Investigation of a Remibrutinib- and Omalizumab-based Treatment Algorithm in Adult Patients With Chronic Spontaneous Urticaria Inadequately Controlled by H1-antihistamines Within 24 Weeks

A Global, Multi-center, Open-label Study, Investigating a Remibrutinib- and Omalizumab-Based Treatment Algorithm in Adult Patients With Chronic Spontaneous Urticaria Inadequately Controlled by H1-Antihistamines, to Achieve Fast and Well-Controlled Disease Within 24 Weeks

The purpose of this open-label study is to assess the efficacy and safety of a novel treatment algorithm for sequencing remibrutinib and omalizumab in the treatment of adult participants with chronic spontaneous urticaria (CSU) who are inadequately controlled by second-generation H1-antihistamines (sgH1-AH).

This is a global, multi-center, open-label study, investigating a remibrutinib- and omalizumab-based treatment algorithm in adult patients with CSU inadequately controlled by sgH1-AH, to achieve fast and well-controlled disease within 24 weeks.

Key Inclusion Criteria:

1. Male and female adults (age ≥18 years) at the time of signing the informed consent.

2. CSU duration for ≥2 months prior to screening (defined as the onset of CSU determined by the Investigator based on all available supporting documentation).

3. Diagnosis of CSU inadequately controlled by sgH1-AH at baseline defined as:

   • The presence of itch and hives for ≥6 consecutive weeks prior to screening despite the use of sgH1-AH during this time period.
   • UAS7 score (range: 0-42) ≥16.

4. Documentation of hives within two months prior to baseline (either at screening and/or at baseline; or documented in the participant's medical history).

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

6. Participants must not have had more than one missing UPDD entry (either morning or evening) in the 7 days prior to enrollment (Day 1).

Key Exclusion Criteria:

1. Previous use of remibrutinib, other Bruton's tyrosine kinase (BTK) inhibitors or prior exposure to biologics with any effect in CSU (e.g., ligelizumab, omalizumab, dupilumab, barzolvolimab).
2. Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 12 months prior to Visit 1), neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, gastrointestinal, or hematological disorders, 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 by the participant.
3. Significant bleeding risk or coagulation disorders.
4. History of gastrointestinal bleeding, e.g., in association with use of nonsteroidal anti-inflammatory drugs (NSAIDs), that was clinically relevant (e.g., where intervention was indicated or requiring hospitalization or blood transfusion).
5. Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75mg/d. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited.
6. Requirement for anticoagulant medication (for example, warfarin or Novel Oral Anti- Coagulant - NOAC).
7. History or current hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or aspartate aminotransferase (AST) / alanine aminotransferase (ALT) levels of more than 1.5x upper limit of normal (ULN) or international normalized ratio (INR) of more than 1.5 at screening.

Other protocol-defined inclusion/exclusion criteria may apply.