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

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified July 2026 by Novartis Pharmaceuticals
Sponsor
Novartis Pharmaceuticals
Information Provided by (Responsible Party)
Novartis Pharmaceuticals
Clinicaltrials.gov Identifier
NCT06868212
Other Study ID Numbers:
CLOU064AUS02
First Submitted
March 5, 2025
First Posted
March 9, 2025
Last Update Posted
August 18, 2026
Last Verified
July 2026

ClinicalTrials.gov processed this data on August 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

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 or DiseaseIntervention/Treatment
Chronic Spontaneous Urticaria (CSU)
Drug: RemibrutinibDrug: Remibrutinib matching placebo

Study Design

Study TypeInterventional
Actual Enrollment400 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingTriple
Primary PurposeTreatment
Official TitleA 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
Study Start DateJuly 10, 2025
Actual Primary Completion Date5mos 3w from now
Actual Study Completion Date8mos 2w from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Treatment group 1: Remibrutinib + Placebo
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
Film-coated tablet, oral administration, 25 mg b.i.d.
Treatment group 2: Dupilumab + remibrutinib matching placebo
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
Film-coated tablet, oral administration, b.i.d.

Outcome Measures

Primary Outcome Measures
  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.
Secondary Outcome Measures
  1. Improvement of severity of hives, assessed as absolute change from baseline in HSS7 score at Week 4
    The hives (wheals) severity score, defined by number of hives, will be recorded by the participant twice daily in their eCOA device, on a scale of 0 (none) to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 - 21.
  2. Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score at Week 4
    The severity of the itch will be recorded by the participant twice daily in their eCOA device, on a scale of 0 (none) to 3 (severe). A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 - 21.
  3. Improvement of UAS7, assessed as absolute change from baseline in UAS7 score at Week 1
    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.
  4. Percentage of participants with UAS7 ≤ 6 at Week 4
    Percentage of participants who achieved UAS7 ≤ 6 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.
  5. Percentage of participants with UAS7=0 at Week 4
    Percentage of participants who achieved UAS7 = 0 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.
  6. Percentage of participants with UAS7 ≤ 6 at Week 2
    Percentage of participants who achieved UAS7 ≤ 6 at Week 2. 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.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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

Contacts and Locations

Sponsors and CollaboratorsNovartis Pharmaceuticals
Locations
Allervie Clinical Research | Birmingham Alabama, United States, 35209Cahaba Derm and skin hlth ctr 27 | Birmingham Alabama, United States, 35244Research Solutions of Arizona | Litchfield Park Arizona, United States, 85340Peak Dermatology | Payson Arizona, United States, 85541Premier Allergy Asthma And Immunology | Phoenix Arizona, United States, 85032Avacare Center for Dermatology | Phoenix Arizona, United States, 85044Orso Health | Scottsdale Arizona, United States, 85254Clin Trial Inst of Northwest AR | Fayetteville Arkansas, United States, 72703Acuro Research Inc | Little Rock Arkansas, United States, 72205First OC Dermatology | Fountain Valley California, United States, 92708Ctr for Dermatology Clinical Res | Fremont California, United States, 95438Allergy and Asthma Specialists Group | Huntington Beach California, United States, 92647Orso Health | Long Beach California, United States, 90808Ark Clinical Research | Long Beach California, United States, 90815California Allergy and Asthma Medical Group | Los Angeles California, United States, 90025Dermatology Research Associates | Los Angeles California, United States, 90045One Of A Kind Clinical Research | Napa California, United States, 94558Stanford University Medical Center | Palo Alto California, United States, 94304Empire Clinical Research | Pomona California, United States, 91767Allergy and Asthma Consultants | Redwood City California, United States, 94063Norcal Clinical Research | Rocklin California, United States, 95765Peninsula Research Associates | Rolling Hills Estates California, United States, 90274Integrative Skin Science and Res | Sacramento California, United States, 95815UC Davis Neuromuscular Research Center | Sacramento California, United States, 95817Therapeutics Clinical Research | San Diego California, United States, 92123Dermatology Institute and Skin Care | Santa Monica California, United States, 90403Integrated Research of Inland Inc | Upland California, United States, 91786Allergy and Asthma Clin Res Inc | Walnut Creek California, United States, 94598University of Colorado Hospital - Aurora | Aurora Colorado, United States, 80045Asthma and Allergy Associates P C | Colorado Springs Colorado, United States, 80907Colorado ENT and Allergy | Colorado Springs Colorado, United States, 80909Skylight Health Res Inc Color Spr | Colorado Springs Colorado, United States, 80917UCONN Health Dermatology | Farmington Connecticut, United States, 06030-2840Howard University Hospital Division of Geriatrics | Washington D.C. District of Columbia, United States, 20059Florida Ctr Allergy Asthma Research | Aventura Florida, United States, 33180Florida Ctr Allergy Asthma Research | Aventura Florida, United States, 33180Skin Care Research Inc | Boca Raton Florida, United States, 33486Omnicure Clinical Research | Doral Florida, United States, 33172FXM Clinical Research Ft Laud | Fort Lauderdale Florida, United States, 33308Skin Care Research LLC | Hollywood Florida, United States, 33021Jacksonville Center for Clinical Research | Jacksonville Florida, United States, 32216University of MiamiHealth System | Miami Florida, United States, 33125FXM Clinical Res Miami LLC | Miami Florida, United States, 33175Miami Dade Medical Research | Miami Florida, United States, 33176FXM Clin Res Miramar LLC | Miramar Florida, United States, 33027Ziaderm Research LLC | North Miami Beach Florida, United States, 33162AllerVie Health | Panama Florida, United States, 32405Sarasota Clinical Research | Sarasota Florida, United States, 34233Lenus Research and Med Group LLC | Sweetwater Florida, United States, 33172Olympian Clinical Research | Tampa Florida, United States, 33609Asthma Allergy Immunology Clin Res | Tampa Florida, United States, 33613Conquest Research | Winter Park Florida, United States, 32789AllerVie Clin Res Columbus GA | Columbus Georgia, United States, 31904Cleaver Medical Group | Cumming Georgia, United States, 30040Southeast Dermatology Specialists | Douglasville Georgia, United States, 30135Aeroallergy Research Laboratories | Savannah Georgia, United States, 31406The Allergy Group-Meridian Clinic | Meridian Idaho, United States, 83642NW Uni C and T Sciences Ins | Chicago Illinois, United States, 60611Rush University Medical Center | Chicago Illinois, United States, 60612Midwest Allergy Sinus Asthma SC | Normal Illinois, United States, 61761Clinical Res Ctr of S Illinois | O'Fallon Illinois, United States, 62269Asthma and Allergy Center of Chicago S C | River Forest Illinois, United States, 60305Endeavor Health Clinical Trials Center | Skokie Illinois, United States, 60077Accellacare Duly Health and Care | Wheaton Illinois, United States, 60189Deaconess Clin Allerg Res Inst | Evansville Indiana, United States, 47715Southern IN Clinical Trials | New Albany Indiana, United States, 47150McFarland Clinic PC | Ames Iowa, United States, 50010Equity Medical LLC | Bowling Green Kentucky, United States, 42104Family Allergy And Asthma Rsch Inst | Louisville Kentucky, United States, 40215Allergy and Asthma Specialist P S C | Owensboro Kentucky, United States, 42301Ochsner Health Center | Baton Rouge Louisiana, United States, 70816Velocity Clinical Research | Lafayette Louisiana, United States, 70508Johns Hopkins U School of Med | Baltimore Maryland, United States, 21205Chesapeake Clinical Research Inc | Baltimore Maryland, United States, 21236Institute for Asthma and Allergy PC | Chevy Chase Maryland, United States, 20815AllerVie Clin Res Glenn Dale | Glenn Dale Maryland, United States, 20769Boston Specialists LLC | Boston Massachusetts, United States, 02111Brigham And Womens Hospital | Boston Massachusetts, United States, 02115ClinSite Inc | Ann Arbor Michigan, United States, 48106-0525Derm Institute West Michigan PLLC | Caledonia Michigan, United States, 49316Henry Ford Hospital | Detroit Michigan, United States, 48202Revival Research Institute | Troy Michigan, United States, 48084Somerset Skin Centre | Troy Michigan, United States, 48084Clinical Research Institute | Minneapolis Minnesota, United States, 55402University of Minnesota | Minneapolis Minnesota, United States, 55455Mayo Clinic - Rochester | Rochester Minnesota, United States, 55905ENT and Allergy Center of Missouri | Columbia Missouri, United States, 65201The Clinical Research Center | St Louis Missouri, United States, 63141Washington University | St Louis Missouri, United States, 63141Somnos Clinical Research | Lincoln Nebraska, United States, 68510Allergy and Asthma Center of Las Vegas | Las Vegas Nevada, United States, 89128Las Vegas Dermatology | Las Vegas Nevada, United States, 89144Hudson Essex Allergy-Circuit Clinical | Belleville New Jersey, United States, 07109Circuit Clinical Mercer Algy Pulm | Hamilton New Jersey, United States, 08619Allergy Asthma Assoc Monmouth | Little Silver New Jersey, United States, 07739Allergy Partners of New Jersey PC | Ocean Township New Jersey, United States, 07712Circuit Clinical | Riverdale New Jersey, United States, 07457Equity Medical | The Bronx New York, United States, 10455Montefiore Medical Center | The Bronx New York, United States, 10467Allergy Partners Of West NC | Asheville North Carolina, United States, 28801UNC DermatologyandSkinCancer Ctr | Chapel Hill North Carolina, United States, 27516Bernstein Clinical Research Center | Cincinnati Ohio, United States, 45231CR Services Acquisition US | Columbus Ohio, United States, 43213Optimed Research LLC | Columbus Ohio, United States, 43235Wright State University | Fairborn Ohio, United States, 45324Toledo Institute of Clinical Research | Toledo Ohio, United States, 43617Unity Clinical Research | Oklahoma City Oklahoma, United States, 73118Vital Prospects Clinical Research Institute | Tulsa Oklahoma, United States, 74136Oregon Medical Research Center | Portland Oregon, United States, 97223Oregon Health Sciences University | Portland Oregon, United States, 97239University of Pittsburgh Medical Center | Pittsburgh Pennsylvania, United States, 15213Allergy and Clinical Immunology Associates | Pittsburgh Pennsylvania, United States, 15241Medical Univ Of SC Medical Ctr | Charleston South Carolina, United States, 29425Tribe Clinical Research LLC | Greenville South Carolina, United States, 29601Allergic Disease and Asthma Center | Greenville South Carolina, United States, 29607Charleston ENT and Allergy | North Charleston South Carolina, United States, 29406National Allergy and Asthma Research LLS | North Charleston South Carolina, United States, 29420Goodlettsville Dermatology Research | Goodlettsville Tennessee, United States, 37072-2301International Clinical Research Tennessee LCC | Murfreesboro Tennessee, United States, 37130Arlington Center for Dermatology | Arlington Texas, United States, 76011Orion Clinical Research | Austin Texas, United States, 78759Bellaire Dermatology Associates | Bellaire Texas, United States, 77401Reveal Research Institute | Dallas Texas, United States, 75230Pharma Research and Amp Consult | Dallas Texas, United States, 75231Western Sky Medical Research | El Paso Texas, United States, 79924Center for Clinical Studies | Houston Texas, United States, 77030Sante Clinical Research | Kerrville Texas, United States, 78028RFSA Dermatology | San Antonio Texas, United States, 78213Andante Research | San Antonio Texas, United States, 78229University Of Utah | Murray Utah, United States, 84107Allergy Associates of Utah | Sandy City Utah, United States, 84093Forefront Dermatology | Vienna Virginia, United States, 22182Bellingham Asthma Allergy and Immunology | Bellingham Washington, United States, 98225