Clinical trial NCT03926611: This Was a Dose-finding Study to Evaluate Efficacy and Safety of LOU064 in Patients With CSU Inadequately Controlled by H1-antihistamines
Official title: A Multicenter, Randomized, Double-blind, Placebo- Controlled Phase 2b Dose-finding Study to Investigate the Efficacy, Safety and Tolerability of LOU064 in Adult Chronic Spontaneous Urticaria (CSU) Patients Inadequately Controlled by H1-antihistamines
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Spontaneous Urticaria
Keywords: BTK inhibitor
Urticaria Activity Score
Angioedema Activity Score
CSU
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-04-24
Enrollment: 311
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This was a global Phase 2b multicenter, randomized, double-blind, parallel-group, placebocontrolled study investigating the efficacy, safety and tolerability of 6 dosing groups of oral LOU064 in subjects with inadequately controlled CSU despite treatment with (second generation) H1-antihistamine. Study duration was 18 weeks (2 weeks of screening period; 12 weeks of treatment period and a 4 weeks follow-up period).

Study had 7 arms: 10 mg LOU064 q.d.; 35 mg LOU064 q.d.; 100 mg LOU064 q.d.; 10 mg LOU064 b.i.d.; 25 mg LOU064 b.i.d.; 100 mg LOU064 b.i.d.; and Placebo

Throughout study, subjects were treated with a 2nd generation H1-antihistamine at a locally approved licensed posology ("background medication"). Subjects could take an additional second generation H1-antihistamine that was eliminated primarily via renal excretion (e.g. cetirizine, levocetirizine or bilastine) as rescue medication. Eligible subjects could roll over to extension at Wk 12 or Wk 16
Primary purpose: TREATMENT

Brief summary: This was a multicenter, randomized, double-blind and placebo-controlled phase 2b dose-finding study to assess the efficacy and safety of LOU064 in adults chronic spontaneous urticaria (CSU) patients inadequately controlled by H1-antihistamines

Detailed description: This was a global Phase 2b multicenter, randomized, double-blind, parallel-group, placebo-controlled study investigating the efficacy, safety and tolerability of six dosing groups of oral LOU064 in subjects with inadequately controlled CSU despite treatment with (second generation) H1-antihistamine. The study comprised of the 7 treatment arms: LOU064 10 mg q.d., LOU064 35 mg q.d., LOU064 100 mg q.d., LOU064 10 mg b.i.d, LOU064 25 mg b.i.d., LOU064 100 mg b.i.d. and placebo.

Eligibility criteria: Inclusion Criteria:

* Male and female subjects aged ≥18 years of age
* CSU diagnosis for ≥ 6 months prior to screening
* Presence of itch and hives for ≥6 consecutive weeks prior to screening in spite of use of non-sedating H1-antihistamines according to local Treatment guidelines during this time period
* UAS7 score (range 0-42) ≥16 and HSS7 score (range 0-21) ≥ 8 during 7 days prior to randomization (Day 1)
* Willing and able to complete an Urticaria Participant Daily eDiary (UPDD) for the duration of the study

Exclusion Criteria:

* Hypersensitivity to any of the study treatments
* Clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria)
* Other diseases with symptoms of urticaria or angioedema
* Other skin disease associated with chronic itching that might influence in the investigators opinion the study evaluations and results,
* 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.
* Pregnant or nursing (lactating) women
* Women of child-bearing potential not using highly effective methods of contraception

Primary outcomes:
measure: Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 4
timeFrame: Baseline, Week 4
Secondary outcomes:
measure: Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12
timeFrame: Week 12
measure: Percentage of Participants With Either Complete Absence of Hives and Itch (UAS7=0) or Well-controlled Disease (UAS7<=6)
timeFrame: Week 12
measure: Cumulative Number of Weeks With an AAS7=0 Response
timeFrame: Baseline to Week 12
measure: Percentage of Participants With DLQI Score of 0 or 1
timeFrame: Week 4 and Week 12
measure: Mean Change From Baseline in DLQI Score
timeFrame: Baseline, Week 4 and Week 12
measure: Area Under the Blood Concentration-time Curve (AUC) of LOU064
timeFrame: Week 4 and Week 12
measure: Observed Maximum Blood Concentration (Cmax) of LOU064
timeFrame: Week 4 and Week 12
measure: Time to Reach the Maximum Concentration (Tmax) of LOU064
timeFrame: Week 4 and Week 12
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: Westminster
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: Pierre Benite Cedex
country: France
facility: Novartis Investigative Site
city: Rouen
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Gera
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
state: Hajdu Bihar
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Oroshaza
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: Koto
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Takaoka
country: Japan
facility: Novartis Investigative Site
state: Toyama
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
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: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: St 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 Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: