hUC-MSC-Exosomes for T2DM - Safety & Efficacy

An Exploratory Clinical Study Assessing the Safety and Preliminary Efficacy of Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Adult Type 2 Diabetes Mellitus

The goal of this clinical trial is to Evaluate the Safety and Preliminary Efficacy of Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Adult Type 2 Diabetes Mellitus.

A two-stage, progressive mixed design will be adopted to balance ethical considerations and scientific rigor.

Stage 1 (Open-Label, Before-and-After Study) will employ a sequential, open-label dose-escalation design:

A total of 18 patients will be enrolled, all receiving a 2-month course (once weekly, 8 doses total) of intravenous exosome infusion therapy. This study uses a sequential dose-escalation design with three dose cohorts: low-dose (1×10¹¹ particles), medium-dose (3×10¹¹ particles), and high-dose (9×10¹¹ particles). Dose escalation will strictly adhere to the following procedure:

Sequential Progression: The study for the next dose cohort can only commence after all subjects in the previous dose cohort have completed the required safety observation period (i.e., the 5-week follow-up post-last dose) and the safety data has been reviewed.

Stage 2 (Randomized, Double-Blind, Active-Comparator Parallel Study):

Provided no major safety issues are identified in the first stage, the second stage will commence. This stage plans to enroll 48 patients, randomized 2:1 to either the exosome treatment group (n=32) or the active-comparator control group (n=16).

Follow-up Plan: Multiple visits are scheduled, including a baseline period, treatment period (after each dose), end of treatment (Week 8/Month 2), and post-treatment follow-up periods (Week 12, Month 3, Month 6, Month 12), to systematically evaluate efficacy and safety.

Inclusion Criteria:

1. Age 18-65 years, diagnosed with T2DM for ≥5 years (<20 years).
2. Regular diet and exercise control combined with the following intensive treatment regimens, with screening HbA1c remaining between 7.5% and 9.0% (FBG <13.9mmol/L):Stable dose of insulin (basal or premixed) (<1.5u/kg·d) combined with ≥1 oral antidiabetic drug (OAD) (e.g., Metformin, SGLT2i) for ≥3 months; or Insulin combined with a GLP-1RA (maximum tolerated dose, ≤1mg Qw); or GLP-1RA (maximum tolerated dose, ≤1mg Qw) combined with ≥1 OAD for ≥3 months; or Stable dose of ≥3 OADs (must include Metformin) for ≥3 months.
3. Fasting C-peptide ≥1.0 ng/mL.
4. Glutamic acid decarboxylase (GAD) antibody and Islet cell antibody (IAA) negative.
5. Body Mass Index (BMI) 18.5-35 kg/m ².
6. Subjects voluntarily participate in the study and sign the informed consent form.
7. Female subjects of childbearing potential and non-sterilized male subjects must agree to use highly effective contraceptive methods during the study period and for 1 year following the final infusion.

Exclusion Criteria:

1. Type 1 diabetes or other specific types of diabetes.
2. Occurrence of severe hypoglycemia or diabetic ketoacidosis within the past 6 months.
3. Severe cardiovascular/cerebrovascular diseases, hepatic or renal insufficiency (e.g., eGFR <30 mL/min·1.73m²).
4. Active malignancy, coagulation disorders, immune system diseases.
5. Pregnant or lactating women.
6. Individuals with allergic constitution.
7. Exclusion of subjects currently participating in other clinical trials.
8. Subjects deemed unsuitable for participation by the investigator.