japan
facility: Novartis Investigative Site
state: Hiroshima
city: Obihiro
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Itabashi-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Takaoka
country: Japan
facility: Novartis Investigative Site
state: Toyama
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Rzeszow
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St.-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Stavropol
country: Russian Federation
facility: Novartis Investigative Site
city: Kosice
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Nove Zamky
country: Slovakia
facility: Novartis Investigative Site
city: Svidnik
country: Slovakia
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Alicante
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Denizli
country: Turkey
facility: Novartis Investigative Site
city: Talas / Kayseri
country: Turkey
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Oxford
country: United Kingdom
facility: Novartis Investigative Site
city: Plymouth
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceutical
name: Novartis Pharmaceutical
role: STUDY_DIRECTOR
References: