Novel, Non-InvasiveImaging of Eosinophil-Related Inflammation Throughout the Esophagus in Patients withEosinophilic Esophagitis

嗜酸性粒细胞性食管炎患者食管内嗜酸性粒细胞相关炎症的新型非侵入性成像

• 批准号: 10017684
• 负责人: Gerald J Gleich
• 金额: $ 30万
• 依托单位: NEXEOS DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10017684
• 关键词: Adult; Affect; Age; Area; Binding; Biopsy; Child; Clinical; Clinical Research; Clinical Trials; Coagulation Process; Cystitis; Cytoplasmic Granules; Deglutition; Deglutition Disorders; Detection; Development; Diagnosis; Diagnostic; Diagnostic Imaging; Diagnostic Procedure; Disease; Disease Management; Endoscopic Biopsy; Endoscopy; Enrollment; Eosinophilic Colitis; Eosinophilic Esophagitis; Esophageal Diseases; Esophageal Stenosis; Esophageal Tissue; Esophagitis; Esophagogastroduodenoscopy; Esophagus; Fibrosis; Gastroenteritis; Gastrointestinal Diseases; Goals; Hematoxylin and Eosin Staining Method; Heparin; Human; Image; Immune; Immunofluorescence Immunologic; Immunologist; Infiltration; Inflammation; Informed Consent; Investigation; Label; Laboratories; Liquid substance; Medical; Medical Imaging; Medical center; Methods; Microscopy; Oral; Oral Administration; Oral Diagnosis; Pain; Pamphlets; Participant; Patients; Phase; Prevalence; Procedures; Proteins; Radiolabeled; Research Personnel; Rights; Role; Rupture; Safety; Scanning; Site; Small Business Innovation Research Grant; Specimen; Stains; Symptoms; Technetium; Technetium 99m; Testing; Tissue Stains; Tissues; Universities; Utah; Visit; Visual; Water; X-Ray Computed Tomography; chronic inflammatory disease; chronic rhinosinusitis; clinical development; commercialization; cost; eosinophil; eosinophilic asthma; eosinophilic inflammation; experimental study; imaging agent; imaging biomarker; novel; open label; single photon emission computed tomography; standard of care; uptake

ABSTRACT Eosinophilic Esophagitis (EoE) is a chronic inflammatory disease of the esophagus, characterized by eosinophil infiltration into the esophagus, resulting in pain, dysphagia and, if untreated, eventual esophageal fibrosis and stricture. EoE prevalence in the U.S. is approximately 57/100,000 including patients of all ages, and current evidence suggests that the overall prevalence of EoE continues to increase.. There is a great unmet medical need for a new EoE diagnostic method. The current standard-of-care method involves endoscopy plus biopsies of the esophagus which are difficult, costly, and invasive, creating barriers to both diagnosis and ongoing disease management. As a result, EoE tends to be underdiagnosed and patients’ symptoms and disease less optimally managed. NDX33-o is a novel, non-invasive medical imaging agent that is optimal for identifying eosinophilic inflammation in EoE patients and can be used to image and diagnose patients with EoE in a less invasive manner and with a higher accuracy than today’s current approach. Preliminary clinical results, in a limited number of patients have shown that NDX33-o can detect areas of inflammation in esophagi of EoE patients supporting NDX33-o as a novel detection method for EoE. This project will assess NDX33-o detection of EoE in a larger number of EoE patients. Phase 1 of the project will focus on planning activities for the clinical trial that will be conducted in phase 2. In Phase 1, NexEos Diagnostics, Inc. will complete all planning activities including development of manufacturing methods for a NDX33-o kit for use in the radiopharmacy. NexEos will also seek IND approval from the FDA for the administration of NDX33-o to human participants in the Phase 2 clinical study. After receiving IND approval, Phase 2 of the project will be initiated with a clinical study of 180 patients suffering from EoE symptoms or dysphagia who will be enrolled at the University of Utah. All participants will receive the same treatment – they will first be diagnosed by oral administration of NDX33-o and medical imaging followed several days later, by diagnosis with the current standard-of-care, endoscopy and biopsy. NDX33-o will be evaluated for its accuracy and sensitivity for detecting EoE compared to standard-of-care. Moreover, the safety profile of NDX33-o will be evaluated in all administered patients. Successful completion of the proposed clinical trial will significantly contribute to the development of NDX33-o as an imaging marker for eosinophil-related inflammation in EoE patients, and subsequently for the potential diagnosis of other human eosinophil-associated diseases.

抽象的 嗜酸性粒细胞性食管炎（EoE）是一种食管慢性炎症性疾病，以嗜酸性粒细胞增多为特征。 浸润到食管，导致疼痛、吞咽困难，如果不治疗，最终会导致食管纤维化和 美国 EoE 患病率约为 57/100,000，包括所有年龄段的患者，目前 有证据表明 EoE 的总体患病率持续增加。 需要新的 EoE 诊断方法 目前的标准护理方法包括内窥镜检查加活检。 食管的病变是困难的、昂贵的和侵入性的，给诊断和持续的疾病造成了障碍 因此，EoE 往往诊断不足，患者的症状和疾病也不太理想。 管理。 NDX33-o 是一种新型非侵入性医学成像剂，最适合识别嗜酸性炎症 EoE 患者，可用于以侵入性较小的方式对 EoE 患者进行成像和诊断 在有限数量的患者中，比目前的初步临床结果具有更高的准确性。 表明 NDX33-o 可以检测 EoE 患者食管中的炎症区域，支持 NDX33-o 作为 EoE 的新颖检测方法。 该项目将评估 NDX33-o 在项目第一阶段对大量 EoE 患者的 EoE 检测。 将重点关注第 2 阶段进行的临床试验的规划活动。在第 1 阶段，NexEos Diagnostics, Inc. 将完成所有规划活动，包括开发制造方法 用于放射性药物的 NDX33-o 试剂盒还将寻求 FDA 的 IND 批准。 在 2 期临床研究中向人类参与者施用 NDX33-o。 获得 IND 批准后，该项目的第二阶段将启动，对 180 名患有此病的患者进行临床研究 患有 EoE 症状或吞咽困难的人将被犹他大学录取的所有参与者都将收到。 相同的治疗方法——首先通过口服 NDX33-o 进行诊断，然后进行医学影像检查 几天后，通过当前的护理标准、内窥镜检查和活检进行诊断。 将评估 NDX33-o 与护理标准相比检测 EoE 的准确性和灵敏度。 此外，还将在所有接受治疗的患者中评估 NDX33-o 的安全性。 拟议临床试验的成功完成将极大地促进NDX33-o的开发 作为 EoE 患者嗜酸性粒细胞相关炎症的影像学标志物，以及随后潜在的 其他人类嗜酸性粒细胞相关疾病的诊断。