DoD Amyotrophic Lateral Sclerosis, Therapeutic/Biomarker Pilot Trial Award | W81XWH 21 ALSRP TBPTA

Opportunity Information: Apply for W81XWH 21 ALSRP TBPTA

The DoD Amyotrophic Lateral Sclerosis Research Program (ALSRP) Therapeutic/Biomarker Pilot Trial Award is a clinical-trial focused funding opportunity intended to move promising ALS interventions into human testing quickly, with the explicit goal of generating results that meaningfully shape the next, larger stage of development. It is geared toward Phase 1 through small, pilot-scale Phase 2 studies and is meant to help investigators answer the practical questions that often block progress to later-stage trials, such as whether the intervention is safe enough, feasible to deliver as planned, shows credible signals of biological activity, and produces early evidence that it could benefit relevant ALS patient groups. The emphasis is not on exploratory or purely academic clinical research, but on trials that can directly de-risk and inform subsequent, more definitive studies and ultimately improve treatment or management options for people living with ALS, including genetically defined or phenotypically distinct subpopulations.

A defining feature of this mechanism is that the funded project must be a clinical trial and must include a serious biomarker component that produces compelling data. The program is not designed for standalone biomarker discovery or general preclinical research without a trial; applicants pursuing those types of projects are directed to other ALSRP announcements. Within the context of an intervention trial, biomarker work can include target engagement markers (evidence the drug or device is hitting the intended target), pharmacodynamic biomarkers (evidence the therapy produces a measurable biological effect), and predictive or cohort-selective biomarkers (signals that help identify which patients, or which subgroups, are most likely to respond). Applicants are expected to clearly define the biomarker(s), explain why they matter for this specific intervention and patient population, and show how the biomarker plan will reduce uncertainty and improve the design of later-phase studies. The opportunity references an Attachment 8 Biomarker Statement for additional expectations, reinforcing that biomarker generation is central rather than optional.

The grant uses the standard federal definition of a clinical trial: a study in which human participants are prospectively assigned to one or more interventions, which can include placebo or other controls, to evaluate effects on biomedical or behavioral health-related outcomes. In practice, that means proposals need to look like executable trials with clear objectives, endpoints, oversight, and operational readiness. The DoD expects the trial to be designed in line with Good Clinical Practice (GCP), with appropriately selected outcome measures and a coherent plan for how data will be collected, analyzed, and monitored. Because the point is to inform later-stage development, endpoints and study procedures should be chosen not only to test a hypothesis, but also to generate decision-quality information for the next trial phase.

A strong scientific rationale is required, backed by a critical review of existing literature and preliminary data. Preliminary data relevant to the proposed clinical trial is explicitly required, which signals that this mechanism is aimed at interventions that have already reached a credible level of readiness for human evaluation. In addition, applicants must demonstrate access to an appropriate ALS patient population and provide a realistic recruitment and accrual strategy that fits the proposed timeline. They are also expected to discuss how evolving standards of care could affect enrollment, comparators, background therapies, and the interpretability of outcomes, which is particularly important in ALS where care practices and available therapies can influence both trial participation and measured endpoints.

Operational feasibility and regulatory readiness are major review themes. Applicants must document access to the investigational product or device for the full duration of the study, including evidence of availability and appropriate quality and stability. The materials are expected to meet manufacturing and quality standards aligned with FDA expectations for the intervention type and development stage, such as GMP principles for drugs/biologics or Quality System Regulation considerations for devices. The application should also address the team’s prior interactions with the FDA, including any past submissions when relevant, which helps reviewers gauge whether the investigators understand the regulatory pathway and can execute a compliant trial.

On the methods side, the program expects a well-developed statistical analysis plan, appropriate statistical expertise on the team, and a power analysis that justifies sample size in relation to the trial objectives. The data management plan must also be concrete, including use of an appropriate database to protect data integrity. For FDA-regulated trials, the database must be compliant with 21 CFR Part 11 and should follow suitable data standards, aligning with FDA expectations for electronic submissions and traceable, audit-ready records. Safety oversight is another required pillar: applicants must provide a safety management or pharmacovigilance plan appropriate to the risks of the intervention, and a clinical monitoring plan describing how compliance with GCP and protocol fidelity will be ensured across sites.

The opportunity also signals that successful execution depends on strong project coordination and institutional backing. Applicants should identify a study coordinator (or coordinators) who can shepherd the protocol through IRB review and any additional federal regulatory processes, manage coordination across participating sites, and support participant accrual. Institutional support must be clearly demonstrated, and when applicable the institution should commit to serving as the FDA regulatory sponsor, taking on sponsor responsibilities described in 21 CFR 312 Subpart D. This is a practical requirement that affects whether the trial can legally and operationally proceed, especially for IND-regulated drug studies.

Another major expectation is a credible transition plan. Applicants must explain how the product and the evidence generated will move forward after the pilot trial, including potential funding sources, resources, and next steps that would enable progression to a larger trial phase and/or movement toward market delivery if results justify it. This requirement reinforces that the award is intended to bridge a development gap, not simply to produce a publication. Finally, there are human-subject compliance expectations tied to transparency: funded trials are required to post the informed consent form used to enroll participants on a publicly available federal website in line with federal requirements under 32 CFR 219.

Administratively, this opportunity was issued by the Department of Defense, Department of the Army (USAMRAA) under Funding Opportunity Number W81XWH-21-ALSRP-TBPTA within CFDA 12.420, categorized under science and technology and other R&D. The funding instrument type allows for cooperative agreements and grants, eligibility is described as unrestricted (open to entity types, subject to any additional eligibility text in the full announcement), and the program anticipated making about three awards. The public posting lists an award ceiling as 0, which typically indicates that the cap may be specified elsewhere in the full solicitation or handled through program-specific budgeting guidance rather than being stated in that particular summary field. The original posting dates for this FY21 opportunity show a creation date of February 16, 2021 and an original closing date of July 15, 2021, indicating it was a time-limited competition for that fiscal year.

• The Department of Defense, Dept. of the Army -- USAMRAA in the science and technology and other research and development sector is offering a public funding opportunity titled "DoD Amyotrophic Lateral Sclerosis, Therapeutic/Biomarker Pilot Trial Award" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 12.420.
• This funding opportunity was created on Feb 16, 2021.
• Applicants must submit their applications by Jul 15, 2021. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• The number of recipients for this funding is limited to 3 candidate(s).
• Eligible applicants include: Unrestricted (i.e., open to any type of entity above), subject to any clarification in text field entitled Additional Information on Eligibility.

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