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)

Background
The National Institutes of Health (NIH), specifically the National Institute on Aging (NIA), is issuing this Notice of Funding Opportunity (NOFO) to address the urgent need for effective interventions against Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRD).

With over 6 million Americans aged 65 and older currently living with AD, and projections suggesting this number could rise to 12.7 million by 2050, the economic burden of AD/ADRD is estimated to exceed $355 billion.

The goal of this NOFO is to streamline early-stage clinical trials for promising pharmacological interventions that engage non-amyloid/non-tau mechanisms, targeting cognitive and neuropsychiatric symptoms across various stages of the disease. This initiative aligns with the National Alzheimer's Project Act's objective to prevent and effectively treat AD/ADRD by 2025.

Grant Details
This NOFO invites applications that bundle independent protocols for phase 1 clinical trials with phase 1b/phase 2a clinical trials. The proposed activities include:
- Evaluation of safety and pharmacokinetics of novel therapeutics in healthy volunteers or target populations.
- Projects directed at a phase I trial referencing prior Good Laboratory Practice (GLP) toxicology studies.
- Good manufacturing practice (GMP) for drug substance/product needed for clinical trials.
- Preparation of protocols and acquisition of regulatory approvals.
- Food effect studies.
- Evaluation and optimization of dose, formulation, safety, tolerability, or pharmacokinetics to enable FDA-required activities for starting phase 2a.
- Acquisition and analysis of biomarkers.
- Evaluation of intervention efficacy through human proof-of-concept trials.

Applications must include prespecified go/no-go safety and tolerability milestones that must be met to advance from phase 1 to later stages of clinical development.

Eligibility Requirements
Eligible applicants include higher education institutions, nonprofits, for-profit organizations (including small businesses), local governments, state governments, tribal governments, federal agencies, foreign organizations, and other entities such as public housing authorities. Individuals from diverse backgrounds are encouraged to apply.

Period of Performance
The UG3 phase must not exceed 2 years, while the total duration for both UG3/UH3 phases combined must not exceed 5 years.

Grant Value
Application budgets are not limited but must reflect the actual needs of the proposed project. The number of awards will depend on NIH appropriations and the submission of meritorious applications.