A first in human clinical study of TT101, a synthetic immunomodulatory material to build new functional tissue over exposed bone as a one time treatment for diabetic limb preservation patients

总结/摘要 根据美国疾病控制中心的数据，3400万美国人患有糖尿病。之一 糖尿病最常见的并发症是糖尿病足溃疡（DFU）。大约25%的糖尿病患者 在他们的一生中患上不愈合的足部溃疡。DFU极易感染和组织坏死 这需要极端的外科手术来切除大量坏死组织并保留肢体。不幸的是， 组织损伤通常是如此广泛以致于这些外科手术留下复杂的伤口 暴露的骨、肌腱和/或筋膜-其是众所周知的难以愈合的，并且目前的生物工程 皮肤产品没有益处。事实上，足部溃疡是下肢溃疡最常见的单一前兆， 糖尿病患者中截肢，是约85%的下肢截肢的前兆。 截肢在这个人群中-仅在美国每年就超过10万。此外，报告的死亡率 DFU患者5年后的发病率为55%至74%，高于前列腺癌，乳腺癌， 和结肠。 目前复杂伤口的治疗选择很少。生物工程皮肤无法构建 新的组织覆盖在这些暴露的骨表面上，基本的伤口护理也几乎没有效果。负压 伤口治疗（NPWT）已显示出愈合改善，但这种管理工具需要密集的门诊 照顾和繁琐。有一个明确的需要再生疗法，可以在'垂直'的效果 在伤口愈合阶段，建立新的组织体积对成功至关重要。这一重大临床 这就创造了巨大的市场机会。 为了满足这一市场需求，克里思治疗公司开发了MAP伤口基质-一种可流动的合成 组织支架基于我们专有的微孔退火颗粒（MAP）技术。MAP伤口矩阵 是可流动的（易于应用），并填充任何形状和大小的伤口，然后转化为多孔的 暴露于白色光后，伤口部位出现海绵状网络。超高孔隙率的几何结构促进了快速 肉芽组织和早期血管形成，当与主要的脱细胞组织基质相比时， 在包括糖尿病猪的多种动物模型中具有最小的炎症反应。不像大多数这些 矩阵，MAP不需要多次应用。克里思已经完成了必要的研究， 提供安全性和性能数据，支持向FDA提交的临床试验申请， 产品制造 在拟定的直接进入第二阶段的工作中，我们将继续开发MAP伤口基质，并进行 评价其治疗糖尿病患者复杂伤口的有效性和安全性的多中心、随机、初步临床研究 患者本研究的成功完成将为MAP Wound Matrix的性能提供临床证据 以及设置下一个更大的临床研究以推动伤口护理行业采用的关键信息。

SUMMARY / ABSTRACT According to the United States Centers for Disease Control, 34 million Americans have diabetes. One of the most prevalent complications of diabetes is the diabetic foot ulcer (DFU). Approximately 25% of diabetics will develop a non-healing foot ulcer in their lifetime. DFUs are highly susceptible to infection and tissue necrosis that require extreme surgical interventions to remove extensive dead tissue and preserve the limb. Unfortunately, tissue damage is often so extensive that these surgical procedures leave behind complex wounds with exposed bone, tendon, and or fascia – which are notoriously difficult to heal and where current bioengineered skin products do not have benefit. Indeed, foot ulceration is the most common single precursor of lower extremity amputations among persons with diabetes and is a precursor to approximately 85% of the lower extremity amputations within this population – exceeding 100K every year in the US alone. Furthermore, reported mortality rates for DFU patients range from 55 to 74% after 5 years, which are above cancers such as prostate, breast, and colon. The current treatment options for complex wounds are scarce. Bioengineered skin sheets are unable to build new tissue over these exposed bone surfaces, and basic wound care has little effect as well. Negative Pressure Wound Therapy (NPWT) has shown improved healing, but this management tool requires intensive outpatient care and is cumbersome. There is a clear need for a regenerative therapy that can have effect in the ‘vertical’ phase of wound healing, where building new tissue volume is paramount to success. This significant clinical need creates a considerable market opportunity. To answer this market need, Tempo Therapeutics has developed the MAP Wound Matrix – a flowable synthetic tissue scaffold based on our proprietary Microporous Annealed Particle (MAP) technology. MAP Wound Matrix is flowable (ease of application) and fills wounds of any shapes and sizes, and then converts to a hyper-porous sponge-like network in the wound site after exposure to white light. The hyper-porosity geometry promotes fast granulation tissue, and early vascularization, when compared to leading decellularized tissue-based matrices, with minimal inflammatory response in multiple animal models including diabetic pigs. Unlike most of these matrices, MAP does not require multiple applications. Tempo has already completed the necessary studies to support clinical trial application to FDA with safety and performance data and has completed initial scale-up of product manufacturing. In the proposed Direct-to-Phase II work, we will pursue the development of MAP Wound Matrix and conduct a multicenter, randomized pilot clinical study to evaluate its efficacy and safety to treat complex wounds in diabetic patients. Successful completion of this study will bring clinical evidence of the performance of MAP Wound Matrix as well as crucial information to set the next larger clinical study in order to drive adoption in wound care industry.