A 52-week Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess Efficacy and Safety of Remibrutinib (LOU064) in Adult and Adolescent Participants With IgE-mediated Food Allergy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 576
- 试验地点
- 10
- 主要终点
- Sub-study 1: Number of participants achieving response status (tolerated at least 600 mg of peanut protein)
研究概览
简要总结
The purpose of this Phase III study is to evaluate the clinical efficacy and safety of remibrutinib in participants with peanut, or cow's milk ("milk", cooked and uncooked) or hen's egg ("egg", cooked and uncooked) immunoglobulin E (IgE)- mediated allergy in comparison to placebo.
详细描述
This study is a Phase III, 52-week, multi-center, placebo controlled pivotal study to evaluate the efficacy and safety of remibrutinib compared to placebo in adolescent and adult participants with peanut, milk, or egg IgE-mediated allergy.
This study will be conducted in 4 Sub-studies: Sub-study 1 to evaluate response to peanut allergen at Week 24, Sub-study 2 to evaluate response to milk allergen at Week 24, Sub-study 3 to evaluate response to egg allergen at Week 24, and Sub-study 4 to evaluate response to peanut or milk, or egg allergen at Week 4.
Treatment period 1: Participants will receive one of the two treatment groups, double-blind remibrutinib or placebo, for a period up to 24 weeks for Sub-studies 1, 2, and 3, and up to 4 weeks for Sub-study 4.
Treatment period 2: For all Sub-studies, the open label period starts at Week 24, except for Sub-study 4, where the open label period starts at Week 4. Participants from each Sub-study will continue in the study and receive, or initiate, active open label remibrutinib until Week 52.
Following completion of the treatment period 2, eligible participants may enroll in a separate open-label post-trial access study and receive remibrutinib to evaluate long-term treatment effects. Participants who do not enroll in the post-trial access study will enter a 4-week safety follow-up period off treatment, during which adverse events will be monitored.
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)
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent and/or assent (where applicable) must be obtained prior to study participation. Participant (and parent/legal guardian for adolescents) must be able to understand and provide informed consent and assent, as applicable. If a minor participant providing assent reaches the age of legal majority (as defined by local law), he/she must be re-consented (ICF) at the next study visit.
- •Male or female participants who are 12 to 65 years of age, inclusive, at the time of signing informed consent/assent.
- •Positive allergen-specific (peanut, milk, or egg), IgE (≥ 0.35 kUA/L) at Screening Visit
- •Positive Skin Prick Testing (SPT) for peanut, milk, or egg at Screening Visit
- •This is defined as the average diameter (longest diameter and mid-point orthogonal diameter) ≥ 4 mm wheal compared to the negative control.
- •A positive DBPCFC at baseline (Screening Visit 2), defined as the occurrence of dose-limiting symptoms at a single dose:
- •≤ 100 mg of peanut allergen protein
- •≤ 300 mg for milk or egg allergen protein
- •Participants must be able and willing to participate in the DBPCFC and must be willing to continue avoiding exposure to peanut, milk (cooked and uncooked), or egg (cooked and uncooked) and any other foods that they are allergic to throughout this study.
排除标准
- •Previous use of remibrutinib or other Bruton Tyrosine Kinase (BTK) inhibitors.
- •History of hypersensitivity to study drug or its excipients or to drugs of similar chemical classes.
- •Hypersensitivity or intolerance to any of the matrix components used within the material for the DBPCFC.
- •Any occurrence of dose-limiting symptoms against placebo allergen at baseline DBPCFC (Screening Visit Part 1 and/or Part 2).
- •Medical examination, medical conditions or laboratory findings that, in the opinion of the investigator, renders the participant unsuitable for the study.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Sub-study 4- LOU064
Participants with peanut, cow's milk, and hen's egg allergy will receive remibrutinib during the double-blind treatment period (up to Week 4), followed by open-label remibrutinib treatment through Week 52.
干预措施: Placebo (Drug)
Sub-study 1- LOU064
Participants with peanut allergy will receive remibrutinib during the double-blind treatment period (up to Week 24), followed by open-label remibrutinib treatment through Week 52.
干预措施: Placebo (Drug)
Sub-study 1- Placebo
Participants with peanut allergy will receive matching placebo during the double-blind treatment period (up to Week 24), followed by open-label remibrutinib treatment through Week 52.
干预措施: Placebo (Drug)
Sub-study 3- LOU064
Participants with hen's egg allergy will receive remibrutinib during the double-blind treatment period (up to Week 24), followed by open-label remibrutinib treatment through Week 52.
干预措施: Placebo (Drug)
Sub-study 2- LOU064
Participants with cow's milk allergy will receive remibrutinib during the double-blind treatment period (up to Week 24), followed by open-label remibrutinib treatment through Week 52.
干预措施: Remibrutinib (Drug)
Sub-study 2- LOU064
Participants with cow's milk allergy will receive remibrutinib during the double-blind treatment period (up to Week 24), followed by open-label remibrutinib treatment through Week 52.
干预措施: Placebo (Drug)
Sub-study 1- LOU064
Participants with peanut allergy will receive remibrutinib during the double-blind treatment period (up to Week 24), followed by open-label remibrutinib treatment through Week 52.
干预措施: Remibrutinib (Drug)
Sub-study 2- Placebo
Participants with cow's milk allergy will receive matching placebo during the double-blind treatment period (up to Week 24), followed by open-label remibrutinib treatment through Week 52.
干预措施: Placebo (Drug)
Sub-study 4- LOU064
Participants with peanut, cow's milk, and hen's egg allergy will receive remibrutinib during the double-blind treatment period (up to Week 4), followed by open-label remibrutinib treatment through Week 52.
干预措施: Remibrutinib (Drug)
Sub-study 3- LOU064
Participants with hen's egg allergy will receive remibrutinib during the double-blind treatment period (up to Week 24), followed by open-label remibrutinib treatment through Week 52.
干预措施: Remibrutinib (Drug)
Sub-study 3- Placebo
Participants with hen's egg allergy will receive matching placebo during the double-blind treatment period (up to Week 24), followed by open-label remibrutinib treatment through Week 52.
干预措施: Placebo (Drug)
Sub-study 4- Placebo
Participants with peanut, cow's milk, and hen's egg allergy will receive matching placebo during the double-blind treatment period (up to Week 4), followed by open-label remibrutinib treatment through Week 52.
干预措施: Placebo (Drug)
结局指标
主要结局
Sub-study 1: Number of participants achieving response status (tolerated at least 600 mg of peanut protein)
时间窗: Week 24
Response status is defined as tolerating an oral dose of at least 600 mg peanut protein (1044 mg cumulative tolerated dose) without dose-limiting symptoms during the double-blind placebo-controlled food challenge (DBPCFC).
Sub-study 2: Number of participants achieving response status (tolerated at least 1000 mg of milk protein)
时间窗: Week 24
Response status is defined as tolerating an oral dose of at least 1000 mg milk protein (2044 mg cumulative tolerated dose) without dose-limiting symptoms during the double-blind placebo-controlled food challenge (DBPCFC).
Sub-study 3: Number of participants achieving response status (tolerated at least 1000 mg of egg protein)
时间窗: Week 24
Response status is defined as tolerating an oral dose of at least 1000 mg egg protein (2044 mg cumulative tolerated dose) without dose-limiting symptoms during the double-blind placebo-controlled food challenge (DBPCFC).
次要结局
- Sub-study 1: Number of participants achieving response status (tolerated at least 1000 mg of peanut protein)(Week 24)
- Sub-study 1: Change from baseline in Log10-Transformed Maximum Tolerated Single Dose of peanut protein(Baseline and Week 24)
- Sub-study 2: Change from baseline in Log10-Transformed Maximum Tolerated Single Dose of milk protein(Baseline and Week 24)
- Sub-study 3: Change from baseline in Log10-Transformed Maximum Tolerated Single Dose of egg protein(Baseline and Week 24)
- Sub-study 1: Number of participants by Maximum Symptom Severity During Peanut Protein Challenge(Week 24)
- Sub-study 2: Number of participants by Maximum Symptom Severity During Milk Protein Challenge(Week 24)
- Sub-study 3: Number of participants by Maximum Symptom Severity During Egg Protein Challenge(Week 24)
- Sub-study 1: Number of participants achieving response status (tolerated at least 3000 mg of peanut protein)(Week 24)
- Sub-study 2: Number of participants achieving response status (tolerated at least 3000 mg of milk protein)(Week 24)
- Sub-study 3: Number of participants achieving response status (tolerated at least 3000 mg of egg protein)(Week 24)
- Sub-study 4: Number of participants achieving combined response status (tolerated at least 600 mg of peanut protein, or at least 1000 mg of milk or egg protein)(Week 4)
- Sub-study 4: Number of participants achieving combined response status (tolerated at least 1000 mg of peanut, milk or egg protein)(Week 4)
- Sub-study 4: Change from baseline in Log10-Transformed Maximum Tolerated Single Dose(Baseline and Week 4)
- Sub-study 4: Number of participants by Maximum Symptom Severity During Food Challenge(Week 4)
- Sub-study 4: Number of participants achieving combined response status (tolerated at least 3000 mg of peanut, milk or egg protein)(Week 4)
- Sub-studies 1, 2, 3 and 4: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 56 weeks)