The Exploratory Clinical Trial Grants in Arthritis and Musculoskeletal and Skin Diseases (R61 Clinical Trial Required) funding opportunity, issued by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) within the National Institutes of Health (NIH), is designed to support short-term, interventional clinical trials. These trials must address research questions related to NIAMS’s mission of advancing prevention, diagnosis, and treatment of rheumatic, musculoskeletal, or skin diseases. The primary goal of this program is to generate clinically meaningful improvements in patient outcomes, function, or symptom management.

This funding opportunity supports a broad range of exploratory studies, including proof-of-concept, first-in-human, Phase I, and Phase II clinical trials. Trials may involve interventions such as drugs, biologics, devices, surgical methods, dietary strategies, behavioral therapies, and rehabilitation techniques. Applications must focus on unmet medical needs, plausible biological mechanisms, or compelling preclinical or early clinical data. While preliminary clinical data is not required, it can be included if available. Special consideration will be given to applications addressing rare diseases or incorporating biomarker evaluations. This NOFO is not intended for large-scale efficacy or effectiveness trials.

The program allows a maximum budget of $600,000 in direct costs over a three-year period, with no more than $300,000 requested in any single year. The maximum project period is three years, and applications must include a well-justified rationale for the study, clear scientific goals, and feasible timelines. Proposals must adhere to rigorous standards of study design, data monitoring, and participant safety. NIAMS requires applicants to submit a Clinical Monitoring and Data Management Plan, as well as specific intervention-related documents, such as Investigator’s Brochures or Intervention Monitoring Manuals.

Eligible applicants include higher education institutions, nonprofits, for-profit organizations, state and local governments, tribal organizations, independent school districts, public housing authorities, and regional organizations. Foreign organizations and components of U.S. institutions are not eligible. Applicant organizations must complete registrations in systems such as SAM.gov, eRA Commons, and Grants.gov prior to submission. Program Directors or Principal Investigators (PDs/PIs) must have eRA Commons accounts. Applications must comply with NIH submission requirements, including formatting, page limits, and required attachments.

Applications will be evaluated based on NIH peer review criteria, which include significance, innovation, approach, investigator qualifications, and the feasibility of the proposed study. Special emphasis will be placed on the clinical significance, biological rationale, scientific rigor, and feasibility of achieving milestones and timelines. Reviewers will also assess the adequacy of clinical monitoring and data management plans, as well as the appropriateness of intervention-related documents. Inclusion plans to ensure participant diversity, particularly with respect to sex, age, and race/ethnicity, are critical for evaluation.

The first application due date is March 4, 2025, with additional deadlines on July 2, 2025, and November 4, 2025. Subsequent deadlines are scheduled through November 2026. Applications are due by 5:00 PM local time of the applicant organization. Awards are contingent upon scientific merit, availability of funds, and relevance to NIAMS program priorities. Successful applicants will receive a Notice of Award (NoA) and must adhere to NIH data and safety monitoring policies, including ClinicalTrials.gov registration requirements.

For further information, applicants are encouraged to consult NIAMS program staff early in the application process. Specific contacts are available for research areas such as rheumatic diseases, osteoarthritis, muscle and bone diseases, orthopedics, and skin diseases. Administrative and technical support is also provided for application submission and post-award management. Complete details, including application instructions and submission requirements, are available in the NIH Application Guide and related resources.