A phase IIA trial for the safety and tolerability of CD24Fc in prophylaxis of graft vs host disease.

Project Summary AbstractAcute graft versus host diseaseaGVHDis a principal contributor to transplant related mortalityTRMand develops in approximatelyof recipients receiving unrelated donor hematopoietic stem cell transplantationHSCTdespite standard immunosuppressive prophylaxisThusnovel GVHD prophylaxis treatments which successfully attenuate aGVHD and related complications such as infection are urgently neededIn additionan important function of allogeneic HSCT is to use donor T cells to eliminate allogeneic leukemia cellsthis is called the graft versus leukemiaGVLHowevercurrent prophylaxis and treatment of GVHD is based on general immunosuppressionwhich causes high risk of infection and cause significant mortalitywhile contributing to leukemia relapse by reducing GVLThe ultimate goal of this research project is to further the clinical development of a novel drug candidate for the prophylactic treatment of aGVHD in leukemia patients undergoing allogeneic myeloablative HSCTIn preclinical testing in murine modelsthe drug candidateCDFchas been shown to significantly reduce GVHD severity and improve in survival while preserving GVLmaking it an ideal drug for prophylaxis of GVHD in leukemia patientsThe activity associated with GHVD reduction and GVL preservation is strongly supported by in vitro data that describes the mechanism of action of the CDFc drug productCDFc has been demonstrated to be safe in healthy human subjects in a Phase I clinical trial and the current projecta Phase IIa clinical trialaims to provide the first toxicity safetypharmacokineticspharmacodynamics and biological activity data for CDFc in human HSCT transplantation patientsThese data demonstrate that we have more than reached the milestones typically set for phase I SBIR grantand thus qualify us for phase II direct SBIR applicationThe proposed Phase IIa trial is a randomized double blind single ascending dose trial comprised ofdosing cohorts ofpatientstreatment placebofor a total planned enrollment ofsubjectsThe clinical trial will have two specific aims addressed by different phasesspecific aim I will determine the safety and tolerability of CDFc in a single ascending dose escalation studyand define the recommended Phase II doseor Maximum Tolerated Dosefor prophylaxis of GVHD in a large Phase IIb expansion trialand specific aim II will assess the pharmacokinetics and in human activity of CDFc in leukemia and myeloid dysplasia syndrome patients receiving HSCTCDFc will be administered to patients on a background of standard of care prophylaxis comprising a calcineurin inhibitor and methotrexate to maximize patient safetyThe proposed study represents a major milestone necessary not only for the development of the novel immunomodulating drug for a GVHDbut also for commercialization effort of the company Project NarrativeThe proposed project will enable development of our lead productCDFcthrough a Phase IIa clinical trial towards the development of a novel drug for the prevention of acute graft versus host diseaseGVHDin leukemia patients undergoing allogeneic hematopoietic stem cell transplantationHSCTAcute GVHD is the principle contributor to transplant related mortalityTRMand develops in approximatelyof recipients receiving unrelated donor HSCT despite standard immunosuppressive prophylaxisThusnovel GVHD prophylaxis treatments which successfully attenuate acute GVHD and related complications such as infection are urgently needed