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.

总结-临床核心 在美国，花生过敏影响约2.2%的儿童，1.8%的成人，并可能是致命的， 终身，并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） 使用低毫克剂量已经被FDA批准用于4-17岁的儿童。这个昂贵的产品是 在口服期间对143 mg累积剂量的花生或更少（低阈值）有反应的儿童中进行测试 食物挑战（OFC），目标是300 mg的最大治疗剂量，这一剂量类似于一个大的 花生仁研究表明，超过一半的花生过敏人群的阈值高于此 其用于测试商业花生OIT产品，高阈值表型。我们目前 AADCRC已经完成了一项研究的入组，该研究评价了该高阈值组的OIT，其中受试者 用自制的花生酱处理我们的初步结果表明这是一个容易治疗的群体 副作用少，成功率高，包括治疗中断时的持续脱敏。 这些观察结果告知临床需要确定精确的过敏反应阈值， 准确的免疫治疗选择（路径），这是本临床核心的基础。测定 阈值允许对接受商业OIT的低阈值儿童进行个性化治疗， 以低得多的费用获得家庭测量的花生的门槛很高。重要的是，我们不 理解为什么有些孩子有难以治疗的表型，严重的反应，或特定的阈值， 我们不知道为什么或如何对免疫治疗的反应在严重程度和阈值上有所不同。项目1 （ROSETTA）和2（IMPALA）在我们的AADCRC中的表达将决定新的转录组学和免疫过程 在这些表型中表征内型，阐明机制，告知精确护理，并识别 新疗法的机会。在PATHWAYS临床核心研究中，受益于 用于临床目的的阈值确定将进行双盲、安慰剂对照的OFC， 在OFC期间进行测试和连续采血以用于研究目的，沿着反应测定 严重程度和对OIT治疗的反应（出于临床目的，在研究之外提供）。Pathway临床核心是 旨在为初级和次级疾病提供阈值和严重程度范围内的样本和数据， 正在ROSETTA和IMPALA进行验证研究。我们将继续努力， 在我们目前的AADCRC中，我们在所有时间点获得了310例患者中97.5%的血液， OFC达到所需体积的100%。来自PATHWAYS的临床数据和生物样本将为这部小说提供动力 ROSETTA和IMPALA研究项目的调查。我们的综合计划将丰富机械 理解，推进个性化医疗，并确定新的治疗靶点。