NINDS Exploratory Clinical Trials (UG3/UH3 Clinical Trial Required) | PAR 25 054

Opportunity Information: Apply for PAR 25 054

NINDS Exploratory Clinical Trials (UG3/UH3 Clinical Trial Required), Funding Opportunity Number PAR 25 054, is a National Institutes of Health (NIH) funding opportunity from the National Institute of Neurological Disorders and Stroke (NINDS) aimed at supporting investigator-initiated, early-stage clinical trials in neurology and related areas that fit squarely within the NINDS mission. The main idea is to help researchers move promising interventions from early human testing toward the kind of evidence needed to justify a later, definitive efficacy study. These projects are meant to generate practical, decision-driving clinical data, not just exploratory signals, so that a future Phase 3, Phase 4, or pivotal trial can be designed with a stronger foundation and a clearer rationale.

The FOA is specifically focused on exploratory clinical trials, generally in Phase 1 and Phase 2 territory. It allows a wide range of intervention types as long as they are relevant to neurological disorders and stroke research priorities: Phase 1 and Phase 2 trials of drugs and biologics, feasibility studies for devices (including early feasibility work), and early clinical studies of surgical approaches, behavioral interventions, or rehabilitation therapies. Regardless of modality, the expectation is that the trial will answer focused clinical questions that reduce uncertainty and directly inform the next stage of development. In other words, the trial should not be an endpoint in itself; it should produce evidence that helps determine whether and how to proceed to a later efficacy-establishing trial.

This opportunity uses the UG3/UH3 phased cooperative agreement mechanism, which is designed for projects that need a structured, milestone-driven pathway from planning and initial execution into a larger clinical trial effort. Under this model, the project begins in the UG3 phase, where the team completes key preparatory work and, depending on the intervention, may conduct early clinical activities (including Phase 1 execution for certain products). Only projects that meet pre-specified, agreed-upon milestones can transition into the UH3 phase. The UH3 phase is where the more advanced clinical trial execution occurs, and it is not automatic; it depends on demonstrating satisfactory progress during UG3.

For drugs, biologics, or devices that have not yet completed a Phase 1 or early feasibility study, the FOA lays out a clear development path. The UG3 portion is used to plan and carry out the Phase 1 trial or trials. If those Phase 1 efforts are successful, the UG3 period can also cover planning for a Phase 2 trial. The UH3 phase then supports the execution of the Phase 2 clinical trial itself. The handoff from UG3 to UH3 is explicitly tied to reaching the milestones established with NINDS, reinforcing that this is a go/no-go structure intended to manage risk and ensure readiness before scaling into Phase 2.

Administratively, this is a discretionary federal funding opportunity with a Cooperative Agreement as the funding instrument type, reflecting NIH staff involvement typical of cooperative agreements, especially for clinical trial oversight and milestone monitoring. The activity category is Health, and the CFDA number listed is 93.853. The opportunity was created on 2024-11-12, and the original closing date provided is 2025-03-10. An award ceiling and expected number of awards are not specified in the provided listing, which often means applicants should consult the full FOA text and NIH guidance for budget expectations, limits (if any), and programmatic considerations.

Eligibility is broad and includes many common applicant types: state, county, city or township governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations (including those other than federally recognized tribal governments); public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (when not institutions of higher education); for-profit organizations (other than small businesses); small businesses; and other eligible entities. The FOA also highlights additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISISs, Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-U.S. entities (foreign organizations). Taken together, the eligibility language signals an intent to encourage diverse institutional participation, including community-linked organizations and international partners where appropriate, as long as the proposed clinical trial aligns with NINDS priorities and meets NIH clinical trial and regulatory expectations.

Overall, this FOA is best understood as a structured pathway for early clinical testing in neurological disorders and stroke, with an emphasis on milestone-based progression from initial planning and early human evaluation into a more substantial Phase 2 effort. The central requirement is that the exploratory trial produces credible, actionable evidence that strengthens the scientific and operational case for a later definitive efficacy trial.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "NINDS Exploratory Clinical Trials (UG3/UH3 Clinical Trial Required)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.853.
• This funding opportunity was created on 2024-11-12.
• Applicants must submit their applications by 2025-03-10. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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