A Study to Investigate Efficacy, Safety, and Tolerability of Remibrutinib Compared With Placebo in Adults With CINDU Inadequately Controlled by H1-antihistamines

NCT05976243 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CLOU064M123012023-505739-12-00
• Study Type: interventional
• Target: 362
• Locations: 28 countries
• Sites: 133

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

Conditions

Chronic Inducible Urticaria

Keywords

CINDU; Chronic inducible urticaria; BTK; remibrutinib; symptomatic dermographsim; cold urticaria; cholinergic urticaria

Outcome Measures

Primary Outcomes (3)

• Proportion of participants with complete response in Total Fric Score; symptomatic dermographism

  Total Fric score (a scale from 0-4 where a positive response with all of the four pins is TFS = 4, while a positive response with only one pin - the largest pin is TFS = 1)

  Week 12

• Proportion of participants with complete response in critical temperature threshold; cold urticaria

  The Temptest is used to induce itch and hives in participants with cold urticaria. Critical temperature threshold (CTT), as measured by the Temptest, determines the highest temperature that induces symptoms.

  Week 12

• Proportion of participants with itch numerical rating scale =0; cholinergic urticaria

  Itch numerical rating scale, a scale from 0 to 10 Patients are asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 ("no itch") to 10 ("worst itch imaginable")

  Week 12

Secondary Outcomes (21)

• Change from baseline in Total Fric score; symptomatic dermographism

  Week 12

• Change from baseline in criticial temperature threshold following Temptest; cold urticaria

  Week 12

• Change from baseline in itch numerical rating scale; cholinergic urticaria

  Week 12

• proportion of participants with Physician Global Assessment (PGA) severity of hives =0; cholinergic urticaria

  Week 12

• Proportion of participants with complete response in TFS; symptomatic dermographism

  Week 24

Study Arms (6)

Remibrutinib, symptomatic dermographism group

EXPERIMENTAL

Remibrutinib oral twice daily in participants with symptomatic dermographism

Drug: Remibrutinib

Placebo, symptomatic dermographism group

PLACEBO COMPARATOR

Placebo oral twice daily, symptomatic dermographism

Other: Placebo

Remibrutinib, cold urticaria group

EXPERIMENTAL

Remibrutinib oral twice daily, cold urticaria

Drug: Remibrutinib

Placebo, cold urticaria group

PLACEBO COMPARATOR

Placebo oral twice daily, cold urticaria

Other: Placebo

Remibrutinib, cholinergic urticaria group

EXPERIMENTAL

Remibrutinib oral twice daily, cholinergic urticaria

Drug: Remibrutinib

Placebo, cholinergic urticaria

PLACEBO COMPARATOR

Placebo oral twice daily, cholinergic urticaria

Other: Placebo

Interventions

Remibrutinib DRUG

Remibrutinib treated groups and arms

Remibrutinib, cholinergic urticaria group; Remibrutinib, cold urticaria group; Remibrutinib, symptomatic dermographism group

Placebo OTHER

Placebo treated groups and arms

Placebo, cholinergic urticaria; Placebo, cold urticaria group; Placebo, symptomatic dermographism group

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants ≥18 years of age at the time of signing of the ICFs
• 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
• 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.
• Cold Urticaria: Positive ice-cube test resulting in hives at the provocation site for participants at Screening.
• Cholinergic urticaria: Participants must show sweating in performing the pulse-controlled ergometry test on day of randomization. Participants with anhidrosis must not be included.
• Participants who have completed the Core period up to Week 52 and are willing to enter the OLE period

You may not qualify if:

• \. Previous use of remibrutinib or other BTK inhibitors.
• Participants who have concomitant CSU at screening. Participants with resolved CSU at the time of screening can be included in the study.
• 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
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (133)

Allervie Clinical Research

Birmingham, Alabama, 35209, United States

Location

Acuro Research Inc

Little Rock, Arkansas, 72205, United States

Location

Kern Research

Bakersfield, California, 93301, United States

Location

Allergy and Asthma Specialists Group

Huntington Beach, California, 92647, United States

Location

Antelope Valley Clinical Trials

Lancaster, California, 93534, United States

Location

Asthma and Allergy Associates P C

Colorado Springs, Colorado, 80907, United States

Location

Florida Ctr Allergy Asthma Research

Aventura, Florida, 33180, United States

Location

Sarasota Clinical Research

Sarasota, Florida, 34233, United States

Location

Univ of South Florida Asthma Allergy and Immunology CRU

Tampa, Florida, 33613, United States

Location

Aeroallergy Research Laboratories

Savannah, Georgia, 31406, United States

Location

Treasure Valley Medical Research

Boise, Idaho, 83706, United States

Location

Endeavor Health

Glenview, Illinois, 60077, United States

Location

Asthma and Allergy Center of Chicago S C

River Forest, Illinois, 60305, United States

Location

The Indiana Clinical Trials Center

Plainfield, Indiana, 46168, United States

Location

Allergy and Asthma Specialist P S C

Owensboro, Kentucky, 42301, United States

Location

John Hopkins University

Baltimore, Maryland, 21204, United States

Location

Allergy Asthma and Clinical Research

Oklahoma City, Oklahoma, 73120, United States

Location

Allergy and Clinical Immunology Associates

Pittsburgh, Pennsylvania, 15241, United States

Location

National Allergy and Asthma Research LLS

North Charleston, South Carolina, 29420, United States

Location

PanAmerican Clinical Research

Brownsville, Texas, 78520, United States

Location

Western Sky Medical Research

El Paso, Texas, 79924, United States

Location

RFSA Dermatology

San Antonio, Texas, 78213, United States

Location

STAAMP Research LLC

San Antonio, Texas, 78229, United States

Location

Complete Dermatology

Sugar Land, Texas, 77479, United States

Location

Allergy Associates of Utah

Sandy City, Utah, 84093, United States

Location

Novartis Investigative Site

Caba, Buenos Aires, C1121ABE, Argentina

Location

Novartis Investigative Site

CABA, Buenos Aires, C1414AIF, Argentina

Location

Novartis Investigative Site

Rosario, Santa Fe Province, 2000, Argentina

Location

Novartis Investigative Site

CABA, C1181ACH, Argentina

Location

Novartis Investigative Site

Woolloongabba, Queensland, 4102, Australia

Location

Novartis Investigative Site

Carlton, Victoria, 3053, Australia

Location

Novartis Investigative Site

Melbourne, Victoria, 3004, Australia

Location

Novartis Investigative Site

Alphaville Barueri, São Paulo, 06454-010, Brazil

Location

Novartis Investigative Site

Santo André, São Paulo, 09060-870, Brazil

Location

Novartis Investigative Site

Sorocaba, São Paulo, 18040-425, Brazil

Location

Novartis Investigative Site

Winnipeg, Manitoba, R3J 0S9, Canada

Location

Novartis Investigative Site

Hamilton, Ontario, L8L 3C3, Canada

Location

Novartis Investigative Site

Trois-Rivières, Quebec, G8T 7A1, Canada

Location

Novartis Investigative Site

Fuzhou, Fujian, 350025, China

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510091, China

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510630, China

Location

Novartis Investigative Site

Changsha, Hunan, 410008, China

Location

Novartis Investigative Site

Wuxi, Jiangsu, 214002, China

Location

Novartis Investigative Site

Changchun, Jilin, 130021, China

Location

Novartis Investigative Site

Jinan, Shandong, 250022, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610072, China

Location

Novartis Investigative Site

Ürümqi, Xinjiang, 830001, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310001, China

Location

Novartis Investigative Site

Yiwu, Zhejiang, 322000, China

Location

Novartis Investigative Site

Beijing, 100050, China

Location

Novartis Investigative Site

Beijing, 100730, China

Location

Novartis Investigative Site

Jinan, 250012, China

Location

Novartis Investigative Site

Shanghai, 200040, China

Location

Novartis Investigative Site

Tianjin, 300052, China

Location

Novartis Investigative Site

Barranquilla, Atlántico, 080002, Colombia

Location

Novartis Investigative Site

Barranquilla, Atlántico, 080020, Colombia

Location

Novartis Investigative Site

Clermont-Ferrand, 63003, France

Location

Novartis Investigative Site

Grenoble, 38043, France

Location

Novartis Investigative Site

Montpellier, 34295, France

Location

Novartis Investigative Site

Nantes, 44093, France

Location

Novartis Investigative Site

Paris, 75970, France

Location

Novartis Investigative Site

Pierre-Bénite, 69495, France

Location

Novartis Investigative Site

Rouen, 76031, France

Location

Novartis Investigative Site

Toulouse, 31400, France

Location

Novartis Investigative Site

Göttingen, Lower Saxony, 37075, Germany

Location

Novartis Investigative Site

Stade, Lower Saxony, 21682, Germany

Location

Novartis Investigative Site

Dresden, Saxony, 01307, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Novartis Investigative Site

Münster, 48149, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Hong Kong, 999999, Hong Kong

Location

Novartis Investigative Site

Debrecen, Hajdu Bihar Megye, 4032, Hungary

Location

Novartis Investigative Site

Debrecen, Hajdú-Bihar, 4031, Hungary

Location

Novartis Investigative Site

Szolnok, Jász-Nagykun-Szolnok, 5000, Hungary

Location

Novartis Investigative Site

Bangalore, Karnataka, 560004, India

Location

Novartis Investigative Site

Mysore, Karnataka, 570001, India

Location

Novartis Investigative Site

Haifa, 3104802, Israel

Location

Novartis Investigative Site

Jerusalem, 9112001, Israel

Location

Novartis Investigative Site

Ramat Gan, 5265601, Israel

Location

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

Novartis Investigative Site

Ancona, AN, 60126, Italy

Location

Novartis Investigative Site

Milan, MI, 20122, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Kitakyushu, Fukuoka, 8078556, Japan

Location

Novartis Investigative Site

Sapporo, Hokkaido, 0608543, Japan

Location

Novartis Investigative Site

Kamimashi-gun, Kumamoto, 861-3106, Japan

Location

Novartis Investigative Site

Habikino, Osaka, 5838588, Japan

Location

Novartis Investigative Site

Takatsuki, Osaka, 5698686, Japan

Location

Novartis Investigative Site

Ohtsu, Shiga, 5202192, Japan

Location

Novartis Investigative Site

Izumo, Shimane, 693 8501, Japan

Location

Novartis Investigative Site

Bunkyo-ku, Tokyo, 1138519, Japan

Location

Novartis Investigative Site

Itabashi-ku, Tokyo, 1738610, Japan

Location

Novartis Investigative Site

Shinjuku Ku, Tokyo, 160-0023, Japan

Location

Novartis Investigative Site

Tachikawa, Tokyo, 1900023, Japan

Location

Novartis Investigative Site

Hiroshima, 7308518, Japan

Location

Novartis Investigative Site

Muar town, Johor, 84000, Malaysia

Location

Novartis Investigative Site

Ipoh, Perak, 30450, Malaysia

Location

Novartis Investigative Site

George Town, Pulau Pinang, 10450, Malaysia

Location

Novartis Investigative Site

Utrecht, 3584 CX, Netherlands

Location

Novartis Investigative Site

Bydgoszcz, 85-094, Poland

Location

Novartis Investigative Site

Rzeszów, 35 055, Poland

Location

Novartis Investigative Site

Warsaw, 02-962, Poland

Location

Novartis Investigative Site

Coimbra, 3004-561, Portugal

Location

Novartis Investigative Site

Lisbon, 1649-035, Portugal

Location

Novartis Investigative Site

Vila Nova de Gaia, 4434 502, Portugal

Location

Novartis Investigative Site

Bucharest, District 2, 020762, Romania

Location

Novartis Investigative Site

Singapore, 308205, Singapore

Location

Novartis Investigative Site

Kežmarok, 060 01, Slovakia

Location

Novartis Investigative Site

Trnava, 917 02, Slovakia

Location

Novartis Investigative Site

Žilina, 012 07, Slovakia

Location

Novartis Investigative Site

Suwon, Gyeonggi-do, 16499, South Korea

Location

Novartis Investigative Site

Seoul, 03722, South Korea

Location

Novartis Investigative Site

Santiago, A Coruna, 15702, Spain

Location

Novartis Investigative Site

Granada, Andalusia, 18014, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

Location

Novartis Investigative Site

Alicante, 03010, Spain

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28041, Spain

Location

Novartis Investigative Site

Madrid, 280796, Spain

Location

Novartis Investigative Site

Valencia, 46015, Spain

Location

Novartis Investigative Site

Bangkok, 10400, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Chiang Mai, 50200, Thailand

Location

Novartis Investigative Site

Sakarya, Adapazari, 54290, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, Basaksehir, 34480, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, Fatih, 34093, Turkey (Türkiye)

Location

Novartis Investigative Site

Kayseri, Melikgazi, 38039, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, Uskudar, 34662, Turkey (Türkiye)

Location

Novartis Investigative Site

Oxford, OX3 7LE, United Kingdom

Location

Novartis Investigative Site

Hanoi, 100000, Vietnam

Location

Novartis Investigative Site

Ho Chi Minh City, 700000, Vietnam

Location

MeSH Terms

Conditions

Chronic Inducible Urticaria; Cold Urticaria

Interventions

remibrutinib

Condition Hierarchy (Ancestors)

Chronic Urticaria; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This masking applies to the core period. There is no masking in the open-label extension (OLE).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2023
• First Posted: August 4, 2023
• Study Start: December 7, 2023
• Primary Completion (Estimated): May 22, 2026
• Study Completion (Estimated): June 15, 2029
• Last Updated: March 3, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

AU (3); JP (12); VN (2); KR (2); AR (4); IN (2); BR (3); HU (3); IL (4); IT (3); PL (3); CA (3); NL (1); US (25); CN (17); DE (7); CO (2); PT (3); RO (1); SL (3); ES (8); SG (1); TU (5); GB (1); HK (1); FR (8); TH (3); MY (3)