A Study to Evaluate Efficacy of Remibrutinib Compared to Dupilumab at Early Timepoints in Adults With Chronic Spontaneous Urticaria Inadequately Controlled by Second Generation H1-antihistamines

Last Update: Dec 22, 2025

A US Phase 3b, Multi-center, Randomized, Double-blind, Double-Dummy Study to Evaluate Efficacy of Remibrutinib Compared to Dupilumab at Early Timepoints in Adults With Chronic Spontaneous Urticaria Inadequately Controlled by Second Generation H1-Antihistamines

ClinicalTrials.gov Identifier:

NCT06868212

Novartis Reference Number:CLOU064AUS02

See if you Pre-qualify

All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

This is a US, multi-center, randomized, double-blind, double-dummy, Phase 3b study to evaluate efficacy of remibrutinib (25 mg twice daily \[b.i.d.\] by mouth \[p.o.\]) compared to dupilumab (600 mg loading dose administered subcutaneously (s.c.) followed by 300 mg every 2 weeks s.c.) at early timepoints (4 weeks and earlier), when administered as an add-on treatment to second generation H1-antihistamines (sgH1-AH) (standard label dose as background therapy) in adult US participants with moderate to severe chronic spontaneous urticaria (CSU) inadequately controlled by sgH1-AHs. This study consists of a screening period (up to 4 weeks), a core treatment period (12 weeks double-blind, double-dummy), an optional open-label extension \[OLE\] period, and safety follow-up period.

Screening period: participants will have a screening period of a minimum of 7 days up to a maximum of 28 days to establish eligibility for the study. Participants meeting all the inclusion criteria and none of the exclusion criteria will be eligible to participate in the study.

Core treatment period (double-blind, double-dummy): approximately, 400 participants diagnosed with CSU inadequately controlled by sgH1-AH will be randomized in this study. Participants will be stratified based on prior exposure to anti-IgE biologics.

Eligible participants will be randomized in a 1:1 ratio to receive remibrutinib and placebo solution for injection or dupilumab and remibrutinib matching placebo, both as an add-on treatment to once daily standard label dose of sgH1-AH background therapy, until the Week 12 visit.

Additionally, all participants will be on a stable, standard label dose of a sgH1-AH ("background therapy") throughout the entire core treatment period (starting a minimum of 7 days prior to randomization until the end of Week 12). To treat unbearable symptoms of CSU, participants will be allowed to add more of the same sgH1-AH on an as-needed basis ("rescue therapy"). The total maximum daily dose of sgH1-AH (background plus rescue) should not exceed 4 tablets/day (4-fold the standard label dose).

Optional open-label extension \[OLE\] period: At the end of the 12-week double-blind treatment period, and in case remibrutinib is not commercially available, participants from both arms will be given the choice to roll over into an optional OLE safety period and receive remibrutinib (25 mg b.i.d. p.o.) for 12 weeks (up to Week 24).

Safety follow-up period:

* For participants who do not enter the OLE period: there will be a safety follow-up for 12 weeks with safety follow-up phone calls at Week 16 and Week 24 (Week 24 will be end of study).
* For participants who enter the OLE period: there will be 2 options at the end of Week 24:
* If remibrutinib is commercially available: participants will discontinue study treatment, perform their EOT visit and receive a safety follow-up phone call 4 weeks after the last dose of remibrutinib (this will be the EOS).
* If remibrutinib is not commercially available, participants may continue on remibrutinib 25 mg b.i.d. until its commercial availability and return for site visits for safety follow up and treatment dispensation every 3 months. When remibrutinib becomes commercially available, the participant will be contacted for a site visit to complete the EOT visit and will receive a safety follow-up phone call 4 weeks after the last dose of remibrutinib (this will be the EOS).

Condition

Chronic Spontaneous Urticaria (CSU)

Phase

Phase3

Overall Status

Recruiting

Number of Participants

400

Start Date

Jul 11, 2025

Completion Date

May 17, 2027

Gender

All

Age(s)

18 Years - (Adult, Older Adult)

Interventions

Drug

Dupilumab

Solution for injection in pre-filled syringe 600 mg loading dose followed by 300 mg dose every 2 weeks

Drug

Placebo solution for injection

Solution for injection in pre-filled syringe every 2 weeks

Drug

Remibrutinib

Film-coated tablet, oral administration, 25 mg b.i.d.

Drug

Remibrutinib matching placebo

Film-coated tablet, oral administration, b.i.d.

Eligibility Criteria

Inclusion Criteria:

* Adults ≥ 18 years of age at the time of signing the informed consent
* CSU duration for ≥ 6 months prior to screening (defined as the onset of CSU determined by the Investigator based on all available supporting documentation)
* Diagnosis of CSU inadequately controlled by sgH1-AH at the time of randomization, defined as:
* The presence of itch and hives for ≥ 6 consecutive weeks prior to screening despite the use of sgH1-AH during the 7 days prior to randomization (Day 1):
* UAS7 score (range, 0-42) ≥ 16, and
* ISS7 score (range, 0-21) ≥ 6, and
* HSS7 score (range, 0-21) ≥ 6
* Documentation of hives within 3 months before randomization (either at screening and/or at randomization); or documented in the participants medical history
* Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration of the study and adhere to the study protocol
* Participants must not have had more than one missing UPDD entry (either morning or evening) in the 7 days prior to randomization (Day 1)

Exclusion Criteria:

* Previous use of remibrutinib or other bruton's tyrosine kinase (BTK) inhibitors
* Previous use of dupilumab
* Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 12 months prior to Visit 1), neurological, psychiatric, pulmonary, renal, hepatic (past history or current), endocrine or metabolic disorder, 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.
* Evidence of hematological disorders (including coagulation disorders or significant bleeding risk)
* History or evidence of gastrointestinal disease (including gastrointestinal bleeding, e.g., in association with use of nonsteroidal anti-inflammatory drugs (NSAID), that was clinically relevant (e.g., where intervention was indicated or requiring hospitalization or blood transfusion)
* Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited.
* Requirement for anticoagulant medication (for example, warfarin or Novel Oral Anti-Coagulants \[NOAC\])
* History or current hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or hepatic parameters at screening: Aspartate Aminotransferase (AST)/ Alanine Aminotransferase (ALT) levels more than 1.5x ULN or International Normalized Ratio (INR) \> 1.5 at screening

Conquest Research

Recruiting

Winter Park,Florida,32789,United States

A Study to Evaluate Efficacy of Remibrutinib Compared to Dupilumab at Early Timepoints in Adults With Chronic Spontaneous Urticaria Inadequately Controlled by Second Generation H1-antihistamines

Study Description

Interventions

Dupilumab

Placebo solution for injection

Remibrutinib

Remibrutinib matching placebo

Eligibility Criteria

Conquest Research

Michael Wangia

Sandy Pate

Allergy and Asthma Specialist P S C

Angela Haynes

Lee Clore

Arlington Center for Dermatology

Angela Moore

Yariana Canini

Acuro Research Inc

Karl Sitz

Mindy Demarco

Ctr for Dermatology Clinical Res

Evguenia Vals

Sunil Dhawan

California Allergy and Asthma Medical Group

Clare Kanchana

Ricardo Tan

Dermatology Research Associates

Howard Lee Sofen

Justin An

UCONN Health Dermatology

Ektor Rafti

Jun Lu

Florida Ctr Allergy Asthma Research

Aixa Valdes

Alexandra Villa

Ileana Rodicio

Jaime Landman

Skin Care Research Inc

Ann Reed

Esther Perez

Skin Care Research LLC

Eduardo Weiss

Lucy Vargas

Ziaderm Research LLC

Daine Velazco

Tory Sullivan

Somerset Skin Centre

Ali Moiin

George Murakawa

Manali Ambegaonkar

Tiffany Rothenhauser

Clinical Research Institute

Amy Saykao

Hemalini Mehta

Las Vegas Dermatology

David Graham Cotter

Faith Limon

Vital Prospects Clinical Research Institute

Ashley Brown

Iftikhar Hussain

Allergy and Clinical Immunology Associates

Michael Palumbo

Susan Shidel

Allergic Disease and Asthma Center

Elissa Peery

Neil L Kao

National Allergy and Asthma Research LLS

Faye Singleton

John T Ramey

Orion Clinical Research

Amber Ogden

William Howland III

Allergy Associates of Utah

Andrew Smith

Sandy Warr

Allervie Clinical Research

Abbey Patrick

Weily Soong

Research Solutions of Arizona

Connie Hsu