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.
- Registration Number
- NCT05795153
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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)).
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 144
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description LOU064 (remibrutinib) LOU064 All participants were assigned to remibrutinib 25 mg b.i.d. for 12 weeks.
- Primary Outcome Measures
Name Time Method Estimated Mean Change From Baseline at Week 4 in 24-hour Systolic Blood Pressure (SBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM) Baseline, Week 4 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.
- Secondary Outcome Measures
Name Time Method Observed Mean Change From Baseline to Week 4 in 24-hour Weighted Average Systolic Blood Pressure (SBP) Measured by ABPM Baseline, Week 4 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.Estimated Mean Change From Baseline at Week 4 in 24-hour Diastolic Blood Pressure (DBP) Measured by ABPM Baseline, Week 4 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.Estimated Mean Change From Baseline at Week 4 in Daytime and Nighttime Average SBP Measured by ABPM Baseline, Week 4 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.
Estimated Mean Change From Baseline at Week 4 in Daytime and Nighttime Average DBP Measured by ABPM Baseline, Week 4 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.
Trial Locations
- Locations (11)
Acuro Research Inc
šŗšøLittle Rock, Arkansas, United States
Florida Ctr Allergy Asthma Research
šŗšøAventura, Florida, United States
Finlay Medical Research
šŗšøGreenacres City, Florida, United States
Treasure Valley Medical Research
šŗšøBoise, Idaho, United States
Endeavor Health
šŗšøGlenview, Illinois, United States
Allergy and Asthma Specialist P S C
šŗšøOwensboro, Kentucky, United States
Allergy Asthma and Clinical Research
šŗšøOklahoma City, Oklahoma, United States
Allergy and Clinical Immunology Associates
šŗšøPittsburgh, Pennsylvania, United States
Western Sky Medical Research
šŗšøEl Paso, Texas, United States
Allergy Asthma and amp Sinus Ctr S C
šŗšøGreenfield, Wisconsin, United States
Novartis Investigative Site
š¹š·Samsun, Turkey