Clinical trial NCT05513001: An Extension Study of Long-term Efficacy, Safety and Tolerability of Remibrutinib in Chronic Spontaneous Urticaria Patients Who Completed Preceding Studies With Remibrutinib
Official title: A Multicenter, Double-blind, Placebo-controlled, Randomized Withdrawal and Open-label Extension Study Followed by Long-term Open-label Treatment Cycles to Assess the Efficacy, Safety and Tolerability of Remibrutinib (LOU064) in Adult Chronic Spontaneous Urticaria Patients Who Completed the Preceding Remibrutinib Phase 3 Studies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Chronic Spontaneous Urticaria
Keywords: CSU
Brutons Tyrosine Kinase (BTK) inhibitor
Chronic Spontaneous Urticaria
Urticaria activity score
Hives severity score
Itch severity score
Extension
Randomized withdrawal
Retreatment upon relapse
Remibrutinib
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-08-23
Enrollment: 695
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this extension study is to collect long-term efficacy, safety and tolerability data on remibrutinib in a selected group of participants with Chronic Spontaneous Urticaria (CSU) who previously completed the treatment phase of remibrutinib preceding Phase 3 studies.

This study will also fulfill the Novartis commitment to provide post-trial access to participants who have completed the preceding Phase 3 studies, where applicable.

Detailed description: This is a global, multicenter, randomized, double-blind, placebo-controlled, randomized withdrawal Phase 3b extension study, followed by long-term open label treatment cycles to assess the efficacy, safety and tolerability of remibrutinib in adult participants with CSU inadequately controlled by H1-AH. The study comprises 2 Epochs. Epoch 1 is the initial study period for participants who completed preceding remibrutinib Phase 3 studies. Epoch 1 comprises of a 24-week randomized withdrawal period with remibrutinib or placebo for patients with UAS7\<16 OR a 24 week Open-label treatment period with remibrutinib for patients with UAS7≥16.

Participants will be randomized in a 1:1 ratio to enter the double-blind placebo-controlled 24-week withdrawal phase. In case of relapse (UAS7≥16) in the blinded group, participants enter the (Re-)treatment period Epoch 1 and receive 24 weeks of Open-label treatment with remibrutinib. At the end of the (Re-)treatment period Epoch 1, participants will move to Epoch 2.

Epoch 2 is the second subsequent study period and consists of 24-week cycles that could either encompass treatment-free Observation and/or Open-label (Re-)treatment periods with remibrutinib, with or without background H1-AH.

In case of relapse (UAS7≥16) during an Observation period, participants enter the next (Re-)treatment period and receive 24 weeks of treatment with remibrutinib. Participants completing an Observation period 2/3/4/5 with a UAS7≤6 will complete the study. Participants with a UAS7 \>6 -\<16 can enter the next (Re-)treatment period if continuous treatment is considered necessary and beneficial for the individual participant. For participants with a UAS7\<16 that enter the next (Re-)treatment period, remibrutinib monotherapy treatment (without background H1-AH) is required.

Eligibility criteria: Inclusion Criteria:

* Written informed consent must be obtained before any assessment is performed.
* Male and female, adult participants ≥18 years of age.
* Participants who successfully completed the preceding core studies CLOU064A2301, CLOU064A2302, CLOU064A1301, CLOU064A2304 or CLOU064A2305 according to the respective protocols.
* Willing and able to adhere to the study protocol and visit schedule.

Exclusion Criteria:

* Significant bleeding risk or coagulation disorders.
* History of gastrointestinal bleeding.
* Requirement for anti-platelet medication.
* Requirement for anticoagulant medication.
* History or current hepatic disease.
* Evidence of clinically significant cardiovascular, neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders, gastrointestinal disease or immunodeficiency that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant.

Primary outcomes:
measure: Time to first composite event (i.e., relapse (UAS7≥16)
timeFrame: 24 weeks
Secondary outcomes:
measure: Number of participants with treatment-emergent (serious and non-serious) adverse events
timeFrame: 160 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Allervie Clinical Research
state: Alabama
city: Birmingham
country: United States
facility: Cahaba Derm and skin hlth ctr 27
state: Alabama
city: Litchfield Park
country: United States
facility: Research Solutions of Arizona
state: Arizona
city: Little Rock
country: United States
facility: Acuro Research Inc
state: Arkansas
city: North Little Rock
country: United States
facility: Arkansas Research Trials
state: Arkansas
city: Bakersfield
country: United States
facility: Kern Research
state: California
city: Lancaster
country: United States
facility: Antelope Valley Clinical Trials
state: California
city: Redwood City
country: United States
facility: Allergy and Asthma Consultants
state: California
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates P C
state: Colorado
city: Denver
country: United States
facility: Colorado Allergy and Asthma Ctr PC
state: Colorado
city: Farmington
country: United States
facility: UCONN Health Dermatology
state: Connecticut
city: Aventura
country: United States
facility: Florida Ctr Allergy Asthma Research
state: Florida
city: Greenacres City
country: United States
facility: Finlay Medical Research
state: Florida
city: Miami
country: United States
facility: Miami Dade Medical Research
state: Florida
city: Sarasota
country: United States
facility: Sarasota Clinical Research
state: Florida
city: Tallahassee
country: United States
facility: Allergy and Asthma Diagnostic Treatment Center
state: Florida
city: Savannah
country: United States
facility: AeroAllergy Research Laboratories of Savannah Inc
state: Georgia
city: Boise
country: United States
facility: Treasure Valley Medical Research
state: Idaho
city: Glenview
country: United States
facility: Endeavor Health
state: Illinois
city: River Forest
country: United States
facility: Asthma and Allergy Center of Chicago S C
state: Illinois
city: Evansville
country: United States
facility: Deaconess Clin Allerg Res Inst
state: Indiana
city: Plainfield
country: United States
facility: The Indiana Clinical Trials Center
state: Indiana
city: Owensboro
country: United States
facility: Allergy and Asthma Specialist P S C
state: Kentucky
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Chevy Chase
country: United States
facility: Institute for Asthma and Allergy PC
state: Maryland
city: Saint Louis
country: United States
facility: The Clinical Research Center
state: Missouri
city: Lincoln
country: United States
facility: Somnos Clinical Research
state: Nebraska
city: Little Silver
country: United States
facility: Allergy Asthma Assoc Monmouth
state: New Jersey
city: Athens
country: United States
facility: Oakview Dermatology
state: Ohio
city: Columbus
country: United States
facility: Optimed Research LLC
state: Ohio
city: Dublin
country: United States
facility: CR Services Acquisition US
state: Ohio
city: Toledo
country: United States
facility: Toledo Institute of Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Allergy Asthma and Clinical Research
state: Oklahoma
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute
state: Oklahoma
city: Pittsburgh
country: United States
facility: Allergy and Clinical Immunology Associates
state: Pennsylvania
city: North Charleston
country: United States
facility: National Allergy and Asthma Research LLS
state: South Carolina
city: Austin
country: United States
facility: Orion Clinical Research
state: Texas
city: El Paso
country: United States
facility: Western Sky Medical Research
state: Texas
city: San Antonio
country: United States
facility: RFSA Dermatology
state: Texas
city: Sandy
country: United States
facility: Allergy Associates of Utah
state: Utah
city: Bellingham
country: United States
facility: Bellingham Asthma Allergy and Immunology
state: Washington
city: Seattle
country: United States
facility: Seattle Allergy and Asthma Rsch
state: Washington
city: Greenfield
country: United States
facility: Allergy Asthma and amp Sinus Ctr S C
state: Wisconsin
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: La Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
state: Nueve De Julio
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Bahia Blanca
country: Argentina
facility: Novartis Investigative Site
city: Capital Federal
country: Argentina
facility: Novartis Investigative Site
city: Santa Fe
country: Argentina
facility: Novartis Investigative Site
city: East Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Santo Andre
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Pleven
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Calgary
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Fredericton
country: Canada
facility: Novartis Investigative Site
state: New Brunswick
city: Kingston
country: Canada
facility: Novartis Investigative Site
state: Ontario
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: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Verdun
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guangdong
country: China
facility: Novartis Investigative Site
state: Guangzhou
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Wuxi
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Chang Chun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Medellin
country: Colombia
facility: Novartis Investigative Site
state: Antioquia
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
state: Atlantico
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Brno
country: Czechia
facility: Novartis Investigative Site
city: Olomouc
country: Czechia
facility: Novartis Investigative Site
city: Plzen
country: Czechia
facility: Novartis Investigative Site
city: Praha 5
country: Czechia
facility: Novartis Investigative Site
city: Hellerup
country: Denmark
facility: Novartis Investigative Site
city: Kobenhavn N V
country: Denmark
facility: Novartis Investigative Site
city: Angers Cedex 9
country: France
facility: Novartis Investigative Site
city: Antony
country: France
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Brest
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Nice
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Pierre Benite
country: France
facility: Novartis Investigative Site
city: Reims
country: France
facility: Novartis Investigative Site
city: Rouen
country: France
facility: Novartis Investigative Site
city: Saint Mande
country: France
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
city: Bramsche
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Goettingen
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Halle Saale
country: Germany
facility: Novartis Investigative Site
state: Sachsen-Anhalt
city: Halle Saale
country: Germany
facility: Novartis Investigative Site
state: Sachsen-Anhalt
city: Leipzig
country: Germany
facility: Novartis Investigative Site
state: Sachsen
city: Bad Bentheim
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Luebeck
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Marburg
country: Germany
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city: Merzig
country: Germany
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city: Muenchen
country: Germany
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city: Muenchen
country: Germany
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city: Debrecen
country: Hungary
facility: Novartis Investigative Site
state: Hajdu Bihar
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Belgavi
country: India
facility: Novartis Investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Urayasu
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Obihiro
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kamimashi-gun
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Izumiotsu
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Neyagawa
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Sakai
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Takatsuki
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Takatsuki
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Izumo-city
country: Japan
facility: Novartis Investigative Site
state: Shimane
city: Itabashi-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Koto
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Minato
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Ota-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Hiroshima
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Daegu
country: Korea, Republic of
facility: Novartis Investigative Site
state: Dalseo Gu
city: Hwaseong si
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Suwon si
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Gwangju
country: Korea, Republic of
facility: Novartis Investigative Site
city: Incheon
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Muar
country: Malaysia
facility: Novartis Investigative Site
state: Johor
city: Ipoh
country: Malaysia
facility: Novartis Investigative Site
state: Perak
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
state: Wilayah Persekutuan
city: Pulau Pinang
country: Malaysia
facility: Novartis Investigative Site
city: Wilayah Persekutuan
country: Malaysia
facility: Novartis Investigative Site
city: Bialystok
country: Poland
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Carolina
country: Puerto Rico
facility: Alma Cruz-Santana Private Practice
city: Izhevsk
country: Russian Federation
facility: Novartis Investigative Site
city: Ryazan
country: Russian Federation
facility: Novartis Investigative Site
city: Ryazan
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: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Kezmarok
country: Slovakia
facility: Novartis Investigative Site
city: Komarno
country: Slovakia
facility: Novartis Investigative Site
city: Kosice
country: Slovakia
facility: Novartis Investigative Site
city: Levice
country: Slovakia
facility: Novartis Investigative Site
city: Nove Zamky
country: Slovakia
facility: Novartis Investigative Site
city: Svidnik
country: Slovakia
facility: Novartis Investigative Site
city: Pretoria
country: South Africa
facility: Novartis Investigative Site
state: Gauteng
city: Cape Town
country: South Africa
facility: Novartis Investigative Site
state: Western Province
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: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Las Palmas de Gran Canaria
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Bern
country: Switzerland
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Khon Kaen
country: Thailand
facility: Novartis Investigative Site
state: THA
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Chiang Mai
country: Thailand
facility: Novartis Investigative Site
city: Aydin
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Kayseri
country: Turkey
facility: Novartis Investigative Site
city: Sakarya
country: Turkey
facility: Novartis Investigative Site
city: Samsun
country: Turkey
facility: Novartis Investigative Site
city: Talas Kayseri
country: Turkey
facility: Novartis Investigative Site
city: Cardiff
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: