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

项目摘要 儿童和成人食物过敏的发病率和患病率正在上升，花生和坚果是 最常见的食物过敏原目前的口服免疫治疗（OIT）方案使患者对罪魁祸首脱敏 过敏原与影响OIT依从性和疗效的副作用有关。超过30%的患者 食物过敏的人对不止一种食物过敏。更安全的OIT方案，最大限度地减少副作用， 需要提高对多种过敏原的挑战阈值，以能够解决这种食物过敏 疫情为了应对这些挑战，我们建议在儿童和成人中进行多中心2期临床研究 花生和树坚果过敏的患者使用奥马珠单抗奥马珠单抗是一种抗IgE单克隆抗体， 降低血液中、肥大细胞和嗜碱性粒细胞上的游离IgE，以最大限度地减少过敏性炎症。我们 假设奥马珠单抗预治疗后低剂量多食物OIT维持治疗将 最大限度地减少副作用，同时提高多食物过敏患者的挑战阈值。我们的做法是 设计一项随机、对照、2期研究，分为两组：奥马珠单抗+低剂量多食物OIT 与奥马珠单抗+高剂量多食物OIT相比， 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， CoFAR和患者样本中多个研究中心的临床结局，以了解治疗机制 成功我们的具体目标是：1）测试Omalizumab和食物OIT治疗儿童和成人是否有效 花生和核桃增加了通过食物挑战的能力，至少有2个过敏原：花生和 核桃; 2）确定是否治疗儿童和成人在低vs高维护武器的多种食物 使用奥马珠单抗的OIT更安全;以及3）评估实验室和临床测试方法（即， 食物过敏患者的内型和表型）与安全性和有效性结果（在 特定目的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 副作用最小，成功率最高

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.