Development, Preclinical and Preanalytical Evaluation of a Rapid Point-of-Care NAAT Device to determine Ciprofloxacin Sensitivity of Gonococci in Urogenital Samples

Click Diagnostics has developed a PCR based diagnostic test that is rapidsample to answer andltminsmallportabledisposable and that automatically performs and integrates sample processingPCR amplificationand amplicon detectionUnlike other PCR platformsthe Click device does not require a separate instrumentThe first clinical application of the Click platform will simultaneously detectSTIsNgonorrhoeaeNGCtrachomatisCTand TvaginalisTVin self collected vaginal swabsand has entered a pivotalk CLIA waivedNIAID funded clinical trialwith expected FDA approval inIn this FastTrack projectwe propose to add a critical new function to the existing multiplexed devicedetermine whether an NG strain is ciprofloxacin sensitiveThe CDC has identified drug resistant Neisseria gonorrhoeae as an urgent threatnearlyof thenew Neisseria gonorrhoeaeNGinfections each year are antibiotic resistant and have the potential to become virtually untreatableAlthough onlyof gonorrhea cases are ciprofloxacin resistantthe CDC recommends physicians prescribe ceftriaxonea last resort antibioticfor all cases of gonorrheaExtensive scientific and clinical data suggest that ciprofloxacin resistant isolates harbor a single nucleotide polymorphismSNPat codonof the gyrase A geneThereforeby identifying patients with the WT Serin the gyrase A gene will provide individualized treatment to those susceptible to ciprofloxacinthus minimizing the use of ceftriaxoneClick s fastaccuratepatient side test identifying antibiotic susceptibility would dramatically improve patient managementwhile extending the utility of last resort antibioticsThe goal of this project is to addin Phase Ithe capacity to detect WT gyrase A at Serto the current Click STI assay and in Phase IIto integrate this assay onto the Click platform and carry out systematic preanalytical and preclinical testing to qualify the product for a clinical trialClick has partnered with Jeff KlausnerMDUCLAa leading authority on diagnostics and treatment of STIsand John SantaLuciaPhDDNA Softwareto assist in silico probe designassay developmentand testingIn Phase IClick will optimize our probe detection method to ciprofloxacin sensitive WT Serin the gyrA geneNextwe will add the new NG cipro susceptibility assay into the existing multiplexed assay and demonstrate that the new assay maintains the functionality of the current one with similar limits of detectionPCR efficiencysensitivityand specificityIn Phase IIClick will modify the device to integrate the multiplexed CT NG TV NGciproS assay and enable volume manufacturing by reducing sizeweightand complexity of partsFinallywe will perform preclinical and preanalytical studies on deidentified clinical isolates obtained from UCLA archivewhich will provide preliminary sensitivity and specificity data and inform any assay and device adjustments required for analytical and clinical studies ahead of FDA approvalSuccessful completion of this work will yield a production version of a rapidpatient side device capable of identifying CT NG TV and ciprofloxacin susceptible NG that is ready for clinical testing Withnew Neisseria gonorrhoeaeNGinfections each year andof all NG strains showing resistance to antibioticsdrug resistant gonorrhea is now an urgent public health threatIn this projectClick Diagnostics will add the capability to identify ciprofloxacin susceptible NG strains to our current diagnostic deviceallowing approximatelyof gonorrhea infected patients to be treated with oral ciprofloxacinrather than the current dual therapy recommendation of ceftriaxone and azithromycinA point of care device that integrates drug susceptibility information with diagnosis of sexually transmitted infections will guide treatment decisions to improve patient outcomeswhile reducing the unnecessary use of extended spectrum cephalosporinsand extending the life of older antibiotics