A randomized, double blind, placebo controlled, phase 2 study testing the use of combination multi-allergen food desensitization with dupilumab or omalizumab in multi-food allergic individuals

一项随机、双盲、安慰剂对照 2 期研究，测试在多种食物过敏个体中使用多过敏原食物脱敏联合 dupilumab 或 omalizumab

• 批准号: 10092906
• 负责人: R. Sharon Chinthrajah
• 金额: $ 18.83万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10092906
• 关键词: Accident and Emergency department; Adult; Adverse event; Adverse reactions; Aftercare; Allergens; Allergic; Allergic Disease; Allergy to peanuts; Anaphylaxis; Antibodies; Asthma; B-Lymphocytes; Basophils; Biopsy; Blood; Blood Cells; Blood Tests; Cessation of life; Child; Clinical; Clonal Expansion; Data; Data Analyses; Development; Diagnosis; Disease; Dose; Double-Blind Method; Event; Exhibits; Food; Food Hypersensitivity; Functional disorder; Genomics; Goals; High-Throughput DNA Sequencing; Hospitals; Human; Hypersensitivity; Immune; Immune response; Immune system; Immunologic Monitoring; Immunophenotyping; Immunotherapy; Individual; Ingestion; Interleukin 4 Receptor; Laboratories; Maintenance; Measurement; Measures; Methods; Monitor; Nature; Nuts; Oral; Participant; Patients; Phase; Phase II Clinical Trials; Phenotype; Pilot Projects; Placebos; Population; Prediction of Response to Therapy; Protocols documentation; Randomized; Regimen; Regulatory T-Lymphocyte; Research; Research Personnel; Resources; Risk; Safety; Sampling; Serology; Severities; Site; Specimen; Sum; Surveys; T-Lymphocyte; Testing; Tissues; Treatment Protocols; Trees; allergic response; analytical method; anti-IgE; clinical predictors; desensitization; effective therapy; experience; food allergen; food challenge; improved; individual patient; individualized medicine; innovation; multidisciplinary; novel strategies; omalizumab; oral immunotherapy; patient response; peripheral blood; phase 2 study; predictive marker; success; treatment response

PROJECT SUMMARY   Food allergies (FAs) are a world-­wide problem, and allergies to multiple foods are particularly problematic. In  the U.S., ingestion of offending food allergens is the most common cause of anaphylaxis seen in hospital  emergency departments (EDs), and it is estimated that ~30,000 food-­induced anaphylactic events are seen in  U.S. EDs each year;? sadly, ~200 of these events prove fatal. Peanuts or tree nuts cause the majority of these  deaths, and a recent survey in the U.S. found that 1.4% of the population is allergic to peanuts or tree nuts and  ~30% of patients with FAs have allergies to multiple foods. In peanut allergy (PA), landmark studies by A.  Wesley Burks and colleagues have shown that children can be desensitized to peanut via an oral  immunotherapy (OIT) protocol. We have replicated these results in adults and children, and also have carried  out a pilot study showing that FA patients can be desensitized to multiple food allergens simultaneously (i.e.,  multi-­OIT). Moreover, we found that there were fewer adverse events in the build-­up phase of multi-­OIT if  patients received the anti-­IgE antibody, omalizumab, concomitantly with multi-­OIT.      In an effort to improve understanding of the systemic and local (i.e., GI) immune responses that underlie PA  and therapeutic responses to OIT, we are currently conducting a placebo-­controlled, randomized, phase 2  clinical trial of OIT in 120 children and adults with PA (the POISED trial), and are applying state-­of-­the-­art  human immune monitoring methods to analyze blood and GI tissue specimens of participants in that study. In  this AADCRC U19 renewal application, we propose to conduct a pilot, placebo-­controlled, randomized, phase  2 clinical trial of OIT with or without omalizumab or the anti-­IL-­4Rα antibody, dupilumab, in children and adults  with multiple FAs (multi-­FAs). We propose to measure a broad range of blood and GI biopsy cellular findings,  as well as serologic and clinical findings, in longitudinal samples from multi-­FA participants undergoing the trial,  as well as from appropriate control participants (i.e., multi-­FA participants who are not treated, healthy controls,  and atopic controls without FA). We will use these data to define how key systemic or GI tissue immune  parameters change during multi-­OIT, and which are most predictive of the nature and durability of patient  responses to this therapy. Specifically, we will evaluate whether there are blood-­ or GI tissue-­derived  biomarkers that predict therapeutic responses to individual allergens, or to all allergens, in multi-­OIT. In  addition, we will seek to identify immune monitoring parameters, including findings derived from analyses of  basophil phenotype and function that can be rapidly performed in a clinical laboratory using small amounts of  blood, that could be used to predict the clinical reactivity to offending allergens in multi-­FA subjects, to improve  the safety and efficacy of OIT protocols, and/or to tailor the OIT protocol to each individual subject.

项目总结