Transdermal Test for Active Tuberculosis

活动性结核病的透皮测试

• 批准号: 6403452
• 负责人: Carol A. Nacy
• 金额: $ 23.2万
• 依托单位: SEQUELLA, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2002-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6403452
• 关键词: Mycobacterium tuberculosis; bacterial antigens; bacterial proteins; delayed hypersensitivity; diagnosis design /evaluation; technology /technique development; transdermal drug delivery; tuberculin test; tuberculosis

DESCRIPTION (provided by applicant):This proposal seeks to establish a development program to transition an experimental Transdermal Tuberculosis Skin Test into a commercial product. This technology has already demonstrated a remarkable ability to specifically identify AFB+ TB patients by adminstering a small amount of a TB protein (MPB64) to the skin and monitoring for an erythemic skin response. PPD+ symptomless individuals are non-reactive to the protein. The MPB-64 Transdermal Patch was applied to sixty-two patients, 49 with sputum-positive active disease and 13 who had completed TB chemotherapy, and 28 non-TB but tuberculin-positive controls. The results were read at 72h. The sensitivity of the Transdermal Patch was 87.8 percent, efficacy 92.9 percent, and specificity 100 percent. The thirteen TB patients who had each completed 6 months of TB chemotherapy showed different reactions to MPB64 patch test: those who had completed chemotherapy less than 4 months before testing were positive; 50 percent of patients who completed chemotherapy 5 months prior were positive; and those who had completed chemotherapy 7 and 8 months before were negative. All the non-TB controls with positive tuberculin tests were negative to the MPB-64 Transdermal Patch, even at the highest protein dose tested. This test may be a useful method to distinguish active TB patients from TB-infected but asymptomatic individuals. The current version of the technology is a research grade patch. This proposal will outline a development pathway to improve product packaging, ease of use and product stability. Initial efforts will be to characterize a unique animal model for use in examining component materials and technologies. Our specific aims are 1. Validate an animal model to test variables in the formulation and transdermal delivery of the skin test antigen, 2. Establish the most cost effective source of MPB64, 3. Establish the best packaging / delivery technology for the patch, 4. Establish animal test procedures for toxicity, product release and to test product stability. Phase II aims include optimizing protein production and manufacturing scale up, and performance of clinical trials for product registration. PROPOSED COMMERCIAL APPLICATION: The proposed commercial application would be to develop a patch test for diagnostic screening of active cases of tuberculosis by using transdermal delivery of MPB64 protein. The patch test could be used in place of other screening tests, such as the PPD skin test or the AFB smear, as a means of diagnosing patients with active tuberculosis.

描述（申请人提供）：该提案旨在建立 过渡实验性透皮结核病皮肤的开发计划 测试商业产品。这项技术已经证明了 出色的能力，可以通过招致A 少量的TB蛋白（MPB64）到皮肤并监测 红斑皮肤反应。 PPD+无症状的个体对 蛋白质。 MPB-64透皮贴剂适用于62例患者，49例 痰阳性活性疾病和13例完成了结核病化疗，28 非TB但结核蛋白阳性对照。结果在72H时读取。这 透皮斑块的敏感性为87.8％，功效92.9％，敏感性为92.9％ 和特异性100％。每个完成的13名结核病患者6 TB化疗的月份显示出与MPB64补丁测试的不同反应： 在测试前不到4个月完成化学疗法的人是阳性的； 5个月前完成化学疗法的患者中有50％为阳性； 那些在7个月前完成化疗的人是阴性的。 所有具有阳性结核蛋白测试的非TB对照对 MPB-64透皮贴片，即使在最高蛋白质剂量下也测试。这个测试 可能是区分活性结核病患者与TB感染但 无症状的个体。 该技术的当前版本是研究级补丁。这个建议 将概述改善产品包装，易用性的开发途径 和产品稳定性。最初的努力是描述独特的动物 用于检查组件材料和技术的模型。我们的具体 目的是1。验证动物模型以测试配方中的变量 皮肤测试抗原的透皮递送，2。建立最高成本 MPB64，3。建立最佳包装 /交付的有效来源 补丁的技术，4。建立动物测试程序的毒性， 产品释放和测试产品稳定性。第二阶段的目的包括优化 蛋白质生产和制造规模缩小以及临床表现 产品注册的试验。 拟议的商业应用： 拟议的商业应用程序将是开发诊断筛查的补丁测试 通过使用透皮递送MPB64蛋白的活性结核病病例。 补丁 可以使用测试代替其他筛查测试，例如PPD皮肤测试或AFB 涂抹，作为诊断活性结核病患者的一种手段。