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，花生过敏影响了大约2.2%的儿童和1.8%的成年人，并可能是致命的， 终生的，并对生活质量产生不利影响。一种治疗花生过敏的商业化口服免疫疗法 FDA已批准对4-17岁的儿童使用低毫克剂量的药物。这款昂贵的产品 在口服过程中对143毫克或更少(低阈值)花生有反应的儿童进行了测试 食物挑战(OFC)，目标是最大治疗剂量为300毫克，相当于一个大剂量 花生仁。研究表明，超过一半的花生过敏人群的阈值超过了这一标准。 用于检测商品花生油产品的高门槛表型。我们目前的情况 AADCRC已经完成了一项研究的登记，该研究评估了这一高门槛群体的OIT，其中受试者是 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，包括在治疗中断时持续脱敏。 这些观察结果提示临床需要确定准确的过敏阈值，目的是 准确的免疫治疗选择(途径)，这是这一临床核心的基础。测定法 Of Threshold允许对门槛低的儿童进行个性化治疗，以获得商业OIT和 门槛很高，可以以低得多的费用获得家庭测量的花生。重要的是，我们没有 理解为什么一些儿童有难以治疗的表型、严重的反应或特定的阈值， 我们不知道为什么或如何在不同的严重程度和阈值免疫治疗的反应不同。项目1 (Rosetta)和2(Impala)将决定新的转录和免疫过程 通过这些表型来表征内型，阐明机制，提供精确护理信息，并识别 新疗法的机会。在路径临床核心，受试者将受益于 临床阈值的确定将接受双盲、安慰剂对照的皮肤OFC 为研究目的，在OFC期间进行检测和连续采血，以及确定反应 OIT治疗的严重程度和反应(在研究之外用于临床目的)。临床路径的核心是 旨在提供跨阈值和严重性范围的样本和数据，用于主要和 正在罗塞塔和英帕拉进行验证研究。我们将在我们出色的记录基础上再接再厉 在我们目前的AADCRC中成功地进行了生物采样，在310个时间点中，我们在所有时间点都获得了97.5%的血液 以所需数量的100%进行离岸控制。临床数据和来自路径的生物样本将为这部小说提供动力 对罗塞塔和黑斑羚研究项目的调查。我们的综合计划将丰富机械 认识，推进个体化用药，确定新的治疗靶点。