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: 10326178
• 负责人: Stephanie Deshayes
• 金额: $ 136.81万
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10326178
• 关键词: Adoption; Adverse event; Ambulatory Care; American; Amputation; Animal Model; Area; Bandage; Biocompatible Materials; Biodegradation; Biological; Biological Factors; 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; 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