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-22-035 - 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-22-036 - 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 thatthe National Institute of Neurological Disorders and Stroke (NINDS) intends to publish a Funding Opportunity Announcement (FOA) that will solicit applications for the Stroke Preclinical Assessment Network (SPAN) Testing Laboratories. 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. Testing laboratories will be expected to work with the SPAN Coordinating Center and Intervention Contributors to facilitate the parallel testing of multiple cerebroprotective interventions 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 the SPAN Testing Laboratories. Each testing laboratory will conduct tests of selected cerebroprotective interventions that will be chosen from well-scoring applications submitted under the companion intervention RFA. Testing laboratory applications should focus solely on the expertise and infrastructure that each prospective site can bring to SPAN. It is expected that SPAN sites will be academic or other preclinical research laboratories with documented expertise in the transient middle cerebral occlusion (tMCAo) model of ischemic stroke and relevant comorbidities (e.g., aging, hypertension, diabetes, hyperlipidemia, obesity, etc.). In addition, laboratories must demonstrate expertise in the assessment of clinically relevant, long-term functional outcome measures, with a particular emphasis on small rodent neuroimaging and behavioral testing- it is an absolute requirement that laboratories have expertise in and access to animal MRI facilities. All applicants must agree to test multiple interventions in collaboration with the other testing laboratories in a randomized and blinded fashion. SPAN testing laboratories 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 sites, the PD/PI of each proposed intervention, and NINDS Program staff.