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)皮肤测试转化为商业产品的开发计划。这项名为“经皮释放结核分枝杆菌复合体蛋白”(MPB/T-)的第一代技术已在菲律宾和日本进行的三项临床试验中得到测试：该技术显示出非凡的特异性识别结核病活动病例(涂阳肺结核患者)的能力，而对于无论是接种卡介苗或既往治愈肺结核而PPD呈阳性的无症状个人，该技术均无反应。Sequella从日本卡介苗实验室获得了这项令人兴奋的技术的许可，重组MPT64的GMP生产于2003年1月开始。我们将于2003年3月在南非开始一项由世界卫生组织支持的临床试验，以测试这种第一代试验的敏感性和特异性。 我们相信，经皮结核病皮肤试验将是抗击结核病的宝贵工具。由于对活动性结核病的快速诊断的需求令人难以置信，我们希望利用现有的检测形式尽快开始在发展中国家分发。然而，该产品还有很多方面需要改进，我们希望在这份提案中开发出更有效的第二代产品。我们的具体目标包括： 具体目标一：我们将优化MPT64的表达、纯化和质量控制方案。 具体目标二：我们将完成第二代贴片技术的开发，将蛋白质直接整合到贴片粘合剂中。 具体目标三：我们将使用良好的制造规范生产用于临床研究的第二代贴片。 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.