A Multicenter, Open-label Phase 3 Study: Ambulatory Blood Pressure Monitoring in Adult Patients With Chronic Spontaneous Urticaria Inadequately Controlled by H1-antihistamines Treated With Remibrutinib up to 12 Weeks.

Study Overview
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Brief Summary
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The primary objective of the study is to rule out an increase of >3mmHg in 24-hour average Systolic Blood Pressure at steady state (Week 4) compared to baseline. ABPM was chosen for the blood pressure assessment in this trial as recommended by the FDA for drugs intended for chronic use (Assessment of Pressor Effects of Drugs Guidance for Industry (FDA 2022)).

Detailed Description
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The primary objective of the study is to rule out an increase of >3mmHg in 24-hour average Systolic Blood Pressure at steady state (Week 4) compared to baseline. ABPM was chosen for the blood pressure assessment in this trial as recommended by the FDA for drugs intended for chronic use (Assessment of Pressor Effects of Drugs Guidance for Industry (FDA 2022)). It allows the observation over a 24-hour period and the measure of an individual's blood pressure throughout an entire day. This ABPM study will be performed in a patient population similar to the ongoing Phase 3 studies. The study duration will be up to 20 weeks. The treatment duration will be up to 12 weeks and the visit frequency will be once every 4 weeks with additional 2 visits for application of the ABPM device before baseline and Week 4 visits.

Official Title
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A Multicenter, Open-label Phase 3 Study: Ambulatory Blood Pressure Monitoring in Adult Patients With Chronic Spontaneous Urticaria Inadequately Controlled by H1-antihistamines Treated With Remibrutinib up to 12 Weeks.

Conditions
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Chronic Spontaneous Urticaria

Intervention / Treatment
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* Drug: LOU064


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Male and female adult participants ≥18 years of age at the time of screening. CSU duration for ≥ 6 months prior to screening (defined as the onset of CSU determined by the investigator based on all available supporting documentation). Diagnosis of CSU inadequately controlled by second generation H1-AH at the time of baseline (Day 1) defined as: The presence of itch and hives for ≥6 consecutive weeks prior to screening despite the use of second generation H1-AH 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 baseline (Day 1). Documentation of hives within three months before baseline (either at screening and/or at baseline (Day 1); or documented in the participants' medical history). Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration of the study and adhere to the study protocol. Participants must not have had more than two missing UPDD entry (either morning or evening) in the 7 days prior to baseline (Day 1). Exclusion Criteria: Use of other investigational drugs within 5 half-lives or within 30 days (for small molecules) prior to Screening or until the expected pharmacodynamic (PD) effect has returned to baseline (for biologics), whichever is longer; or longer if required by local regulations. Previous use of remibrutinib or other BTK inhibitors. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes. Participants having a clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria) including urticaria factitia (symptomatic dermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact-urticaria. Ongoing or past history of hypertension and/or SBP ≥140 or ≤90 and/or DBP ≥90 or ≤60 mmHg at screening. Participants unable to tolerate 24-hour ambulatory blood pressure measurement prior to baseline. Participants with an arm circumference greater than 50cm.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LOU064 (remibrutinib)<br>Open label single arm trial. | Drug: LOU064<br>* LOU064 (Open-Label) taken orally for 12 weeks<br>* Other names: remibrutinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ambulatory blood pressure monitoring (ABPM) measurement | The change in the Ambulatory blood pressure monitoring (ABPM)-measured 24-hour weighted average systolic blood pressure (SBP) at Week 4 compared to baseline | Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CSU, remibrutinib