A Two-part, Phase I/II, Randomized, Single-blind Study to Evaluate the Efficacy and Safety of UMC119-06-05 in Older Adults With Pre-frailty & Frailty
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 66
- 试验地点
- 2
- 主要终点
- vital signs
研究概览
简要总结
This Phase I/II study is designed to evaluate the efficacy and safety of UMC119-06-05, an allogeneic umbilical cord mesenchymal stem cells, in older adults with frailty syndrome. This study will also seek to determine the long-term safety and clinical outcomes of UMC119-06-05 in subjects with frailty syndrome, which will provide information for subsequent clinical trials with UMC119-06-05.
详细描述
Frailty is a disorder of several inter-related physiological systems, including genetic and environmental factors in combination with epigenetic mechanisms, which regulate the differential expression of genes in cells and could be especially important in ageing. Frailty syndrome characterized by a progressive decline in health and clinical symptoms of exhaustion, weight loss, a feeling of slowing down, and a decrease in functional capacity. Current interventions focus on interdisciplinary approaches which include nutritional supplementation, physical exercise, and cognitive intervention. The lack of standardized treatment of the disease resulted in the increasing number of elders diagnosed with frailty. Therefore, development of new therapeutic modalities to improve the clinical outcomes and prognosis of frailty syndrome in adult patients is of urgent need. Recently, preclinical and clinical studies support a cell-based, regenerative treatment strategy i.e., allogenic umbilical cord mesenchymal stem cell therapy may represent a novel therapy for aging frailty. This clinical trial is a phase I/II study. Phase I is an open-label study and all eligible subjects will receive a single-dose IV infusion of UMC119-06-05. Phase II study is a randomized, placebo-controlled, single-blind study and half of eligible subjects will receive a single-dose IV infusion of UMC119-06-05, the others will receive placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects will be eligible for enrollment in the study only if they meet ALL of the following criteria:
- •Subjects of age ≥ 65 years old at screening.
- •Subjects show signs of frailty as assessed by CHS frailty Scores ≥ 1 at screening.
- •Subjects with body weight between 40 kg to 90 kg.
- •Subjects have received standard of care treatment (including exercise and nutritional supplementation) for FS for at least 30 days prior to the study.
- •Subject is willing to provide written informed consent to participate in the study after reading the informed consent form and the information provided.
排除标准
- •Subjects will be eligible for enrollment in the study only if they meet NONE of the following criteria:
- •Subjects unwilling or unable to perform any of the assessments required by endpoint analysis.
- •Subjects who have a significant comorbid medical condition(s), as judged by the investigator, including, but not limited to:
- •Confirmed diagnosis of disabling neurologic disorder, including but not limited to Parkinson's disease, Amyotrophic lateral sclerosis, Stroke, or dementia, that significantly impact the assessments for endpoint analysis;
- •Severe kidney disease requiring hemodialysis or peritoneal dialysis;
- •Advanced liver disease such as hepatitis or liver cirrhosis;
- •Severe congestive heart failure (New York Heart Association [NYHA] class 3 and 4);
- •Autoimmune disease (rheumatoid arthritis, psoriasis/psoriatic arthritis, multiple sclerosis, systemic lupus erythematosus, etc.);
- •Hearing or visual impairment that significantly impact the assessments for endpoint analysis;
- •Pulmonary dysfunction requiring steroid therapy or O2 supplementation
- •Uncontrolled metabolic diseases including type II diabetes mellitus (hemoglobin A1c [HbA1c] > 8.5%)
- •Subjects carry history of malignancy of any organ system (other than curatively treated localized basal or squamous cell carcinoma of the skin, cervical carcinoma in situ) within 5 years prior to the screening visit.
- •Subjects using chronic high dose of steroid (> 5 mg prednisolone or equivalent), immunosuppressant therapy, or TNF-α antagonists.
- •Subjects with human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or hepatitis C virus (HCV) infections.
- •Subjects with known allergy or hypersensitivity to any component of the formulation (normal saline, human serum albumin, or dimethyl sulfoxide).
- •Subjects who have participated in another clinical study of new investigational therapies within 3 months before the study drug administration.
- •Subjects who have received any other stem cell therapy within 12 months before the study drug administration.
- •Subjects have a history of moderate to severe substance use disorder (including alcohol, cannabis, hallucinogens, inhalants, opioids, sedatives/hypnotics/anxiolytics, and stimulants [e.g., amphetamine-type substance, cocaine]) based on Diagnostic and Statistical Manual of Mental Disorders (DSM-5) within the past 3 years.
- •Subjects who have any hospitalization record within one month before the study drug administration (except for the scheduled admission in this study, if required).
- •Subjects who have dramatic change in their standard of care treatment (including exercise and nutritional supplements) for improvement of frailty within one month prior to study treatment, as judged by the investigator.
- •Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study.
研究组 & 干预措施
Phase II Placebo Arm
Peripheral IV infusion of placebo at baseline.
干预措施: umbilical cord mesenchymal stem cells (Biological)
Phase II Treatment Arm
umbilical cord mesenchymal stem cells, 100×10^6 cells/subject, single treatment by intravenous infusion in phase II.
干预措施: umbilical cord mesenchymal stem cells (Biological)
Phase I Treatment Arm
umbilical cord mesenchymal stem cells, 100×10^6 cells/subject, single treatment by intravenous infusion in phase I.
干预措施: umbilical cord mesenchymal stem cells (Biological)
结局指标
主要结局
vital signs
时间窗: Up to 12 months through study
Phase I: change in vital signs
Incidence of Treatment-Emergent Adverse Events (TEAEs)/ Serious Adverse Events (SAEs).
时间窗: Up to 12 months through study
Phase I : Incidence of any treatment-emergent serious adverse events (SAE), defined as the composite of: death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities.
physical examination
时间窗: Up to 12 months through study
Phase I: change in physical examination
electrocardiogram
时间窗: Up to 12 months through study
Phase I: change in electrocardiogram
clinical laboratory test results
时间窗: Up to 12 months through study
Phase I: change in clinical laboratory test results
Incidence of withdrawals due to adverse events
时间窗: Up to 12 months through study
Phase I: Incidence of any treatment-emergent serious adverse events (SAE), defined as the composite of: death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities.
次要结局
- Mean change from baseline in frailty status (Cardiovascular Health Study [CHS] frailty score(change from baseline to Day 91, Day 181, and Day 361)
- Mean change from baseline in quality of life measured by change in SF-12(change from baseline to Day 91, Day 181, and Day 361)
- Mean change from baseline in grip strength(change from baseline to Day 91, Day 181, and Day 361)
- Mean change from baseline in chair-stand test(change from baseline to Day 91, Day 181, and Day 361)
- Mean change from baseline in muscle mass and bone density(change from baseline to Day 91, Day 181, and Day 361)