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.

衰老衰弱是一种生物驱动的多系统生理衰退的老年综合症，与 正常衰老并且不成比例地增加了不良临床结果的脆弱性。 65 岁及以上人群中 10% 的患病率，并且老年人社区越来越意识到 诊断和治疗这种情况，因为它不是衰老的必然结果。 协会出版了“老年病学评估和管理工具——虚弱”，以帮助执业医师 由于迫切需要对衰老衰弱进行诊断，并且专门研究衰弱的协会和期刊现在已经存在 目前尚无 FDA 批准的治疗衰老衰弱的疗法，但有一种生物学方法。 驱动的细胞疗法可能会产生重大的有益影响。 衰老衰弱的病理生理学包括加剧的促炎症状态，可以促进 间充质系统干细胞 (MSC) 具有有效的抗 炎症和促再生特性，使它们成为衰老衰弱的理想治疗候选者。 Longeveron 是同种异体间充质干细胞 (LMSC) 专有配方的制造商，该配方正在被 在此 2b 期试验中评估了治疗衰老衰弱的疗效。 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 该试验不仅证明了这种治疗方法的高安全性，而且 提供了显示疗效的临时数据。该提案的 2b 期试验代表了临床的下一步。 开发 LMSC 作为治疗衰老衰弱的候选药物 该试验是在指导下设计的。 来自 FDA 和老年病学领域国际领导者的意见，用于定义入组标准和终点。 FDA 对该临床计划的指导是，注册终点需要是以下内容的组合： 长期临床结果（例如跌倒、骨折、住院、住院和死亡）的替代指标。 具体来说，该复合材料将涉及与衰老衰弱相关的 3 个领域的端点：功能指标 能力；患者报告的结果（PRO）；以及该 2b 期试验旨在检查。 这 3 个领域中的端点，以便开发一个复合端点，最终在一个阶段进行前瞻性测试 3 以注册为目的的学习。 该提案提出了一种真正新颖的细胞疗法应用，可能成为 FDA 的第一个 经批准的治疗衰老衰弱的方法 我们相信衰老衰弱是一个杰出的候选适应症。 LMSC疗法得到了作用机制、临床前数据和Longeveron的1/2期临床数据的支持， 并得到了该领域主要意见领袖的支持和认可。因此，本研究得到了高度评​​价。 及时，并且很有可能对未满足的主要需求以及对 再生医学。

项目成果

Ultrastructural changes of the human enteric nervous system and interstitial cells of Cajal in diverticular disease.

憩室病中人肠神经系统和卡哈尔间质细胞的超微结构变化。

• 发表时间: 2020-02
• 影响因子: 2
• 作者: Alaburda, Paulius;Lukosiene, Jaune I;Pauza, Audrys G;Rysevaite;Kupcinskas, Juozas;Saladzinskas, Zilvinas;Tamelis, Algimantas;Pauziene, Neringa
• 通讯作者: Pauziene, Neringa

The transcription factor YY2 has less momentous properties of an intrinsically disordered protein than its paralog YY1.

转录因子 YY2 的本质无序蛋白质特性不如其旁系同源物 YY1 重要。

• 发表时间: 2019
• 影响因子: 3.5
• 作者: Figiel, Małgorzata;Łakomska, Julia;Miłek, Piotr;Dziedzicka;Górecki, Andrzej
• 通讯作者: Górecki, Andrzej