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.

摘要 嗜酸性食管炎（EoE）是一种以嗜酸性粒细胞增多为特征的慢性食管炎性疾病 渗透到食管中，导致疼痛、吞咽困难，如果不治疗，最终导致食管纤维化， 狭窄美国的EoE患病率约为57/100，000，包括所有年龄段的患者， 有证据表明，EoE的总体患病率继续上升。有一个伟大的未满足的医疗 需要新的EoE诊断方法。目前的标准治疗方法包括内窥镜检查加活检 困难、昂贵和侵入性的食管，对诊断和正在进行的疾病造成障碍 管理因此，EoE往往诊断不足，患者的症状和疾病不太理想 管理。 NDX 33-o是一种新型的非侵入性医学成像剂，最适合用于识别嗜酸性粒细胞炎症 在EoE患者中，可用于以微创方式对EoE患者进行成像和诊断， 比目前的方法更精确。初步临床结果，在有限数量的患者中， 显示NDX 33-o可以检测EoE患者食管中的炎症区域，支持NDX 33-o作为 EoE的新检测方法。 该项目将评估NDX 33-o在大量EoE患者中的EoE检测。项目第1阶段 将专注于计划将在第2阶段进行的临床试验活动。在第1阶段，NexEos 诊断公司将完成所有规划活动，包括开发制造方法， NDX 33-o试剂盒用于放射性药物学。NexEos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NDX 33-o。 在获得IND批准后，该项目的第2阶段将启动180名患者的临床研究， 患有EoE症状或吞咽困难的患者，他们将被犹他州大学录取。所有参加者将获得 相同的治疗-他们将首先通过口服NDX 33-o和随后的医学成像进行诊断 几天后，通过目前的标准护理、内窥镜检查和活检进行诊断。 与标准治疗相比，将评价NDX 33-o检测EoE的准确度和灵敏度。 此外，将在所有施用的患者中评价NDX 33-o的安全性特征。 成功完成拟议的临床试验将大大有助于NDX 33-o的开发 作为EoE患者中嗜酸性粒细胞相关炎症的成像标志物， 其他人类嗜酸性粒细胞相关疾病的诊断。