Tuberculosis (TB) poses a severe global public health problem that is exacerbated by co-infection with HIV and growing drug resistance to current treatments. Today's efforts to develop improved TB treatments, are markedly hindered by the long duration and laborious, costly nature of late-stage clinical TB drug trials. The availability of biomarkers that could: 1) streamline Phase 2 development, and 2) distinguish patients, at the end of treatment or sooner, who have achieved stable cure from those at high risk for relapse, would facilitate triaging of novel treatments worthy of phase 3 evaluation, and shorten pivotal trials by at least 1-2 years, markedly increasing feasibility for development of improved TB therapies, and dramatically speeding the evaluation and ultimately, registration, of improved treatment regimens for TB patients. Discovery and qualification of such biomarkers will only be possible if the relevant, high quality, well-documented, clinical specimens are available to the biomarker research community. We therefore request funding to support the Consortium for TB Biomarkers (CTB2), composed of three organizations central to TB clinical drug development, each having plans to conduct late stage TB drug trials: NIAID's AIDS Clinical Trials Group (ACTG), CDC's TB Trials Consortium (TBTC), and the Global Alliance for TB Drug Development (TB Alliance). The CTB2 has agreed on a core set of samples to be collected, processed and stored based on established standards and procedures, including use of common data elements, and has received initial, seed funding from the FDA Office of Critical Path Programs. This R24 award will provide crucial bridge funding to enable establishment of the Biorepository composed of the agreed upon samples, storage for up to five years (additional funding to be sought for storage up to a total often years), and downstream, distribution to qualified investigators through a peer review system. This project brings together for the first time three leading organizations in TB drug trials to enable discovery and qualification of biomarkers of TB drug effect, including a marker of stable TB cure vs. relapse as the first priority - an achievement that will dramatically facilitate development of crucial, improved TB treatments.
TB, the second most deadly infectious disease in the world, is treated with a cocktail of drugs several decades old. Efforts to develop improved TB treatments are severely hampered by very lengthy and cost-intensive late-stage clinical trials. Establishment of a biorepository of well-characterized, serial clinical specimens from TB patients from diagnosis to cure or relapse in a safe and readily retrievable format will enable discovery and qualification of biomarkers to speed clinical development of improved TB treatments.