NIAID seeks applications for mid-stage research developing candidate medical countermeasures (MCMs) already demonstrating efficacy to mitigate or treat radiation injuries through the notice of funding opportunity (NOFO) Development of Candidate Radiation/Nuclear Medical Countermeasures (MCMs) (U01, Clinical Trial Not Allowed).
The mission of the Radiation and Nuclear Countermeasures Program (RNCP), guided by the NIH Strategic Plan and Research Agenda for Medical Countermeasures Against Radiological and Nuclear Threats, is to accelerate the development of approaches to diagnose, mitigate, and treat radiation injuries resulting from a mass casualty, radiological, or nuclear incident.
Research Objectives and Scope
The focus of this NOFO is to advance development of candidate MCMs with post-irradiation exposure administration data demonstrating efficacy to mitigate or treat radiation injuries from acute radiation syndrome (ARS) or the delayed effects of acute radiation exposure (DEARE). Product development should focus on mitigating ARS or DEARE. Additionally, researchers will elucidate mechanisms of action of MCMs to meet product licensure requirements.
NIAID will support studies that propose topics such as:
- Research and development of a lead MCM to enhance survival (primary endpoint) or mitigate major morbidities in irradiated animal models predictive of human responses, when administered as a single or multiple-dose regimen after radiation exposure (with administration of the first dose beginning at a minimum of 24 hours or later post-irradiation, and 48 hours or later for neutropenia or thrombocytopenia-targeted hematopoietic subsyndrome (H-ARS) products), with emphasis on broad activity (e.g., multi-syndrome, multi-organ).
- Research and development of MCMs for mitigation or treatment of potentially lethal ARS, or DEARE, including radiation injuries to the gastrointestinal, cutaneous, pulmonary, renal, cardiovascular, or central nervous system compartments of the body. In addition, MCMs intended to address hematopoietic injuries not associated with neutrophil or platelet loss are of interest; however, if amelioration of radiation-induced neutropenia or thrombocytopenia is the target of the MCM, they must be effective when administered at time points no earlier than 48 hours post-irradiation.
- MCMs to treat radiation combined injuries (e.g., radiation exposure concomitant with burn, wound, infection, or other physiological trauma).
- Formulations of products or improvements to existing products for civilian populations that can be easily administered in a mass casualty scenario either by first responders or self-administered are preferred (e.g., via oral, subcutaneous, trans-cutaneous, intramuscular, or inhalation routes, as opposed to intravenous routes which are challenging in a mass casualty setting).
- Testing of candidate MCMs in animal models that are representative of adult, pediatric, or geriatric human populations, and consideration of any possible sex differences of the radiation or drug response in these models.
- Testing of small molecules, biologics, and cell products for ARS or DEARE.
- Identification of early surrogate markers of candidate MCM efficacy post-irradiation (e.g., in hematologic parameters, cytokine or enzyme profiles, histological markers, inflammatory responses) that could potentially be used as secondary endpoints/observations to support mechanisms of action and linkage of pharmacodynamic effects across species.
- Product development efforts to support submission of an investigational new drug (IND) application to the FDA to facilitate licensure and potential inclusion in the Strategic National Stockpile. Examples include the following:
- Efficacy studies to optimize formulation, dose, and dose scheduling, and to inform the design of subsequent Good Laboratory Practice (GLP).
- Pivotal efficacy study protocols.
- Drug product stability studies.
- Drug product current Good Manufacturing Practice manufacturing scale-up.
- GLP toxicology and pharmacology safety studies.
- Pharmacokinetic (PK) and pharmacodynamic (PD) studies.
These product development efforts will advance the development of MCMs of radiation injury toward Phase I clinical trial safety studies or GLP animal model pivotal efficacy studies for FDA licensure.
While basic testing of compound efficacy or formulation work may not be considered inherently innovative, application and optimization in target tissues are highly valued.
Nonresponsive Research Applications
Do not propose the following research topics in your application or NIAID will consider it nonresponsive and not review it.
- Studies proposing testing for a radio-protectant compound(s) that must be administered prior to radiation exposure to be efficacious.
- Studies proposing administration of a candidate MCM at times earlier than 24 hours after radiation exposure (or earlier than 48 hours after radiation exposure for MCMs targeting neutropenia or thrombocytopenia resulting from H-ARS).
- Clinical trials (all phases).
- Work proposing dose ranges or exposure parameters that are not relevant to a radiation accident or attack (e.g., studies using fractionated radiation exposures, unless justified by opportunity to collect samples from radiotherapy patients).
- Biodosimetry devices and biomarkers to be used to determine radiation dose received (radiation triage).
- Studies to investigate MCMs for thermal-only burns; radiation-induced cancers; cataracts; or other ocular, reproductive, or muscular damage.
- Lack of preliminary data or milestones.
- Studies that primarily focus on HIV/AIDS-related research.
Keep in mind, your research plan must include specific, detailed, explicit, and quantitative annual milestones.
Budget, Deadline, and Project Period Information
Application budgets are not expected to exceed $350,000 in direct costs per year and should reflect the actual needs of the proposed project. The scope of the proposed project should determine the project period and the maximum project period is 5 years.
Applications are due by January 26, 2024, at 5 p.m. local time of the applicant organization.
Contact Information
Direct any questions to Dr. Carmen Rios, NIAID’s scientific/research contact at carmen.rios@nih.gov or 240-627-3553. If you have peer review questions, contact Dr. Hiten Chand, NIAID’s peer review contact, at hiten.chand@nih.gov or 240-627-3245.