Evaluating the role of allergen dose and duration in the safety and efficacy of multi-allergen oral immunotherapy with Omalizumab

评估过敏原剂量和持续时间在奥马珠单抗多过敏原口服免疫治疗的安全性和有效性中的作用

• 批准号: 10347358
• 负责人: R. Sharon Chinthrajah
• 金额: $ 23.5万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10347358
• 关键词: Address; Adult; Adverse event; Affect; Age; Allergens; Allergic; Allergic Reaction; Allergic inflammation; Anaphylaxis; Basophils; Biological Assay; Blood; Blood specimen; Bystander Effect; Cashew nut; Child; Clinical; Clinical Research; Complex; Data; Data Set; Dose; Dropout; Epidemic; Fabaceae; Food; Food Hypersensitivity; Frequencies; GTP-Binding Proteins; Hazelnuts; Hypersensitivity; Hypersensitivity skin testing; IgE; IgG4; Immune response; Immunotherapy; Incidence; Individual; Juglans; Laboratories; Leadership; Literature; Maintenance; Maintenance Therapy; Measurement; Methods; Mission; Monoclonal Antibodies; Multicenter Studies; Nut Hypersensitivity; Nuts; Outcome; Participant; Patients; Pecans; Persons; Phase; Phenotype; Pistachio Nuts; Prevalence; Proteins; Protocols documentation; Publishing; Randomized; Regimen; Respiratory Signs and Symptoms; Risk; Role; Safety; Sampling; Site; Skin; Symptoms; Testing; Time; Trees; anti-IgE; arm; clinical phenotype; desensitization; design; effective therapy; efficacy outcomes; experience; food allergen; food challenge; gastrointestinal; immunotherapy trials; improved; mast cell; omalizumab; optimal treatments; oral immunotherapy; phase 2 study; research clinical testing; respiratory; safety outcomes; screening; side effect; soy; success

Project Summary The incidence and prevalence of food allergies is rising in children and adults, with peanut and tree nut being the most common food allergens. Current oral immunotherapy (OIT) protocols to desensitize patients to culprit allergens are associated with side effects that affect compliance and efficacy of OIT. More than 30% of patients with food allergies are allergic to more than one food. Safer OIT protocols that minimize side effects while improving challenge thresholds to multiple allergens are needed to be able to address this food allergy epidemic. To address these challenges, we propose a multi-site phase 2 clinical study in children and adults with peanut and tree nut allergies, using Omalizumab. Omalizumab is an anti-IgE monoclonal antibody which decreases free IgE in the blood and on mast cells and basophils, to minimize allergic inflammation. We hypothesize that omalizumab pre-treatment followed by low dose maintenance therapy of multi-food OIT will minimize side effects while increasing the challenge thresholds for multi-food allergic patients. Our approach is to design a randomized, controlled Phase 2 study with two arms: Omalizumab plus low dose multi-food OIT versus Omalizumab plus high dose multi-food OIT to contribute to the overall CoFAR objectives of improving safety and efficacy of OIT protocols. In implementing this study, we will create a comprehensive dataset of clinical outcomes from multiple sites within CoFAR and patient samples to understand mechanisms of treatment success. Our specific aims are 1) Test whether treatment of children and adults with Omalizumab and food OIT to peanut and walnut increases the ability to pass a food challenge to 2g of at least 2 allergens: peanut and walnut; 2) Determine whether treatment of children and adults in low vs high maintenance arms of multi food OIT with omalizumab is safer; and 3) Evaluate to what degree laboratory and clinical testing methods (i.e. endotypes and phenotypes of food allergic patients) are associated with safety and efficacy outcomes (in Specific Aims 1 and 2) in low dose versus high dose maintenance groups. If the aims of our proposal are met, we will determine the optimal maintenance dose protocol for desensitization to multiple foods with omalizumab that causes minimal side effects with optimal success rates.

项目概要 儿童和成人食物过敏的发生率和患病率正在上升，其中花生和坚果过敏 最常见的食物过敏原。目前的口服免疫疗法 (OIT) 方案可让患者对罪魁祸首脱敏 过敏原与影响 OIT 依从性和功效的副作用有关。超过30%的患者 食物过敏是指对一种以上的食物过敏。更安全的 OIT 协议可最大限度地减少副作用，同时 需要提高多种过敏原的挑战阈值才能解决这种食物过敏问题 流行性。为了应对这些挑战，我们提出了一项针对儿童和成人的多中心 2 期临床研究 对花生和坚果过敏，使用奥马珠单抗。奥马珠单抗是一种抗 IgE 单克隆抗体， 减少血液、肥大细胞和嗜碱性粒细胞中的游离 IgE，以最大程度地减少过敏性炎症。我们 假设奥马珠单抗预处理后进行低剂量多食物 OIT 维持治疗将 最大限度地减少副作用，同时提高多种食物过敏患者的挑战阈值。我们的方法是 设计一项具有两个组的随机对照 2 期研究：奥马珠单抗加低剂量多种食物 OIT 与奥马珠单抗加高剂量多种食物 OIT 相比，有助于改善 CoFAR 的总体目标 OIT 方案的安全性和有效性。在实施这项研究时，我们将创建一个全面的数据集 来自 CoFAR 和患者样本中多个位点的临床结果，以了解治疗机制 成功。我们的具体目标是 1) 测试奥马珠单抗和食品 OIT 是否可以治疗儿童和成人 花生和核桃可提高通过 2 克至少 2 种过敏原的食物挑战的能力：花生和 核桃; 2) 确定儿童和成人是否接受低维持组和高维持组的多种食物治疗 奥马珠单抗 OIT 更安全； 3) 评估实验室和临床检测方法的程度（即 食物过敏患者的内型和表型）与安全性和有效性结果相关（在 低剂量与高剂量维持组的具体目标 1 和 2)。如果我们提案的目标得以实现， 我们将确定奥马珠单抗对多种食物脱敏的最佳维持剂量方案 这会导致最小的副作用和最佳的成功率。