Seamless Early-Stage Clinical Drug Development (Phase 1 to 2a) for Novel therapeutic Agents for the Spectrum of Alzheimer's Disease (AD) and AD-related Dementias (ADRD) (UG3/UH3 Clinical Trial Required)

The National Institute on Aging (NIA) invites applications under its Seamless Early-Stage Clinical Drug Development program for interventions targeting Alzheimer's disease (AD) and related dementias (ADRD). This funding opportunity supports the UG3/UH3 phased award mechanism to bundle early clinical trials, facilitating the transition from Phase 1 studies to Phase 1b/2a trials based on safety and tolerability milestones. The program focuses on novel pharmacological interventions, such as small molecules and biologics, that engage non-amyloid/non-tau mechanisms and address cognitive or neuropsychiatric symptoms across the AD/ADRD spectrum, from pre-symptomatic to severe stages. Applicants must propose protocols that include Good Laboratory Practice toxicology studies, evaluation of pharmacokinetics, safety, tolerability, and dose optimization. Phase 1 trials should generate critical safety data and inform go/no-go decisions for Phase 2a trials, which aim to explore target engagement and early evidence of efficacy. Biomarker development and biosample collection are essential components of the research, with the requirement to make data and biosamples publicly accessible within a specified timeframe. Eligible applicants include higher education institutions, nonprofits, small businesses, state and local governments, and foreign organizations. Applications must include detailed project plans for both phases, with a combined project period not exceeding five years. Milestones for progression between phases must be clearly defined and achievable. Non-responsive applications include proposals for Phase 3 trials, stand-alone UG3 or UH3 activities, or those without clinical trial components. Funding is not capped but must reflect the project’s actual needs. Applicants are required to include plans for participant diversity, recruitment strategies, and data management and sharing. Applications must comply with NIH rigor and reproducibility standards and address NIH guidelines for data and safety monitoring, informed consent, and ClinicalTrials.gov registration. Applications are due on standard NIH dates, beginning February 21, 2025, and the opportunity expires on November 20, 2026. Prospective applicants are encouraged to consult NIA staff at least 12 weeks before submission to refine their project plans and ensure alignment with program priorities. This funding opportunity represents NIA’s commitment to accelerating therapeutic development and addressing critical gaps in AD/ADRD research.