Commercialization Readiness Pilot (CRP) program support for: Direct-from-specimen identification of pathogens common in endocarditis

商业化准备试点 (CRP) 计划支持： 直接从样本鉴定心内膜炎常见病原体

• 批准号: 10758417
• 负责人: Alon Singer
• 金额: $ 100万
• 依托单位: HELIXBIND, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-20 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10758417
• 关键词: Acceleration; Address; Affect; Antibiotic Resistance; Antimicrobial Resistance; Automation; Autopsy; Award; Bacteria; Biological; Biological Assay; Biopsy; Blinded; Blood; Blood Circulation; Breakthrough device; Cardiac; Cardiology; Caring; Clinic; Clinical; Clinical Microbiology; Clinical Research; Clinical assessments; Communicable Diseases; Coxiella burnetii; Development; Diagnosis; Diagnostic; Disease; Disease Progression; Early identification; Economic Burden; Endocarditis; Engineering; Ensure; Evaluation; Exhibits; Feedback; Freeze Drying; Grant; Heart; Hospitalization; Hospitals; Hour; Impairment; Infection; Infective endocarditis; Intervention; Leadership; Lesion; Life; Manuals; Marketing; Medical center; Methods; Morbidity - disease rate; National Institute of Allergy and Infectious Disease; Nature; Organism; Patient Care; Patient-Focused Outcomes; Patients; Performance; Phase; Quality of life; Readiness; Reagent; Resistance; Resistance development; Resolution; Risk; Sampling; Sensitivity and Specificity; Sepsis; Septicemia; Site; Small Business Innovation Research Grant; Specific qualifier value; Specificity; Specimen; Surface; Symptoms; Technology; Temperature; Testing; Time; Tissues; University Hospitals; Whole Blood; analytical method; antimicrobial; assay development; commercialization; commercialization readiness; design; diagnostic strategy; evidence base; experience; fungus; improved; improved outcome; instrument; interest; manufacture; manufacturing process; manufacturing scale-up; member; microbial; microorganism; mortality; novel; novel diagnostics; pathogen; pathogenic bacteria; pathogenic fungus; prevent; programs; standard of care; success; validation studies; verification and validation

PROJECT SUMMARY Infective Endocarditis (IE) occurs when bacteria or fungi adhere to the endocardial surface forming small lesions. This invasive disease is characterized by a mortality rate exceeding 25%, is associated with extended hospitalization, and often impairs the quality of life for those who survive. Early microbial diagnosis and antimicrobial intervention are crucial to improved patient outcomes and reduced hospitalization time. However, currently accepted diagnostic approaches still rely on primary blood culture, which exhibits long and variable turnaround times and can provide false-negative results. There is therefore a significant need for new diagnostic approaches that do not require culture and provide faster, more accurate results. To address this unmet need, HelixBind developed RaPID/IE, a fully automated sample-to-answer test which identifies and characterizes these infections directly from blood in ~3 hours, without cultures. Implemented on the RaPID (Resistance and Pathogen IDentification) platform and appropriate for placement throughout the hospital, RaPID/IE incorporates a broad test menu including both bacterial and fungal pathogens, as well as a marker of antimicrobial resistance. Crucially, the test is not compromised by prior antimicrobial treatment and provides species level detail with single CFUs/ml sensitivity, enabling selection of appropriate antimicrobials. Commercialization of RaPID/IE will provide timely identification and characterization of the invasive agent and thus enable intervention with targeted antimicrobial treatment. This is expected to result in improved patient outcomes and a reduction in the use of unnecessary antimicrobials, slowing the rise of antimicrobial resistance. HelixBind has met and exceeded all the Specific Aims defined in the Phase II SBIR. This included menu expansion to cover antibiotic resistance as well as pathogens associated with IE which cannot be recovered by clinical cultures, automation of the assay onto single-use disposables operated by a benchtop instrument, and testing of clinical specimens. Clinical results demonstrate a sensitivity and specificity of 92.7% and 98.8%, respectively. In addition, based on feedback from potential customers, the test menu was expanded further to include coverage of pathogens associated with conditions sharing symptoms with IE. The disposable and instrument were transitioned to manufacturing and extensive analytical testing was performed to ensure the assay meets specifications associated with regulatory and market requirements. In this CRP program, HelixBind will build on our success in Phase II to prepare for regulatory clearance and market launch. This includes (1) development of analytical methods, based on FDA feedback, required to successfully complete analytical and clinical validation studies; and (2) development of scalable manufacturing processes for certain reagent sets to ensure 12-month, room temperature stability, of tests cassettes, and (3) completion of an on-site analytical evaluation and blinded, clinical assessment study. Upon completion of this project, we will be well placed to initiate formal analytical and clinical studies for FDA clearance of RaPID/IE.

项目摘要 感染性心内膜炎（IE）发生时，细菌或真菌粘附在心内膜表面形成小病变。 这种侵袭性疾病的特点是死亡率超过25%，与扩展的 住院治疗，并往往损害那些幸存者的生活质量。早期微生物诊断和 抗菌干预对于改善患者预后和缩短住院时间至关重要。然而，在这方面， 目前接受的诊断方法仍然依赖于原代血培养， 周转时间，并可能提供假阴性结果。因此，对新的诊断方法的需求很大。 这些方法不需要培养，并提供更快，更准确的结果。 为了解决这一未满足的需求，HelixBind开发了RaPID/IE，这是一种全自动的样本到答案测试， 在约3小时内直接从血液中识别和表征这些感染，无需培养。日实施 RaPID（抗性和病原体鉴定）平台，适合在整个 医院，RaPID/IE结合了广泛的测试菜单，包括细菌和真菌病原体，以及 抗生素耐药性的标志。至关重要的是，测试不受先前抗菌治疗的影响， 提供物种级别的细节，具有单个CFU/ml灵敏度，从而能够选择适当的抗菌剂。 RaPID/IE的商业化将提供侵入性试剂的及时识别和表征， 从而能够用靶向抗菌治疗进行干预。预计这将改善患者 减少不必要的抗菌药物的使用，减缓抗菌药物耐药性的上升。 HelixBind已经达到并超过了第二阶段SBIR中定义的所有具体目标。此包含菜单 扩大范围，以涵盖抗生素耐药性以及与IE相关的病原体，这些病原体无法通过 临床培养物，通过台式仪器操作的一次性用品上的自动化测定，以及 检测临床标本。临床结果表明，敏感性和特异性分别为92.7%和98.8%， 分别此外，根据潜在客户的反馈，测试菜单进一步扩展， 包括与IE共有症状的病症相关的病原体的覆盖范围。一次性的和 仪器已过渡到生产阶段，并进行了广泛的分析测试，以确保 含量测定符合与法规和市场要求相关的质量标准。 在这个CRP项目中，HelixBind将在我们第二阶段成功的基础上为监管许可做准备， 市场推出。这包括：（1）根据FDA的反馈，开发分析方法， 成功完成分析和临床验证研究;（2）开发可扩展的生产 某些试剂组的工艺，以确保检测卡的12个月室温稳定性，以及（3） 完成现场分析评估和设盲临床评估研究。在完成此 项目，我们将有能力启动正式的分析和临床研究，以获得FDA对RaPID/IE的批准。