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.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 144
- 试验地点
- 11
- 主要终点
- Estimated Mean Change From Baseline at Week 4 in 24-hour Systolic Blood Pressure (SBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM)
研究概览
简要总结
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)).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
LOU064 (remibrutinib)
All participants were assigned to remibrutinib 25 mg b.i.d. for 12 weeks.
干预措施: LOU064 (Drug)
结局指标
主要结局
Estimated Mean Change From Baseline at Week 4 in 24-hour Systolic Blood Pressure (SBP) Measured by Ambulatory Blood Pressure Monitoring (ABPM)
时间窗: 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.
次要结局
- Observed Mean Change From Baseline to Week 4 in 24-hour Weighted Average Systolic Blood Pressure (SBP) Measured by ABPM(Baseline, Week 4)
- Estimated Mean Change From Baseline at Week 4 in 24-hour Diastolic Blood Pressure (DBP) Measured by ABPM(Baseline, Week 4)
- Estimated Mean Change From Baseline at Week 4 in Daytime and Nighttime Average SBP Measured by ABPM(Baseline, Week 4)
- Estimated Mean Change From Baseline at Week 4 in Daytime and Nighttime Average DBP Measured by ABPM(Baseline, Week 4)