Safety and Tolerability of Shrimp Oral Immunotherapy in Shrimp Allergic Subjects

点击翻译按钮获取中文摘要

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.