Safety and Tolerability of Shrimp Oral Immunotherapy in Shrimp Allergic Subjects

项目总结/摘要 在美国，超过600万人患有虾过敏症（SA）。意外暴露于 虾是急诊室就诊的主要原因， 50%的人与SA一起生活。避免仍然是这种终身疾病患者的唯一选择， 目前还没有关于SA治疗的公开研究。尽管它很突出，但我们没有有效的治疗方法， SA的预防策略，我们的理解远远落后于其他常见的过敏原 比如坚果牛奶和鸡蛋认识到这一关键需求，我们提供了一个计划的描述，以制定一个 1/2A期双盲随机安慰剂对照（DBRPC）虾口服免疫疗法（SOIT）试验。 尽管OIT与过敏不良事件有关，但奥马珠单抗是一种被证明可以减少过敏不良事件的生物疗法 严重过敏反应和增加食物过敏性疾病患者的耐受剂量。我们有 在以下研究中，有证据表明，在虾过敏患者中，SOIT给药递增时间缩短 SOIT联合和不联合奥马珠单抗。本研究的中心假设是，SOIT的发展 用奥马珠单抗预处理将导致对虾过敏的安全和可耐受的治疗。我们 具体目标1是为DBRPC多中心SOIT开发数据和协调中心， 在贝勒大学临床和转化研究所建立一个领导小组， 医学，将与参与研究中心合作，通过兼容的临床 试验数据管理系统。我们的具体目标2是生产SOIT安慰剂的食品 通过与所有参与研究中心建立供应商关系进行对照试验， Farfantepenaeus azteca虾产品和安慰剂虾味燕麦四种的组合， 双盲安慰剂对照食物激发和每日给药。机制研究将包括 测量体液应答（虾和表位特异性免疫球蛋白E和免疫球蛋白G4）， 效应细胞反应（速发型超敏反应皮肤点刺试验和嗜碱性粒细胞活化试验），Th 2 细胞因子应答和RNA测序与流式细胞术细胞验证。这项研究将指导 在1/2A期试验中，使用奥马珠单抗对虾产品进行适当给药，以最大限度地提高疗效和安全性。 研究和深入了解影响对虾成功脱敏的机制因素， 使用奥马珠单抗进行SOIT。最近完成的食物OIT功效试验为确定OIT的有效性打开了大门。 临床试验，以确定SOIT的安全性和耐受性。

PROJECT SUMMARY/ABSTRACT More than 6 million people in the United States are living with shrimp allergy (SA). Accidental exposure to shrimp is a major cause of visits to the emergency room, with life threatening anaphylaxis occurring in up to 50% of those living with SA. Avoidance remains the only option for patients with this lifelong disease and there are no published studies of treatment for SA. Despite its prominence, we have no effective treatment or prevention strategies for SA and our understanding lags considerably behind that of other common allergens like nuts, milk, and egg. Recognizing this critical need, we provide a description of the plan to develop a Phase 1/2A double-blind randomized placebo-controlled (DBRPC) shrimp oral immunotherapy (SOIT) trial. Although OIT is associated with allergic adverse events, omalizumab is a biologic therapy proven to decrease severe allergic reactions and increase tolerated doses in patients with food allergic disease. We have evidence that the time to escalation of dosing in SOIT is decreased in shrimp allergic patients in studies of SOIT with and without omalizumab. The central hypothesis of this study is that the development of a SOIT with pre-treatment with omalizumab will result in a safe and tolerable treatment for shrimp allergy. Our Specific Aim 1 is to develop a Data and Coordinating Center for a DBRPC multi-center SOIT through establishment of a lead team at the Institute for Clinical and Translational Research at Baylor College of Medicine which will work with the participating sites to capture data in real time through a compatible clinical trial data management system. Our Specific Aim 2 is to produce the food product for the SOIT placebo controlled trial through development of the supplier relationship with all participating research sites for the use of the Farfantepenaeus azteca shrimp product and placebo shrimp flavored oat four with vehicle selection for double-blind placebo controlled food challenges and daily dosing. Mechanistic studies will include measurement of humoral responses (shrimp and epitope specific immunoglobulin E and immunoglobulin G4), effector cell responses (immediate hypersensitivity skin prick testing and basophil activation testing), Th2 cytokine responses and RNA sequencing with flow cytometric cell validation. The proposed study will guide appropriate dosing of a shrimp product with omalizumab to maximize the efficacy and safety in a Phase 1/2A study and gain insight into mechanistic factors that affect the successful desensitization to shrimp through SOIT with omalizumab. The recent completion of efficacy trials for food OIT opens the door to a definitive clinical trial to determine the safety and tolerability of SOIT.