Trial Outcomes & Findings for A Safety and Efficacy Study of Remibrutinib in the Treatment of CSU in Japanese Adults Inadequately Controlled by H1-antihistamines (NCT NCT05048342)

NCT ID: NCT05048342

Last Updated: 2025-04-08

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 71 participants
• Primary outcome timeframe: Baseline up to 30 days after last dose of study medication, assessed up to approximately 56 weeks
• Results posted on: 2025-04-08

Participant Flow

This study was conducted at 13 centers in Japan.

Participant milestones

Measure	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.
Overall Study STARTED	71
Overall Study COMPLETED	68
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	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.
Overall Study Adverse Event	1
Overall Study Subject decision	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	LOU064 25 mg b.i.d. n=71 Participants 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.
Age, Continuous	43.5 Years STANDARD_DEVIATION 12.52 • n=93 Participants
Age, Customized >= 18 and < 65 years	66 Participants n=93 Participants
Age, Customized >= 65 and < 85 years	5 Participants n=93 Participants
Sex: Female, Male Female	54 Participants n=93 Participants
Sex: Female, Male Male	17 Participants n=93 Participants
Race/Ethnicity, Customized Asian	71 Participants n=93 Participants

PRIMARY outcome

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

Population: Safety Set (SAF)

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.

Outcome measures

Measure	LOU064 25 mg b.i.d. n=71 Participants 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.
Number of Participants With Treatment Emergent Adverse Events Subjects with at least one Adverse Event (AE)	62 Participants
Number of Participants With Treatment Emergent Adverse Events Subjects with serious or other significant events - Death	0 Participants
Number of Participants With Treatment Emergent Adverse Events Subjects with serious or other significant events - Non-fatal SAE(s)	3 Participants
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 outcome

Timeframe: Baseline, Week 12

Population: Full Analysis Set (FAS)

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).

Outcome measures

Measure	LOU064 25 mg b.i.d. n=71 Participants 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.
Mean Change From Baseline in Weekly Urticaria Activity Score (UAS7) at Week 12	-18.14 Unit on a scale Standard Deviation 10.992

SECONDARY outcome

Timeframe: Week 12

Population: Full Analysis Set (FAS)

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).

Outcome measures

Measure	LOU064 25 mg b.i.d. n=71 Participants 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.
Number of Participants Who Achieved Disease Activity Control (UAS7 =< 6) at Week 12	30 Participants

SECONDARY outcome

Timeframe: Week 12

Population: Full Analysis Set (FAS)

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).

Outcome measures

Measure	LOU064 25 mg b.i.d. n=71 Participants 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.
Number of Participants Who Achieved Complete Absence of Hives and Itch (UAS7 = 0) at Week 12	15 Participants

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Full Analysis Set (FAS)

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).

Outcome measures

Measure	LOU064 25 mg b.i.d. n=71 Participants 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.
Change From Baseline in Weekly Itch Severity Score (ISS7) at Week 12	-8.01 Unit on a scale Standard Deviation 4.703

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Full Analysis Set (FAS)

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).

Outcome measures

Measure	LOU064 25 mg b.i.d. n=71 Participants 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.
Change From Baseline in Weekly Hives Severity Score (HSS7) at Week 12	-10.12 Unit on a scale Standard Deviation 6.845

SECONDARY outcome

Timeframe: Week 2

Population: Full Analysis Set (FAS)

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).

Outcome measures

Measure	LOU064 25 mg b.i.d. n=71 Participants 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.
Number of Participants Who Achieved Early Onset of Disease Activity Control (UAS7 =< 6) at Week 2	29 Participants

SECONDARY outcome

Timeframe: Week 12

Population: Full Analysis Set (FAS)

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).

Outcome measures

Measure	LOU064 25 mg b.i.d. n=71 Participants 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.
Number of Participants Who Achieved Dermatology Life Quality Index (DLQI) = 0-1 at Week 12	39 Participants

SECONDARY outcome

Timeframe: Up to Week 12

Population: Full Analysis Set (FAS)

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).

Outcome measures

Measure	LOU064 25 mg b.i.d. n=71 Participants 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.
Mean Cumulative Number of Weeks With Disease Activity Control (UAS7 =< 6) up to Week 12	4.6 Weeks Standard Deviation 4.86

SECONDARY outcome

Timeframe: Up to Week 12

Population: Full Analysis Set (FAS)

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).

Outcome measures

Measure	LOU064 25 mg b.i.d. n=71 Participants 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.
Mean Cumulative Number of Angioedema Occurrence-free Weeks (AAS7 = 0 Response) up to Week 12	10.0 Weeks Standard Deviation 3.63

Adverse Events

LOU064 25 mg b.i.d.

Serious events: 3 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Measure	LOU064 25 mg b.i.d. n=71 participants at risk 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.
Ear and labyrinth disorders Meniere's disease	1.4% 1/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Eye disorders Epiretinal membrane	1.4% 1/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Eye disorders Rhegmatogenous retinal detachment	1.4% 1/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.

Other adverse events

Measure	LOU064 25 mg b.i.d. n=71 participants at risk 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.
Gastrointestinal disorders Diarrhoea	8.5% 6/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
General disorders Pyrexia	5.6% 4/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Infections and infestations COVID-19	19.7% 14/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Infections and infestations Cystitis	5.6% 4/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Infections and infestations Nasopharyngitis	9.9% 7/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Infections and infestations Tonsillitis	7.0% 5/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Metabolism and nutrition disorders Dyslipidaemia	5.6% 4/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Nervous system disorders Headache	12.7% 9/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Acne	7.0% 5/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Dermatitis atopic	9.9% 7/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Dermatitis contact	5.6% 4/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Eczema	8.5% 6/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Eczema asteatotic	5.6% 4/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Purpura	5.6% 4/71 • On-treatment adverse events and deaths were reported from first dose of study medication up to 30 days after last dose of study medication, assessed up to approximately 56 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: Novartis.email@Novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER