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

TT101 是一种合成免疫调节材料，可在暴露的骨骼上构建新的功能组织，作为糖尿病肢体保留患者的一次性治疗，这是首次进行人体临床研究

• 批准号: 10582523
• 负责人: Stephanie Deshayes
• 金额: $ 118.14万
• 依托单位: TEMPO THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10582523
• 关键词: Adoption; Adverse event; Ambulatory Care; American; Amputation; Animal Model; Area; Bandage; Biocompatible Materials; Biodegradation; Biological Products; Biology; Biomechanics; Biomedical Engineering; Blood Vessels; Bone Surface; Breast; CSPG4 gene; Canis familiaris; Cartilage; Case Study; Cells; Centers for Disease Control and Prevention (U.S.); Cessation of life; Characteristics; Chemicals; Chronic; Clinical; Clinical Data; Clinical Research; Clinical Trials; Colon; Complex; Complications of Diabetes Mellitus; Contracts; Cyclic GMP; Data; Dermis; Development; Devices; Diabetes Mellitus; Diabetic Foot Ulcer; Direct Costs; Edema; Engineering; Epithelial; Exposure to; Extracellular Matrix; Family suidae; Fascia; Foot Ulcer; Foundations; Geometry; Gold; Granulation Tissue; Growth Factor; Hemorrhage; Immune; Immunity; In Situ; Incidence; Industry; Infection; Inflammatory Response; Investigation; Journals; Kinetics; Light; Limb structure; Lower Extremity; Malignant Neoplasms; Measures; Mechanics; Mediating; Operative Surgical Procedures; Osteomyelitis; Pain; Pathway interactions; Patients; Performance; Persons; Phase; Physicians; Podiatry; Population; Porifera; Porosity; Pre-Clinical Model; Procedures; Property; Prostate; Publishing; Randomized; Reporting; Safety; Shapes; Site; Skin; Skin Substitutes; Surface; Surgeon; Swelling; Technology; Tendon structure; Therapeutic; Time; Tissue Preservation; Tissues; Vascularization; Veterinary Medicine; Work; automated image analysis; base; bone; capsule; clinical center; clinically relevant; compliance behavior; cost; crosslink; design; diabetic; diabetic patient; digital imaging; efficacy evaluation; efficacy testing; first-in-human; healing; high risk; immunoregulation; improved; manufacturing process; mortality; necrotic tissue; non-healing wounds; particle; patient population; preclinical safety; preservation; pressure; programs; readmission rates; recruit; regenerative; regenerative therapy; response; safety testing; scaffold; scale up; secondary endpoint; stem cells; success; synthetic tissue scaffolding; tissue regeneration; tool; treatment group; wound; wound care; wound closure; wound healing; wound treatment

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.

摘要/摘要 据美国疾病控制中心称，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% 的糖尿病患者会出现糖尿病足溃疡。 一生中出现无法治愈的足部溃疡的人极易受到感染和组织坏死。 需要极端的手术干预来去除坏死组织并保留肢体。 组织损伤往往非常广泛，以至于这些外科手术会留下复杂的伤口 暴露的骨骼、肌腱和/或筋膜——众所周知，它们很难愈合，并且目前的生物工程技术 事实上，足部溃疡是下肢最常见的单一前兆。 糖尿病患者截肢，是大约 85% 下肢截肢的先兆 仅在美国，该人群的截肢人数就超过 10 万。此外，据报告的死亡率。 5 年后 DFU 患者的发生率为 55% 至 74%，高于前列腺癌、乳腺癌、 和冒号。 目前针对复杂伤口的治疗方案很少，无法构建生物工程皮肤片。 这些暴露的骨表面上的新组织和基本的伤口护理也没有什么影响。 伤口治疗 (NPWT) 已显示出愈合效果有所改善，但这种管理工具需要大量门诊病人 显然需要一种能够在“垂直”方面发挥作用的再生疗法。 伤口愈合阶段，建立新的组织体积对于这一重要的临床成功至关重要。 需求创造了巨大的市场机会。 为了满足这一市场需求，Tempo Therapeutics 开发了 MAP Wound Matrix – 一种可流动的合成材料 基于我们专有的微孔退火颗粒 (MAP) 技术的组织支架。 具有流动性（易于使用），可填充任何形状和大小的伤口，然后转化为超多孔材料 暴露于白光后伤口部位的海绵状网络促进快速。 与领先的脱细胞组织基质相比，肉芽组织和早期血管化， 与大多数动物模型不同，包括糖尿病猪在内的多种动物模型中的炎症反应最小。 矩阵，MAP 不需要多次应用程序，已经完成了必要的研究。 支持向 FDA 提交临床试验申请并提供安全性和性能数据，并已完成初步放大 产品制造。 在拟议的直接进入第二阶段工作中，我们将继续开发 MAP Wound Matrix 并进行 多中心、随机试点临床研究，评估其治疗糖尿病复杂伤口的有效性和安全性 这项研究的成功完成将为 MAP Wound Matrix 的性能提供临床证据。 以及制定下一个更大规模临床研究的重要信息，以推动伤口护理行业的采用。