A novel agent to manage thrombocytopenic patients with platelet transfusion refractoriness

治疗血小板输注无效的血小板减少症患者的新药

• 批准号: 10250676
• 负责人: Richard Yen
• 金额: $ 25.37万
• 依托单位: FIBROPLATE, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10250676
• 关键词: Albumins; Allogenic; Alloimmunization; Animal Model; Animals; Antibodies; Antibody Specificity; Autopsy; Biological Availability; Biological Products; Bleeding time procedure; Blood; Blood Platelets; Blood Vessels; Body Weight Changes; Characteristics; Chicago; Chronic; Clinical; Clinical Chemistry; Clinical Management; Coagulation Process; Collaborations; Consumption; Detection; Ear; Endothelium; Event; FPS-FES Oncogene; Factor XIII; Failure; Fibrinogen; Generations; Hematology; Hemorrhage; Hemostatic Agents; Hemostatic function; Hospital Costs; Human; Illinois; Immune; Incidence; Intravenous; Leadership; Length of Stay; Modeling; Monitor; Myelosuppression; Nanosphere; Necrosis; Oncology; Oryctolagus cuniculus; Patients; Petechiae; Pharmaceutical Preparations; Phase; Plasma; Platelet Transfusion; Pre-Clinical Model; Procedures; Radiation; Recombinants; Refractory; Residual state; Risk; Rodent Model; Safety; Saline; Site; Small Business Innovation Research Grant; Spleen; Splenomegaly; Surgical incisions; Survival Rate; Suspensions; Testing; Thick; Thrombocytopenia; Thrombopoietin; Thrombosis; Time; Toxicology; Transfusion; United States National Institutes of Health; Universities; Validation; base; cancer therapy; comparative efficacy; cost; effective therapy; healing; high risk; improved; intravenous injection; mimetics; mortality; novel; novel strategies; pre-clinical; preclinical study; repaired; skin ulcer; standard of care; treatment center; wound; wound healing

PROJECT SUMMARY 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. PTR condition is associated with a high risk of severe bleeding complications and reduced survival rate, longer hospital stays and higher hospital costs. Existing management strategies are based on the transfusion of leukodepleted products, HLA-matched platelets, or cross-matched platelets which are obtained after lengthy and expensive procedures. Alternatives consisting of thrombopoietin mimetics, or recombinant factor XIII have not shown the ability to reduce mortality. Fibroplate is proposing a new approach to manage bleeding in 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 bleeding time and improves overall survival rate associated with radiation-induced thrombocytopenia in preclinical rodent models through the formation of co-aggregates with the residual activated platelets at wound sites on the endothelium of the blood vessel. Various preclinical studies demonstrated that FPS is safe and does not induce intravascular coagulation. Remarkably, FPS is not sequestered in the spleen, and FPS specific antibodies have not been detected after its administration in humans. These characteristics, together with its hemostatic capacity support the use of FPS in the management of thrombocytopenic patients with immune and non-immune PTR. However, their efficacy and safety need validation in a thrombocytopenic preclinical model under PTR conditions. This NIH SBIR Phase I aims at investigating i) the efficacy of FPS in reducing bleeding parameters in an established (double) model of thrombocytopenia and PTR (TPTR) preclinically in rabbits and ii) the safety of the proposed approach. By offering effective treatment, Fibroplate is expected to reduce bleeding complications and improve and promote survival in thrombocytopenic patients with PTR.

项目摘要 血小板输血（PTR）或未能达到所需的血小板水平的血小板 血小板输血，阻碍血小板减少患者的出血发作的管理。 ptr 病情与严重出血并发症和存活率降低的高风险有关，更长 医院住院和更高的医院费用。现有的管理策略是基于输血 leukodepleted产品，HLA匹配的血小板或交叉匹配的血小板，在冗长之后获得 和昂贵的程序。由血小板蛋白模拟物或重组因子XIII组成的替代方法 尚未表现出降低死亡率的能力。纤维化酸盐正在提出一种管理出血的新方法 在静脉注射纤维链纤维酸S（FPS）的静脉注射基础上，患有PTR的血小板减少型患者中， 纤维蛋白原胶白蛋白纳米球的现成悬浮液。 FPS大大减少了出血 时间并提高与临床前辐射诱导的血小板减少症相关的总体生存率 啮齿动物模型通过与残留活化的血小板在伤口部位形成共聚集的模型 血管内皮。各种临床前研究表明，FPS是安全的，并且不 诱导血管内凝血。值得注意的是，FPS不会在脾脏中隔离，而FPS也没有 在人类给药后尚未检测到抗体。这些特征及其 止血能力支持FPS在治疗的血小板减少患者的治疗中使用 和非免疫性PTR。但是，它们的功效和安全性需要在血小板减少临床前验证 在PTR条件下的模型。这项NIH SBIR阶段I的目的是研究I）FPS降低的功效 在建立的（双）模型的血小板减少症和PTR（TPTR）中的出血参数在 兔子和ii）拟议方法的安全。通过提供有效的治疗，纤维板有望 减少出血并发症并改善和促进PTR血小板减少患者的生存。