NINDS Exploratory Clinical Trials (UG3/UH3 Clinical Trial Required) | PAR 22 142

Opportunity Information: Apply for PAR 22 142

The NINDS Exploratory Clinical Trials (UG3/UH3 Clinical Trial Required) funding opportunity (PAR-22-142) is a National Institutes of Health cooperative agreement designed to support investigator-initiated, early-stage clinical trials in neurological disorders and stroke. Its core aim is to help researchers generate the practical, decision-making evidence needed to justify and shape a later, definitive efficacy study, such as a Phase 3, Phase 4, or pivotal trial. In other words, these studies are meant to reduce uncertainty, test key assumptions, and produce the kind of early human data that lets a research team confidently decide whether and how to move forward into a larger, more expensive trial meant to prove clinical benefit.

The FOA is broadly focused on exploratory clinical trials that fit within the mission and research priorities of the National Institute of Neurological Disorders and Stroke. It can support Phase 1 and Phase 2 trials for drugs and biologics, early feasibility work for devices, and early clinical studies of surgical approaches, behavioral interventions, or rehabilitation therapies. Regardless of intervention type, the common requirement is that the trial should answer targeted questions that will directly inform the design and justification of a future efficacy trial. This might include clarifying safety and tolerability in humans, selecting dose or regimen, confirming feasibility of recruitment and adherence, testing operational aspects of trial conduct, refining endpoints, or producing preliminary signals that help pick the right population and outcome measures for the next stage.

A defining feature of this opportunity is the two-stage UG3/UH3 structure. The UG3 phase functions as a milestone-driven start-up and early execution period, and only projects that meet agreed-upon milestones are allowed to transition into the UH3 phase. This creates a built-in checkpoint: the project must show satisfactory progress in planning and early trial activities before NIH support continues into the later stage. The cooperative agreement format also signals substantial NIH involvement compared with a standard grant, typically meaning closer coordination around milestones, trial oversight expectations, and study management requirements.

The FOA is specifically intended for drugs, biologics, or devices that have not yet completed a Phase 1 or early feasibility trial. Under this arrangement, the UG3 portion is used to plan and conduct the Phase 1 trial work. If those Phase 1 activities are successful, the UG3 can also cover planning for a Phase 2 trial. The UH3 phase then supports execution of the Phase 2 clinical trial. Progression from UG3 to UH3 is not automatic; it depends on whether the project meets predefined milestones that are negotiated and agreed upon with NINDS. This milestone-based transition is central to the program and is meant to ensure that only studies demonstrating readiness and viability proceed to the more resource-intensive Phase 2 portion.

The FOA also makes clear what should not be submitted. If a drug, biologic, or device has already successfully completed Phase 1 or early feasibility studies, applicants are instructed not to use this FOA and instead apply to a separate companion FOA (listed as "XXX" in the provided text). Similarly, genetic studies are explicitly directed elsewhere, to a different FOA (also indicated as "XXX" in the provided text). These exclusions matter because they define the program as a pathway for interventions still needing first-in-human or early feasibility clinical work before moving into Phase 2 testing.

Eligibility is broad and includes many organization types that commonly participate in NIH clinical research. Eligible applicants listed include state, county, city/township, and special district governments; independent school districts; public and state-controlled and private institutions of higher education; federally recognized Native American tribal governments; other Native American tribal organizations; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (other than institutions of higher education); for-profit organizations (other than small businesses) as well as small businesses; and additional categories. The FOA also highlights a wide set of "other eligible applicants," including Alaska Native and Native Hawaiian Serving Institutions, AANAPISISs, Hispanic-serving Institutions, HBCUs, tribally controlled colleges and universities, faith-based or community-based organizations, eligible federal agencies, non-U.S. entities (foreign organizations), regional organizations, tribal governments that are not federally recognized, and U.S. territories or possessions. This reflects an intent to allow a diverse set of institutions and communities to lead or participate in early neurological clinical trials, provided the proposed work aligns with NINDS priorities and meets clinical trial and milestone requirements.

Key administrative details from the source information include that the sponsoring agency is the National Institutes of Health, the activity category is Health, and the CFDA/Assistance Listing number is 93.853. The funding instrument is a cooperative agreement, consistent with the milestone-driven UG3/UH3 structure and closer NIH involvement. The original closing date listed is March 10, 2025, and the opportunity was created on April 18, 2022. The source text does not provide an award ceiling or expected number of awards, so applicants would need to consult the full FOA in NIH systems for budgetary limits, project period parameters, and any institute-specific expectations about scope, milestones, and trial operations.

Overall, this opportunity is best understood as a structured on-ramp for early clinical testing in neurology: it supports the critical first steps of translating an intervention into humans (Phase 1/early feasibility) and, if those steps succeed, advancing into Phase 2 execution, all while requiring that the work produce concrete evidence and decisions that set up 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 2022-04-18.
• 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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