Umbilical Cord Mesenchymal Stem Cells (UC-MSC) in the Treatment of Systemic Sclerosis

Prior treatment

• Previously diagnosed with moderate or severe pulmonary arterial hypertension, or systolic pulmonary artery pressure \>45 mmHg measured by echocardiography at screening.
• Receipt of inactivated or live-attenuated vaccine within 2 months prior to enrollment.
• Any of the following within 3 months prior to enrollment:
  • ① Major trauma or major surgery (including joint surgery), or need for major surgery during the study period that, in the investigator's opinion, would pose an unacceptable risk to the subject.
  • ② Treatment with plasmapheresis or extracorporeal photopheresis.
  • ③ Participation in any other interventional clinical trial.
• Prior treatment with stem cell-based therapy less than 3 months before enrollment.
• History of any malignancy within 5 years prior to enrollment, except for adequately treated or resected basal cell carcinoma or squamous cell carcinoma of the skin, or cervical carcinoma in situ.
• Heavy smoking, heavy drinking, or drug abuse within 12 months prior to screening or during the screening period:
  • ① Heavy smoking defined as an average of ≥5 cigarettes per day within 3 months prior to screening.
  • ② Heavy drinking defined as consumption of more than 14 units of alcohol per week within 3 months prior to screening (1 unit = 350 mL of beer, 45 mL of liquor, or 150 mL of wine).
  • ③ Drug abuse defined as a history of drug addiction or drug abuse.

Other illness

• Presence of other autoimmune connective tissue diseases other than systemic sclerosis at screening, except for patients with secondary Sjögren's syndrome who are permitted to participate in this trial.
• Positive test for human immunodeficiency virus antibody (anti-HIV-Ab), active syphilis, active hepatitis C (positive for HCV antibody with detectable HCV-RNA), or positive for HBsAg with detectable HBV-DNA at screening; or history of severe active or recurrent bacterial, viral, fungal, parasitic, or other infections at screening.
• Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation in this study.

Lab values

• Presence of newly onset or worsening of pre-existing clinical symptoms requiring hospitalization as judged by the investigator prior to screening, including the following:
  • ① Myocardial infarction, stroke, scleroderma renal crisis, severe intestinal disease, or uncontrolled severe hypertension (≥160/100 mmHg) with newly onset or worsening of pre-existing clinical symptoms within 6 months.
  • ② Unstable ischemic heart disease, uncontrolled cardiac arrhythmia, heart failure (New York Heart Association Class III/IV), left ventricular ejection fraction \<50% by echocardiography, renal insufficiency, or renovascular hypertension within 3 months.
• Any of the following laboratory abnormalities at screening:
  • ① Hematologic abnormalities: hemoglobin \<90 g/L; white blood cell count \<3.0×10\^9 /L; absolute neutrophil count \<1.5×10\^9 /L; platelet count \<90×10\^9 /L.
  • ② Hepatic abnormalities: ALT or AST \>3× upper limit of normal (ULN); total bilirubin \>3× ULN.
  • ③ Renal abnormalities: estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m², or any uncontrolled, clinically significant laboratory abnormality that may interfere with data interpretation or subject participation.
• Intolerance or contraindication to the study treatment, including any of the following:
  • ① Allergy to albumin contained in the excipients of the investigational product.
  • ② Absence of peripheral venous access.

Other

• At screening, the patient's percent predicted forced vital capacity (FVC) is \<50%.
• Plan to father or bear children within at least 6 months following the last dose, or unwilling to use effective contraception with their partner, or plan to donate sperm or eggs.

• Voluntarily signed informed consent form.
• Age 18 to 65 years, inclusive, male or female.
• Diagnosis of systemic sclerosis (SSc) according to the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria.
• Diagnosis of diffuse cutaneous systemic sclerosis at screening, with disease duration ≤5 years (disease onset defined as the time of initial SSc diagnosis).
• Prior treatment with at least two of the following: corticosteroids, immunosuppressants, or biologic agents, and a modified Rodnan skin score (mRSS) between 10 and 30, inclusive.
• Female subjects must meet one of the following:
  • Of non-childbearing potential, defined as at least one year postmenopausal or surgically sterilized; or
  • Of childbearing potential and agree to use effective contraception from the signing of informed consent through at least 6 months after the last dose of study drug, with a negative serum pregnancy test at screening.