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 根据美国疾病控制中心的数据，有3400万美国人患有糖尿病。中的一个 糖尿病最普遍的并发症是糖尿病足溃疡（DFU）。大约25％的糖尿病患者将 DFU非常容易受到感染和组织坏死 这需要极端的手术干预措施，以去除大量的死组织并保留肢体。很遗憾， 组织损伤通常是如此广泛，以至于这些手术程序留下了复杂的伤口 暴露的骨头，肌腱和或筋膜 - 众所周知，这些骨骼很难治愈，并且在当前生物工程的地方 皮肤产品没有好处。实际上，脚溃疡是下肢最常见的单一前体 糖尿病患者的截肢者，是下肢约85％的前体 该人群中的截肢 - 仅在美国，就每年超过100K。此外，报道了死亡率 5年后，DFU患者的比率从55％到74％不等，这些癌症以前，例如前列腺，乳房，， 和结肠。 当前的复杂伤口治疗选择很少。生物工程的皮肤表无法构建 这些裸露的骨表面上的新组织，基本伤口护理也没有影响。负压 伤口疗法（NPWT）显示出改善的愈合，但是该管理工具需要大量的门诊病人 关心，很麻烦。显然需要对“垂直”有效的再生疗法 伤口愈合的阶段，其中建立新的组织体积对于成功至关重要。这种重要的临床 需求创造了相当大的市场机会。 为了满足这个市场需求，Tempo Therapeutics开发了地图伤口矩阵 - 可流动的合成 基于我们专有的微孔退火粒子（MAP）技术的组织支架。地图伤口矩阵 可流动（易于应用），并填充任何形状和尺寸的伤口，然后转换为超孔 暴露于白光后伤口部位的赞助商状网络。高孔隙度几何形状迅速促进 与领先的脱细胞组织物质相比，肉芽组织和早期血管形成 在包括糖尿病猪在内的多种动物模型中，炎症反应最小。与大多数 矩阵，地图不需要多个应用程序。节奏已经完成了必要的研究 通过安全性和性能数据支持向FDA申请临床试验，并完成了最初的规模 产品制造。 在拟议的直接到相位II工作中，我们将追求MAP伤口矩阵的开发并进行 多中心，随机试验临床研究，以评估其有效性和安全性治疗糖尿病中的复杂伤口 患者。这项研究的成功完成将带来MAP伤口矩阵性能的临床证据 以及为了设定下一项更大的临床研究以推动伤口护理行业采用的重要信息。