A Safety and Efficacy Study of Remibrutinib in the Treatment of CSU in Japanese Adults Inadequately Controlled by H1-antihistamines

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of remibrutinib (LOU064) in adult Japanese chronic spontaneous urticaria (CSU) participants inadequately controlled by second generation H1-antihistamines.

Detailed Description
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This is a Phase 3 multi-center, open-label, single arm study investigating the safety, tolerability and efficacy of remibrutinib in participants with CSU inadequately controlled by second generation H1-antihistamines. Inadequate control of CSU by second generation H1-antihistamines is defined as: The presence of itch and hives for ≥ 6 consecutive weeks prior to screening despite the use of second generation H1-antihistamines during this time period Urticaria Activity Score (UAS7) score (range 0-42) ≥ 16, Itch Severity Score (ISS7) score (range 0-21) ≥ 6 and Hives Severity Score (HSS7) score (range 0-21) ≥ 6 during the 7 days prior to baseline (Day 1). The study consists of three periods, the total study duration is up to 60 weeks: screening period of up to 4 weeks, open-label treatment period of 52 weeks, and a treatment free follow-up period of 4 weeks.

Official Title
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A Multicenter, Open-label Phase 3 Study of Remibrutinib (LOU064) to Investigate the Safety, Tolerability and Efficacy for 52 Weeks in Adult Japanese Chronic Spontaneous Urticaria Patients Inadequately Controlled by H1-antihistamines

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 participants ≥18 years of age. 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-antihistamines at baseline defined as: The presence of itch and hives for ≥ 6 consecutive weeks prior to screening despite the 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 baseline (Day 1) Documentation of hives within three months before baseline (either at screening and/or at baseline; 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 one missing UPDD entry (either morning or evening) in the 7 days prior to baseline (Day 1). Exclusion Criteria: 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 Other diseases with symptoms of urticaria or angioedema, including but not limited to 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 the investigator'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 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, hematological disorders, gastrointestinal disease 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 of the participant Significant bleeding risk or coagulation disorders History of gastrointestinal bleeding, e.g., in association with use of nonsteroidal anti- nflammatory drugs (NSAID), that was clinically relevant (e.g., requiring hospitalization or blood transfusion) Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited. Requirement for anticoagulant medication (for example, warfarin or Novel Oral Anti-Coagulants (NOAC)) 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 1.5 x upper limit of normal (ULN) or International Normalized Ratio (INR) of more than 1.5 at screening

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>LOU064 open-label treatment taken orally for 52 weeks. | Drug: LOU064<br>* Arm 1: LOU064 (open label)<br>* Other names: remibrutinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number and the proportion of participants with treatment-emergent adverse event | To evaluate the overall safety data of remibrutinib in CSU patients assessed as treatment emergent adverse events during the study. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in UAS7 | To evaluate the efficacy of remibrutinib measured by absolute change from baseline in UAS7 at Week 12. | 12 weeks | 
| Disease activity control (UAS7≤ 6) | To evaluate the efficacy of remibrutinib as measured by proportion of participants achieving disease activity control (UAS7 ≤ 6) at Week 12. | 12 weeks | 
| Complete absence of hives and itch (UAS7 = 0) | To evaluate the efficacy of remibrutinib as measured by Proportion of participants achieving complete absence of hives and itch (UAS7 = 0) at Week 12. | 12 weeks | 
| Change from baseline in ISS7 score | To evaluate the efficacy of remibrutinib as measured by absolute change from baseline in ISS7 score at Week 12. | 12 weeks | 
| Change from baseline in HSS7 score | To evaluate the efficacy of remibrutinib as measured by absolute change from baseline in HSS7 score at Week 12. | 12 weeks | 
| Early onset of disease activity control (UAS7 ≤ 6 at 2 weeks) | To evaluate the efficacy of remibrutinib as proportion of participants achieving disease activity control (UAS7 ≤ 6) at Week 2 | 2 weeks | 
| Sustained disease activity control UAS7 ≤ 6 | To evaluate the efficacy of remibrutinib by achieving sustained disease activity control, assessed as cumulative number of weeks with an UAS7≤6 response between baseline and Week 12. | 12 weeks | 
| Achievement of Dermatology Life Quality Index (DLQI) = 0-1 | To evaluate the efficacy of remibrutinib by assessing achievement of DLQI = 0-1 at Week 12. | 12 weeks | 
| Number of weeks without angioedema (AAS = 0) | To evaluate the efficacy of remibrutinib assessed by the cumulative number of weeks with an AAS7= 0 response between baseline and Week 12. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BTK inhibitor, Chronic spontaneous urticaria, Urticaria Activity Score, Hives Severity Score, Itch Severity Score