RFA-NS-22-004 - Limited Competition: Stroke Preclinical Assessment Network (SPAN) to Support Translational Studies for Acute Cerebroprotection - Coordinating Center (U24 Clinical Trial Not Allowed)

NOT-NS-22-034 - Notice of Intent to Publish a Funding Opportunity Announcement for Stroke Preclinical Assessment Network (SPAN) to Support Translational Studies for Acute Cerebroprotection - Testing Laboratories (U01 Clinical Trial Not Allowed)

NOT-NS-22-036 - Notice of Intent to Publish a Funding Opportunity Announcement for Stroke Preclinical Assessment Network (SPAN) to Support Translational Studies For Acute Cerebroprotection - Interventions (U01 CT Not Allowed)

NOT-NS-22-037 - Notice of Intent to Publish a Funding Opportunity Announcement for Stroke Preclinical Assessment Network (SPAN) to Support Translational Studies for Acute Cerebroprotection - Interventions from Small Businesses (U44 CT Not Allowed)

National Institute of Neurological Disorders and Stroke (NINDS)

The purpose of this Notice is to inform the community that the National Institute of Neurological Disorders and Stroke (NINDS) intends to publish a Limited Competition Funding Opportunity Announcement (FOA) that will solicit an application for the Stroke Preclinical Assessment Network (SPAN) Coordinating Center. SPAN supports late-stage preclinical efficacy studies of putative cerebroprotectants to be given prior to or at the time of reperfusion in experimental stroke models. Parallel testing of the most promising interventions in a network structure will help to determine if an intervention can improve stroke outcome as compared to reperfusion alone and/or extend the therapeutic window for reperfusion, with the overall goal of guiding the selection of the most promising agent(s) to transition to future Phase II clinical trials (to be conducted through StrokeNet). SPAN will consist of one Coordinating Center (CC), several testing laboratories, as well as intervention contributors. This infrastructure is expected to test multiple interventions in animal models of transient cerebral ischemia.

This limited competition FOA is expected to be published in the early Winter of 2021. It will utilize the U24 cooperative agreement mechanism. The CC will be expected to work with SPAN testing laboratories and intervention contributors to provide centralized administrative oversight and efficient coordination of all aspects of the network.

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects. The only institutions that will be eligible to apply are those who were previously awarded a cooperative agreement under RFA-NS-18-034.

Three open competition companion FOAs for other aspects of the SPAN network are also expected to be published in the early Winter of 2021. Details of these other opportunities are covered in companion notices.

Ischemic stroke remains a leading cause of adult disability and death across the world and is currently the 5^th leading cause of death in the United States and the 3^rd cause of death worldwide. Over the past several years, acute endovascular therapy (EVT) with stent-retriever devices and access to advanced neuroimaging modalities have transformed the standard of care for ischemic stroke, offering the unprecedented opportunity to significantly improve clinical outcome in selected patients treated as late as 24 hours after stroke onset. However, despite these successful advances, not all patients respond to recanalization with a complete cure which supports an urgent need to further develop effective adjunctive treatments for acute stroke that can be given prior to or at the time of reperfusion. Specifically, a cerebroprotectant that can stabilize the stroke penumbra or reduce the rate of infarct core expansion may offer significant benefit if administered as early as possible in a stroke’s evolution.

In 2018, NINDS launched the Stroke Preclinical Assessment Network (SPAN), the first iteration of which consisted of one coordinating center (CC) (RFA-NS-18-034) and six study sites (RFANS-18-033), each of which proposed a promising cerebroprotective modality, all selected through rigorous NIH peer review. The network was designed to perform highly rigorous and reliable preclinical testing with a timeline and resources that would not be possible for a single laboratory, while at the same time allowing a blinded head-to-head comparison of each putative cerebroprotective therapy.

During the first funding cycle, the SPAN network successfully demonstrated its ability to perform parallel testing of multiple interventions in a time and cost-effective manner. As a result, the NINDS now intends to publish multiple new RFAs to further expand SPAN activities (Coordinating Center, Testing Laboratories, Interventions, and Interventions from Small Businesses- see companion notices for descriptions of each activity).

There will be a limited competition for the SPAN Coordinating Center. The CC will work collaboratively with all SPAN testing laboratories, intervention contributors, small business partners, and the NINDS to provide overall study coordination. The CC will be supported using the U24 cooperative agreement mechanism, and only institutions who have been previously supported under RFA-NS-18-034 will be eligible to apply.

The overall governing body of the network will be a SPAN Steering Committee (appointed by the CC in conjunction with the NINDS), which will consist of the PD/PI of the CC, the PD/PI of each of the network's testing laboratories, the PD/PI of each proposed intervention, and NINDS Program staff.