A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Dupilumab and Milk Oral Immunotherapy for the Treatment of Patients With Cow's Milk Allergy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 33
- 试验地点
- 3
- 主要终点
- Proportion of Participants Treated With Dupilumab Plus Milk Protein OIT vs Placebo Plus Milk Protein OIT Who Tolerate at Least 2040 mg (Cumulative) Cow's Milk Protein During DBPCFC to Milk at Week 18
研究概览
简要总结
This is a phase 2, multicenter, randomized, double-blind, parallel group, 2 arm study in approximately 40 subjects aged 4 to 50 years, inclusive, who are allergic to cow's milk. The primary objective is to assess whether dupilumab as an adjunct to milk oral immunotherapy (OIT) compared to placebo improves the safety of milk OIT and rates of desensitization, defined as an increase in the proportion of subjects who pass a double-blind placebo-controlled food challenge (DBPCFC) to at least 2040 mg cumulative milk protein at week 18.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 4 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 4 to 50 years (inclusive)
- •Clinical history of allergy to cow's milk or milk-containing foods
- •Serum IgE to milk of >4 kUA/L within the last 12 months and/or a SPT to milk ≥6 mm compared to a negative control
- •Experience clinical reaction at or before 444 mg cumulative protein dose of cow's milk protein on Screening DBPCFC
- •No clinical reaction observed during the placebo (oat) Screening DBPCFC
- •Subjects with other known food allergies must agree to eliminate these other food items from their diet so as not to confound the safety and efficacy data from the study
- •Use of effective birth control by female participants of childbearing potential
排除标准
- •Any previous exposure to dupilumab
- •Known hypersensitivity to dupilumab or any of its excipients
- •Known hypersensitivity to epinephrine or any of its excipients
- •Allergy to oat (placebo in DBPCFC)
- •History of severe anaphylaxis to cow's milk, defined as neurological compromise or requiring intubation
- •Recent history of frequent severe, life-threatening episodes of anaphylaxis or anaphylactic shock as defined as 3 or more episodes of anaphylaxis within the past year
- •Inability to tolerate biological (antibody) therapies
- •Body weight <5 kg at the time of screening
- •History of eosinophilic esophagitis (EoE), other eosinophilic gastrointestinal disease, chronic, recurrent, or severe gastroesophageal reflux disease (GERD), symptoms of dysphagia (e.g., difficulty swallowing, food "getting stuck"), or recurrent gastrointestinal symptoms of undiagnosed etiology
- •History of cardiovascular disease, including uncontrolled or inadequately controlled hypertension
- •History of a mast cell disorder
- •Established diagnosis of a primary immunodeficiency disorder
- •Severe asthma or mild or moderate asthma if uncontrolled or difficult to control
- •Current participation or within the last 4 months in any other interventional study
- •Use of medication such as beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) or calcium channel blockers
- •Pregnant or breastfeeding women
研究组 & 干预措施
Dupilumab
24-week treatment period, which includes a 4-week run-in period with dupilumab followed by 12 weeks of treatment with dupilumab in combination with a gradual up-dosing of milk protein OIT, then followed by 8 weeks of milk OIT dosing with no dupilumab
干预措施: Dupilumab (Drug)
Placebo
24-week treatment period, which includes a 4-week run-in period with placebo for dupilumab followed by 12 weeks of treatment with placebo for dupilumab in combination with a gradual up-dosing of milk protein OIT, then followed by 8 weeks of milk OIT dosing with no placebo
干预措施: Placebo (Other)
结局指标
主要结局
Proportion of Participants Treated With Dupilumab Plus Milk Protein OIT vs Placebo Plus Milk Protein OIT Who Tolerate at Least 2040 mg (Cumulative) Cow's Milk Protein During DBPCFC to Milk at Week 18
时间窗: Week 18
DBPCFC double-blind, placebo-controlled food challenge; OIT oral immunotherapy; withdrawals are imputed as failures
次要结局
- Proportion of Participants Who Tolerate at Least 1040 mg Cumulative Milk Protein at Week 24 DBPCFC(week 24)
- Proportion of Participants Who Tolerate at Least 1040 mg Cumulative Milk Protein at Week 18 DBPCFC(Week 18)
- Proportion of Participants Who Tolerate 4040 mg Cumulative Milk Protein at Week 24 DBPCFC(Week 24)
- Proportion of Participants Who Tolerate 4040 mg Cumulative Milk Protein at Week 18 DBPCFC(Week 18)
- Proportion of Participants Who Tolerate at Least 2040 mg Cumulative Milk Protein at Week 24 DBPCFC(Week 24)
- Change in the Cumulative Tolerated Dose (CTD) of Milk Protein During DBPCFC From Baseline to Week 18 Across Cohorts as Pairwise Comparisons of All Treatment Groups(Baseline and week 18)
- Change in the Cumulative Tolerated Dose (CTD) of Milk Protein During DBPCFC From Baseline to Week 24 Across Cohorts as Pairwise Comparisons of All Treatment Groups(Baseline and week 24)
研究者
Andrew J Long, PharmD
Pharmacist
Stanford University