Precision Allergy Thresholds With Accurate immunotherapy Selection -Clinical Core

精确的过敏阈值和准确的免疫疗法选择 - 临床核心

• 批准号: 10635813
• 负责人: SCOTT H SICHERER
• 金额: $ 34.19万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-06 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10635813
• 关键词: 17 year old; Adult; Adverse event; Affect; Age; Allergy to peanuts; Anaphylaxis; Blood; Blood specimen; Child; Clinical; Clinical Data; Consumption; Data; Data Collection; Dietitian; Dose; Double-Blind Method; Eating; Enrollment; Ensure; Exposure to; FDA approved; Food Hypersensitivity; Foundations; Goals; Home; Hypersensitivity; Hypersensitivity skin testing; Immune; Immunotherapy; Ingestion; Interruption; Investigation; Maintenance; Measures; Molecular; Nurses; Oral; Outcome; Participant; Pathway interactions; Patients; Phenotype; Placebo Control; Population; Precision therapeutics; Procedures; Process; Proteins; Quality of life; Randomized; Reaction; Regimen; Research; Research Personnel; Research Project Grants; Safety; Sampling; Selection for Treatments; Severities; Symptoms; Testing; Therapeutic; Time; cost; desensitization; design; experience; food challenge; milligram; new therapeutic target; novel; novel therapeutics; oral immunotherapy; peanut butter; personalized care; personalized medicine; programs; response; side effect; success; transcriptomics; treatment program; treatment response; validation studies

SUMMARY - Clinical Core In the US, peanut allergy affects approximately 2.2% of children, 1.8% of adults, and can be potentially fatal, life-long, and has adverse impacts on quality of life. A commercial oral immunotherapy (OIT) for peanut allergy using low milligram doses has been FDA approved for children 4-17 years of age. This costly product was tested on children who reacted to a 143 mg cumulative dose of peanut or less (low threshold) during an oral food challenge (OFC) and aims for a maximum treatment dose of 300 mg, an amount similar to one large peanut kernel. Studies suggest that more than half of the peanut allergy population has a threshold above that which was used for testing the commercial peanut OIT product, a high threshold phenotype. Our current AADCRC has completed enrollment for a study evaluating OIT for this high threshold group where subjects are treated with home-measured peanut butter. Our preliminary results suggest that this is an easy-to-treat group with few side effects and high success rates, including persistent desensitization when therapy is interrupted. These observations inform a clinical need to determine Precise Allergy Thresholds With the purpose of Accurate immunotherapy Selection (PATHWAYS), which is the foundation for this Clinical Core. Determination of threshold allows personalized therapy for children with a low threshold to receive commercial OIT and those with a high threshold to receive home measured peanut at much lower expense. Importantly, we do not understand why some children have a difficult to treat phenotype, severe reactions, or a particular threshold, and we do not know why or how responses to immunotherapy differ across severity and threshold. Projects 1 (ROSETTA) and 2 (IMPALA) in our AADCRC will determine novel transcriptomic and immune processes across these phenotypes to characterize endotypes, elucidate mechanisms, inform precision care, and identify opportunities for novel therapeutics. Within the PATHWAYS Clinical Core, subjects who will benefit from threshold determination for clinical purposes will undergo double-blind, placebo-controlled OFCs with skin testing and serial blood sampling during the OFC for research purposes, along with determination of reaction severity and response to OIT treatment (given for clinical purposes off study). The PATHWAYS Clinical Core is designed to provide samples and data across the threshold and severity spectrum, for both primary and validation studies being undertaken in ROSETTA and IMPALA. We will build upon our stellar track record of successful biosampling in our current AADCRC, where we obtained blood at all time points in 97.5% of 310 OFCs at 100% of the required volume. The clinical data and biosamples from PATHWAYS will fuel the novel investigations of the ROSETTA and IMPALA research projects. Our integrated program will enrich mechanistic understandings, advance personalized medicine, and identify new therapeutic targets.

摘要 - 临床核心 在美国，花生过敏影响约2.2％的儿童，1.8％的成年人，可能是致命的， 终身，对生活质量产生不利影响。花生过敏的商业口服免疫疗法（OIT） 使用低毫克剂量已获得4-17岁儿童的FDA批准。这个昂贵的产品是 对对143毫克累积剂量花生或更少（低阈值）反应的儿童进行了测试 食品挑战（OFC），目的是最高治疗剂量为300 mg，类似于一个大的剂量 花生内核。研究表明，超过一半的花生过敏种群具有高于此的阈值 用于测试商业花生OIT产品，这是高阈值表型。我们的目前 AADCRC已完成评估该高阈值组的研究的研究，该阈值是受试者是 用家庭测量的花生酱处理。我们的初步结果表明这是一个易于治疗的组 几乎没有副作用和高成功率，包括当治疗中断时持续脱敏。 这些观察结果为确定精确过敏阈值的临床需要，目的 准确的免疫疗法选择（途径），这是该临床核心的基础。决心 阈值允许针对阈值低的儿童进行个性化治疗，可以接受商业OIT和那些 阈值高，以低得多的费用接收房屋测量的花生。重要的是，我们没有 了解为什么有些孩子难以治疗表型，严重的反应或特定阈值 而且我们不知道为什么在严重程度和阈值中对免疫疗法的反应有所不同。项目1 我们AADCRC中（Rosetta）和2（Impala）将确定新的转录组和免疫过程 在这些表型中，以表征内型，阐明机制，为精确护理提供信息，并确定 新型治疗学的机会。在临床核心的路径内，将从中受益的受试者 用于临床目的的阈值确定将经历双盲，安慰剂对照的OFC与皮肤 用于研究目的的OFC期间的测试和连续抽样，并确定反应 严重性和对OIT治疗的反应（用于临床目的而给予研究）。途径临床核心是 旨在为初级和 在Rosetta和Impala进行了验证研究。我们将基于我们出色的往绩记录 在我们当前的AADCRC中成功的生物采样，我们在310的97.5％的所有时间点都获得了血液 OFC处于所需量的100％。途径的临床数据和生物样本将为新颖 Rosetta和Impala研究项目的调查。我们的集成程序将丰富机械 理解，推进个性化医学并确定新的治疗靶点。