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| ID | Type | Description | Link |
|---|---|---|---|
| 2022-002838-13 | EudraCT Number |
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The purpose of this study was to assess the effect of remibrutinib 25 mg twice a day (b.i.d.) open-label on Systolic Blood Pressure (SBP) measured as a change in 24-hour weighted average SBP from baseline to Week 4 assessed by Ambulator Blood Pressure Monitoring (ABPM); and to assess overall safety and efficacy over 12 weeks in adult participants with Chronic Spontaneous Urticaria (CSU) inadequately controlled with second generation H1 antihistamines (H1-AH) treatment. 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)).
This study consisted of a screening period of up to 4 weeks, a 12-week open-label treatment period and a treatment-free follow-up period of 4 weeks, with a total study duration of up to 20 weeks.
At the end of the treatment phase, participants had the option to continue in an extension study (CLOU064A2303B (NCT05513001)) if approved in the country and at the site.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LOU064 (remibrutinib) | Experimental | All participants were assigned to remibrutinib 25 mg b.i.d. for 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LOU064 | Drug | One film-coated tablet (25 mg) was to be taken in the morning and evening, respectively, with a 12-hour interval at approximately the same time everyday. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Estimated Mean Change From Baseline at Week 4 in 24-hour Systolic Blood Pressure (SBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM) | A linear regression with SBP as a covariate was employed. The change in SBP from baseline to Week 4 was predicted at the median baseline level. The change from baseline in the 24-hour weighted average SBP was calculated using the time weighted average of the area under the curve (AUC) of SBP obtained over a 24-hour period as measured by ABPM. That is, the time weighted average of AUC of 24-hour SBP obtained at baseline was subtracted from corresponding time weighted average of AUC of SBP at Week 4. In the analysis, if participants took prohibited antihypertensive treatment before Week 4, their subsequent measurements were excluded. In such cases, the excluded measurements were imputed by increasing the 24-hour SBP by 3 mmHg from the baseline value at Week 4. Moreover, participants who discontinued of study treatment due to any reason prior to the Week 4 were excluded from the analysis. The Mixed Models for Repeated Measures (MMRM) approach was used. | Baseline, Week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Observed Mean Change From Baseline to Week 4 in 24-hour Weighted Average Systolic Blood Pressure (SBP) Measured by ABPM | The change from baseline in the 24-hour weighted average systolic blood pressure (SBP) was calculated using the time weighted average of the area under the curve (AUC) of SBP obtained over a 24-hour period as measured by ABPM. This analysis was conducted using the observed data. Data was computed taking weighted averages over time and discarding time intervals of more than 1 hour without measurements. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Acuro Research Inc | Little Rock | Arkansas | 72205 | United States | ||
| Florida Ctr Allergy Asthma Research |
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| 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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Participants underwent a screening period of up to 4 weeks.
This study was conducted globally across 10 countries: Argentina (4 centers), Canada (2 centers), France (8 centers), Germany (6 centers), Republic of Korea (3 centers), Singapore (1 center), Slovakia (3 centers), Spain (4 centers), Turkey (3 centers), and USA (11 centers).
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| ID | Title | Description |
|---|---|---|
| FG000 | LOU064 (Remibrutinib) | All participants were assigned to remibrutinib 25 mg b.i.d. for 12 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 | Oct 7, 2022 | Apr 10, 2025 |
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| Baseline, Week 4 |
| Estimated Mean Change From Baseline at Week 4 in 24-hour Diastolic Blood Pressure (DBP) Measured by ABPM | A linear regression with DBP as a covariate was employed. The change in DBP from baseline to Week 4 was predicted at the median baseline level. The change from baseline in the 24-hour weighted average DBP was calculated using the time weighted average of the area under the curve (AUC) of DBP obtained over a 24-hour period as measured by ABPM. That is, the time weighted average of AUC of 24-hour DBP obtained at baseline was subtracted from corresponding time weighted average of AUC of DBP at Week 4. In the analysis, if participants took prohibited antihypertensive treatment before Week 4, their subsequent measurements were excluded. In such cases, the excluded measurements were imputed by increasing the 24-hour DBP by 3 mmHg from the baseline value at Week 4. Moreover, participants who discontinued of study treatment due to any reason prior to the Week 4 were excluded from the analysis. The Mixed Models for Repeated Measures (MMRM) approach was used. | Baseline, Week 4 |
| Estimated Mean Change From Baseline at Week 4 in Daytime and Nighttime Average SBP Measured by ABPM | The change in daytime (respectively nighttime) weighted average SBP was analyzed using linear regression model with baseline weighted average daytime SBP (respectively nighttime) as a covariate. The change in daytime (respectively nighttime) SBP from baseline to Week 4 was predicted at the median baseline level. The change from baseline of daytime (respectively nighttime) SBP was calculated using the time weighted average of the AUC of DBP obtained over daytime (respectively nighttime) In the analysis, if participants took prohibited antihypertensive treatment before Week 4, their subsequent measurements were excluded. In such cases, the excluded measurements were imputed by increasing the 24-hour SBP by 3 mmHg from the baseline value at Week 4. Moreover, participants who discontinued of study treatment due to any reason prior to the Week 4 were excluded from the analysis. The multiple imputation approach was used. Daytime: from 7am until 10 pm. Nighttime: from 10pm until 7 am. | Baseline, Week 4 |
| Estimated Mean Change From Baseline at Week 4 in Daytime and Nighttime Average DBP Measured by ABPM | The change in daytime (respectively nighttime) weighted average DBP was analyzed using linear regression model with baseline weighted average daytime DBP (respectively nighttime) as a covariate. The change in daytime (respectively nighttime) DBP from baseline to Week 4 was predicted at the median baseline level. The change from baseline of daytime (respectively nighttime) DBP was calculated using the time weighted average of the AUC of DBP obtained over daytime (respectively nighttime) In the analysis, if participants took prohibited antihypertensive treatment before Week 4, their subsequent measurements were excluded. In such cases, the excluded measurements were imputed by increasing the 24-hour DBP by 3 mmHg from the baseline value at Week 4. Moreover, participants who discontinued of study treatment due to any reason prior to the Week 4 were excluded from the analysis. The multiple imputation approach was used. Daytime: from 7am until 10 pm. Nighttime: from 10pm until 7 am. | Baseline, Week 4 |
| Aventura |
| Florida |
| 33180 |
| United States |
| Finlay Medical Research | Greenacres City | Florida | 33467 | United States |
| Treasure Valley Medical Research | Boise | Idaho | 83706 | United States |
| Endeavor Health | Glenview | Illinois | 60077 | United States |
| Allergy and Asthma Specialist P S C | Owensboro | Kentucky | 42301 | United States |
| Allergy Asthma and Clinical Research | Oklahoma City | Oklahoma | 73120 | United States |
| Allergy and Clinical Immunology Associates | Pittsburgh | Pennsylvania | 15241 | United States |
| Western Sky Medical Research | El Paso | Texas | 79924 | United States |
| Allergy Asthma and amp Sinus Ctr S C | Greenfield | Wisconsin | 53228 | United States |
| Novartis Investigative Site | Nueve de Julio | Buenos Aires | B6500BWQ | Argentina |
| Novartis Investigative Site | Sourigues | Buenos Aires | B1837 | Argentina |
| Novartis Investigative Site | Santa Fe | Rosario | S2000DBS | Argentina |
| Novartis Investigative Site | Rosario | Santa Fe Province | S2000JKR | Argentina |
| Novartis Investigative Site | Calgary | Alberta | T2M 1A6 | Canada |
| Novartis Investigative Site | Montreal | Quebec | H2V 2K1 | Canada |
| Novartis Investigative Site | Angers | 49933 | France |
| Novartis Investigative Site | Antony | 92160 | France |
| Novartis Investigative Site | Brest | 29609 | France |
| Novartis Investigative Site | Montpellier | 34295 | France |
| Novartis Investigative Site | Paris | 75970 | France |
| Novartis Investigative Site | Reims | 51100 | France |
| Novartis Investigative Site | Saint-Mandé | 94160 | France |
| Novartis Investigative Site | Toulouse | 31400 | France |
| Novartis Investigative Site | Bramsche | Lower Saxony | 49565 | Germany |
| Novartis Investigative Site | Göttingen | Lower Saxony | 37075 | Germany |
| Novartis Investigative Site | Halle | Saxony-Anhalt | 06108 | Germany |
| Novartis Investigative Site | Erlangen | 91054 | Germany |
| Novartis Investigative Site | Hanover | 30625 | Germany |
| Novartis Investigative Site | Marburg | 35039 | Germany |
| Novartis Investigative Site | Singapore | 308205 | Singapore |
| Novartis Investigative Site | Komárno | 945 01 | Slovakia |
| Novartis Investigative Site | Levice | 934 01 | Slovakia |
| Novartis Investigative Site | Nové Zámky | 940 34 | Slovakia |
| Novartis Investigative Site | Daegu | Dalseo Gu | 41931 | South Korea |
| Novartis Investigative Site | Suwon | Gyeonggi-do | 16499 | South Korea |
| Novartis Investigative Site | Seoul | 03080 | South Korea |
| Novartis Investigative Site | Alicante | Valencia | 03010 | Spain |
| Novartis Investigative Site | Valencia | Valencia | 46014 | Spain |
| Novartis Investigative Site | Madrid | 28006 | Spain |
| Novartis Investigative Site | Madrid | 28041 | Spain |
| Novartis Investigative Site | Izmir | 35140 | Turkey (Türkiye) |
| Novartis Investigative Site | Kayseri | 38070 | Turkey (Türkiye) |
| Novartis Investigative Site | Samsun | 55139 | Turkey (Türkiye) |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | LOU064 (Remibrutinib) | All participants were assigned to remibrutinib 25 mg b.i.d. for 12 weeks. |
| Units | Counts |
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| 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 |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Baseline Systolic Blood Pressure (SBP) | Mean | Standard Deviation | millimeter of mercury (mmHg) |
| |||||||||||||||||
| Baseline Diastolic Blood Pressure (DBP) | Mean | Standard Deviation | millimeter of mercury (mmHg) |
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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 | Estimated Mean Change From Baseline at Week 4 in 24-hour Systolic Blood Pressure (SBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM) | A linear regression with SBP as a covariate was employed. The change in SBP from baseline to Week 4 was predicted at the median baseline level. The change from baseline in the 24-hour weighted average SBP was calculated using the time weighted average of the area under the curve (AUC) of SBP obtained over a 24-hour period as measured by ABPM. That is, the time weighted average of AUC of 24-hour SBP obtained at baseline was subtracted from corresponding time weighted average of AUC of SBP at Week 4. In the analysis, if participants took prohibited antihypertensive treatment before Week 4, their subsequent measurements were excluded. In such cases, the excluded measurements were imputed by increasing the 24-hour SBP by 3 mmHg from the baseline value at Week 4. Moreover, participants who discontinued of study treatment due to any reason prior to the Week 4 were excluded from the analysis. The Mixed Models for Repeated Measures (MMRM) approach was used. | Full Analysis Set (FAS): all participants to whom study treatment was assigned and received at least one dose of treatment. Participants who discontinued treatment prior to Week 4 were excluded from the analysis. | Posted | Mean | 95% Confidence Interval | millimeter of mercury (mmHg) | Baseline, Week 4 |
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| Secondary | Observed Mean Change From Baseline to Week 4 in 24-hour Weighted Average Systolic Blood Pressure (SBP) Measured by ABPM | The change from baseline in the 24-hour weighted average systolic blood pressure (SBP) was calculated using the time weighted average of the area under the curve (AUC) of SBP obtained over a 24-hour period as measured by ABPM. This analysis was conducted using the observed data. Data was computed taking weighted averages over time and discarding time intervals of more than 1 hour without measurements. | Full Analysis Set (FAS): all participants to whom study treatment was assigned and received at least one dose of treatment. Only participants with a value at both baseline and Week 4 were included. | Posted | Mean | Standard Deviation | millimeter of mercury (mmHg) | Baseline, Week 4 |
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| Secondary | Estimated Mean Change From Baseline at Week 4 in 24-hour Diastolic Blood Pressure (DBP) Measured by ABPM | A linear regression with DBP as a covariate was employed. The change in DBP from baseline to Week 4 was predicted at the median baseline level. The change from baseline in the 24-hour weighted average DBP was calculated using the time weighted average of the area under the curve (AUC) of DBP obtained over a 24-hour period as measured by ABPM. That is, the time weighted average of AUC of 24-hour DBP obtained at baseline was subtracted from corresponding time weighted average of AUC of DBP at Week 4. In the analysis, if participants took prohibited antihypertensive treatment before Week 4, their subsequent measurements were excluded. In such cases, the excluded measurements were imputed by increasing the 24-hour DBP by 3 mmHg from the baseline value at Week 4. Moreover, participants who discontinued of study treatment due to any reason prior to the Week 4 were excluded from the analysis. The Mixed Models for Repeated Measures (MMRM) approach was used. | FAS: all participants to whom study treatment was assigned and received at least one dose of treatment. Participants who discontinued treatment prior to Week 4 were excluded from the analysis. | Posted | Mean | 95% Confidence Interval | millimeter of mercury (mmHg) | Baseline, Week 4 |
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| Secondary | Estimated Mean Change From Baseline at Week 4 in Daytime and Nighttime Average SBP Measured by ABPM | The change in daytime (respectively nighttime) weighted average SBP was analyzed using linear regression model with baseline weighted average daytime SBP (respectively nighttime) as a covariate. The change in daytime (respectively nighttime) SBP from baseline to Week 4 was predicted at the median baseline level. The change from baseline of daytime (respectively nighttime) SBP was calculated using the time weighted average of the AUC of DBP obtained over daytime (respectively nighttime) In the analysis, if participants took prohibited antihypertensive treatment before Week 4, their subsequent measurements were excluded. In such cases, the excluded measurements were imputed by increasing the 24-hour SBP by 3 mmHg from the baseline value at Week 4. Moreover, participants who discontinued of study treatment due to any reason prior to the Week 4 were excluded from the analysis. The multiple imputation approach was used. Daytime: from 7am until 10 pm. Nighttime: from 10pm until 7 am. | FAS: all participants to whom study treatment was assigned and received at least one dose of treatment. Participants who discontinued treatment prior to Week 4 were excluded from the analysis. | Posted | Mean | 95% Confidence Interval | millimeter of mercury (mmHg) | Baseline, Week 4 |
| |||||||||||||||||||||||||||
| Secondary | Estimated Mean Change From Baseline at Week 4 in Daytime and Nighttime Average DBP Measured by ABPM | The change in daytime (respectively nighttime) weighted average DBP was analyzed using linear regression model with baseline weighted average daytime DBP (respectively nighttime) as a covariate. The change in daytime (respectively nighttime) DBP from baseline to Week 4 was predicted at the median baseline level. The change from baseline of daytime (respectively nighttime) DBP was calculated using the time weighted average of the AUC of DBP obtained over daytime (respectively nighttime) In the analysis, if participants took prohibited antihypertensive treatment before Week 4, their subsequent measurements were excluded. In such cases, the excluded measurements were imputed by increasing the 24-hour DBP by 3 mmHg from the baseline value at Week 4. Moreover, participants who discontinued of study treatment due to any reason prior to the Week 4 were excluded from the analysis. The multiple imputation approach was used. Daytime: from 7am until 10 pm. Nighttime: from 10pm until 7 am. | FAS: all participants to whom study treatment was assigned and received at least one dose of treatment. Participants who discontinued treatment prior to Week 4 were excluded from the analysis. | Posted | Mean | 95% Confidence Interval | millimeter of mercury (mmHg) | Baseline, Week 4 |
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On-treatment adverse events and deaths were reported from first dose of study medication up to 28 days after last dose of study medication, assessed up to approximately 18 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 enrolled 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 (Remibrutinib) | All participants were assigned to remibrutinib 25 mg b.i.d. for 12 weeks | 0 | 144 | 4 | 144 | 32 | 144 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cholecystitis acute | Hepatobiliary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Chronic spontaneous urticaria | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Aortic dissection | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
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| Chronic spontaneous urticaria | Skin and subcutaneous tissue disorders | MedDRA (27.0) | 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 | Sep 18, 2024 | Apr 10, 2025 | 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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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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