Funding Opportunity for Consortium for Design of TB Drug Regimens (US)

The National Institutes of Health (NIH) is inviting applications for the Project entitled "Consortium for Design of TB Drug Regimens (UM1 Clinical Trial Not Allowed)".

The purpose of this Funding Opportunity Announcement (FOA) is to establish a Consortium of tuberculosis (TB) preclinical and clinical experts to systematically refine preclinical models by analyses of relevant pre-clinical and clinical data and to provide results from optimized models to identify the most efficacious combination regimens for future clinical testing through model-informed research.

Specific Objectives of the Consortium

• The proposed Consortium would establish a collaborative, multidisciplinary research platform to systematically evaluate new candidate agents in combination. These agents may originate from academic, public-private partnerships, and pharmaceutical industry research efforts and will be evaluated for their potential for incorporation into new TB drug regimens across the human lifespan including young children. By generating adequate and comparable preclinical data on regimen efficacy, pharmacometrics, toxicities, drug-drug interactions, and other factors essential for human clinical trials, the consortium will increase efficiency, accelerate development of new combinations, and identify the most promising regimens for future clinical testing to effect shorter, relapse-free cures of pulmonary TB in adults, children, and persons being treated for HIV.

• The TB Drug Regimen Consortium aims to address this by:

  • Providing an open platform for uniting preclinical and clinical TB experts (U.S. and international) in the systematic analysis of available preclinical and clinical efficacy and safety data to identify preclinical research projects, scientific needs/gaps and set an agenda of cooperative goals and research priorities.

  • Optimizing preclinical models with back-translation of clinical data from recent trials into animal and other model development.

  • Facilitating communication, coordination and planning of preclinical research to inform NIH-supported clinical trial networks (both adult and pediatric focused) and other sponsors/investigators by review and discussion of all available information on new agents/combinations, and ongoing and anticipated research. These discussions will guide plans for optimized drug combinations, eliminate duplication, and ensure efficiency by identification and, when appropriate, performance of key preclinical experiments by the Consortium's Preclinical Laboratories.

  • Incorporating pediatric-focused research to stimulate pre-clinical, translational activities that can enable accelerated clinical testing and earlier introduction of new TB drugs and regimens in pediatric populations, with an emphasis on young children (aged 6 years or younger).

  • Performing preclinical evaluations of mechanisms of action of individual and combination drug candidates. Performing preclinical animal model studies (with emphasis on new drug combination efficacy comparisons) identified as needed by the Consortium leadership executive committee after review and approval by NIAID.

  • Providing compiled data and analyses on evaluated combination regimens with priority ranking assessment for consideration by clinical trial networks to guide optimized and coordinated choices of new regimens for phase 2 and 3 trials.

  • Assessing evolving clinical research challenges and opportunities for potential inclusion of special populations, new technologies (including biomarkers), and the broader spectrum of TB disease into the Consortium research agenda.

Funding Information

• NIAID intends to commit $7.2 million in FY 2024 to fund one award.

• Duration: The total project period may not exceed five years.

Expected Characteristics of the Consortium

• Scientific and Fiscal Flexibility

  • The Consortium will use a strategic planning process for its scientific and translational activities and is expected to actively engage major sponsors, researchers, and communities within and outside of the Consortium in establishing and refining the research agenda for treatment of TB diseases. The Consortium Scientific Leadership Group Executive Committee (SLG Ex Com) will work to ensure that the research remains coordinated and complementary to other TB drug research enterprises.

• The TB Consortium Organizational Structure

  • The overall Consortium structure is intended to facilitate coordinated and efficient TB drug regimen development. The Consortium must include a Scientific Leadership Group (SLG) including a Pediatric Focus Committee led by a SLG Executive Committee, a Preclinical Laboratory Group (PLG), a Data Science and Modelling Group (DSMG), and an Administrative Group (AG). These functional areas will be integrally connected to all aspects of the research agenda for the treatment of TB diseases, focusing primarily on pulmonary TB in both adults and young children.

• The Scientific Leadership Group (SLG): led by the PD(s)/PI(s) of the Consortium, is responsible for review and discussion of scientific direction, oversight, and evaluation of consortium activities. The SLG will include the Leaders of all Groups and Laboratories, the Pediatric Focus Committee, representatives of participating TB clinical research networks (both adult and pediatric), pharmacology modelling experts in adult and pediatric research, product development partnerships, the pharmaceutical industry involved with new TB therapeutics, and NIAID staff, as well as other experts identified and recommended by the Consortium PD(s)/PI(s).

  • The SLG Executive Committee (SLG Ex Com) will include the Consortium PD(s)/PI(s): the Leaders of Preclinical Laboratories and the Data Science and Modelling Group, the Chair of the Pediatric Focus Committee, NIAID clinical trial network representatives, and NIAID scientific representatives. This group will be responsible for final decisions on prioritized research to be performed, ensuring progress, and providing administrative oversight.

  • The Pediatric Focus Committee (PFC) will work to ensure that pediatric populations benefit from the research undertaken by the Consortium, including suggesting additional research needed to extend the impact of Consortium activities towards pediatric populations (especially related to pediatric pulmonary TB). The Chair of this committee will be identified as key personnel in the application.

• The Preclinical Laboratory Group (PLG) will consist of Preclinical Laboratories (PLs) and will be responsible for designing and implementing in vitro and in vivo studies of efficacy, mechanisms of action, safety, and pharmacometrics of drugs/combinations approved by the SLG Ex Com. At least two PLs will operate mouse models of TB pulmonary disease with pharmacology/pharmacodynamic capabilities for each drug tested and will have experience in successfully informing clinical trial design.

• The Data Science and Modelling Group (DSMG) will summarize and model data for the Consortium to review. The DSMG will be responsible for collecting, organizing, validating, and analyzing existing preclinical and clinical data from completed studies and trials, from across the published literature, and from clinical trial Meta data provided by associated networks/sponsors of adult and pediatric studies. The DSMG will define common data elements, conduct integration, harmonization, analysis, and modeling of data generated externally or by the PLG, including translational PK-PD or antiretroviral (ARV) drug-drug interactions modeling approaches, that can enable pediatric dose selection and formulation development.

• The Administrative Group (AG) provides administrative support for the group, organizes meetings, compiles summaries, facilitates communications, and prepares reports. The AG will coordinate research and data sharing agreements and organize experimental results into formats suitable for regulatory filings. The AG will develop and prepare effective legal agreements between participating parties for maximum disclosure of data to protect intellectual property.