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-22-035 - Notice of Intent to Publish a Funding Opportunity Announcement for Limited Competition: Stroke Preclinical Assessment Network (SPAN) to Support Translational Studies for Acute Cerebroprotection - Coordinating Center (U24 Clinical Trial 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 thatthe National Institute of Neurological Disorders and Stroke (NINDS) intends to publish a Funding Opportunity Announcement (FOA) that will solicit applications for Stroke Preclinical Assessment Network (SPAN) Interventions. 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 outcome as compared to reperfusion alone and/or extend the therapeutic window for reperfusion, with the overall end 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, and intervention contributors. This infrastructure is expected to test multiple interventions in animal models of transient cerebral ischemia.

This upcoming FOA is expected to be published in the early Winter of 2021. It will utilize the U01 cooperative agreement mechanism. Intervention contributors will be expected to propose a promising cerebroprotective intervention, which will be tested head-to-head with other candidate therapeutics using the SPAN infrastructure in experimental models of ischemic stroke.

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects. This will be an open competition- applicants who did not previously participate in the first funding cycle of SPAN will be welcome to apply.

Three companion SPAN FOAs (two open competition, one limited competition) are also expected to be published in the early Winter of 2021. Details of these other reissues 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 (RFA NS-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 an open competition for SPAN Interventions. Prospective applicants can propose a specific cerebroprotective intervention which will be tested by the network testing laboratories. All proposed interventions must be supported by extensive and rigorously obtained preliminary efficacy data (published and/or unpublished) in a relevant experimental stroke model (transient middle cerebral artery occlusion). While applications can be submitted to both the SPAN testing laboratory and intervention RFAs, an award would only be made for one or the other to avoid a conflict of interest (i.e., a PD/PI can serve as either a testing laboratory or intervention contributor, but not both). SPAN interventions will be supported using the U01 cooperative agreement mechanism.

The overall governing body of the network will be a SPAN Steering Committee (appointed by the CC in conjunction with 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.