Safety and Efficacy of Amyloid-Beta Directed Antibody Therapy in Mild Cognitive Impairment and Dementia with Evidence of Lewy Body Dementia and Amyloid-Beta Pathology (U01 - Clinical Trial Required) | RFA NS 25 010

Opportunity Information: Apply for RFA NS 25 010

This funding opportunity (RFA-NS-25-010) from the National Institutes of Health invites applications for a U01 cooperative agreement to run placebo-controlled clinical trials testing whether FDA-approved monoclonal antibody therapies that target amyloid-beta are safe and effective in people with mixed-etiology dementia, with a particular emphasis on Lewy Body Dementias (LBD). The intent is not to develop new drugs, but to rigorously evaluate existing, FDA-approved anti-amyloid antibodies in patient groups that are common in real-world clinics yet often underrepresented in traditional Alzheimer disease trials: individuals who have both biological evidence of Alzheimer-type pathology and a clinical diagnosis of LBD.

The population of interest is mild cognitive impairment or dementia where participants show canonical biomarkers of Alzheimer pathology and also meet clinical criteria for Lewy body-related dementia. On the Alzheimer biomarker side, the NOFO highlights measures such as amyloid deposition on PET imaging and/or cerebrospinal fluid profiles consistent with amyloid pathology (for example, low Abeta42 in combination with elevated phosphorylated tau). On the Lewy body side, the focus is specifically on clinically diagnosed dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD). In other words, the trials are meant to address the common scenario of overlapping pathologies, rather than treating Alzheimer disease and LBD as completely separate conditions.

The trials must be placebo-controlled and designed to determine both efficacy and safety of the anti-amyloid antibody therapy compared with placebo in these mixed dementia groups. The NOFO explicitly encourages modern statistical and trial-design approaches, especially Bayesian methods and response-adaptive randomization, to allow investigators to learn efficiently and to examine whether particular subgroups respond differently. That encouragement signals an interest in designs that can adapt based on accumulating data, while still maintaining the rigor needed to produce interpretable, decision-quality results.

A central requirement is that proposed studies be adequately powered and intentionally structured to enroll participants who reflect the demographics of the disease across the United States. Applications are expected to demonstrate recruitment and retention plans that achieve meaningful representation by sex, race and ethnicity, and geography. This is framed as more than a general aspiration: the expectation is that the study sample should resemble the real distribution of these conditions in the U.S., which typically requires deliberate site selection, community partnerships, culturally competent outreach, and careful monitoring of enrollment metrics throughout the trial.

Another major emphasis is patient and community engagement. Applications must include engagement elements that are built into all stages of program development and embedded at every level of the organizational structure. Practically, that points to activities like involving patients and care partners in protocol development, improving feasibility and acceptability of study procedures, informing outcome selection, shaping recruitment materials, advising on burden and accessibility, and supporting dissemination of results back to participating communities. The language suggests NIH is looking for engagement that is continuous and operational, not a one-time advisory meeting.

Mechanistically, this is a cooperative agreement (U01), which generally means NIH program staff will have substantial involvement with awardees compared with a typical research project grant. Applicants should therefore anticipate an active partnership model, including coordination with NIH expectations around milestones, reporting, and potentially harmonization across funded projects if multiple awards are made.

Eligibility is broad across U.S.-based organizations, spanning state, county, and local governments; public and private institutions of higher education; federally recognized tribal governments; tribal organizations; independent school districts; special district governments; public housing authorities; nonprofits (with or without 501(c)(3) status); for-profit organizations (other than small businesses) as well as small businesses; and other entities. The NOFO also calls out additional eligible applicant types such as Historically Black Colleges and Universities, Hispanic-serving institutions, Tribally Controlled Colleges and Universities, Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions, faith-based and community-based organizations, regional organizations, U.S. territories or possessions, and eligible federal agencies. Foreign (non-U.S.) entities are not eligible to apply, and non-U.S. components of U.S. organizations are not eligible; however, foreign components, as defined by NIH policy, are allowed, which typically means discrete elements of the project may be performed abroad when well-justified and compliant with NIH rules.

Key administrative details included in the listing are an original application due date of January 24, 2025, an award ceiling of $6,700,000, and classification under CFDA numbers 93.853 and 93.866. Overall, the opportunity is aimed at generating clear clinical evidence about whether anti-amyloid antibody treatment helps, harms, or has a mixed profile in people who have both Alzheimer-type amyloid biology and clinically diagnosed Lewy body dementia syndromes, while ensuring the evidence produced is generalizable to the diverse populations affected in the United States.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Safety and Efficacy of Amyloid-Beta Directed Antibody Therapy in Mild Cognitive Impairment and Dementia with Evidence of Lewy Body Dementia and Amyloid-Beta Pathology (U01 - 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, 93.866.
• This funding opportunity was created on 2024-05-21.
• Applicants must submit their applications by 2025-01-24. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $6,700,000.00 in funding.
• 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.

Apply for RFA NS 25 010

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