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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LOU064 25 mg b.i.d. | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LOU064 | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline up to 30 days after last dose of study medication, assessed up to approximately 56 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in Weekly Urticaria Activity Score (UAS7) at 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). |
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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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Nagoya | Aichi-ken | 454-0012 | Japan | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41712058 | Derived | Hayama K, Chinuki Y, Yagami A, Kume A, Morita A, Miyazu S, Lheritier K, Jaskiewicz L, Haemmerle S, Hide M. Remibrutinib Showed a Favorable Safety Profile and Sustained Efficacy in Japanese Patients with Chronic Spontaneous Urticaria Over 52 Weeks. Dermatol Ther (Heidelb). 2026 Mar;16(3):1707-1721. doi: 10.1007/s13555-026-01666-5. Epub 2026 Feb 19. |
| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on www.novctrd.com | View source |
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Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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This study was conducted at 13 centers in Japan.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 11, 2022 | Oct 7, 2024 |
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| Baseline, Week 12 |
| Number of Participants Who Achieved Disease Activity Control (UAS7 =< 6) at 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). | Week 12 |
| Number of Participants Who Achieved Complete Absence of Hives and Itch (UAS7 = 0) at 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). | Week 12 |
| Change From Baseline in Weekly Itch Severity Score (ISS7) at 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). | Baseline, Week 12 |
| 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). | Baseline, Week 12 |
| Number of Participants Who Achieved Early Onset of Disease Activity Control (UAS7 =< 6) at 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). | Week 2 |
| Number of Participants Who Achieved Dermatology Life Quality Index (DLQI) = 0-1 at 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). | Week 12 |
| Mean Cumulative Number of Weeks With Disease Activity Control (UAS7 =< 6) 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). | Up to Week 12 |
| Mean Cumulative Number of Angioedema Occurrence-free Weeks (AAS7 = 0 Response) 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). | Up to Week 12 |
| Urayasu |
| Chiba |
| 279-0011 |
| Japan |
| Novartis Investigative Site | Izumiōtsu | Osaka | 595-0025 | Japan |
| Novartis Investigative Site | Neyagawa | Osaka | 572-0838 | Japan |
| Novartis Investigative Site | Sakai | Osaka | 593-8324 | Japan |
| Novartis Investigative Site | Takatsuki | Osaka | 569-0824 | Japan |
| Novartis Investigative Site | Izumo | Shimane | 693 8501 | Japan |
| Novartis Investigative Site | Itabashi-ku | Tokyo | 173-8610 | Japan |
| Novartis Investigative Site | Minato | Tokyo | 108-0014 | Japan |
| Novartis Investigative Site | Ōta-ku | Tokyo | 143-0023 | Japan |
| Novartis Investigative Site | Fukuoka | 811-1302 | Japan |
| Novartis Investigative Site | Osaka | 554 0014 | Japan |
| Novartis Investigative Site | Osaka | 558-0003 | Japan |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Age, Customized | Number | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Safety Set (SAF) | Posted | Count of Participants | Participants | Baseline up to 30 days after last dose of study medication, assessed up to approximately 56 weeks |
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| Secondary | Mean Change From Baseline in Weekly Urticaria Activity Score (UAS7) at 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). | Full Analysis Set (FAS) | Posted | Mean | Standard Deviation | Unit on a scale | Baseline, Week 12 |
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| Secondary | Number of Participants Who Achieved Disease Activity Control (UAS7 =< 6) at 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). | Full Analysis Set (FAS) | Posted | Count of Participants | Participants | Week 12 |
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| Secondary | Number of Participants Who Achieved Complete Absence of Hives and Itch (UAS7 = 0) at 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). | Full Analysis Set (FAS) | Posted | Count of Participants | Participants | Week 12 |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Weekly Itch Severity Score (ISS7) at 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). | Full Analysis Set (FAS) | Posted | Mean | Standard Deviation | Unit on a scale | Baseline, Week 12 |
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| 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). | Full Analysis Set (FAS) | Posted | Mean | Standard Deviation | Unit on a scale | Baseline, Week 12 |
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| Secondary | Number of Participants Who Achieved Early Onset of Disease Activity Control (UAS7 =< 6) at 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). | Full Analysis Set (FAS) | Posted | Count of Participants | Participants | Week 2 |
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| Secondary | Number of Participants Who Achieved Dermatology Life Quality Index (DLQI) = 0-1 at 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). | Full Analysis Set (FAS) | Posted | Count of Participants | Participants | Week 12 |
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| Secondary | Mean Cumulative Number of Weeks With Disease Activity Control (UAS7 =< 6) 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). | Full Analysis Set (FAS) | Posted | Mean | Standard Deviation | Weeks | Up to Week 12 |
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| Secondary | Mean Cumulative Number of Angioedema Occurrence-free Weeks (AAS7 = 0 Response) 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). | Full Analysis Set (FAS) | Posted | Mean | Standard Deviation | Weeks | Up to Week 12 |
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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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 71 | 3 | 71 | 53 | 71 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Meniere's disease | Ear and labyrinth disorders | MedDRA (26.1) | Systematic Assessment |
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| Epiretinal membrane | Eye disorders | MedDRA (26.1) | Systematic Assessment |
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| Rhegmatogenous retinal detachment | Eye disorders | MedDRA (26.1) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (26.1) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (26.1) | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA (26.1) | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA (26.1) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (26.1) | Systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA (26.1) | Systematic Assessment |
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| Dyslipidaemia | Metabolism and nutrition disorders | MedDRA (26.1) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (26.1) | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA (26.1) | Systematic Assessment |
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| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA (26.1) | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (26.1) | Systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | MedDRA (26.1) | Systematic Assessment |
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| Eczema asteatotic | Skin and subcutaneous tissue disorders | MedDRA (26.1) | Systematic Assessment |
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| Purpura | Skin and subcutaneous tissue disorders | MedDRA (26.1) | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | + 1 862 778 8300 | Novartis.email@Novartis.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 9, 2024 | Oct 7, 2024 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000080223 | Chronic Urticaria |
| ID | Term |
|---|---|
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000722911 | remibrutinib |
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| Subjects with serious or other significant events - Discontinued study treatment due to any AE(s) |
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