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.
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)
UAS7 score (range, 0-42) ≥ 16, and
ISS7 score (range, 0-21) ≥ 6, and
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)
Parallel
Remibrutinib
DrugFilm-coated tablet, oral administration, 25 mg b.i.d.
Remibrutinib matching placebo
DrugFilm-coated tablet, oral administration, b.i.d.
Dupilumab
DrugSolution for injection in pre-filled syringe 600 mg loading dose followed by 300 mg dose every 2 weeks
Placebo solution for injection
DrugSolution for injection in pre-filled syringe every 2 weeks
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.
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.
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.
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.
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.
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