NCT05677451进行中（未招募）3 期
A Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy, Pharmacokinetics and Safety of Remibrutinib (LOU064) for 24 Weeks in Adolescents From 12 to Less Than 18 Years of Age With Chronic Spontaneous Urticaria Inadequately Controlled by H1-antihistamines Followed by an Optional Open-label Extension for up to Another 3 Years and an Optional Safety Long-term Treatment-free Follow-up Period for up to an Additional 3 Years
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 100
- 试验地点
- 62
- 主要终点
- Change fron baseline in ISS7
研究概览
简要总结
The purpose of this trial is:
- to assess the efficacy, pharmacokinetics, and safety of remibrutinib vs. placebo in adolescents from 12 to < 18 years of age suffering from chronic spontaneous urticaria inadequately controlled by H1-antihistamines
- to collect long-term efficacy, safety and tolerability data on remibrutinib in adolescents after having completed 24 weeks of treatment
- to collect safety data in this population for up to three years after the last dose of study treatment
详细描述
This trial consists of 3 different periods:
- the "core period", which is randomized and double-blind, during which 2/3 participants will receive remibrutinib and 1/3 will receive placebo for 24 weeks. Total duration: approximately 32 weeks (10 site visits).
- an optional "open-label extension (OLE) period" proposed to all participants who completed 24 weeks of treatment of the "core period" and all scheduled assessments planned at week 24 visit . Depending on their CSU symptoms (as assessed by the doctor), participants will either receive remibrutinib for 24 weeks, or enter an observational treatment-free period for 1 year. If the CSU symptoms return during the observational period, the participants can switch to the treatment period at any time (decided by the doctor). At the end of the 24-week treatment period, if CSU is controlled, participants will enter the 1-year observational period, otherwise, they can continue with another cycle of 24-week remibrutinib treatment. The number of remibrutinib treatment or observational cycles will be limited to 6 times each. Total duration: from 1 year to approximately 3 years, and number of visits: from 3 to 15 (depending on the CSU symptoms).
- an optional "long-term treatment-free follow-up period" proposed to all participants who completed at least 4 months treatment in the "OLE period". No treatment will be given. Duration: 3 years with 1 site visit and up to 4 phone call follow-up visits.
The primary clinical question of interest is what is the effect of remibrutinib treatment versus placebo on the change from baseline in UAS7, ISS7 and HSS7 scores after 12 weeks of treatment
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female adolescent participants aged >= 12 to < 18 years of age at the time of signing the informed consent
- •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 randomization defined as:
- •The presence of itch and hives for ≥ 6 consecutive weeks prior to screening despite the use of second-generation H1-AH during this time period according to local treatment guidelines
- •UAS7 score (range 0 - 42) >= 16, ISS7 score (range 0 - 21) >= 6 and HSS7 score (range 0 - 21) >= 6 during the 7 days prior to randomization (Day 1)
- •Documentation of hives within three months before randomization (either at screening and/or at randomization; or documented in the participants' medical history)
排除标准
- •Previous use of remibrutinib or other BTK inhibitors
- •Significant bleeding risk or coagulation disorders
- •History of gastrointestinal bleeding
- •Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited
- •History or current hepatic disease
- •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
- •History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes
- •Participants having a clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria) including urticaria factitia (symptomatic dermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact-urticaria
- •Other diseases with symptoms of urticaria or angioedema, including but not limited to urticaria vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary angioedema, or drug-induced urticaria
- •Any other skin disease associated with chronic itching that might influence in the investigator's opinion the study evaluations and results, e.g., atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Arm 1: LOU064 (blinded)
Experimental
LOU064 (blinded) taken orally b.i.d. for 24 weeks, followed by LOU064 (open-label) taken orally b.i.d. for up to 6 cycles of 24 weeks.
干预措施: LOU064 (blinded) (Drug)
Arm 2: LOU064 placebo (blinded)
Placebo Comparator
LOU064 placebo (blinded) taken orally b.i.d. for 24 weeks (randomized in a 2:1 ratio arm 1: arm 2)
干预措施: placebo (Drug)
结局指标
主要结局
Change fron baseline in ISS7
时间窗: Baseline, Week 12
Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate). Negative change from baseline indicates improvement.
Change from baseline in UAS7
时间窗: Baseline, week 12
The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0. Negative change from baseline indicates improvement.
Change from baseline in HSS7
时间窗: Baseline, Week 12
Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (\>12 hives/12 hours). Negative change from baseline indicates improvement.
次要结局
- AUClast of remibrutinib(At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake)
- Achievement of UAS7 = 0 (yes/no)(Week 12 and over time)
- Tmax of remibrutinib(At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake)
- Absolute change from baseline in HSS7(Baseline - Week 12)
- Absolute change from baseline in ISS7(Baseline - Week 12)
- Achievement of UAS7 ≤ 6 (yes/no)(Week 12 and over time)
- Absolute change from baseline in CDLQI score(Week 12)
- Number of weeks without angioedema, assessed by the cumulative number of weeks with an AAS7 = 0 response(baseline - Week 12)
- Cmax of remibrutinib(At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake)
- Occurrence of treatment emergent AEs, and SAEs during the Open Label Extension (OLE) period(3 years)
- Occurrence of treatment-emergent adverse events (AE) and serious adverse events (SAE) during the core period(28 weeks)
研究者
研究点 (62)
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