Safety and Tolerability of Shrimp Oral Immunotherapy in Shrimp Allergic Subjects

虾过敏受试者口服虾免疫疗法的安全性和耐受性

基本信息

批准号：
10163490
负责人：
CARLA M. DAVIS
金额：
$ 31.26万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-15 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10163490
关键词：
Accident and Emergency department Adult Adverse event Affect Aftercare Allergens Allergic Allergic Disease Allergic Reaction Anaphylaxis Avena sativa Basophils Biological Response Modifier Therapy Case Report Form Cells Childhood Clinical Clinical Research Clinical Trials Clinical trial protocol document Data Data Coordinating Center Data Management Resources Databases Densitometry Development Dictyoptera Disease Dose Double-Blind Method Effector Cell Emergency Situation Epitopes Exposure to Flavoring Food Food Hypersensitivity Human Resources Hypersensitivity IgE Immediate hypersensitivity Immunoglobulins Immunologics Institutes Lead Life Manuals Mass Spectrum Analysis Measurement Measures Mediating Medicine Milk Mission Multi-Institutional Clinical Trial Nuts Pathogenesis Patients Phase Placebos Population Preparation Prevention strategy Probability Procedures Process Proteins Public Health Publishing Randomized Research Risk Role Safety Serum Shrimp Site Standardization Test Result Testing Therapeutic Intervention Time Translational Research United States United States National Institutes of Health Validation Visit Western Blotting Work allergic response appropriate dose base clinical phenotype clinical research site college cross reactivity cytokine data management data sharing desensitization effective therapy efficacy evaluation efficacy trial egg food challenge immunotherapy clinical trials immunotherapy trials insight novel omalizumab oral immunotherapy placebo controlled trial pyroglyphid response safety assessment sample collection skin prick test tool development transcriptome sequencing treatment strategy

项目摘要

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.

项目摘要/摘要美国有超过600万人患有虾过敏（SA）。意外暴露虾是访问急诊室的主要原因，在与SA一起生活的人中有50％。避免仍然是这种终身疾病患者的唯一选择和没有关于SA治疗的已发表研究。尽管它突出，但我们没有有效的治疗或 SA的预防策略和我们的理解滞后落后于其他常见的过敏原像坚果，牛奶和鸡蛋一样。认识到这种批判性需求，我们提供了制定计划的计划的描述阶段1/2a双盲随机安慰剂对照（DBRPC）虾口服免疫疗法（SOIT）试验。尽管OIT与过敏性不良事件有关，但Omalizumab是一种生物疗法，证明是一种降低的食物过敏性疾病患者的严重过敏反应并增加耐受剂量。我们有虾过敏患者在研究中降低了soIT的升级时间的证据有或没有粘胶的肥皂。这项研究的核心假设是SOIT的发展在使用omalizumab的预处理后，将对虾过敏产生安全可耐受的治疗方法。我们的特定目的1是为DBRPC多中心SOIT开发数据和协调中心在贝勒学院的临床与翻译研究所建立领导团队医学将与参与站点一起使用，通过兼容的临床实时捕获数据试验数据管理系统。我们的特定目的2是为Soit安慰剂生产食品通过与所有参与研究站点建立供应商关系的控制试验 Farfantepenaeus azteca虾产品和安慰剂虾调味的燕麦四，可用于车辆的选择双盲安慰剂控制的食物挑战和每日给药。机械研究将包括测量体液反应（虾和表位特异性免疫球蛋白E和免疫球蛋白G4），G4）效应细胞反应（立即进行超敏性皮肤刺测试和嗜碱性激活测试），TH2 通过流式细胞术细胞验证的细胞因子反应和RNA测序。拟议的研究将指导适当剂量用omalizumab的虾产品，以最大化1/2a阶段的功效和安全性研究并了解影响成功脱敏虾的机理因素与omalizumab soit。最近完成的食品效力试验已为确定性打开了大门临床试验以确定SOIT的安全性和耐受性。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

DOI：
10.1111/all.15363
发表时间：
2022-09
期刊：
ALLERGY
影响因子：
12.4
作者：
Anvari, Sara;Brunner, Shea;Tuano, Karen S.;Bin Su, Brenda;Karnaneedi, Shaymaviswanathan;Lopata, Andreas L.;Davis, Carla M.
通讯作者：
Davis, Carla M.

Immune response evolution in peanut epicutaneous immunotherapy for peanut-allergic children.

花生过敏儿童花生表皮免疫治疗的免疫反应演变。

DOI：
10.1111/all.15709
发表时间：
2023
期刊：
Allergy
影响因子：
12.4
作者：
Bastin,Marie;Carr,WarnerW;Davis,CarlaM;Fleischer,DavidM;Lieberman,JayA;Mustafa,SShahzad;Helleputte,Thibault;Bois,Timothée;Campbell,DianneE;Green,ToddD;Greenhawt,Matthew
通讯作者：
Greenhawt,Matthew

Shrimp-allergic patients in a multi-food oral immunotherapy trial.

DOI：
10.1111/pai.13679
发表时间：
2022-01
期刊：
PEDIATRIC ALLERGY AND IMMUNOLOGY
影响因子：
4.4
作者：
Nguyen, Diem-Tran I.;Sindher, Sayantani B.;Chinthrajah, R. Sharon;Nadeau, Kari;Davis, Carla M.
通讯作者：
Davis, Carla M.

Diversity, Disparities, and the Allergy Immunology Pipeline.