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Remibrutinib versus dupilumab as add-on therapy for adults with chronic spontaneous urticaria

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

Phase 3 Interventional Novartis · NCT06868212

This test compares remibrutinib (an oral BTK inhibitor) and dupilumab (an injectable biologic), each added to daily antihistamines, to see which reduces hives and itch faster in adults whose chronic spontaneous urticaria isn't controlled by antihistamines.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment400 (estimated)
Ages18 Years and up
SexAll
SponsorNovartis Industry-sponsored
Drugs / interventionsdupilumab, remibrutinib
Locations114 sites (Birmingham, Alabama and 113 other locations)
Trial IDNCT06868212 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, double-dummy Phase 3b study in the US will compare oral remibrutinib 25 mg twice daily with subcutaneous dupilumab (600 mg loading then 300 mg every 2 weeks) as add-on therapy to standard-dose second-generation H1-antihistamines in adults with moderate-to-severe CSU inadequately controlled by antihistamines. Approximately 400 participants will be stratified by prior anti-IgE biologic exposure and randomized 1:1 for a 12-week core treatment period after up to 28 days of screening, with an optional open-label extension and safety follow-up. The double-dummy design means all participants receive both oral and injection forms (active drug plus matching placebo) to maintain blinding, and rescue antihistamine dosing is allowed within specified limits. Outcomes focus on early timepoints (four weeks and earlier) using daily patient diaries and standard scores for urticaria activity, hives severity, and itch severity.

Who should consider this trial

Good fit: Adults 18 or older with chronic spontaneous urticaria for at least 6 months whose symptoms remain inadequately controlled on standard-dose second-generation H1-antihistamines (UAS7 ≥16, ISS7 ≥6, HSS7 ≥6) and who can complete daily diaries and follow study procedures are ideal candidates.

Not a fit: People whose CSU is well controlled on antihistamines, those with non-CSU causes of hives, or those with contraindications to the study medications or recent use of disallowed biologics are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this could provide a faster-acting oral treatment option or clarify a preferred biologic approach to reduce hives and itch sooner for adults not controlled by antihistamines.

How similar studies have performed: Earlier clinical work has shown promise for BTK inhibitors like remibrutinib and for biologics targeting type 2 inflammation, but direct head-to-head comparisons at very early timepoints are limited.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

Birmingham, Alabama and 113 other locations

+64 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Chronic Spontaneous UrticariaBTK inhibitorchronic spontaneous urticariaUrticaria activity scoreHives severity scoreItch severity score
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.