Evaluating the role of allergen dose and duration in the safety and efficacy of multi-allergen oral immunotherapy with Omalizumab

评估过敏原剂量和持续时间在奥马珠单抗多过敏原口服免疫治疗的安全性和有效性中的作用

• 批准号: 10576846
• 负责人: R. Sharon Chinthrajah
• 金额: $ 23.5万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10576846
• 关键词: Address; Adult; Adverse event; Affect; Age; Allergens; Allergic; Allergic Reaction; Allergic inflammation; Anaphylaxis; Basophils; Biological Assay; Blood; Blood specimen; Bystander Effect; Cashew nut; Child; Clinical; Clinical Research; Complex; Data; Data Set; Dose; Dropout; Epidemic; Fabaceae; Food; Food Hypersensitivity; Frequencies; GTP-Binding Proteins; Hazelnuts; Hypersensitivity; Hypersensitivity skin testing; IgE; IgG4; Immune response; Immunotherapy; Incidence; Individual; Juglans; Laboratories; Leadership; Literature; Maintenance; Maintenance Therapy; Measurement; Methods; Mission; Monoclonal Antibodies; Multicenter Studies; Nut Hypersensitivity; Nuts; Outcome; Participant; Patients; Pecans; Persons; Phase; Phenotype; Pistachio Nuts; Prevalence; Proteins; Protocols documentation; Publishing; Randomized; Regimen; Respiratory Signs and Symptoms; Risk; Role; Safety; Sampling; Site; Skin; Symptoms; Testing; Time; Trees; anti-IgE; arm; clinical phenotype; desensitization; design; effective therapy; efficacy outcomes; experience; food allergen; food challenge; gastrointestinal; immunotherapy trials; improved; mast cell; omalizumab; optimal treatments; oral immunotherapy; phase 2 study; research clinical testing; respiratory; safety outcomes; screening; side effect; soy; success

Project Summary The incidence and prevalence of food allergies is rising in children and adults, with peanut and tree nut being the most common food allergens. Current oral immunotherapy (OIT) protocols to desensitize patients to culprit allergens are associated with side effects that affect compliance and efficacy of OIT. More than 30% of patients with food allergies are allergic to more than one food. Safer OIT protocols that minimize side effects while improving challenge thresholds to multiple allergens are needed to be able to address this food allergy epidemic. To address these challenges, we propose a multi-site phase 2 clinical study in children and adults with peanut and tree nut allergies, using Omalizumab. Omalizumab is an anti-IgE monoclonal antibody which decreases free IgE in the blood and on mast cells and basophils, to minimize allergic inflammation. We hypothesize that omalizumab pre-treatment followed by low dose maintenance therapy of multi-food OIT will minimize side effects while increasing the challenge thresholds for multi-food allergic patients. Our approach is to design a randomized, controlled Phase 2 study with two arms: Omalizumab plus low dose multi-food OIT versus Omalizumab plus high dose multi-food OIT to contribute to the overall CoFAR objectives of improving safety and efficacy of OIT protocols. In implementing this study, we will create a comprehensive dataset of clinical outcomes from multiple sites within CoFAR and patient samples to understand mechanisms of treatment success. Our specific aims are 1) Test whether treatment of children and adults with Omalizumab and food OIT to peanut and walnut increases the ability to pass a food challenge to 2g of at least 2 allergens: peanut and walnut; 2) Determine whether treatment of children and adults in low vs high maintenance arms of multi food OIT with omalizumab is safer; and 3) Evaluate to what degree laboratory and clinical testing methods (i.e. endotypes and phenotypes of food allergic patients) are associated with safety and efficacy outcomes (in Specific Aims 1 and 2) in low dose versus high dose maintenance groups. If the aims of our proposal are met, we will determine the optimal maintenance dose protocol for desensitization to multiple foods with omalizumab that causes minimal side effects with optimal success rates.

项目摘要 食物过敏的发病率和患病率在儿童和成人中升高，花生和螺母是 最常见的食物过敏原。目前的口服免疫疗法（OIT）方案使患者脱敏 过敏原与影响OIT合规性和功效的副作用有关。超过30％的患者 食物过敏对多种食物过敏。更安全的OIT协议可最大程度地减少副作用 需要提高对多种过敏原的挑战阈值才能解决这种食物过敏 流行性。为了应对这些挑战，我们提出了一项在儿童和成人的多站点2期临床研究 使用花生和树坚果过敏，使用Omalizumab。 Omalizumab是一种抗IgE单克隆抗体 减少血液中的自由IgE，肥大细胞和嗜碱性粒细胞，以最大程度地减少过敏性炎症。我们 假设Omalizumab预处理，然后进行低剂量维持治疗多食品OIT 最小化副作用，同时增加多食物过敏患者的挑战阈值。我们的方法是 设计一项随机，受控的2阶段研究，其中有两个臂：omalizumab和低剂量多食OIT 与Omalizumab和高剂量多食品OIT相比，为改进的总体Cofar目标做出了贡献 OIT方案的安全性和功效。在实施这项研究时，我们将创建一个全面的数据集 来自Cofar和患者样本中多个地点的临床结果，以了解治疗机制 成功。我们的具体目的是1）测试是否治疗子宫单抗和食物OIT的儿童和成人是否治疗 花生和胡桃木增加了将食物挑战通过2G至少2种过敏原的能力：花生和 核桃; 2）确定在低和高维护多食物中对儿童和成人的治疗是否 OIT与Omalizumab更安全； 3）评估实验室和临床测试方法的程度（即 食物过敏患者的内型和表型）与安全性和功效结果有关（在 具体目的1和2）在低剂量与高剂量维持组中。如果满足我们的提案的目的， 我们将确定脱敏到多种食物的最佳维持剂量方案 这会导致最小的副作用，并获得最佳的成功率。

项目成果

Advances and potential of omics studies for understanding the development of food allergy.

• DOI: 10.3389/falgy.2023.1149008
• 发表时间: 2023
• 期刊: FRONTIERS IN ALLERGY
• 作者: Sindher, Sayantani B.;Chin, Andrew R.;Aghaeepour, Nima;Prince, Lawrence;Maecker, Holden;Shaw, Gary M.;Stevenson, David K.;Nadeau, Kari C.;Snyder, Michael;Khatri, Purvesh;Boyd, Scott D.;Winn, Virginia D.;Angst, Martin S.;Chinthrajah, R. Sharon
• 通讯作者: Chinthrajah, R. Sharon

Current insights: a systemic review of therapeutic options for peanut allergy.

• DOI: 10.1097/aci.0000000000000824
• 发表时间: 2022-06-01
• 期刊: Current opinion in allergy and clinical immunology
• 影响因子: 2.8

Phase 2, randomized multi oral immunotherapy with omalizumab 'real life' study.

第 2 期，使用奥马珠单抗的随机多口服免疫疗法“现实生活”研究。

• DOI: 10.1111/all.15217
• 发表时间: 2022
• 期刊: Allergy
• 影响因子: 12.4
• 作者: Sindher,SayantaniB;Kumar,Divya;Cao,Shu;Purington,Natasha;Long,Andrew;Sampath,Vanitha;Zedeck,StaceyS;Woch,MargaretA;Garcia-Lloret,Maria;Chinthrajah,RebeccaSharon
• 通讯作者: Chinthrajah,RebeccaSharon