Safety, Tolerability, and Preliminary Efficacy of Human Umbilical Cord Mesenchymal Stem Cell Injection Via Intravenous Infusion in Type 2 Diabetic Nephropathy: A Phase I/IIa Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Phase I: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory tests
研究概览
简要总结
Diabetic nephropathy (DN) is a chronic kidney disease caused by diabetes. It is one of the most common and most serious microvascular complications of diabetes. Current treatment options for DN are limited. Mesenchymal stem cells (MSCs) are considered one of the promising treatments for DN. This study aims to evaluate the safety, tolerability, and preliminary efficacy of human umbilical cord mesenchymal stem cell injection in patients with type 2 DN.
详细描述
This is a Phase I/IIa clinical trial evaluating the safety, tolerability, and preliminary efficacy of human umbilical cord mesenchymal stem cell injection in patients with type 2 DN. Phase I is a single-center, prospective, open-label, self-controlled study to evaluate the safety and tolerability of MSCs and determine the recommended Phase II dose (RP2D). Phase IIa is a randomized, open-label, standard treatment-controlled study to preliminarily evaluate efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 80 years, with no gender and ethnicity restrictions.
- •Patients who meet the diagnostic criteria for type 2 diabetes mellitus (T2DM) as defined by the Chinese Guideline for the Prevention and Treatment of Type 2 Diabetes Mellitus (2020 Edition), with:
- •Baseline serum C-peptide concentrations ranging from 0.3 to 3.0 ng/mL;
- •Stable antihyperglycemic and antihypertensive medication regimen for at least 3 months prior to screening, defined as dosage adjustment less than 25%.
- •Urinary albumin-to-creatinine ratio (UACR) ≥ 30 and ≤ 5000 mg/g together with estimated glomerular filtration rate (eGFR) ≥ 30 and < 90 mL/min/1.73 m².
- •Patients are required to have renal biopsy-proven DN glomerulopathy with Tervaert Class IIa to Class III glomerular lesions.
- •Patients voluntarily agree to participate and provide written informed consent after full disclosure of the study's purpose, procedures, nature, and potential adverse reactions.
排除标准
- •Other non-T2DM, such as type 1 diabetes.
- •Individuals allergic to MSCs or their preservation solution.
- •Individuals with any of the following conditions during screening:
- •History of acute diabetic complications within the past 6 months, including diabetic ketoacidosis, hyperglycemic hyperosmolar state, or lactic acidosis;
- •Unstable disease status or severe diabetic complications within the past 6 months, such as proliferative diabetic retinopathy or macular edema, severe diabetic neuropathy, intermittent claudication, active diabetic foot lesions;
- •History of three or more Level 3 hypoglycemic events within the past 6 months, as defined by the Guidelines for the Management of Type 2 Diabetes in China (2020 Edition);
- •History of any of the following cardiac conditions within the past 6 months: decompensated heart failure (New York Heart Association Class III-IV); unstable angina, myocardial infarction, coronary artery bypass grafting, or coronary stent implantation; severe arrhythmias requiring treatment, including second-degree or third-degree atrioventricular block, long QT syndrome, or QTc interval prolongation ≥ 500 ms, and deemed by the investigator to render the subject unsuitable for study participation;
- •History of hemorrhagic or ischemic stroke within the past 6 months deemed by the investigator to render the subject unsuitable for study participation;
- •History of other severe endocrine disorders affecting glucose metabolism, such as multiple endocrine neoplasia, acromegaly, and Cushing's syndrome, deemed by the investigator to render the subject unsuitable for study participation;
- •History of severe digestive system diseases, nutritional and metabolic disorders, or rheumatologic diseases, deemed by the investigator to render the subject unsuitable for study participation;
- •Concurrent malignancy or history of malignancy (except malignancies with at least 5 years of disease-free survival);
- •Severe psychiatric disorder or speech impairment, or the subject is unwilling or unable to fully understand and comply with study requirements;
- •Severe infection or major surgery within the past 6 months, deemed by the investigator to render the subject unsuitable for study participation;
- •Acquired Immunodeficiency Syndrome, active hepatitis B, hepatitis C infection, or other acute or chronic infectious diseases;
- •Poorly controlled blood pressure, defined as a systolic blood pressure > 180mmHg and/or diastolic blood pressure > 110mmHg.
- •Laboratory test results meet the following criteria:
- •Alanine aminotransferase or aspartate aminotransferase ≥ 2.5 times the upper limit of normal (ULN);
- •Total bilirubin ≥ 2.0 times ULN;
- •Currently suffering from severe renal disease, or eGFR (CKD-EPI2012Scr-CysC) < 30 mL/min/1.73 m²;
- •Fasting triglycerides > 5.6 mmol/L;
- •Serum amylase or serum lipase ≥ 1.5 times ULN;
- •Hemoglobin < 10.0 g/dL (100 g/L), serum albumin < 30 g/L;
- •Glycosylated hemoglobin ≥ 10%.
- •History of long-term systemic corticosteroid administration (consecutive or cumulative ≥ 7 days) within 1 month prior to screening (including but not limited to intravenous administration, oral administration, or intramuscular injection).
- •Renal replacement therapy within 3 months prior to screening, current ongoing, or planned initiation within the next 3 months (including hemodialysis, peritoneal dialysis, continuous renal replacement therapy).
- •Participation in other drug or device clinical trials within 3 months prior to screening.
- •Previous use of other stem cell treatments.
- •Use of immunosuppressants, tripterygium glycosides, eplerenone, spironolactone, or similar agents within 3 months prior to screening.
- •Pregnancy, lactation, or intention to become pregnant during the study period.
- •Any other condition that, in the investigator's judgment, would make the subject unsuitable for the study.
- •Renal biopsy revealing DN with coexisting non-DN pathology.
结局指标
主要结局
Phase I: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory tests
时间窗: From enrollment to 6 months after the end of treatment
AEs and SAEs will be graded according to the NCI-CTCAE version 5.0. Changes in vital signs, ECG, and routine laboratory tests will be monitored throughout the study. The recommended Phase II dose (RP2D) will be determined from Phase I results.
Phase IIa: Proportion of participants achieving marked response or moderate response to human umbilical cord mesenchymal stem cell injection for type 2 DN
时间窗: From enrollment to 6 months after the end of treatment
Marked response is defined as significant improvement in clinical symptoms together with complete remission of proteinuria \[urinary albumin-to-creatinine ratio (UACR) \<30 mg/g\], or significant improvement in estimated glomerular filtration rate (eGFR) (serum creatinine reduced by ≥20%). Moderate response is defined as partial alleviation of clinical symptoms and partial remission of proteinuria without complete resolution; either the UACR or 24-hour urinary protein level decreases by ≥50%, or eGFR improves (serum creatinine reduced by ≥10%). No response is defined as no improvement in clinical symptoms and no remission of proteinuria. The reduction of either UACR or 24-hour urinary protein level is less than 50%, and there is no improvement in eGFR (serum creatinine reduced by \<10%).
次要结局
- Phase I: Proportion of participants achieving marked response or moderate response to human umbilical cord mesenchymal stem cell injection for type 2 DN(From enrollment to 6 months after the end of treatment)
- Phase IIa: Incidence and severity of AEs and serious SAEs and clinically significant abnormalities in vital signs, ECG, and laboratory tests(From enrollment to 6 months after the end of treatment)
- Renal function(From enrollment to 6 months after the end of treatment)
- 24-Hour urinary protein quantification(From enrollment to 6 months after the end of treatment)
- UACR(From enrollment to 6 months after the end of treatment)
- Glycated hemoglobin (HbA1c)(From enrollment to 6 months after the end of treatment)
- Fasting blood glucose(From enrollment to 6 months after the end of treatment)
- 2-Hour postprandial blood glucose(From enrollment to 6 months after the end of treatment)
- Fasting insulin(From enrollment to 6 months after the end of treatment)
- Fasting C-Peptide(From enrollment to 6 months after the end of treatment)
- Fasting lipid profile(From enrollment to 6 months after the end of treatment)
- Serum albumin(From enrollment to 6 months after the end of treatment)
- Oral glucose tolerance test (OGTT)(From enrollment to 6 months after the end of treatment)
- C-peptide release test(From enrollment to 6 months after the end of treatment)
- Fasting body weight(From enrollment to 6 months after the end of treatment)
- Body mass index(From enrollment to 6 months after the end of treatment)
- Waist circumference(From enrollment to 6 months after the end of treatment)
- Hip Circumference(From enrollment to 6 months after the end of treatment)
- Waist-to-hip ratio(From enrollment to 6 months after the end of treatment)