NINDS Exploratory Clinical Trials (UG3/UH3 Clinical Trial Required)

The National Institute of Neurological Disorders and Stroke (NINDS) is offering funding through the Notice of Funding Opportunity (NOFO) titled "NINDS Exploratory Clinical Trials" (UG3/UH3 Clinical Trial Required), designated as Funding Opportunity Number PAR-25-054. This funding opportunity supports investigator-initiated exploratory Phase 1 and Phase 2 clinical trials that address critical research questions relevant to NINDS's mission. These trials may involve studies of drugs, biologics, devices, or behavioral interventions focused on neurological disorders. The UG3/UH3 phased mechanism is intended to facilitate early-stage clinical trials that justify and gather data to support future efficacy studies. The NOFO encourages robust trial designs that meet rigorous standards of scientific rigor and transparency, and applicants are advised to discuss the biological rationale and anticipated clinical value of the intervention, as well as any preliminary data supporting the trial. The UG3/UH3 funding mechanism operates in two phases: the UG3 phase is an initial planning phase that may last up to two years, allowing time for Phase 1 studies or planning for a Phase 2 trial, while the UH3 phase, which can last up to four years, funds the execution of the clinical trial contingent on achieving specific milestones in the UG3 phase. The entire project period may not exceed five years. For multi-site Phase 2 trials, applicants should engage with NINDS staff to determine if NIH resources such as StrokeNet or NeuroNEXT networks are appropriate. Trials must produce data that is necessary for the continued clinical development of the intervention, and proposed studies should include justification of safety, dosage, pharmacokinetics, and potential efficacy signals. Applicants may address various clinical trial types, such as Phase 1 safety studies, preliminary efficacy trials for devices, or early feasibility studies of behavioral interventions or surgical procedures. Projects under this NOFO should not primarily focus on measuring intervention effect size, conducting Phase 3 trials, or exploring basic science questions. The NOFO encourages the involvement of patient advocacy groups in trial design to ensure the study’s clinical relevance. Applications involving medical devices or specific trial designs (e.g., crossover, adaptive) are encouraged to consult NINDS Program staff early in the process to ensure alignment with funding guidelines. Eligible applicants include higher education institutions, nonprofits, for-profit organizations, and local and federal government entities, including foreign organizations. Submission requirements include SAM, NCAGE, UEI, eRA Commons, and Grants.gov registrations. Applications must comply with the NIH’s rigor and transparency policies and should include a well-defined plan for transitioning between the UG3 and UH3 phases, with clearly stated go/no-go criteria. Detailed justifications for trial design, control groups, and patient population selection are required, and applicants must submit a letter of intent 30 days prior to the application due date. The initial submission date is February 10, 2025, with applications reviewed for scientific and technical merit by an appropriate review group. NINDS encourages diverse, multidisciplinary research teams and recommends the use of NIH resources such as the Clinical and Translational Science Awards (CTSA) Program and standardized data tools (e.g., NeuroQOL, PROMIS). Trials should also address the inclusion of women, minorities, and individuals across the lifespan. Applications exceeding $500,000 in direct costs in any year must contact NINDS scientific staff at least six weeks prior to submission. Additional support letters, including patient organization endorsements and industry partnerships, may strengthen applications. Funding decisions will be based on factors including scientific and technical merit, availability of funds, and program priorities. Award recipients must comply with data sharing policies, including uploading results to ClinicalTrials.gov, and maintain regulatory compliance, such as FDA Investigational New Drug (IND) or Investigational Device Exemption (IDE) status if applicable.