A Phase 2b Clinical Trial to Study the Efficacy of Longeveron Mesenchymal Stem Cells (LMSCs) to Treat Aging Frailty

研究 Longeveron 间充质干细胞 (LMSC) 治疗衰老衰弱功效的 2b 期临床试验

• 批准号: 9922198
• 负责人: Joshua M Hare
• 金额: $ 197.43万
• 依托单位: LONGEVERON, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9922198
• 关键词: Activities of Daily Living; Address; Admission activity; Affect; Age; Aging; Allogenic; American; Anti-Inflammatory Agents; Assisted Living Facilities; Awareness; Biological; Biological Markers; Cell Therapy; Cessation of life; Chronic; Clinical; Clinical Data; Clinical Research; Clinical Trials; Communities; Data; Diagnosis; Elderly; Enrollment; Evaluation; Exercise Tolerance; FDA approved; Formulation; Fracture; Functional disorder; Geriatrics; Health care facility; Hospitalization; Inflammaging; Inflammation; Inflammatory; Institutionalization; Interleukin-1; Interleukin-10; Interleukin-6; International; Journals; Long-Term Care; Manufacturer Name; Measures; Medical; Mental Depression; Mesenchymal Stem Cells; Muscular Atrophy; Nursing Homes; Outcome; Patient Outcomes Assessments; Performance; Phase; Phase I/II Clinical Trial; Phase III Clinical Trials; Phenotype; Physical Function; Physical Performance; Physicians; Physiological; Placebos; Prevalence; Probability; Property; Publishing; Regenerative Medicine; S Phase; Safety; Sample Size; Serum; Societies; Syndrome; TNF gene; Testing; Therapeutic; Time; Tissues; Treatment Efficacy; Upper Extremity; Walking; base; clinical development; cognitive performance; cognitive testing; combinatorial; design; effective intervention; efficacy study; falls; follow-up; frailty; geriatric depression; improved; insight; mental state; normal aging; novel; patient population; phase 3 study; pre-clinical; primary endpoint; programs; prospective test; pulmonary function; regenerative; secondary endpoint; stem cell therapy; therapeutic candidate; tool; trend; walking speed

Aging Frailty is a biologically driven geriatric syndrome of multisystem physiological decline that is distinct from normal aging and disproportionately increases vulnerability to adverse clinical outcomes. Frailty has an overall prevalence of 10% of those 65 years and older, and there is growing awareness in the geriatric community to diagnose and treat this condition, as it is not an inevitable consequence of aging. The American Geriatrics Society has published a “Geriatrics Evaluation & Management Tools—Frailty” to aid practicing physicians in the diagnosis of Aging Frailty, and frailty-dedicated societies and journals now exist due to the urgent need to develop effective intervention. There are no FDA-approved therapies for treating Aging Frailty, but a biologically driven cell-based therapy could have a major beneficial impact. The pathophysiology of Aging Frailty includes an accentuated pro-inflammatory state that can promote systemic tissue damage, including muscle atrophy. Mesenchymal stem cells (MSCs) have potent anti- inflammatory and pro-regenerative properties, making them an ideal therapeutic candidate for Aging Frailty. Longeveron is a manufacturer of a proprietary formulation of allogeneic MSCs, called LMSCs, which are being evaluated for therapeutic efficacy to treat Aging Frailty in this Phase 2b trial. We recently completed a Phase 1/2 clinical trial to demonstrate the safety and tolerability of this approach for treating Aging Frailty. That trial not only demonstrated the high safety profile of this therapeutic approach, it provided provisional data showing efficacy. The Phase 2b trial of this proposal represents the next step in clinical development of LMSCs as a therapeutic candidate for Aging Frailty. This trial has been designed with guidance from FDA and international leaders in geriatrics, which was used to define enrollment criteria and endpoints. FDA guidance for this clinical program is that a registrational endpoint would need to be a composite of surrogates for long-term clinical outcomes (e.g., falls, fractures, hospitalizations, institutionalization, and death). Specifically, this composite would entail endpoints in 3 domains relevant to Aging Frailty: a metric of functional capacity; a patient-reported outcome (PRO); and a biomarker. This Phase 2b trial is designed to examine endpoints in these 3 domains in order to develop a composite endpoint to ultimately test prospectively in a Phase 3 study for registrational purposes. This proposal addresses a truly novel application of cell-based therapy that could become the first FDA- approved treatment for Aging Frailty. We believe that Aging Frailty is an outstanding candidate indication for LMSC therapy, supported by mechanism of action, preclinical data, and Longeveron’s Phase 1/2 clinical data, and has gained the support and endorsement of key opinion leaders in the field. Accordingly, this study is highly timely, and has a high probability of making an extraordinary impact on a major unmet need, as well as on regenerative medicine.

衰老脆弱是多系统衰落的生物学驱动的老年综合症，与众不同 正常的衰老和不成比例增加了对不良临床结果的脆弱性。脆弱的总体 在65岁以上的这65岁以上的患病率是10％，老年社区的认识越来越高 诊断和治疗这种情况，因为这不是衰老的必然结果。美国老年病 社会已经发表了“老年评估与管理工具”，以帮助练习医生 由于迫切需要，现在存在诊断衰老脆弱的社会和期刊和期刊的诊断 开发有效的干预措施。没有FDA批准的疗法可以治疗衰老，但在生物学上 驱动的基于细胞的疗法可能会产生重大的有益影响。 衰老脆弱的病理生理学包括一种强调的促炎状态，可以促进 全身组织损伤，包括肌肉萎缩。间充质干细胞（MSC）具有潜在的抗 炎症和促进性的特性，使其成为衰老衰老的理想治疗候选者。 Longeveron是同种异体MSC的专有公式的制造商，称为LMSC，正在 评估了在此2B期试验中治疗衰老脆弱的治疗效率。 我们最近完成了一项1/2期临床试验，以证明这种方法的安全性和耐受性 治疗衰老脆弱。该试验不仅证明了这种治疗方法的高安全性，还表明 提供了显示有效性的临时数据。该提案的2B阶段试验代表了临床的下一步 开发LMSC作为衰老衰老的治疗候选者。该试验是在指导的设计 来自FDA和老年医学领域的国际领导人，该领导者用于定义入学标准和终点。 该临床计划的FDA指南是注册端点需要是 替代长期临床结果（例如瀑布，骨折，住院，制度化和死亡）。 具体而言，该复合材料将需要与衰老脆弱相关的3个域中的端点：功能指标 容量;患者报告的结果（PRO）；和一个生物标志物。此2B阶段试验旨在检查 这三个域中的端点是为了开发一个复合端点，以最终在一个阶段进行测试 3用于注册目的的研究。 该建议涉及基于细胞疗法的真正新颖的应用，这可能成为第一个FDA- 经过批准的衰老疗法。我们认为，衰老脆弱是一个出色的候选人指标 LMSC疗法，由作用机理，临床前数据和长寿1/2阶段临床数据的支持， 并获得了该领域关键意见领袖的支持和认可。彼此之间，这项研究很高 及时，并且很有可能对主要的未满足需求产生极大的影响以及 再生医学。