A multivalent, easy-to-use product to mitigate and treat radiation exposure

一种多价、易于使用的产品，用于减轻和治疗辐射暴露

• 批准号: 10011227
• 负责人: Richard Yen
• 金额: $ 93.38万
• 依托单位: FIBROPLATE, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011227
• 关键词: Acute; Albumins; Amelia; Animal Model; Animals; Appearance; Biological Products; Bleeding time procedure; Blood Platelets; CCL2 gene; Charge; Chicago; Clinical; Collaborations; Cutaneous; Cyclic GMP; Data; Dose; Emergency Situation; Event; Exposure to; Feasibility Studies; Fibrinogen; Future; Goals; Government Agencies; Healthcare Market; Hematopoietic; Hematopoietic Stem Cell Mobilization; Hemostatic function; Humidity; Illinois; Individual; Injectable; Injections; Injury; Interleukin-17; Intravenous; Ionizing radiation; Lesion; Leukocytes; Life; Link; Measures; Medical; Miniature Swine; Modeling; Nanosphere; Necrosis; Neutropenia; Nuclear Accidents; Nuclear Radiology; Nuclear Warfare; Patients; Phase; Pilot Projects; Population; Production; Property; Protocols documentation; Public Health; RAS genes; Radiation; Radiation Accidents; Radiation Syndromes; Radiation Toxicity; Radiation exposure; Radiation therapy; Rattus; Risk; Rodent; Safety; Site; Skin injury; Small Business Innovation Research Grant; Survival Rate; Syndrome; Temperature; Testing; Therapeutic; Thrombocytopenia; Time; Tissues; Toxic effect; Toxicity Tests; Toxicology; Ulcer; Universities; Validation; Vision; Work; animal efficacy; animal rule; base; blood perfusion; chemokine; clinical development; cost; cytokine; design; efficacy study; healing; improved; innovation; irradiation; manufacturing process; manufacturing scale-up; medical countermeasure; meetings; pre-clinical; preclinical study; prophylactic; radiation mitigator; recruit; response; scale up; side effect; skin lesion; skin ulcer; stem cell biology; stem cells; tissue regeneration; tissue repair; wound healing; Acute; Albumins; Amelia; Animal Model; Animals; Appearance; Biological Products; Bleeding time procedure; Blood Platelets; CCL2 gene; Charge; Chicago; Clinical; Collaborations; Cutaneous; Cyclic GMP; Data; Dose; Emergency Situation; Event; Exposure to; Feasibility Studies; Fibrinogen; Future; Goals; Government Agencies; Healthcare Market; Hematopoietic; Hematopoietic Stem Cell Mobilization; Hemostatic function; Humidity; Illinois; Individual; Injectable; Injections; Injury; Interleukin-17; Intravenous; Ionizing radiation; Lesion; Leukocytes; Life; Link; Measures; Medical; Miniature Swine; Modeling; Nanosphere; Necrosis; Neutropenia; Nuclear Accidents; Nuclear Radiology; Nuclear Warfare; Patients; Phase; Pilot Projects; Population; Production; Property; Protocols documentation; Public Health; RAS genes; Radiation; Radiation Accidents; Radiation Syndromes; Radiation Toxicity; Radiation exposure; Radiation therapy; Rattus; Risk; Rodent; Safety; Site; Skin injury; Small Business Innovation Research Grant; Survival Rate; Syndrome; Temperature; Testing; Therapeutic; Thrombocytopenia; Time; Tissues; Toxic effect; Toxicity Tests; Toxicology; Ulcer; Universities; Validation; Vision; Work; animal efficacy; animal rule; base; blood perfusion; chemokine; clinical development; cost; cytokine; design; efficacy study; healing; improved; innovation; irradiation; manufacturing process; manufacturing scale-up; medical countermeasure; meetings; pre-clinical; preclinical study; prophylactic; radiation mitigator; recruit; response; scale up; side effect; skin lesion; skin ulcer; stem cell biology; stem cells; tissue regeneration; tissue repair; wound healing

ABSTRACT The threat of radiological and nuclear accidents or attacks demands effective radiation medical countermeasures (MCM) able to mitigate and treat the effects of exposure to ionizing radiations. Hematopoietic acute radiation syndrome (HRAS) and cutaneous radiation syndrome (CRS) pose severe, life-threatening risks to exposed individuals. Currently no effective radio-mitigator (to be administered after radiation exposure but prior to tissue toxicity manifestation) or radio-therapeutic (to be administered after tissue toxicity manifestation) has yet received FDA approval. Fibroplate, Inc. developed Fibrinoplate-S (FPS), an intravenous injectable solution of Fibrinogen-coated Albumin nano-Spheres originally developed to augment hemostatic functions in multiple clinical settings. Preliminary studies conducted on irradiated rodents suggested that FAS administered after ionizing radiation exposure has a unique potential as a multi-valent MCM against radiations. In particular, it was demonstrated that FPS has prophylactic properties against Radiation-induced Skin Injuries (RSI). During the SBIR Phase I project, a preclinical feasibility study in rats was performed to demonstrate FPS’ efficacy as a therapeutic treatment for RSI. Several objectives were accomplished: 1) The efficacy of FPS as both prophylactic and therapeutic treatment for RSI was demonstrated. 2) An FPS-induced stem cells mobilization towards the lesion was observed. 3) The efficacy of FPS as a mitigator for neutropenia and thrombocytopenia was confirmed. 4) A regulatory effect of FPS on the cytokine profile was discovered. Results obtained in Phase I represent the perfect starting point for this SBIR Phase II project, where additional preclinical studies will be performed and used to complete an IND submission package to the FDA, to pursue FDA approval according to the Animal Efficacy Rule. In this SBIR Phase II project, Fibroplate aims at: i) Demonstrate FPS efficacy as a therapeutic treatment for RSI in minipigs, as a second animal model. ii) Assess FPS toxicology profile in rats, iii) Assess FPS stability and shelf-life, iv) Scale-up current manufacturing process to reach production volumes sufficient to sustain the clinical development. Obtaining FDA approval for FPS will pave the way for its inclusion in the Strategic National Stockpile as MCM for radiological/nuclear emergencies. 1

抽象的 放射学和核事故或攻击的威胁需要有效的放射医学对策 （MCM）可以减轻和治疗暴露于电离辐射的影响。造血急性辐射 综合征（HRA）和皮肤辐射综合征（CRS）构成严重的，威胁生命的风险 个人。目前尚无有效的放射性降低器（在辐射暴露后要施用，但在组织之前 毒性表现）或放射性治疗（在组织毒性表现后要施用） 获得了FDA批准。纤维纤维板，Inc。开发了纤维纤维板S（FPS），这是一种静脉注射溶液的 纤维蛋白原涂的白蛋白纳米球形最初是为了增强多种止血功能而开发的 临床环境。对辐照啮齿动物进行的初步研究表明，在 电离辐射暴露具有独特的潜力，它是针对辐射的多价MCM。特别是 证明FPS具有针对辐射引起的皮肤损伤（RSI）的预防性特性。在 SBIR I期项目，进行了大鼠的临床前可行性研究，以证明FPS的效率为 RSI的治疗治疗。完成了几个物体：1）FPS的效率是预防性的 证明了RSI的治疗治疗。 2）FPS诱导的干细胞朝向 观察到病变。 3）证实了FPS作为中性减少症和血小板减少症的缓解剂的效率。 4）发现FPS对细胞因子谱的调节作用。在第一阶段获得的结果表示 SBIR II期项目的完美起点，将进行其他临床前研究，并 用于完成给FDA的IND提交包，以根据动物购买FDA批准 功效规则。在这个SBIR II期项目中，纤维板的目的是：i）证明FPS效率作为治疗 Minipigs中的RSI作为第二动物模型。 ii）评估大鼠的FPS毒理学特征，iii）评估FPS 稳定性和保质期，iv）扩大当前的制造过程，以达到足以达到的生产量 维持临床发展。获得FPS的FDA批准将为包含在内的道路铺平 战略性国家作为放射线/核紧急情况的MCM。 1