Neonatal sepsis is a life-threatening disease that affects 2 out of every 1,000 live births in the US. Caused by an invasive bloodstream infection (BSI) occurring either at the time of birth or soon thereafter, the disease's initial clinical manifestations are often non-specific, variable, at times subtle, and often common to signs of stress. Early diagnosis followed by appropriate antimicrobial intervention is a key predictor of outcomes. Selection of appropriate antimicrobials is limited by the current diagnostic process for detection and identification of BSIs which all rely on primary blood cultures. Cultures are slow, often requiring days to yield a result, and prone to false-negatives due to maternal antibiotics. In the absence of diagnostic confirmation, treatment is initiated upon suspicion of sepsis with broad spectrum antibiotics. Unfortunately, this strategy often misses the target and is associated with side effects, including damage to developing microbiomes. It is therefore critical to advance innovative diagnostic approaches which do not rely on culturing in order to facilitate accurate diagnosis and timely transition to evidence-based treatments. To address this unmet need, HelixBind developed RaPID/neo, a fully automated, sample-to-answer test for identifying BSIs directly from newborn blood within ~3 hours, without cultures. The test incorporates a broad test menu of 18 bacterial and fungal pathogens that make up the vast majority of neonatal sepsis cases. RaPID/neo is implemented on the RaPID (Resistance and Pathogen IDentification) platform, incorporating single-use test cassettes and a bench top Analyzer. RaPID/neo provides single CFUs/ml sensitivity across its test menu and is not confounded by polymicrobial infections nor prior antimicrobial treatment. In a preliminary clinical assessment, RaPID/neo demonstrated >92% sensitivity and 99% specificity across the assay. In this proposed Direct-to-Phase II project, HelixBind will build on its preliminary data to further product development by addressing analytical challenges associated with developing a test targeting this vulnerable patient population. We will review our findings and proposed studies for regulatory clearance with the FDA during a Pre-Submission process with the agency. Leveraging agency feedback, we will design an in-hospital study aimed at challenging our clinical studies plan in preparation for the pivotal trials for FDA clearance. To succeed in this endeavor, we have assembled an accomplished team with expertise in assay development, instrumentation, consumables manufacturing, clinical microbiology, and infectious disease as well as a successful track record of commercializing IVD platforms and assays. Together, we will build upon our preliminary work to complete product development, finalize a regulatory pathway, and challenge the system with an in-hospital study. Upon completion of this project, we will be well placed to initiate formal Analytical and Clinical studies for FDA clearance of RaPID/neo.
Public Health Relevance Statement: PROJECT NARRATIVE Neonatal sepsis, induced by a microbial infection of the bloodstream, is a serious and life-threatening disease. Timely diagnosis, identification of the etiological agent supporting administration of appropriate antimicrobials is critical for successful outcomes for these vulnerable patients. Unfortunately, current best practices are far too slow in identifying the infection and often fail due to the presence of maternal antibiotics. HelixBind has developed a diagnostic test allowing the detection and identification of the infection's etiological agent both days faster than currently possible as well as in the presence of common antimicrobials. The efforts described in this proposal will advance the maturity of the product culminating in an in-hospital study mirroring that which will be completed for FDA clearance. Success in this program will result in a critically needed diagnostic device, ready for manufacturing scale up as required for FDA trials and market launch.
Project Terms: Accounting; Adult; 21+ years old; Adult Human; adulthood; Affect; Antibiotics; Antibiotic Agents; Antibiotic Drugs; Miscellaneous Antibiotic; Biological Assay; Assay; Bioassay; Biologic Assays; Birth; Parturition; Blood; Blood Reticuloendothelial System; Blood Volume; Budgets; Chicago; Clinical Research; Clinical Study; Communicable Diseases; Infectious Disease Pathway; Infectious Diseases; Infectious Disorder; Diagnosis; Disease; Disorder; Exhibits; Feedback; Hospitals; Pediatric Hospitals; Children's Hospital; University Hospitals; Newborn Infant; 0-4 weeks old; Newborns; newborn child; newborn children; Infection; instrumentation; Laboratories; Methods; Morbidity - disease rate; Morbidity; mortality; neonatal mortalities; newborn death; newborn mortality; Neonatal Mortality; Patients; Risk; Sensitivity and Specificity; Specificity; Stress; Technology; Temperature; Testing; Time; Work; Diagnostic tests; TimeLine; base; Blood specimen; Blood Sample; Clinical; Phase; Ensure; pediatric; Childhood; instrument; Diagnostic; Whole Blood; Life; programs; Adopted; Hour; Clinic; System; neonatal sepsis; intrapartum; Live Birth; Diagnostic Device; Diagnostic Equipment; meetings; Medical center; early detection; Early Diagnosis; experience; Performance; success; microbial; member; Devices; Position; Positioning Attribute; Sampling; performance tests; assay development; cross reactivity; Intervention Strategies; interventional strategy; Intervention; Causality; causation; disease causation; Etiology; Clinical Microbiology; Address; Antimicrobial resistant; Resistance to antimicrobial; anti-microbial resistance; anti-microbial resistant; resistance to anti-microbial; resistant to anti-microbial; resistant to antimicrobial; Antimicrobial Resistance; Data; Detection; Regulatory Pathway; Preparation; Molecular; Process; Development; developmental; Evidence based treatment; microbiome; neonate; cost; design; designing; Sepsis; blood infection; bloodstream infection; Clinical assessments; Outcome; pathogen; pathogenic bacteria; bacteria pathogen; bacterial pathogen; Population; innovation; innovate; innovative; Resistance; resistant; antimicrobial; anti-microbial; patient population; product development; manufacturing scale-up; resistance gene; resistance locus; resistant gene; accurate diagnosis; diagnostic assay; outcome prediction; predictive outcomes; predictors of outcomes; DNA sequencing; DNA seq; DNAseq; pathogenic fungus; fungal pathogen; fungi pathogen; side effect; systemic inflammatory response; systemic inflammation; in-vitro diagnostics; diagnostic platform; diagnostic system; diagnostic strategy; diagnostic approach
