Candidate Acute Traumatic Brain Injury (TBI) Management Capabilities (CATMC) and Acute TBI Diagnostics and Monitoring (ATDM) in Austere Environments
Current wartime operations assume that the United States and our allies will maintain air, land, maritime, space and cyber superiority. Future conflicts against peer and near-peer adversaries are expected to be layered stand-offs, fought across multiple domains (Multi-Domain Operations, MDO). Mission success will be determined by our ability to compete to expand the competitive space, penetrate both strategic and operationally, disintegrate enemy’s defenses, exploit enemy weaknesses and re-compete to consolidate gains. Medical plays a critical role in each aspect of MDO and must modernize rapidly to maintain Force readiness and increase soldier lethality. Diagnosis, treatment, monitoring, and maintenance of TBI casualties in the acute setting can significantly improve long-term functional outcomes and reduce injury severity. Development of diagnosis and treatment interventions to reduce injury severity and improve casualty maintenance that can be employed at Role 1 (far-forward medical care), over the course of the subsequent 1-3 days following injury, will facilitate reductions in permanent brain damage, better Warfighter care and improved return-to-duty times.
Traumatic brain injury (TBI) is a major health burden in both military and civilian populations. In the last two decades, there have been approximately 420,000 documented incidents of Service members sustaining at least one TBI. Future combat operations are expected to result in an increase in time to evacuation, delaying TBI diagnosis and treatment during the most critical period after injury. This MTEC RPP is aimed at acute diagnostic, therapeutic and management
technologies across the spectrum of TBI severities capable of being used in a far-forward operational environment. The CCCRP has identified two focus areas for funding. To meet the intent of this RPP, each Solution Brief MUST specifically address only ONE of the two Focus Areas described below. Offerors are not limited to a Solution Brief submission. Projects not aligned to at least one of these Focus Areas will not be considered for funding.
- FOCUS AREA #1 (Treatments): Development of a treatment (pharmaceutical, technological, etc.) for traumatic brain injury. Despite the enormous burden of TBI on Service members and their family, there is no effective FDA-approved therapeutic intervention. In addition to the complexities of treating TBI, future operational environments pose an addition barrier to the treatment of TBI: time and location. Therefore, the intent of this focus area is to enable the advancement of candidate treatments (pharmaceutical, technological, etc.) applicable to the far forward environment through Phase I clinical trials for the treatment of TBI.
- FOCUS AREA #2 (Diagnostics): Diagnostic, prognostic and management technologies for TBI, most likely requiring FDA clearance. Currently, TBI severity is stratified by Glasgow Coma Scale (GSC)- mild (GCS 14-15), moderate (GCS 9- 13), and severe (GCS 3-8); however, a more thorough classification of TBI based on endophenotypic characterization of the injury (neurological exam, imaging, blood-based biomarkers, symptomology, etc.) would provide a more comprehensive picture of the overall injury burden. Additionally, in future combat operations, delayed evacuation times will create a prolonged care scenario that will require TBI casualty management for periods in excess of 24 hours. Therefore, the intent of this focus area is to enable the advancement of candidate technologies for the objective diagnosis, prognosis, and/or management of TBI. Project proposals are currently under evaluation.
The research project award recipients were selected from the Offerors who responded to MTEC’s Request for Project Proposals (20-15-TBI).
BurRapid Intracranial Pressure Monitor Attachment for Traumatic Brain Injury
Project Team: Critical Innovations
Award Amount: $1.47M (additional cost share = $361K)
Project Duration: 14 months
Project Objective: The patented BurRapid™ Intracranial Access Platform focuses on task shifting already-established, evidence-based neurosurgical care out of the operating room and into the hands of far forward providers at point-of-need. The proposed BurRapid™ ICP Monitor Attachment provides a minimally-invasive diagnostic and prognostic technology for managing moderate-severe TBI in the Role 1 and later combat environments, especially during prolonged field care.
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending-Dose Trial to Evaluate the Safety, Tolerability, Immunogenicity, and Pharmacokinetics of Intravenous PNT001 in Hospitalized Patients with Acute Traumatic Brain Injury (TBI)
Project Team: Pinteon Therapeutics
Award Amount: $3.00M (additional cost share = $3.71M)
Project Duration: 25 months
Project Objective: Pinteon Therapeutics is proposing to conduct a Phase 1, randomized, double-blind, placebo-controlled, multiple-ascending-dose trial to evaluate the safety, tolerability, immunogenicity, and pharmacokinetics of intravenous PNT001 in hospitalized patients with acute Traumatic Brain Injury (TBI). PNT001 is a humanized full-length IgG4 S228P monoclonal antibody targeting the cis conformation of the phosphorylated Thr231-Pro232 motif in human full-length (2N4R) tau.
Intracranial Pressure Assessment and Screening System (IPASS): A Portable Device for Non-Invasive Monitoring of Intracranial Pressure (ICP) in Traumatic Brain Injury (TBI)
Project Team: Vivonics
Award Amount: $2.68M (additional cost share = $275K)
Project Duration: 20 months
Project Objective: Vivonics, Inc. is developing a non-invasive, optical device to measure intracranial pressure (ICP), which can elevate in cases of traumatic brain injury (TBI). This device, called IPASS (Intracranial Pressure Assessment and Screening System), is based on non-invasive near-infrared (NIR) measurements, which allows for a fast and easy assessment of TBI conditions, as well as on-going monitoring. The IPASS system is a lightweight handheld device designed for far-forward military applications, where it is not possible to get the wounded warrior to a trauma surgeon within the first “golden hour” after injury. Rapid and continuous non-invasive ICP readings from IPASS provide vital objective, actionable information to manage the patient in the interim helping to avoid secondary brain damage, reduce mortality and improve long-term outcomes. Vivonics has formed CranioSense to attract private investment needed and bring IPASS through FDA clearance and to the market to address both military and civilian needs.
Development of CN-105, a novel neuroprotective peptide, for Treatment of Traumatic Brain Injury
Project Team: AegisCN
Award Amount: $0.83M (additional cost share = $97K)
Project Duration: 18 months
Project Objective: CN-105 is a novel neuroprotective chemical entity for evaluation in traumatic brain injury (TBI) and is the product of an active collaboration between academic investigators at Duke University and the academic spinoff biotech company, AegisCN LLC. CN-105 has demonstrated improvement in histological and behavioral outcomes in multiple preclinical models that recapitulate relevant features of TBI. The objective of the current proposal is to develop a lyophilized drug product that would be optimized for use in the far-forward military setting; design a clinical trial for patients with moderate-severe TBI that would establish dose optimization, safety, and feasibility in conjunction with TRACK-TBI, and receive IND approval for use in this setting. Thus, by meeting all manufacturing, regulatory, and safety requirements necessary to proceed to the TBI Phase 2 Clinical Trial, we will achieve Therapeutic Readiness Level 6 (TRL 6) in the base Period of Performance (POP 1)
Non-Invasive Monitoring of Traumatic Brain Injury Progression using the Infrascanner 1 (MOBI-1)
Project Team: University of Alabama at Birmingham
Award Amount: $2.22M (additional cost share = $572K)
Project Duration: 22 months
Project Objective: The Infrascanner is an existing, hand-held, non-invasive, and easily portable device, which is FDA-cleared to detect traumatic intracranial hematomas. The “Monitoring of Traumatic Brain Injury Progression using the Infrascanner 1” (MOBI-1) study aims to expand the utility of the device by evaluating its ability to serially monitor patients with ICH, following the initial detection, to detect expansion prior to the observance of clinical signs of neurological deterioration.
Role 1 Traumatic Brain Injury Evaluation Using Low Power Radio Frequency
Project Team: Sense Diagnostics
Award Amount: $2.45M (additional cost share = $1.48M)
Project Duration: 19 months
Project Objective: Sense Diagnostics is developing a portable, light weight, non-invasive scanner that uses low power radio waves to detect and monitor traumatic brain injuries in a far forward operating environment.
Clinical Phase 1 Development of Battlefield TBI Therapeutic AST-004
Project Team: Astrocyte Pharmaceuticals
Award Amount: $2.97M (additional cost share = $480K)
Project Duration: 17 months
Project Objective: Astrocyte Pharmaceuticals will conduct a first-in-human single ascending dose (SAD) and multiple ascending dose (MAD) Phase I clinical safety trial of AST-004, a promising novel therapy for traumatic brain injury (TBI). In addition, we will determine the optimal oral formulation of AST-004, which is a stable, small molecule that is highly amenable to battlefield friendly formulations. At project conclusion, Astrocyte Pharmaceuticals will have 1) AST-004’s seven-day safety profile (TRL6) ready for a Phase 2 evaluation of acute TBI efficacy up to at least a 100 mg daily dose, and 2) an optimized oral AST-004 formulation with suitable 6-month stability under extreme conditions.
Clinical Investigation of CMX-2043 for the Acute Treatment of Traumatic Brain Injury (TBI)
Project Team: Ischemix
Award Amount: $2.94M (additional cost share = $518K)
Project Duration: 25 months
Project Objective: The objective of the proposed program is to fund the early stages of clinical development of CMX-2043, a compound for the treatment of acute traumatic brain injury (“TBI”). CMX-2043 is a novel, patented, multi-modal cytoprotective compound whose mechanism of action and preclinical data suggest that intervention with the drug candidate in patients with acute TBI may provide broad neuroprotection, including altering the trajectory of neuronal loss, reducing incremental neural tissue injury and improving clinical neurological outcomes. In PoP1 of this response to the RPP, we propose to complete a Phase 1a Single Ascending Dose (SAD) safety study and a Phase 1b Multiple Ascending Dose (MAD) safety study of CMX-2043 in healthy volunteers, and in PoP2 we propose to complete a Phase 2a safety and Proof of Clinical Concept study of the compound in patients with acute TBI.