R44AI162527

PROJECT SUMMARYNanoPin is advancing a diagnostic for active tuberculosis (TB) that addresses critical unmet clinical needs and its innovation and potential patient impact has resulted in designation as a breakthrough device by the FDA. This device will highly valuable in the global effort to combat TB, which is now the leading cause of death from infectious disease, with an estimated 10.0 million new TB cases and 1.5 million TB-related deaths annually. Key unmet needs for TB diagnosis include a rapid test that is both culture-free and non-sputum-based, is actionable and informative especially in countries with high latent TB rates, can accurately detect both pulmonary and extrapulmonary TB, and can detect across the entire patient spectrum including young children and HIV- coinfected patients. NanoPin’s highly sensitive diagnostic platform rapidly detects species-specific TB antigens directly from blood samples. Our technology is differentiated from all current methods in that we can detect TB no matter where it is in the body and whose body it is in. We can detect TB based in the lungs, kidneys, brain and throughout the body, even when the current “gold standard” cannot. We can detect in difficult cohorts including young children and even infants and HIV co-infected, all of which are poorly served in the market and where conventional sputum methods are not feasible. Ultimately, this technology will enable health care providers to finally mitigate the enduring TB epidemic.The outcomes of successful completion of this proposal will introduce our TB diagnostic device into the market and make it available for routine use in clinics and hospitals by evaluating its performance in a well- structured clinical study in multiple high profile medical centers. We propose four specific aims: 1). To perform analytical validation of the NanoTB Assay Kit and Multiple LC-MS Platforms. Prior to initiating clinical studies, we will determine key quantitative values for the TB assay kits including LoD, LoQ, and cut-values per CLSI C62- A. We will establish multiple LC-MS platforms for clinical studies and regulatory approval which will further our commercialization reach; 2). To perform clinical studies for detection of active TB with NanoTB diagnostic assay kits. The clinical studies proposed in this aim will be the basis for 510k application to the FDA for regulatory approval and marketing of the NanoDetect-TB device. The studies will enroll patients suspected of TB disease and analyze with our TB assay and the primary AFB-culture reference method; 3). To communicate with the FDA for guidance for clinical studies and 510k submission. Interactions with the FDA will guide the efficient and successful implementation of the proposed work. The outcome of this aim is the FDA clearance of the NanoDetectTB device via the De Novo pathway; and 4). To extend clinical studies for pediatric centric and resource limited focus. We will further evaluate the critical pediatric cohort and address challenges for sample collection and handling shipping in resource limited regions in order to ensure our application can be extended to all patients.PROJECT NARRATIVE Global efforts to effectively mitigate the ongoing global tuberculosis (TB) health epidemic are constrained by current diagnostics, which are only partially useful and do not effectively enable health care providers to accurately diagnose all TB cases, resulting in critical unmet clinical need for improved assay methods. NanoPin’s TB assay is a rapid blood test for active TB, which has been designated a breakthrough device by the FDA, since it permits early TB detection, and has high diagnostic sensitivity and selectivity for pulmonary and extrapulmonary TB cases in all patient groups, including the most vulnerable groups (young children and individuals of all ages living with HIV). The studies outlined in this proposal are designed to verify the performance of this device in well-designed clinical studies required for regulatory approval by the FDA prior to introduction to the global healthcare market.