A Phase 3 Study of Efficacy and Safety of Remibrutinib in the Treatment of CSU in Adults Inadequately Controlled by H1 Antihistamines

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study.

• Male and female adult participants ≥18 years of age.

• CSU duration for ≥ 6 months prior to screening (defined as the onset of CSUdetermined by the investigator based on all available supporting documentation).

• Diagnosis of CSU inadequately controlled by second generation H1 antihistamines atthe time of randomization defined as:

• The presence of itch and hives for ≥6 consecutive weeks prior to screening despitethe use of second generation H1-antihistamines during this time period

• UAS7 score (range 0-42) ≥16, ISS7 score (range 0-21) ≥ 6 and HSS7 score (range 0-21) ≥ 6 during the 7 days prior to randomization (Day 1)

• Documentation of hives within three months before randomization (either at screeningand/or at randomization; or documented in the participants medical history).

• Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for theduration of the study and adhere to the study protocol.

• Participants must not have had more than one missing UPDD entry (either morning orevening) in the 7 days prior to randomization (Day 1).

Exclusion Criteria:

• Participants having a clearly defined predominant or sole trigger of their chronicurticaria (chronic inducible urticaria) including urticaria factitia (symptomaticdermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-,cholinergic-, or contact-urticaria

• Other diseases with symptoms of urticaria or angioedema, including but not limitedto urticaria vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis,hereditary urticaria, or drug-induced urticaria

• Any other skin disease associated with chronic itching that might influence in theinvestigator's opinion the study evaluations and results, e.g. atopic dermatitis,bullous pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis

• Evidence of clinically significant cardiovascular (such as but not limited tomyocardial infarction, unstable ischemic heart disease, New York heart association (NYHA) Class III/IV left ventricular failure, arrhythmia and uncontrolledhypertension within 12 months prior to Visit 1), neurological, psychiatric,pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders,gastrointestinal disease or immunodeficiency that, in the investigator's opinion,would compromise the safety of the participant, interfere with the interpretation ofthe study results or otherwise preclude participation or protocol adherence of theparticipant

• Significant bleeding risk or coagulation disorders

• History of gastrointestinal bleeding, e.g. in association with use of nonsteroidalanti-inflammatory drugs (NSAID), that was clinically relevant (e.g. requiringhospitalization or blood transfusion)

• Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100mg/d or clopidogrel. The use of dual anti-platelet therapy (e.g. acetylsalicylicacid + clopidogrel) is prohibited.

• Requirement for anticoagulant medication (for example, warfarin or Novel OralAnti-Coagulants (NOAC))

• History or current hepatic disease including but not limited to acute or chronichepatitis, cirrhosis or hepatic failure or Aspartate Aminotransferase (AST)/ AlanineAminotransferase (ALT) levels of more than 1.5 x upper limit of normal (ULN) orInternational Normalized Ratio (INR) of more than 1.5 at screening