Remibrutinib in Real-world Clinical Practice - a US Sub-study (REASSERT)

Remibrutinib in Real-world Clinical Practice: a Prospective, Multi-country, Non-interventional, Effectiveness and Safety Study - a US Sub-study

Prospective, non-interventional study in patients with CSU where the treatment decision prior enrolment has been made to either escalate current sgH1-AHs treatment or escalate/switch current treatment to remibrutinib. The primary aim of this study is to gather real-world effectiveness and safety data for remibrutinib, a new treatment option, covering a broader, real-world clinical practice population.

Study Overview

• Status: Recruiting
• Conditions: Chronic Spontaneous Urticaria

Detailed Description

This is a prospective, non-interventional study in patients with CSU where the treatment decision prior enrolment has been made to either escalate current sgH1-AHs treatment or escalate/switch current treatment to remibrutinib. The primary aim of this study is to gather real-world effectiveness and safety data for remibrutinib, covering a broader, real-world clinical practice population. This local US study is part of an umbrella design which brings the evidence needs from multiple countries under the REASSERT global program (CLOU064A2402).

• Study Type: Observational
• Enrollment (Estimated): 505

Contacts and Locations

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

Study Locations

• United States
  • Missouri
    • Kirksville, Missouri, United States, 63501
      • Recruiting
      • Cleaver Dermatology

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with CSU where the treatment decision prior enrolment has been made to either escalate current sgH1-AHs treatment or escalate/switch current treatment to remibrutinib

Description

Inclusion Criteria:

• Patients with a confirmed diagnosis of primary CSU by the treating physician.
• Aged at least 18 years on the date of enrolment.
• Written informed consent of the patient to participate in the study (according to country specifications) and willingness to complete full follow-up period of 24 months.

• Cohort-specific observational inclusion criteria:

  • Cohort 1: Inadequate control of CSU despite licensed dose of sgH1-AH (no other pre-treatments permitted) and decision (independent of study enrolment) to escalate sgH1-AH treatment.
  • Cohort 2: Inadequate control of CSU despite licensed dose or escalated sgH1-AH(s) (no other pre-treatment with exception of first generation H1-AH permitted) with decision (independent of study enrolment) to switch to remibrutinib treatment as per local label.
  • Cohort 3: Any other treatment received in addition to H1-AH, any time during patients' CSU treatment history, with decision (independent of study enrolment) to switch to remibrutinib treatment as per local label. Note, occasional steroid rescue medication is out of scope for cohort definition. If a patient had been on continuous steroids for at least three weeks during treatment history, they will be included in cohort 3.

Note: Candidate patients must not have initiated the next escalated treatment step (i.e. up dosed AH for cohort 1, or remibrutinib for cohorts 2 and 3) prior to their enrolment to ensure the baseline visit captures their clinical status before treatment escalation.

Exclusion Criteria:

• Currently enrolled in a clinical trial or on any experimental treatment.
• Patients within the safety follow-up phase of a previous interventional or non-interventional study.
• Patients who received remibrutinib as an investigational medical product during a remibrutinib interventional study or MAP/PSDS at any time in the past.
• Patients not capable or willing to continuously provide ePRO/eDiary data via electronic means throughout the duration of the study.
• Patients who are treated with remibrutinib outside of the local label.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Cohort 1; Inadequate control of CSU despite licensed dose of sgH1-AH (no other pre-treatments permitted) and decision to escalate sgH1-AH treatment
Cohort 2; Inadequate control of CSU despite licensed dose or escalated sgH1-AH(s) (no other pre-treatment with exception of first generation H1-AH permitted) with decision to switch to remibrutinib treatment as per local label
Cohort 3; Any other treatment received in addition to H1-AH, any time during patients' CSU treatment history, with decision to switch to remibrutinib treatment as per local label

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UAS7 score	Urticaria Activity Score over 7 days UAS7 is based on 2 daily questions scored 0-3 per day, ranging from 0 (complete control) to 42 (poor control)	12 weeks after initiating remibrutinib treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UCT7 score	Urticaria Control Test is looking retrospectively for 7 days (UCT7) and consists of 4 questions. Each question is scored 0-4, with a total score range of 0 (poor control) to 16 (well controlled).	12 weeks after initiating remibrutinib treatment
Number and proportion of participants with well-controlled disease and complete disease	Proportion of patients with UCT score ≥12 and UAS7 score ≤6. Urticaria Control Test (UCT) consists of 4 questions scored 0 (very much) to 4 (not at all), with a total score range of 0 to 16. High scores indicates better disease control. Urticaria Activity Score over 7 days (UAS7) is based on 2 daily questions, with daily score of 0 to 6 and weekly score of 0 to 42. Lower scores suggests urticaria free and well controlled urticaria.	Up to 24 months
Change from baseline (CFB) in UCT score	Change in UCT score over time. Urticaria Control Test (UCT) consists of 4 questions scored 0 (very much) to 4 (not at all), with a total score range of 0 to 16. Highest scores indicates better disease control. The study is not powered to detect any specific difference and the purpose is to estimate any observed difference descriptively.	Up to 24 months
Change from Baseline in UAS7 score ≥ minimal important difference	Urticaria Activity Score over 7 days (UAS7) is based on 2 daily questions, with daily score of 0 to 6 and weekly score of 0 to 42. Lower scores suggests urticaria free and well controlled urticaria. The study is not powered to detect any specific difference and the purpose is to estimate any observed difference descriptively.	Up to 24 months
Change in angioedema activity score (AAS7) from baseline	Angioedema Activity Score (AAS7) is assessing disease activity over 7 days in patients with urticaria. The score is based on 5 daily questions scored 0 (no discomfort) to 3 (severe discomfort), with weekly score ranging from 0 to 15. Higher scores indicates greater severity of angioedema.	Up to 24 months
Number of weeks without angioedema	Number of weeks without angioedema evaluated using application entries.	Up to 24 months
Number of participants with rescue medication requirement	Number of participants with rescue medication requirement	Up to 24 months
Characterize CSU relapse	CSU relapse by frequency and presentation	Up to 24 months
UCT score	Urticaria Control Test (UCT) consists of 4 questions scored 0 (very much) to 4 (not at all), with a total score range of 0 to 16. High scores indicates better disease control. The study is not powered to detect any specific difference and the purpose is to estimate any observed difference descriptively.	Up to 24 months
UAS7 score	Urticaria Activity Score over 7 days (UAS7) is based on 2 daily questions, with daily score of 0 to 6 and weekly score of 0 to 42. Lower scores suggests urticaria free and well controlled urticaria. The study is not powered to detect any specific difference, descriptive analysis of difference over time will be presented.	Up to 24 months
Number of participants with administration of remibrutinib as monotherapy	Number of participants with remibrutinib as monotherapy in cohort 2 and 3	Up to 24 months
Monotherapy duration	Duration of remibrutinib as monotherapy expressed by days, weeks or months in cohort 2 and 3	Up to 24 months
Number of participants with Administration of remibrutinib as monotherapy with "on demand" sgH1-AH	Number of participants with Administration of remibrutinib as monotherapy with "on demand" sgH1-AH in cohort 2 and 3	Up to 24 months
Duration of monotherapy with "on demand" sgH1-AH	Duration of remibrutinib therapy with "on demand" sgH1-AH expressed by days, weeks or months in cohort 2 and 3	Up to 24 months
Number of participants with usage of concomitant sgH1-AHs and additional prescribed CSU treatments	Descriptive analysis of concomitant sgH1-AHs	Up to 24 months
Number of participants with administration of CSU-related treatment(s) outside of local and/or international guidelines	Number of participants with administration of CSU-related treatment(s) outside of local and/or international guidelines	Up to 24 months
Demonstrate relationship between non-adherence to local/international guidelines and impact on patient, disease control, treatment patterns and HCRU during early and long-term follow-up	Demonstrate relationship between non-adherence to local/international guidelines and impact on patient, disease control, treatment patterns and HCRU during early and long-term follow-up	Up to 24 months
Delay of treatment escalation contrary to local and/or international guidelines when UCT <12 or UAS>6	Delay of treatment escalation contrary within 2-4 weeks from up-dosed sgH1-AH when UCT <12 or UAS>6 at time points measuring UCT7 (early) / UCT (month 3 onwards) / UAS7 group. This will be measured by time in days/months without escalation, with UCT<12 or UAS7>6 at time points measuring UCT7 / UCT (month 3 onwards) / UAS7 group	Up to 24 months
Time without escalation, with UCT<12 or UAS7>6	Time in days/months without escalation while UCT score is below 12 OR UAS7 score above 6. Urticaria Control Test consists of 4 questions, score below 12 indicates poor disease control. Urticaria Activity Score over 7 days is based on 2 daily questions with a maximum daily score of 6 and weekly total score up to 42. Lower scores indicates better urticaria control.	Up to 24 months
Number of participants with escalation to remibrutinib	Number of patients with escalation to remibrutinib (cohort 1), time to escalate, prior medications/escalations, and disease control at time of escalation will be presented.	Up to 24 months
Number of participants with administration of above the licensed dose of sgH1-AH prior to remibrutinib switch	Number of participants receiving escalated doses of sgH1-AH above the licensed dose (2 times, 3 times, 4 times, >4 times) prior to remibrutinib switch. This will be presented for cohort 1 and 2.	Up to 24 months
Number of sgH1-AH treatment escalations and switches prior to remibrutinib escalation	Number of sgH1-AH treatment escalations and switches prior to remibrutinib escalation	Up to 24 months
Demonstrate benefit of early vs late treatment escalation to remibrutinib	Demonstrate benefit of early vs late treatment escalation to remibrutinib	Up to 24 months
Proportion of patients with uncontrolled angioedema escalated to remibrutinib	Presence of angioedema will be reported through App and/or derived from AAS scores	Up to 24 months
Proportion of patients requiring corticosteroids prior to switch to remibrutinib	Proportion of patients requiring corticosteroids for disease control prior to switch to remibrutinib (cohort 1 and 2)	Up to 24 months
Quality of life measured through DLQI score	Dermatology Life Quality Index (DLQI) score consists of 10 questions scored from 0 (no impact at all) to 3 (very much). Total score ranges from 0 to 30, with lower scores showing lowest impact of disease on quality of life.	Up to 24 months
Quality of life evaluated through Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) questionnaire scores	Change over time in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) questionnaire. CU-Q2oL consists of 20 items rated from 0 (never) to 5 (very often). Total score ranges from 0 to 25, with lower scores showing better urticaria control. The study is not powered to detect any specific difference, descriptive analysis of difference over time will be presented.	Up to 24 months
Quality of life measured through Sleep interference score	Sleep interference will be evaluated though bespoke question. Maximum score along 7 days ranges from 0 to 21, lower scores showing lowest interference of CSU with sleep.	Up to week 12
Quality of life measured through Hospital anxiety and depression scale (HADS)	Quality of life will be evaluated through HADS measuring anxiety and depression components, as well as change from baseline in HADS score. Hospital Anxiety and Depression Score (HADS) is a 14 item questionnaire, 7 item rating anxiety and 7 depression. Responses are rated from 0 (never) to 3 (almost all time) at each question. Total score for anxiety and total score for depression range from 0 to 21, higher scores showing higher anxious/depressive symptomatology. Descriptive analysis will be presented.	Up to 24 months
Number of events related to CSU or Health Care Resource utilisation	Health Care resource utilisation (HCRU) will be evaluated based on quarterly and annualized number of health care resource utilisation related to CSU.	Up to 24 months
Work productivity and activity impairment (WPAI-CU) score	Work productivity assessed through WPAI questionnaire which consists of 6 questions, used to calculate 4 types of scores, absenteeism (work time missed), presenteeism (impairment at work/reduced on the job effectiveness), work productivity loss (overall work impairment), and activity impairment. The scores are expressed in percentage with higher numbers indicating greater impairment and less productivity at work.	Up to 24 months
Incidence of AEs	Incidence of AEs, including serious AEs in patients who initiated remibrutinib and in patients with sgH1-AH treatment alone	Up to 24 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2029

Study Registration Dates

• First Submitted: January 13, 2026
• First Submitted That Met QC Criteria: January 13, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Non-Interventional Study; Chronic Spontaneous Urticaria; Remibrutinib; Second-generation H1 antihistamine
• 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
• Other Study ID Numbers: CLOU064AUS04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO