A Global, Multi-center, Open-label Study, Investigating a Remibrutinib- and Omalizumab-Based Treatment Algorithm in Adult Patients With Chronic Spontaneous Urticaria Inadequately Controlled by H1-Antihistamines, to Achieve Fast and Well-Controlled Disease Within 24 Weeks
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 382
- 主要终点
- Proportion of participants achieving Urticaria Activity Score over 7 days (UAS7) ≤6 (yes/no)
研究概览
简要总结
The purpose of this open-label study is to assess the efficacy and safety of a novel treatment algorithm for sequencing remibrutinib and omalizumab in the treatment of adult participants with chronic spontaneous urticaria (CSU) who are inadequately controlled by second-generation H1-antihistamines (sgH1-AH).
详细描述
This is a global, multi-center, open-label study, investigating a remibrutinib- and omalizumab-based treatment algorithm in adult patients with CSU inadequately controlled by sgH1-AH, to achieve fast and well-controlled disease within 24 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female adults (age ≥18 years) at the time of signing the informed consent.
- •CSU duration for ≥2 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 sgH1-AH at baseline defined as:
- •The presence of itch and hives for ≥6 consecutive weeks prior to screening despite the use of sgH1-AH during this time period.
- •UAS7 score (range: 0-42) ≥
- •Documentation of hives within two months prior to baseline (either at screening and/or at baseline; or documented in the participant's medical history).
- •Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration of the study and adhere to the study protocol.
- •Participants must not have had more than one missing UPDD entry (either morning or evening) in the 7 days prior to enrollment (Day 1).
排除标准
- •Previous use of remibrutinib, other Bruton's tyrosine kinase (BTK) inhibitors or prior exposure to biologics with any effect in CSU (e.g., ligelizumab, omalizumab, dupilumab, barzolvolimab).
- •Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 12 months prior to Visit 1), neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, gastrointestinal, or hematological disorders, 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 by the participant.
- •Significant bleeding risk or coagulation disorders.
- •History of gastrointestinal bleeding, e.g., in association with use of nonsteroidal anti-inflammatory drugs (NSAIDs), that was clinically relevant (e.g., where intervention was indicated or requiring hospitalization or blood transfusion).
- •Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75mg/d. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited.
- •Requirement for anticoagulant medication (for example, warfarin or Novel Oral Anti- Coagulant - NOAC).
- •History or current hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or aspartate aminotransferase (AST) / alanine aminotransferase (ALT) levels of more than 1.5x upper limit of normal (ULN) or international normalized ratio (INR) of more than 1.5 at screening.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Remibrutinib
Participants will receive remibrutinib 25 mg twice a day for 12 weeks.
干预措施: Remibrutinib (Drug)
Remibrutinib or Omalizumab
Participants will receive remibrutinib 25 mg twice a day. At Week 12, well-controlled participants (UCT7 ≥12) continue remibrutinib, while participants with inadequate control (UCT7 <12) escalate to omalizumab 300 mg every 4 weeks.
干预措施: Omalizumab (Drug)
结局指标
主要结局
Proportion of participants achieving Urticaria Activity Score over 7 days (UAS7) ≤6 (yes/no)
时间窗: Week 24
UAS7 is a validated patient-reported measure of chronic spontaneous urticaria disease activity over 7 days. It is calculated as the sum of the weekly Hives Severity Score (HSS7) and the weekly Itch Severity Score (ISS7) and ranges from 0 to 42. Lower scores indicate lower disease activity / better disease control, and a score of ≤6 indicates well-controlled disease. HSS7 and ISS7 are each derived from daily diary entries over the 7 days preceding the visit.
次要结局
- Proportion of participants achieving UAS7 ≤6 (yes/no)(Weeks 16 and 20)
- Proportion of participants achieving UAS7 =0 (yes/no)(Weeks 16, 20, and 24)
- Proportion of participants achieving Angioedema Activity Score over 7 days (AAS7) =0.(Weeks 16, 20, and 24)
- Proportion of participants achieving of Dermatology Life Quality Index (DLQI) =0/1(Weeks 16, 20, and 24)
- Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)(From Day 1 until at least 4 weeks after the last administration of remibrutinib and at least 16 weeks after the last administration of omalizumab)
- Proportion of participants achieving UAS7 ≤6 under the treatment algorithm compared with historical omalizumab (300 mg every 4 weeks) data.(Weeks 16, 20, and 24)
- Proportion of participants achieving UAS7 =0 under the treatment algorithm compared with historical omalizumab (300 mg every 4 weeks) data.(Weeks 16, 20, and 24)