(CLOSED) NIH RFA-OD-20-018 Emergency Awards: Exosome-based Non-traditional Technologies Towards Multi-Parametric and Integrated Approaches for SARS-CoV-2 (U18 Clinical Trial Not Allowed)

The National Institutes of Health (NIH) is issuing this funding opportunity announcement (FOA) in response to the declared public health emergency issued by the Secretary, Department of Health and Human Services (DHHS), for the 2019 Novel Coronavirus (COVID-19). This emergency FOA provides an expedited funding mechanism as part of the Rapid Acceleration of Diagnostics-Radical (RADx-rad) initiative. Specifically, this FOA seeks to use technologies developed for single extracellular vesicle, exosome, and extracellular RNA (exRNA) isolation and analysis and reposition them for the detection of SARS-CoV-2. The funding for this initiative is provided from the Paycheck Protection Program and Health Care Enhancement Act, 2020.

NATURE OF THE RESEARCH

Newly developed technologies for single vesicle, exosome, and exRNA isolation and analyses will be repositioned for the detection of SARS-CoV-2, a coronavirus that has similar physical and chemical properties as exosomes. These technologies will utilize non-invasive, point-of-care sample collection from body fluids to develop non-invasive, reliable, and reproducible COVID-19 diagnostic tests. Applications should state how the proposed SARS-CoV-2 isolation and detection strategy will improve upon current COVID-19 diagnostic testing. Support will be provided for up to two years for the initial proof of concept studies.

Leveraging Existing Research Resources:

Applicants are strongly encouraged to leverage existing research resources for their studies whenever possible. NIH has developed innovative solutions that will improve the efficiency, quality, and impact of the process for turning observations in the laboratory, clinic and community into interventions that improve the health of individuals and the public through programs such as: NCATS Clinical and Translational Science Awards (CTSA) Program, Research Evaluation and Commercialization Hubs (REACH), and Small Business Education and Entrepreneurial Development (SEED) for commercialization of final products. Applicants are encouraged to leverage all available internal (e.g., home institutional) and external (e.g., external institutional, NIH, and/or NCATS) resources to identify clinically relevant COVID-19 populations.

Specific Research Objectives

1. Technology Development. Newly developed technologies and approaches for single exosome and exRNA isolation and analyses will be deployed for detection of SARS-CoV-2 virus RNA and/or protein, and detection of IgA, IgG, and IgM antibodies against the virus.

Activities will include, but are not limited to:

• Development of technologies for screening for SARS-CoV-2 viral infection and COVID-19 based on novel technologies for single vesicle, exosome, and exRNA isolation.
• Demonstration of SAR-CoV-2 isolation effectiveness using clinically relevant biofluids from patients.
• Demonstration of greater than 95% diagnostic reliability, sensitivity, and specificity of detecting SARS-CoV-2.

1. Clinical Testing and Validation. Data training sets must be collected on known (1) COVID-19 positive, symptomatic, (2) COVID-19 positive, asymptomatic and (3) COVID-19 negative subjects as determined by an FDA-approved method.

Activities will include, but are not limited to:

• Validation of technologies and approaches using a cohort of COVID-19 patients and unaffected individuals representing population demographics inclusive of sex/gender, race, age and ethnicity.

NCATS Clinical and Translational Science Awards (CTSA) hubs can be used in the clinical validation for recruitment and trial implementation (https://ncats.nih.gov/ctsa/about/hubs).

1. Regulatory Approval Plan. A plan for the regulatory approval of technologies, tests and approaches should be developed and submitted to the appropriate regulatory agency based on the data generated from research objectives 1 and 2. The application should describe the expected regulatory pathway for the technology and describe foreseeable regulatory risks that could impact the technology development. It should also describe how the technology would fit with current physician practice/standard of care.

Activities will include, but are not limited to:

• Development of a detailed plan for the regulatory approval of technologies, tests and approaches to be submitted to the appropriate regulatory agency.
• Submission of newly developed technologies for detection and/or diagnosis of SARS-CoV-2 virus RNA and/or protein, and detection of antibodies against the virus to the FDA Center for Devices and Radiological Health (CDRH).

The DCC and designated NIH databases will be utilized for the banking and distribution of biological and clinical data.Project PD(s)/PI(s) will be expected to harmonize all data and resource generation with the DCC. The DCC is expected to curate and disseminate information regarding critical reagents, and resources and promote and facilitate cross-project collaborations (see RFA-OD-20-019).