Clinical trial NCT05976243: A Study to Investigate Efficacy, Safety, and Tolerability of Remibrutinib Compared With Placebo in Adults With CINDU Inadequately Controlled by H1-antihistamines
Official title: A 52-week Multi-center, Randomized, Double-blind, Placebo Controlled, Basket Study With an Open-label Extension to Investigate the Efficacy, Safety, and Tolerability of Remibrutinib (LOU064) in Chronic Inducible Urticaria (CINDU) in Adults Inadequately Controlled by H1-antihistamines
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Inducible Urticaria
Keywords: CINDU
Chronic inducible urticaria
BTK
remibrutinib
symptomatic dermographsim
cold urticaria
cholinergic urticaria
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-08-04
Enrollment: 348
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: This is a Phase 3, parallel group, placebo-controlled, double-blind, confirmatory study in patients with CINDU, with an optional Open-label Extension (OLE).

The purpose of the core period (52 weeks of treatment) of this study is to evaluate the efficacy, safety, and tolerability of remibrutinib (LOU064) vs. placebo in adults suffering from CINDU inadequately controlled by H1-antihistamines (H1-AHs).

The purpose of the OLE period is to collect long-term efficacy, safety, and tolerability data on remibrutinib in participants after having completed the Core period

Detailed description: This study consists of a core and extension periods.

The Core period (6 arms) has a total duration of up to 60 weeks including a double-blind placebo-controlled treatment period until Week 24 followed by open-label treatment with remibrutinib up to Week 52. The primary endpoint for all CINDU subtypes is assessed at Week 12.

The Core period consists of:

* Screening period (up to 4 weeks): During the screening period, participants who have provided informed consent will be assessed for study eligibility.
* Double-blind, placebo-controlled treatment period (24 weeks): 24 weeks of double-blind treatment with remibrutinib or placebo.
* Open-label treatment period (28 weeks): 28 weeks of open-label treatment with remibrutinib.
* Follow-up period: 4 weeks of treatment free follow-up. The open-label extension period consists of observation and treatment period. At the end of the core period of the study, if participants continue to experience symptoms, they will transition to the treatment period in OLE. If they do not experience symtpoms they will transition to the observation period in the OLE.

The duration of the Open-label Extension period will be approximately 3 years where participants can switch from observation to treatment depending on if they start developing symptoms. Only those participants participating in the Open-label Extension Treatment period will receive remibrutinib. The participants in the Open-label Extension Observation period will not receive remibrutinib

Eligibility criteria: Inclusion Criteria for core period:

1. Male and female participants ≥18 years of age at the time of signing of the ICFs
2. Confirmed CINDU diagnosis (as per guidelines) for symptomatic dermographism, cold urticaria or cholinergic urticaria for ≥ 4 months (defined as onset of CINDU with supporting documentation (e.g medical record, clinical history, photographs)) and inadequate control with H1-AH at local label approved doses at the time of randomization
3. The following response to the provocation test for each subtype is required at the randomization visit :

   * Symptomatic Dermographism: A Total Fric Score of ≥3 using the FricTest® 4.0 and a numerical rating scale score of ≥5 for itch after the provocation test.
   * Cold Urticaria: A Critical Threshold Temperature of ≥15°C using the TempTest® 4.0 and a numerical rating scale score of ≥5 for itch after the provocation test.
   * Cholinergic Urticaria: A physician global assessment of severity of hives ≥ 2 using the Pulse-controlled ergometry test and a numerical rating scale score of ≥5 for itch after the provocation test.
4. Cold Urticaria: Positive ice-cube test resulting in hives at the provocation site for participants at Screening.
5. Cholinergic urticaria: Participants must show sweating in performing the pulse-controlled ergometry test on day of randomization. Participants with anhidrosis must not be included.

Inclusion criteria for the OLE:

1. Participants who have completed the Core period up to Week 52 and are willing to enter the OLE period

   Exclusion Criteria for core period:
   * 1. Previous use of remibrutinib or other BTK inhibitors.
2. Participants who have concomitant CSU at screening. Participants with resolved CSU at the time of screening can be included in the study.
3. Participants who have a familial form (e.g familial cold autoinflammatory syndrome, familial cold urticaria) of the target CINDU that is being considered for the participant's inclusion in this study.
4. Participants having a more defined other form of inducible urticaria than the target CINDU that is being considered for the participant's inclusion in this study.
5. Diseases, other than chronic inducible urticaria, with urticaria or angioedema symptoms including but not limited to urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema
6. Any other skin disease associated with chronic itching that might influence, in the investigator's opinion, the study evaluations and results (e.g., atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.) or skin diseases associated with only wheals and no itch e.g asymptomatic dermographism

There are no exclusion criteria for OLE

Primary outcomes:
measure: Proportion of participants with complete response in Total Fric Score; symptomatic dermographism
timeFrame: Week 12
measure: Proportion of participants with complete response in critical temperature threshold; cold urticaria
timeFrame: Week 12
measure: Proportion of participants with itch numerical rating scale =0; cholinergic urticaria
timeFrame: Week 12
Secondary outcomes:
measure: Change from baseline in Total Fric score; symptomatic dermographism
timeFrame: Week 12
measure: Change from baseline in criticial temperature threshold following Temptest; cold urticaria
timeFrame: Week 12
measure: Change from baseline in itch numerical rating scale; cholinergic urticaria
timeFrame: Week 12
measure: proportion of participants with Physician Global Assessment (PGA) severity of hives =0; cholinergic urticaria
timeFrame: Week 12
measure: Proportion of participants with complete response in TFS; symptomatic dermographism
timeFrame: Week 24
measure: Proportion of participants with complete response in Critical Temperature threshold; cold urticaria
timeFrame: Week 24
measure: Proportion of participants with complete response in itch numerical rating scale; cholinergic urticaria
timeFrame: Week 24
measure: Change from baseline in itch numerical rating scale in participants with symptomatic dermographism
timeFrame: Week 12
measure: Change from baseline in itch numerical rating scale in participants with cold urticaria
timeFrame: Week 12
measure: Proportion of participants with complete response in Total Fric score; symptomatic dermographism
timeFrame: Week 2
measure: Proportion of participants with complete response in Critical Temperature Threshold; cold urticaria
timeFrame: Week 2
measure: Proportion of participants with itch NRS=0; cholinergic urticaria
timeFrame: Week 2
measure: Change from baseline in TFS in participants with symptomatic dermographism
timeFrame: Week 2
measure: Change from baseline in Critical Temperature Threshold in participants with cold urticaria
timeFrame: Week 2
measure: Change from baseline in itch NRS in participants with cholinergic urticaria
timeFrame: Week 2
measure: Change from baseline in itch NRS in participants with symptomatic dermographism
timeFrame: Week 2
measure: Change from baseline in itch NRS in participants with cold urticaria
timeFrame: Week 2
measure: Proportion of participants with cholinergic urticaria with PGA=0
timeFrame: Week 2
measure: Change from baseline in weekly most bothersome symptom NRS score on the USDD
timeFrame: Week 12
measure: Proportion of participants with DLQI=0-1
timeFrame: Week 12
measure: Occurrence of treatment emergent adverse events and serious adverse events during the study
timeFrame: Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Allervie Clinical Research
state: Alabama
city: Little Rock
country: United States
facility: Acuro Research Inc
state: Arkansas
city: Bakersfield
country: United States
facility: Kern Research
state: California
city: Huntington Beach
country: United States
facility: OC Allergy and Asthma Specialists
state: California
city: Lancaster
country: United States
facility: Antelope Valley Clinical Trials
state: California
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates P C
state: Colorado
city: Aventura
country: United States
facility: Florida Ctr Allergy Asthma Research
state: Florida
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: Sarasota
country: United States
facility: Sarasota Clinical Research
state: Florida
city: Tampa
country: United States
facility: Univ of South Florida Asthma Allergy and Immunology CRU
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: 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: Lincoln
country: United States
facility: Somnos Clinical Research
state: Nebraska
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: 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: Brownsville
country: United States
facility: PanAmerican Clinical Research
state: Texas
city: Dallas
country: United States
facility: Asthma and Allergy Research Assoc
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: San Antonio
country: United States
facility: STAAMP Research LLC
state: Texas
city: Sugar Land
country: United States
facility: Complete Dermatology
state: Texas
city: Sandy
country: United States
facility: Allergy Associates of Utah
state: Utah
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Woolloongabba
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Carlton
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Alphaville Barueri
country: Brazil
facility: Novartis Investigative Site
state: Sao Paulo
city: Santo Andre
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sorocaba
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Winnipeg
country: Canada
facility: Novartis Investigative Site
state: Manitoba
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Trois Rivieres
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Fuzhou
country: China
facility: Novartis Investigative Site
state: Fujian
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guangdong
country: China
facility: Novartis Investigative Site
state: Guangzhou
city: Changsha
country: China
facility: Novartis Investigative Site
state: Hunan
city: Wuxi
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Chang Chun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Jinan
country: China
facility: Novartis Investigative Site
state: Shandong
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Urumqi
country: China
facility: Novartis Investigative Site
state: Xinjiang
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Yi Wu
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: Beijing
country: China
facility: Novartis Investigative Site
city: Chongqing
country: China
facility: Novartis Investigative Site
city: Jinan
country: China
facility: Novartis Investigative Site
city: Nanjing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Tianjin
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facility: Novartis Investigative Site
city: Barranquilla
country: Colombia
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state: Atlantico
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
city: Clermont Ferrand
country: France
facility: Novartis Investigative Site
city: Grenoble
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Nantes
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Pierre Benite
country: France
facility: Novartis Investigative Site
city: Rouen
country: France
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
city: Goettingen
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Luebeck
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Stade
country: Germany
facility: Novartis Investigative Site
city: Tuebingen
country: Germany
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
state: Hajdu Bihar
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Szolnok
country: Hungary
facility: Novartis Investigative Site
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Mysore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Nagpur
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Kfar Saba
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Catania
country: Italy
facility: Novartis Investigative Site
state: CT
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Kitakyushu
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Sapporo
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Kamimashi-gun
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Habikino city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Takatsuki
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Ohtsu
country: Japan
facility: Novartis Investigative Site
state: Shiga
city: Izumo-city
country: Japan
facility: Novartis Investigative Site
state: Shimane
city: Shimotsuga Gun
country: Japan
facility: Novartis Investigative Site
state: Tochigi
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku Ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Tachikawa
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Hiroshima
country: Japan
facility: Novartis Investigative Site
city: Kyoto
country: Japan
facility: Novartis Investigative Site
city: Suwon si
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
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: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Bydgoszcz
country: Poland
facility: Novartis Investigative Site
city: Olsztyn
country: Poland
facility: Novartis Investigative Site
city: Rzeszow
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Coimbra
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Vila Nova De Gaia
country: Portugal
facility: Novartis Investigative Site
city: Bucharest
country: Romania
facility: Novartis Investigative Site
state: District 2
city: Timisoara
country: Romania
facility: Novartis Investigative Site
state: Timis
city: Brasov
country: Romania
facility: Novartis Investigative Site
city: Cluj Napoca
country: Romania
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Kezmarok
country: Slovakia
facility: Novartis Investigative Site
city: Trnava
country: Slovakia
facility: Novartis Investigative Site
city: Zilina
country: Slovakia
facility: Novartis Investigative Site
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: A Coruna
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Granada
country: Spain
facility: Novartis Investigative Site
state: Andalucia
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: Mostoles
country: Spain
facility: Novartis Investigative Site
state: Madrid Communidad De
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
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: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Sakarya
country: Turkey
facility: Novartis Investigative Site
city: Talas Kayseri
country: Turkey
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: Oxford
country: United Kingdom
facility: Novartis Investigative Site
city: Hanoi
country: Vietnam
facility: Novartis Investigative Site
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: