A Phase 2a, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy, Safety, and Tolerability of Tirabrutinib in Subjects With Antihistamine-Resistant Chronic Spontaneous Urticaria
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Week 8.
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of tirabrutinib in reducing disease activity in participants with chronic spontaneous urticaria (CSU) with respect to change from baseline in urticaria activity score over 7 days (UAS7) at Week 8 when added to standard of care.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Study consists a placebo controlled period and an open label extension period. Sponsor is also masked for the placebo controlled period.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of chronic spontaneous urticaria (CSU) (with or without urticarial dermatographism) for ≥ 6 months prior to screening
- •Presence of itch and hives for ≥ 6 consecutive weeks prior to screening, refractory to nonsedating H1-antihistamines (according to local treatment guidelines) during that time
- •Individuals must be maintained on approved H1-antihistamine doses as per the 2018 European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA2LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) guidelines (2018 EAACI/GA2LEN/EDF/WAO; ie, up to 4 times standard dosing) from 7 days prior to randomization.
- •Individuals must have active disease defined as UAS7 ≥ 16 and HSS7 ≥ 8 during the 7 consecutive days (with no missing timepoints) prior to randomization (Day -7 to Day -1).
排除标准
- •Clearly defined underlying etiology for chronic urticaria other than CSU, including:
- •Inducible urticaria as the only manifestation of disease (cold, heat, pressure, delayed pressure, aquagenic, contact, cholinergic, dermatographism)
- •Known underlying genetic cause of urticaria or angioedema such as hereditary angioedema (C1-inhibitor deficiency)
- •Urticarial dermatoses associated with a known diagnosis of an autoinflammatory syndrome or monoclonal gammopathy
- •Diseases with possible urticarial manifestations such as urticarial vasculitis, erythema multiforme, or cutaneous mastocytosis
- •Any other skin disease associated with chronic itching that could confound the study evaluation (eg, atopic dermatitis, psoriasis, bullous pemphigoid, and dermatitis herpetiformis)
- •Previous treatment with omalizumab or any other monoclonal antibody used to treat CSU within 16 weeks prior to randomization
- •Refractory to omalizumab or biosimilar
- •Previous use of a Bruton's tyrosine kinase (BTK) inhibitor
- •Any prior history of anaphylaxis
- •Use of a nonbiologic investigational drug or participation in an investigational study involving biologic therapy within 90 days or 5 half-lives (whichever is greater) prior to randomization
- •Intravenous immunoglobulin (IVIg) or plasmapheresis within 28 days prior to randomization
- •Use of cyclosporine A, methotrexate, mycophenolate mofetil (or mycophenolic acid), or azathioprine within 28 days prior to randomization; or use of dupilumab within 16 weeks prior to randomization
- •Routine (daily or every other day use for 5 or more consecutive days) of systemic corticosteroids within 28 days of randomization
- •Use of intramuscular corticosteroids within 28 days of randomization
- •Any clinically unstable disease states that would likely require rescue corticosteroids (eg, severe asthma) that may interfere with data interpretation
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Tirabrutinib
Participant will receive tirabrutinib twice daily in addition to their standard-of-care therapy for up to 8 weeks.
干预措施: Tirabrutinib (Drug)
Placebo
Participants will receive placebo twice daily in addition to their standard-of-care therapy for up to 8 weeks.
干预措施: Placebo (Drug)
Tirabrutinib, Open Label Extension
At Week 8, participants who have not discontinued the study drug will receive tirabrutinib twice daily in addition to their standard-of-care therapy for up to 16 weeks.
干预措施: Tirabrutinib (Drug)
结局指标
主要结局
Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Week 8.
时间窗: Baseline; Week 8
The UAS7 is the sum of the Hives Severity Score Over 7 Days (HSS7) and Itch Severity Score Over 7 Days (ISS7). The possible range of the UAS7 is 0 to 42. A well-controlled urticaria response is defined as a UAS7 ≤ 6. Higher scores indicate high disease activity in hives and itch. Hives Severity Score (HSS) is defined as the number of hives recorded twice daily by the participant on a scale from 0 (none) to 3 (severe). HSS7 is derived by adding together the daily average scores over a consecutive 7-day period. The severity of itch will be recorded twice daily by the participant using a scale from 0 (none) to 3 (severe). ISS7 is derived by adding together the daily average scores over a consecutive 7-day period.
次要结局
- Change from baseline of Hives Severity Score Over 7 Days (HSS7) at Week 8(Baseline; Week 8)
- Change from baseline of Itch Severity Score Over 7 Days (ISS7) at Week 8(Baseline; Week 8)
- Proportion of Participants Achieving a Complete Response (UAS7 = 0) at Week 8(Week 8)
- Change from Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Week 8(Baseline; Week 8)
- Proportion of Participants Achieving a Complete Angioedema Response (AAS7 = 0) at Week 8(Week 8)
- Change From Baseline in the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) Measurement at Week 8(Baseline; Week 8)
- Proportion of Participants Achieving Well-controlled Urticaria (UAS7 ≤ 6) at Week 8(Week 8)