A Multicenter, Open-label Phase 3 Study: Ambulatory Blood Pressure Monitoring in Adult Patients With Chronic Spontaneous Urticaria Inadequately Controlled by H1-antihistamines Treated With Remibrutinib up to 12 Weeks.

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)).

Study Overview

• Status: Completed
• Conditions: Chronic Spontaneous Urticaria
• Intervention / Treatment: Drug: LOU064

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Nueve de Julio, Buenos Aires, Argentina, B6500BWQ
      • Novartis Investigative Site
    • Sourigues, Buenos Aires, Argentina, B1837
      • Novartis Investigative Site
  • Rosario
    • Santa Fe, Rosario, Argentina, S2000DBS
      • Novartis Investigative Site
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000JKR
      • Novartis Investigative Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2M 1A6
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H2V 2K1
      • Novartis Investigative Site
• France
  • Angers, France, 49933
    • Novartis Investigative Site
  • Antony, France, 92160
    • Novartis Investigative Site
  • Brest, France, 29609
    • Novartis Investigative Site
  • Montpellier, France, 34295
    • Novartis Investigative Site
  • Paris, France, 75970
    • Novartis Investigative Site
  • Reims, France, 51100
    • Novartis Investigative Site
  • Saint-Mandé, France, 94160
    • Novartis Investigative Site
  • Toulouse, France, 31400
    • Novartis Investigative Site
• Germany
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Hanover, Germany, 30625
    • Novartis Investigative Site
  • Marburg, Germany, 35039
    • Novartis Investigative Site
  • Lower Saxony
    • Bramsche, Lower Saxony, Germany, 49565
      • Novartis Investigative Site
    • Göttingen, Lower Saxony, Germany, 37075
      • Novartis Investigative Site
  • Saxony-Anhalt
    • Halle, Saxony-Anhalt, Germany, 06108
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 308205
    • Novartis Investigative Site
• Slovakia
  • Komárno, Slovakia, 945 01
    • Novartis Investigative Site
  • Levice, Slovakia, 934 01
    • Novartis Investigative Site
  • Nové Zámky, Slovakia, 940 34
    • Novartis Investigative Site
• South Korea
  • Seoul, South Korea, 03080
    • Novartis Investigative Site
  • Dalseo Gu
    • Daegu, Dalseo Gu, South Korea, 41931
      • Novartis Investigative Site
  • Gyeonggi-do
    • Suwon, Gyeonggi-do, South Korea, 16499
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28006
    • Novartis Investigative Site
  • Valencia
    • Alicante, Valencia, Spain, 03010
      • Novartis Investigative Site
    • Valencia, Valencia, Spain, 46014
      • Novartis Investigative Site
• Turkey (Türkiye)
  • Izmir, Turkey (Türkiye), 35140
    • Novartis Investigative Site
  • Kayseri, Turkey (Türkiye), 38070
    • Novartis Investigative Site
  • Samsun, Turkey (Türkiye), 55139
    • Novartis Investigative Site
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Acuro Research Inc
  • Florida
    • Aventura, Florida, United States, 33180
      • Florida Ctr Allergy Asthma Research
    • Greenacres City, Florida, United States, 33467
      • Finlay Medical Research
  • Idaho
    • Boise, Idaho, United States, 83706
      • Treasure Valley Medical Research
  • Illinois
    • Glenview, Illinois, United States, 60077
      • Endeavor Health
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • Allergy and Asthma Specialist P S C
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Allergy Asthma and Clinical Research
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15241
      • Allergy and Clinical Immunology Associates
  • Texas
    • El Paso, Texas, United States, 79924
      • Western Sky Medical Research
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228
      • Allergy Asthma and amp Sinus Ctr S C

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Signed informed consent obtained prior to participation in the study
• Male and female adult 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-AH at the time of baseline (Day 1)
• Documentation of hives within three months before baseline (either at screening and/or at baseline (Day 1); 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 protocol
• Participants had no more than 2 missing UPDD entries (either morning or evening) in the 7 days prior to baseline (Day 1).

Key Exclusion Criteria:

• Participants unable to tolerate 24-hour ambulatory blood pressure measurement using automatic ABPM device
• Ongoing or past history of hypertension and/or SBP >= 140 or =< 90 OR DBP >= 90 or =< 60 mmHg at screening
• Participants working night shifts
• Participants taking/requiring medications prohibited by the protocol (including those known to interfere with blood pressure assessments in the study)
• Evidence of clinically significant cardiovascular, 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LOU064 (remibrutinib); All participants were assigned to remibrutinib 25 mg b.i.d. for 12 weeks.	Drug: LOU064; 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.; Other Names: remibrutinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2023
• Primary Completion (Actual): April 25, 2024
• Study Completion (Actual): April 25, 2024

Study Registration Dates

• First Submitted: March 21, 2023
• First Submitted That Met QC Criteria: March 21, 2023
• First Posted (Actual): April 3, 2023

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: remibrutinib; Systolic Blood Pressure (SBP); Diastolic Blood Pressure (DBP); Chronic Spontaneous Urticaria (CSU); Ambulator Blood Pressure Monitoring (ABPM); H1 antihistamines (H1-AH) treatment
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Urticaria; Skin Diseases, Vascular; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Chronic Urticaria; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; remibrutinib
• Other Study ID Numbers: CLOU064A2305; 2022-002838-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No