SBIR-STTR Award

Platelet Transfusion Refractoriness (PTR) or the failure to achieve the desired level of blood platelets afterplatelet transfusion, hampers the management of bleeding episodes in thrombocytopenic patients. PTRcondition is associated with a high risk of severe bleeding complications and reduced survival rate, longerhospital stays and higher hospital costs. Existing management strategies are based on the transfusion ofleukodepleted products, HLA-matched platelets, or cross-matched platelets which are obtained after lengthyand expensive procedures. Alternatives consisting of thrombopoietin mimetics, or recombinant factor XIIIhave not shown the ability to reduce mortality. Fibroplate is proposing a new approach to manage bleedingin thrombocytopenic patients who develop PTR, based on the intravenous injection of Fibrinoplate-S (FPS),a ready-to-use suspension of fibrinogen-coated albumin nanospheres. FPS significantly reduces the bleedingtime and improves overall survival rate associated with radiation-induced thrombocytopenia in preclinicalrodent models through the formation of co-aggregates with the residual activated platelets at wound sites onthe endothelium of the blood vessel. Various preclinical studies demonstrated that FPS is safe and does notinduce intravascular coagulation. Remarkably, FPS is not sequestered in the spleen, and FPS specificantibodies have not been detected after its administration in humans. These characteristics, together with itshemostatic capacity support the use of FPS in the management of thrombocytopenic patients with immuneand non-immune PTR. However, their efficacy and safety need validation in a thrombocytopenic preclinicalmodel under PTR conditions. This NIH SBIR Phase I aims at investigating i) the efficacy of FPS in reducingbleeding parameters in an established (double) model of thrombocytopenia and PTR (TPTR) preclinically inrabbits and ii) the safety of the proposed approach. By offering effective treatment, Fibroplate is expected toreduce bleeding complications and improve and promote survival in thrombocytopenic patients with PTR.

Public Health Relevance Statement:
PROJECT NARRATIVE Platelet Transfusion Refractoriness (PTR or the failure to achieve the desired level of blood platelets after platelet transfusion) hampers the management of bleeding episodes in thrombocytopenic patients and is associated with a high risk of severe bleeding complications, reduced survival rate, longer hospital stays and higher hospital costs. Safe and immediate strategies for breakthrough bleeding in PTR patients are lacking. Fibroplate proposes a new approach to manage breakthrough bleeding in thrombocytopenic PTR patients based on the intravenous injection of Fibrinoplate-S (FPS), a ready-to-use suspension of fibrinogen-coated albumin nanospheres, which has already been shown to be effective in thrombocytopenic patients without PTR.

Project Terms:
Albumins ; Animals ; Antibodies ; Antibody Specificity ; Autopsy ; necropsy ; postmortem ; Biological Availability ; Bioavailability ; Biologic Availability ; Physiologic Availability ; Biological Products ; Biologic Products ; Biological Agent ; biopharmaceutical ; biotherapeutic agent ; Bleeding time procedure ; Bleeding Time ; Blood ; Blood Reticuloendothelial System ; Blood Platelets ; Marrow platelet ; Platelets ; Thrombocytes ; Blood Vessels ; vascular ; Body Weight Changes ; Weight Change ; Clinical Chemistry ; Chicago ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Ear ; Endothelium ; Factor XIII ; Blood Coagulation Factor XIII ; Coagulation Factor XIII ; Factor XIII Transamidase ; Fibrin Stabilizing Factor ; Fibrinase ; Laki-Lorand Factor ; Fibrinogen ; Blood Coagulation Factor I ; Blood Coagulation Factor One ; Blood Factor One ; Coagulation Factor I ; Coagulation Factor One ; Factor I ; Factor One ; Hematology ; Hemorrhage ; Bleeding ; blood loss ; Hemostatic function ; Hemostasis ; Hemostatic Agents ; Hemostatics ; Human ; Modern Man ; Illinois ; Incidence ; intravenous injection ; Leadership ; Length of Stay ; Number of Days in Hospital ; hospital days ; hospital length of stay ; hospital stay ; mortality ; United States National Institutes of Health ; NIH ; National Institutes of Health ; Necrosis ; Necrotic ; Patients ; Petechiae ; Plasma ; Blood Plasma ; Plasma Serum ; Reticuloendothelial System, Serum, Plasma ; Oryctolagus cuniculus ; Domestic Rabbit ; Rabbits ; Rabbits Mammals ; Risk ; Safety ; Saline ; Saline Solution ; skin ulcer ; ulcerative wounds ; Spleen ; Spleen Reticuloendothelial System ; Splenomegaly ; Enlarged Spleen ; Survival Rate ; Suspensions ; Suspension substance ; Testing ; Thrombocytopenia ; Thrombopenia ; Thrombopoietin ; MGDF ; MGDF Factor ; Megakaryocyte Colony Stimulating Factor ; Megakaryocyte Growth and Development Factor ; Myeloproliferative Leukemia Virus Oncogene Ligand ; Thrombocytopoiesis-Stimulating Factor ; Thrombocytopoietin ; c-mpl Ligand ; mpl Ligand ; Thrombosis ; thrombotic disease ; thrombotic disorder ; Time ; Toxicology ; Universities ; wound healing ; Wound Repair ; wound resolution ; Generations ; Platelet Transfusion ; Blood Platelet Transfusion ; Plts ; base ; improved ; Procedures ; Surgical incisions ; Otomy ; incision ; Transfusion ; Site ; Chronic ; Clinical ; Refractory ; repaired ; repair ; Residual state ; Residual ; Phase ; Hospital Costs ; Hospitalization cost ; Failure ; Oncology ; Oncology Cancer ; Collaborations ; Intravenous ; Immunes ; Immune ; Event ; Animal Models and Related Studies ; model of animal ; model organism ; Animal Model ; novel ; FES ; FPS ; Fujinami Sarcoma Virus and Feline Sarcoma Virus Transforming Gene ; Oncogene FES ; FPS-FES Oncogene ; Radiation ; Myelosuppression ; Modeling ; Cancer Treatment ; Malignant Neoplasm Therapy ; Malignant Neoplasm Treatment ; anti-cancer therapy ; anticancer therapy ; cancer-directed therapy ; cancer therapy ; mimetics ; Alloimmunization ; nano sphere ; Nanosphere ; Thickness ; Thick ; Clotting ; Coagulation ; Coagulation Process ; Detection ; Preclinical Models ; Pre-Clinical Model ; Recombinants ; Allogenic ; Clinical Management ; Rodent Model ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Validation ; Monitor ; Characteristics ; pre-clinical ; preclinical ; preclinical study ; pre-clinical study ; cost ; healing ; treatment center ; novel strategies ; new approaches ; novel approaches ; novel strategy ; wound ; tissue wound ; wounding ; wounds ; Consumption ; high risk ; standard of care ; effective therapy ; effective treatment ; comparative efficacy ; compare efficacy ;