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).

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Spontaneous Urticaria
• Intervention / Treatment: Drug: Remibrutinib; Drug: Omalizumab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 382
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +81337978748

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remibrutinib; Participants will receive remibrutinib 25 mg twice a day for 12 weeks.	Drug: Remibrutinib; Remibrutinib 25 mg twice a day.; Other Names: LOU064
Experimental: Remibrutinib or Omalizumab; Participants will receive remibrutinib 25 mg twice a day. At Week 12, well-controlled participants (UCT7 ≥12) continue remibrutinib, while participants with inadequate control (UCT7 <12) escalate to omalizumab 300 mg every 4 weeks.	Drug: Omalizumab; Omalizumab 300 mg every 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants achieving Urticaria Activity Score over 7 days (UAS7) ≤6 (yes/no)	UAS7 is a validated patient-reported measure of chronic spontaneous urticaria disease activity over 7 days. It is calculated as the sum of the weekly Hives Severity Score (HSS7) and the weekly Itch Severity Score (ISS7) and ranges from 0 to 42. Lower scores indicate lower disease activity / better disease control, and a score of ≤6 indicates well-controlled disease. HSS7 and ISS7 are each derived from daily diary entries over the 7 days preceding the visit.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants achieving UAS7 ≤6 (yes/no)	UAS7 is calculated as the sum of the HSS7 and ISS7 and ranges from 0 to 42. Lower scores indicate lower disease activity / better disease control, and a score of ≤6 indicates well-controlled disease. HSS7 and ISS7 are each derived from daily diary entries over the 7 days preceding the visit.	Weeks 16 and 20
Proportion of participants achieving UAS7 =0 (yes/no)	UAS7 is calculated as the sum of the HSS7 and ISS7 and ranges from 0 to 42, with 0 indicating no urticaria activity over the 7-day assessment period and higher scores indicating worse disease activity.	Weeks 16, 20, and 24
Proportion of participants achieving Angioedema Activity Score over 7 days (AAS7) =0.	AAS7 is a validated tool assessing angioedema activity, recorded once daily in the evening in the eDiary. If no angioedema is reported on a given day, the daily score is 0. Weekly AAS7 scores range from 0 to 105, with higher scores indicating greater angioedema severity; therefore, 0 represents absence of angioedema.	Weeks 16, 20, and 24
Proportion of participants achieving of Dermatology Life Quality Index (DLQI) =0/1	DLQI is a 10-item dermatology-specific quality-of-life instrument assessing the impact of skin disease over the previous 7 days. The total score ranges from 0 to 30, with higher scores indicating worse disease-related quality of life. A score of 0-1 corresponds to no effect on the participant's life.	Weeks 16, 20, and 24
Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)	To evaluate the safety and tolerability of LOU064.	From Day 1 until at least 4 weeks after the last administration of remibrutinib and at least 16 weeks after the last administration of omalizumab
Proportion of participants achieving UAS7 ≤6 under the treatment algorithm compared with historical omalizumab (300 mg every 4 weeks) data.	UAS7 is calculated as the sum of the HSS7 and ISS7 and ranges from 0 to 42. Lower scores indicate lower disease activity / better disease control, and a score of ≤6 indicates well-controlled disease. HSS7 and ISS7 are each derived from daily diary entries over the 7 days preceding the visit.	Weeks 16, 20, and 24
Proportion of participants achieving UAS7 =0 under the treatment algorithm compared with historical omalizumab (300 mg every 4 weeks) data.	UAS7 is calculated as the sum of the HSS7 and ISS7 and ranges from 0 to 42, with 0 indicating no urticaria activity over the 7-day assessment period and higher scores indicating worse disease activity.	Weeks 16, 20, and 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): November 9, 2026
• Primary Completion (Estimated): July 17, 2028
• Study Completion (Estimated): July 17, 2028

Study Registration Dates

• First Submitted: September 7, 2026
• First Submitted That Met QC Criteria: September 7, 2026
• First Posted (Actual): September 11, 2026

Study Record Updates

• Last Update Posted (Actual): September 11, 2026
• Last Update Submitted That Met QC Criteria: September 7, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: omalizumab; remibrutinib; LOU064; CSU; UAS7; Treatment algorithm; UCT7; sgH1-AH
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Urticaria; Skin Diseases, Vascular; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Chronic Urticaria; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies, Anti-Idiotypic; Omalizumab; remibrutinib
• Other Study ID Numbers: CLOU064A2307

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No