Clinical Trial Results:
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
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Summary
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EudraCT number |
2022-002838-13 |
Trial protocol |
ES SK DE |
Global end of trial date |
25 Apr 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Apr 2025
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First version publication date |
26 Apr 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CLOU064A2305
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05795153 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
Novartis Campus, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
25 Apr 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Apr 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The purpose of this study was to assess the effect of remibrutinib 25 mg b.i.d. open-label on SBP measured as a change in 24-hour weighted average SBP from baseline to Week 4 assessed by ABPM; and to assess overall safety and efficacy over 12 weeks in adult participants with CSU inadequately controlled with second generation H1-AH treatment.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Apr 2023
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 8
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Country: Number of subjects enrolled |
Canada: 6
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Country: Number of subjects enrolled |
France: 32
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Country: Number of subjects enrolled |
Germany: 18
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Country: Number of subjects enrolled |
Korea, Republic of: 15
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Country: Number of subjects enrolled |
Singapore: 1
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Country: Number of subjects enrolled |
Slovakia: 11
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Country: Number of subjects enrolled |
Spain: 12
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Country: Number of subjects enrolled |
Türkiye: 10
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Country: Number of subjects enrolled |
United States: 31
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Worldwide total number of subjects |
144
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EEA total number of subjects |
73
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
131
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From 65 to 84 years |
13
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85 years and over |
0
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Recruitment
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Recruitment details |
This study was conducted globally across 10 countries: Argentina (4 centers), Canada (2 centers), France (8 centers), Germany (6 centers), Republic of Korea/South Korea (3 centers), Singapore (1 center), Slovakia (3 centers), Spain (4 centers), Turkey (3 centers), and USA (11 centers). | ||||||||||||||||
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Pre-assignment
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Screening details |
Participants underwent a screening period of up to 4 weeks. | ||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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LOU064 (remibrutinib) | ||||||||||||||||
Arm description |
All participants were assigned to remibrutinib 25 mg b.i.d. for 12 weeks. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Remibrutinib
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Investigational medicinal product code |
LOU064
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
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
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Baseline characteristics reporting groups
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Reporting group title |
LOU064 (remibrutinib)
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Reporting group description |
All participants were assigned to remibrutinib 25 mg b.i.d. for 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
LOU064 (remibrutinib)
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Reporting group description |
All participants were assigned to remibrutinib 25 mg b.i.d. for 12 weeks. | ||
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End point title |
Estimated Mean Change from Baseline at Week 4 in 24-hour Systolic Blood Pressure (SBP) measured by Ambulatory Blood Pressure Monitoring (ABPM) [1] | ||||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
Baseline, Week 4
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were planned for the primary endpoint |
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| No statistical analyses for this end point | |||||||||
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End point title |
Observed Mean Change from Baseline to Week 4 in 24-hour weighted average Systolic Blood Pressure (SBP) measured by ABPM | ||||||||
End point description |
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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End point type |
Secondary
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End point timeframe |
Baseline, Week 4
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| No statistical analyses for this end point | |||||||||
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End point title |
Estimated Mean Change from Baseline at Week 4 in 24-hour Diastolic Blood Pressure (DBP) measured by ABPM | ||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 4
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| No statistical analyses for this end point | |||||||||
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End point title |
Estimated Mean Change from Baseline at Week 4 in daytime and nighttime average SBP measured by ABPM | ||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 4
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Estimated Mean Change from Baseline at Week 4 in daytime and nighttime average DBP measured by ABPM | ||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 4
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
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.
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Adverse event reporting additional description |
Consistent with EudraCTdisclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.0
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Reporting groups
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Reporting group title |
LOU064 25mg b.i.d.
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Reporting group description |
LOU064 25mg b.i.d. | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
