A Second-Generation Patch Test for Tuberculosis

描述（由申请人提供）： 该提案概述了将第二代经皮结核病（TB）皮肤试验转变为商业产品的开发计划。第一代的技术，透皮传递的蛋白质的M。在菲律宾和日本进行的三项临床试验中，已经测试了Torii贴片对结核病复合体（MPB/T-64）的作用：它表现出特异性识别活动性TB病例（涂片阳性TB患者）的显著能力，而在BCG疫苗接种或先前TB治愈的PPD阳性的无结核病个体中，它是非反应性的。Sequella从日本BCG实验室获得了这项令人兴奋的技术，重组MPT 64的GMP生产始于2003年1月。我们将于2003年3月在南非开始一项世界卫生组织支持的临床试验，测试第一代检测的敏感性和特异性。 我们相信，透皮结核病皮肤测试将成为对抗结核病的宝贵工具。由于对活动性结核病的快速诊断的需求令人难以置信，我们希望开始尽快在发展中国家使用现有的测试格式进行分发。但是，该产品有许多方面需要改进，我们希望在本提案中开发出更有效的第二代产品。我们的具体目标包括： 具体目标I：我们将优化MPT 64的表达、纯化和质量控制方案。 具体目标II：我们将完成第二代贴片技术的开发，该技术将蛋白质直接掺入贴片粘合剂中。 具体目标III：我们将按照药品生产质量管理规范生产用于临床研究的第二代贴剂。 具体目标四：我们将进行经皮结核病皮肤试验的临床研究。

DESCRIPTION (provided by applicant): This proposal outlines a development program to transition a second generation Transdermal Tuberculosis (TB) Skin Test into a commercial product. The first generation of the technology, transdermal delivery of a protein of the M. tuberculosis complex (MPB/T-64) by a Torii patch, has already been tested in three clinical trials performed in the Philippines and Japan: it demonstrated remarkable ability to specifically identify active cases of TB (smear positive TB patients), while it was non-reactive in symptom-free individuals PPD positive from either BCG vaccination or prior cure of TB. Sequella licensed this exciting technology from the Japan BCG Laboratory, and GMP manufacturing of recombinant MPT64 began in January 2003. We will begin a World Health Organization-supported clinical trial in South Africa in March 2003 that will test the sensitivity and specificity of this first generation test. We believe that the Transdermal TB Skin Test will be an invaluable tool in the fight against TB. Because of the incredible need for a rapid diagnostic for active TB, we hope to begin distribution in the developing world as soon as possible using the existing test format. However, there are many aspects of the product that need to be improved, and we hope to develop a more effective second generation product in this proposal. Our specific aims include: Specific Aim I: We will optimize expression, purification, and quality control protocols for MPT64. Specific Aim II: We will complete development of a second-generation patch technology that incorporates the protein directly into the patch adhesive. Specific Aim III: We will manufacture the second-generation patches for clinical studies using Good Manufacturing Practices. Specific Aim IV: We will perform clinical studies of the Transdermal TB Skin Test.