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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05048342

Acronym

BISCUIT

Enrollment

Registered

2021-09-17

Start date

2022-01-15

Completion date

2023-12-09

Last updated

2025-04-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Spontaneous Urticaria

Keywords

Bruton Tyrosine Kinase (BTK) inhibitor, Chronic Spontaneous Urticaria (CSU), Urticaria Activity Score (UAS), Weekly Urticaria Activity Score (UAS7), Hives Severity Score (HSS), Weekly Hives Severity Score (HSS7), Itch Severity Score (ISS), Weekly Itch Severity Score (ISS7), Angioedema Activity Score (AAS), Weekly Angioedema Activity Score (AAS7), Dermatology Life Quality Index (DLQI)

Brief summary

The purpose of this study was to evaluate the safety, tolerability and efficacy of remibrutinib (LOU064) in adult Japanese patients chronic spontaneous urticaria (CSU), who remain symptomatic despite treatment by H1-antihistamine (H1-AH) at locally label approved doses, for a duration of 52 weeks of treatment with remibrutinib and a post-treatment follow-up period of up to 4 weeks.

Detailed description

The study consisted 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 (remibrutinib 25 mg b.i.d.), and a treatment free follow-up period of 4 weeks. It was planned to include approximately 70 patients in the study; 71 patients were enrolled and included in the analyses.

Interventions

DRUGLOU064

Each patient took one film-coated tablet in the morning and one film-coated tablet in the evening (except the morning dose at the PK sampling visits, which were to be taken on site during the visit).

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 100 Years

Healthy volunteers

Inclusion criteria

* Signed informed consent was required to be obtained prior to participation in the study. * Male and female patients \>= 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-AHs 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-AHs 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 patients' medical history) * Willing and able to complete an UPDD for the duration of the study and adhere to the study protocol * Patients were required to not have more than one missing UPDD entry (either morning or evening) in the 7 days prior to baseline (Day 1)

Exclusion criteria

* Patients 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 angioedema, 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 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 patient, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the patient * Significant bleeding risk or coagulation disorders * History of gastrointestinal bleeding, e.g., in association with use of nonsteroidal anti-inflammatory drugs, that was clinically relevant (e.g., for which intervention was indicated or requiring hospitalization or blood transfusion) * Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d. 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) * History or current hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or AST/ALT levels of more than 1.5 × ULN or International Normalized Ratio (INR) of more than 1.5 at screening

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment Emergent Adverse Events	Baseline up to 30 days after last dose of study medication, assessed up to approximately 56 weeks	An adverse event (AE) is any untoward medical occurrence (e.g., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. Treatment emergent Adverse Event (TEAEs) in this study are events that started after the first dose of study treatment and until 30 days after the last study treatment, or events present prior to the first dose of treatment which increased in severity based on preferred term within 30 days after the last study treatment.

Secondary

Measure	Time frame	Description
Number of Participants Who Achieved Disease Activity Control (UAS7 =< 6) at Week 12	Week 12	The percentage of patients achieving disease activity control (UAS7 =\< 6) at Week 12 was assessed to evaluate the efficacy of Remibrutinib in Chronic Spontaneous Urticaria (CSU) patients. The UAS7 is the sum of the Weekly Hives Severity Score (HSS7) and the Weekly Itch Severity Score (ISS7). The possible range of the UAS7 score is 0 - 42 (highest hives and itch severity).
Number of Participants Who Achieved Complete Absence of Hives and Itch (UAS7 = 0) at Week 12	Week 12	The proportion of patients achieving complete absence of hives and itch (UAS7 = 0) at Week 12 was assessed to evaluate the efficacy of Remibrutinib in Chronic Spontaneous Urticaria (CSU) patients. The UAS7 is the sum of the Weekly Hives Severity Score (HSS7) and the Weekly Itch Severity Score (ISS7). The possible range of the UAS7 score is 0 - 42 (highest hives and itch severity).
Change From Baseline in Weekly Itch Severity Score (ISS7) at Week 12	Baseline, Week 12	The severity of the itch was recorded by the participant twice daily in their electronic Diary, on a scale of 0 (none) to 3 (severe). A weekly score (ISS7) was derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score was therefore 0 - 21 (highest itch severity).
Change From Baseline in Weekly Hives Severity Score (HSS7) at Week 12	Baseline, Week 12	The hives (wheals) severity score, defined by number of hives, was recorded by the participant twice daily in their electronic Diary, on a scale of 0 (none) to 3 (\> 12 hives/12 hours). A weekly score (HSS7) was derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score was therefore 0 - 21 (highest hives activity).
Mean Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12	Baseline, Week 12	Change from Baseline in Weekly Urticaria Activity Score (UAS7) was assessed to evaluate the efficacy of Remibrutinib in Chronic Spontaneous Urticaria (CSU) patients. The Weekly Urticaria Activity Score (UAS7) is the sum of the Weekly Hives Severity Score (HSS7) and the Weekly Itch Severity Score (ISS7). The possible range of the weekly UAS7 score is 0 - 42 (highest hives and itch severity).
Number of Participants Who Achieved Dermatology Life Quality Index (DLQI) = 0-1 at Week 12	Week 12	The Dermatology Life Quality Index (DLQI) is a 10-item (grouped in 6 domains) dermatology-specific quality of life (QoL) measure. Participants are rating their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score is calculated and ranges from 0 to 30 (higher score meaning worse disease-related QoL). Domain scores are calculated for: Symptoms and Feelings (0-6), Daily Activities (0-6), Leisure (0-6), Work and School (0-3), Personal Relationships (0-6), Treatment (0-3). The overall DLQI score range was split into score bands and validated in terms of their meaning/relevance to patients as follows: 0-1 (No effect on patient's life), 2-5 (Small effect on patient's life), 6-10 (Moderate effect on patient's life), 11-20 (Very large effect on patient's life), 21-30 (Extremely large effect on patient's life).
Mean Cumulative Number of Weeks With Disease Activity Control (UAS7 =< 6) up to Week 12	Up to Week 12	Maintaining disease activity control was assessed as cumulative number of weeks with an UAS7 =\< 6 response between baseline and Week 12. The UAS7 is the sum of the Weekly Hives Severity Score (HSS7) and the Weekly Itch Severity Score (ISS7). The possible range of the UAS7 score is 0 - 42 (highest hives and itch severity).
Mean Cumulative Number of Angioedema Occurrence-free Weeks (AAS7 = 0 Response) up to Week 12	Up to Week 12	Angioedema occurrence was recorded once daily in the evening in the electronic Diary by the participant. Reporting the occurrence of angioedema was used as opening question for the assessment of the Angioedema Activity Score (AAS). The AAS consists of 5 questions with 4 answer options (scored 0-3) for each item, with a minimum score of 0 and a maximum score of 15 per day. The AAS score over 7 days (AAS7) ranges from 0 (no angioedema episodes) to 105 (highest angioedema severity).
Number of Participants Who Achieved Early Onset of Disease Activity Control (UAS7 =< 6) at Week 2	Week 2	The percentage of patients achieving disease activity control (UAS7 =\< 6) at Week 2 was assessed to evaluate the efficacy of Remibrutinib in Chronic Spontaneous Urticaria (CSU) patients. The UAS7 is the sum of the Weekly Hives Severity Score (HSS7) and the Weekly Itch Severity Score (ISS7). The possible range of the UAS7 score is 0 - 42 (highest hives and itch severity).

Countries

Japan

Participant flow

Recruitment details

This study was conducted at 13 centers in Japan.

Participants by arm

Arm	Count
LOU064 25 mg b.i.d. Patients were treated with remibrutinib 25 mg bis in die/twice a day (b.i.d.). LOU064 open-label treatment taken orally for 52 weeks.	71
Total	71

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Subject decision	2

Baseline characteristics

Characteristic	LOU064 25 mg b.i.d.
Age, Continuous	43.5 Years STANDARD_DEVIATION 12.52
Age, Customized >= 18 and < 65 years	66 Participants
Age, Customized >= 65 and < 85 years	5 Participants
Race/Ethnicity, Customized Asian	71 Participants
Sex: Female, Male Female	54 Participants
Sex: Female, Male Male	17 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 71
other Total, other adverse events	53 / 71
serious Total, serious adverse events	3 / 71

Outcome results

Primary

Number of Participants With Treatment Emergent Adverse Events

An adverse event (AE) is any untoward medical occurrence (e.g., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. Treatment emergent Adverse Event (TEAEs) in this study are events that started after the first dose of study treatment and until 30 days after the last study treatment, or events present prior to the first dose of treatment which increased in severity based on preferred term within 30 days after the last study treatment.

Time frame: Baseline up to 30 days after last dose of study medication, assessed up to approximately 56 weeks

Population: Safety Set (SAF)

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
LOU064 25 mg b.i.d.	Number of Participants With Treatment Emergent Adverse Events	Subjects with at least one Adverse Event (AE)	62 Participants
LOU064 25 mg b.i.d.	Number of Participants With Treatment Emergent Adverse Events	Subjects with serious or other significant events - Death	0 Participants
LOU064 25 mg b.i.d.	Number of Participants With Treatment Emergent Adverse Events	Subjects with serious or other significant events - Non-fatal SAE(s)	3 Participants
LOU064 25 mg b.i.d.	Number of Participants With Treatment Emergent Adverse Events	Subjects with serious or other significant events - Discontinued study treatment due to any AE(s)	1 Participants

Secondary

Change From Baseline in Weekly Hives Severity Score (HSS7) at Week 12

The hives (wheals) severity score, defined by number of hives, was recorded by the participant twice daily in their electronic Diary, on a scale of 0 (none) to 3 (\> 12 hives/12 hours). A weekly score (HSS7) was derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score was therefore 0 - 21 (highest hives activity).

Time frame: Baseline, Week 12