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

NCT06868212 | Recruiting Phase 3 FDA Drug

• 1 other identifier: CLOU064AUS02
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 114

Brief Summary

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.

Conditions

Chronic Spontaneous Urticaria (CSU)

Keywords

BTK inhibitor; chronic spontaneous urticaria; Urticaria activity score; Hives severity score; Itch severity score

Outcome Measures

Primary Outcomes (1)

• Absolute change from baseline in Weekly Urticaria Activity Score (UAS7) at Week 4

  The UAS7 is the sum of the Weekly Hives Severity (HSS7) score and the Weekly Itch Severity (ISS7) score, and ranges from 0-42. Weekly scores (HSS7 and ISS7 scores) will be derived by adding up the average daily scores of the 7 days preceding the visit.

  Baseline, Week 4

Secondary Outcomes (6)

• Improvement of severity of hives, assessed as absolute change from baseline in HSS7 score at Week 4

  Baseline, Week 4

• Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score at Week 4

  Baseline, Week 4

• Improvement of UAS7, assessed as absolute change from baseline in UAS7 score at Week 1

  Baseline, Week 1

• Percentage of participants with UAS7 ≤ 6 at Week 4

  Week 4

• Percentage of participants with UAS7=0 at Week 4

  Week 4

Study Arms (2)

Treatment group 1: Remibrutinib + Placebo

EXPERIMENTAL

Remibrutinib tablet (25 mg b.i.d. p.o.) + placebo solution for injection in pre-filled syringe (2 s.c. injections at baseline and then 1 s.c. injection every other week \[Weeks 2-10\])

Drug: Remibrutinib; Drug: Placebo solution for injection

Treatment group 2: Dupilumab + remibrutinib matching placebo

ACTIVE COMPARATOR

Dupilumab pre-filled syringe (600 mg loading dose \[2 x 300 mg dupilumab s.c. injection\] at baseline visit followed by dupilumab 300 mg s.c. injection every other week \[Weeks 2-10\]) + remibrutinib matching placebo tablet (1 tablet b.i.d. p.o.)

Drug: Remibrutinib matching placebo; Drug: Dupilumab

Interventions

Remibrutinib DRUG

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

Treatment group 1: Remibrutinib + Placebo

Remibrutinib matching placebo DRUG

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

Treatment group 2: Dupilumab + remibrutinib matching placebo

Dupilumab DRUG

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

Treatment group 2: Dupilumab + remibrutinib matching placebo

Placebo solution for injection DRUG

Solution for injection in pre-filled syringe every 2 weeks

Treatment group 1: Remibrutinib + Placebo

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (114)

Allervie Clinical Research

Birmingham, Alabama, 35209, United States

RECRUITING

Cahaba Derm and skin hlth ctr 27

Birmingham, Alabama, 35244, United States

RECRUITING

Research Solutions of Arizona

Litchfield Park, Arizona, 85340, United States

RECRUITING

Peak Dermatology

Payson, Arizona, 85541, United States

RECRUITING

Premier Allergy Asthma And Immunology

Phoenix, Arizona, 85032, United States

RECRUITING

Avacare Center for Dermatology

Phoenix, Arizona, 85044, United States

RECRUITING

Orso Health

Scottsdale, Arizona, 85254, United States

RECRUITING

Acuro Research Inc

Little Rock, Arkansas, 72205, United States

RECRUITING

First OC Dermatology

Fountain Valley, California, 92708, United States

RECRUITING

Ctr for Dermatology Clinical Res

Fremont, California, 95438, United States

RECRUITING

Allergy and Asthma Specialists Group

Huntington Beach, California, 92647, United States

RECRUITING

Orso Health

Long Beach, California, 90808, United States

RECRUITING

Ark Clinical Research

Long Beach, California, 90815, United States

RECRUITING

California Allergy and Asthma Medical Group

Los Angeles, California, 90025, United States

RECRUITING

Dermatology Research Associates

Los Angeles, California, 90045, United States

RECRUITING

One Of A Kind Clinical Research

Napa, California, 94558, United States

RECRUITING

Empire Clinical Research

Pomona, California, 91767, United States

RECRUITING

Allergy and Asthma Consultants

Redwood City, California, 94063, United States

RECRUITING

Norcal Clinical Research

Rocklin, California, 95765, United States

RECRUITING

Integrative Skin Science and Res

Sacramento, California, 95815, United States

RECRUITING

UC Davis Neuromuscular Research Center

Sacramento, California, 95817, United States

RECRUITING

Therapeutics Clinical Research

San Diego, California, 92123, United States

RECRUITING

Integrated Research of Inland Inc

Upland, California, 91786, United States

RECRUITING

Allergy and Asthma Clin Res Inc

Walnut Creek, California, 94598, United States

RECRUITING

University of Colorado Hospital - Aurora

Aurora, Colorado, 80045, United States

RECRUITING

Asthma and Allergy Associates P C

Colorado Springs, Colorado, 80907, United States

RECRUITING

UCONN Health Dermatology

Farmington, Connecticut, 06030-2840, United States

RECRUITING

Howard University Hospital Division of Geriatrics

Washington D.C., District of Columbia, 20059, United States

RECRUITING

Florida Ctr Allergy Asthma Research

Aventura, Florida, 33180, United States

RECRUITING

Florida Ctr Allergy Asthma Research

Aventura, Florida, 33180, United States

RECRUITING

Skin Care Research Inc

Boca Raton, Florida, 33486, United States

RECRUITING

Omnicure Clinical Research

Doral, Florida, 33172, United States

RECRUITING

Skin Care Research LLC

Hollywood, Florida, 33021, United States

RECRUITING

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

RECRUITING

University of MiamiHealth System

Miami, Florida, 33125, United States

RECRUITING

FXM Clinical Res Miami LLC

Miami, Florida, 33175, United States

RECRUITING

Miami Dade Medical Research

Miami, Florida, 33176, United States

RECRUITING

FXM Clin Res Miramar LLC

Miramar, Florida, 33027, United States

RECRUITING

Ziaderm Research LLC

North Miami Beach, Florida, 33162, United States

RECRUITING

AllerVie Health

Panama, Florida, 32405, United States

RECRUITING

Sarasota Clinical Research

Sarasota, Florida, 34233, United States

RECRUITING

Lenus Research and Med Group LLC

Sweetwater, Florida, 33172, United States

RECRUITING

Olympian Clinical Research

Tampa, Florida, 33609, United States

RECRUITING

Asthma Allergy Immunology Clin Res

Tampa, Florida, 33613, United States

RECRUITING

Conquest Research

Winter Park, Florida, 32789, United States

RECRUITING

AllerVie Clin Res Columbus GA

Columbus, Georgia, 31904, United States

RECRUITING

Cleaver Medical Group

Cumming, Georgia, 30040, United States

RECRUITING

Southeast Dermatology Specialists

Douglasville, Georgia, 30135, United States

RECRUITING

Aeroallergy Research Laboratories

Savannah, Georgia, 31406, United States

RECRUITING

The Allergy Group-Meridian Clinic

Meridian, Idaho, 83642, United States

RECRUITING

Midwest Allergy Sinus Asthma SC

Normal, Illinois, 61761, United States

RECRUITING

Clinical Res Ctr of S Illinois

O'Fallon, Illinois, 62269, United States

RECRUITING

Asthma and Allergy Center of Chicago S C

River Forest, Illinois, 60305, United States

RECRUITING

Endeavor Health Clinical Trials Center

Skokie, Illinois, 60077, United States

RECRUITING

Deaconess Clin Allerg Res Inst

Evansville, Indiana, 47715, United States

RECRUITING

Southern IN Clinical Trials

New Albany, Indiana, 47150, United States

RECRUITING

Equity Medical LLC

Bowling Green, Kentucky, 42104, United States

RECRUITING

Family Allergy And Asthma Rsch Inst

Louisville, Kentucky, 40215, United States

RECRUITING

Allergy and Asthma Specialist P S C

Owensboro, Kentucky, 42301, United States

RECRUITING

Ochsner Health Center

Baton Rouge, Louisiana, 70816, United States

RECRUITING

Velocity Clinical Research

Lafayette, Louisiana, 70508, United States

RECRUITING

Johns Hopkins U School of Med

Baltimore, Maryland, 21205, United States

RECRUITING

Chesapeake Clinical Research Inc

Baltimore, Maryland, 21236, United States

RECRUITING

Institute for Asthma and Allergy PC

Chevy Chase, Maryland, 20815, United States

RECRUITING

AllerVie Clin Res Glenn Dale

Glenn Dale, Maryland, 20769, United States

RECRUITING

Boston Specialists LLC

Boston, Massachusetts, 02111, United States

RECRUITING

ClinSite Inc

Ann Arbor, Michigan, 48106-0525, United States

RECRUITING

Derm Institute West Michigan PLLC

Caledonia, Michigan, 49316, United States

RECRUITING

Henry Ford Hospital

Detroit, Michigan, 48202, United States

RECRUITING

Revival Research Institute

Troy, Michigan, 48084, United States

RECRUITING

Somerset Skin Centre

Troy, Michigan, 48084, United States

RECRUITING

Clinical Research Institute

Minneapolis, Minnesota, 55402, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

The Clinical Research Center

St Louis, Missouri, 63141, United States

RECRUITING

Washington University

St Louis, Missouri, 63141, United States

RECRUITING

Las Vegas Dermatology

Las Vegas, Nevada, 89144, United States

RECRUITING

Hudson Essex Allergy-Circuit Clinical

Belleville, New Jersey, 07109, United States

RECRUITING

Circuit Clinical Mercer Algy Pulm

Hamilton, New Jersey, 08619, United States

RECRUITING

Allergy Asthma Assoc Monmouth

Little Silver, New Jersey, 07739, United States

RECRUITING

Circuit Clinical

Riverdale, New Jersey, 07457, United States

RECRUITING

Equity Medical

The Bronx, New York, 10455, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10467, United States

RECRUITING

UNC DermatologyandSkinCancer Ctr

Chapel Hill, North Carolina, 27516, United States

RECRUITING

Bernstein Clinical Research Center

Cincinnati, Ohio, 45231, United States

RECRUITING

CR Services Acquisition US

Columbus, Ohio, 43213, United States

RECRUITING

Optimed Research LLC

Columbus, Ohio, 43235, United States

WITHDRAWN

Wright State University

Fairborn, Ohio, 45324, United States

RECRUITING

Toledo Institute of Clinical Research

Toledo, Ohio, 43617, United States

RECRUITING

Unity Clinical Research

Oklahoma City, Oklahoma, 73118, United States

RECRUITING

Vital Prospects Clinical Research Institute

Tulsa, Oklahoma, 74136, United States

RECRUITING

Oregon Medical Research Center

Portland, Oregon, 97223, United States

RECRUITING

Oregon Health Sciences University

Portland, Oregon, 97239, United States

RECRUITING

Allergy and Clinical Immunology Associates

Pittsburgh, Pennsylvania, 15241, United States

RECRUITING

Medical Univ Of SC Medical Ctr

Charleston, South Carolina, 29425, United States

RECRUITING

Tribe Clinical Research LLC

Greenville, South Carolina, 29601, United States

RECRUITING

Allergic Disease and Asthma Center

Greenville, South Carolina, 29607, United States

RECRUITING

Charleston ENT and Allergy

North Charleston, South Carolina, 29406, United States

RECRUITING

National Allergy and Asthma Research LLS

North Charleston, South Carolina, 29420, United States

RECRUITING

International Clinical Research Tennessee, LCC

Murfreesboro, Tennessee, 37130, United States

RECRUITING

Arlington Center for Dermatology

Arlington, Texas, 76011, United States

RECRUITING

Orion Clinical Research

Austin, Texas, 78759, United States

RECRUITING

Bellaire Dermatology Associates

Bellaire, Texas, 77401, United States

RECRUITING

Reveal Research Institute

Dallas, Texas, 75230, United States

RECRUITING

Pharma Research and Amp Consult

Dallas, Texas, 75231, United States

RECRUITING

Western Sky Medical Research

El Paso, Texas, 79924, United States

RECRUITING

Center for Clinical Studies

Houston, Texas, 77030, United States

RECRUITING

Sante Clinical Research

Kerrville, Texas, 78028, United States

RECRUITING

RFSA Dermatology

San Antonio, Texas, 78213, United States

RECRUITING

Andante Research

San Antonio, Texas, 78229, United States

RECRUITING

University Of Utah

Murray, Utah, 84107, United States

RECRUITING

Allergy Associates of Utah

Sandy City, Utah, 84093, United States

RECRUITING

Forefront Dermatology

Vienna, Virginia, 22182, United States

RECRUITING

Bellingham Asthma Allergy and Immunology

Bellingham, Washington, 98225, United States

RECRUITING

Related Publications (1)

• Yosipovitch G, Mosnaim G, Ortmann CE, Griswold N, Mast J, Martzloff ED, Rodrigues J, Hawkes JE. Efficacy of Remibrutinib versus Dupilumab at Early Timepoints in Chronic Spontaneous Urticaria: US Phase 3b Study Design (RECLAIM). Dermatol Ther (Heidelb). 2026 Mar 19. doi: 10.1007/s13555-026-01716-y. Online ahead of print.

  PMID: 41854973 DERIVED

MeSH Terms

Conditions

Chronic Urticaria

Interventions

remibrutinib; dupilumab; Injections

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 or dupilumab and remibrutinib matching placebo or placebo solution for injection, both as an add-on treatment to once daily standard label dose of sgH1-AH background therapy, until the Week 12 visit. 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 open label extension (OLE) period and receive remibrutinib (25 mg b.i.d. p.o.) for 12 weeks (up to Week 24).

Study Record Dates

• First Submitted: March 6, 2025
• First Posted: March 10, 2025
• Study Start: July 11, 2025
• Primary Completion (Estimated): February 22, 2027
• Study Completion (Estimated): May 17, 2027
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (114)