Phase I/II Trial of Human Umbilical Cord Mesenchymal Stromal Cells for UDCA-Refractory Primary Biliary Cholangitis

Prior treatment

• Concurrent or previous other liver diseases, including but not limited to: chronic hepatitis B, chronic hepatitis C, primary sclerosing cholangitis (PSC), complete biliary obstruction, alcoholic liver disease, autoimmune hepatitis or overlap with other autoimmune liver diseases, non-alcoholic steatohepatitis (NASH), suspected or confirmed Gilbert's syndrome.
• Use of prohibited medications within specified washout periods:
  • Within 2 months before screening: fibrates and glitazones;
  • Within 3 months before screening: obeticholic acid, azathioprine, cyclosporine, methotrexate, mycophenolate mofetil, pentoxifylline, budesonide and other systemic corticosteroids by long-term parenteral or oral administration only, and hepatotoxic drugs (e.g., α-methyldopa, valproate, isoniazid, nitrofurantoin);
  • Within 12 months before screening: antibodies or immunotherapies targeting interleukins or other cytokines/chemokines.
• Received any other investigational drug or participated in another interventional clinical trial within 3 months before screening; prior use of elafibranor or seladelpar.

Other illness

• History of malignancy within the past 2 years (except localized squamous cell carcinoma of skin or treated cervical intraepithelial neoplasia), regardless of treatment or evidence of local recurrence/metastasis.
• History of drug or alcohol abuse within 1 year before screening.
• Co-infection with HIV or syphilis.
• Known allergy to any component of the study drug.
• Any other condition judged by the investigator as unsuitable for enrollment, or that may interfere with the analysis of study results.

Lab values

• Decompensated cirrhosis (defined as presence of at least one of: esophageal/gastric variceal bleeding, hepatic encephalopathy, ascites, hepatorenal syndrome) based on clinical, laboratory, imaging, or histopathological findings.
• Any of the following laboratory abnormalities at screening: creatinine ≥1.5×ULN or creatinine clearance \<60 mL/min; ALT and/or AST \>5×ULN; albumin \<30 g/L; creatine kinase \>2×ULN; platelet count \< lower limit of normal; INR ≥1.5 or prothrombin activity ≤40%.
• Diseases that may cause non-hepatic elevation of alkaline phosphatase (e.g., Paget's disease).

Age

• Uncontrolled cardiovascular, digestive, respiratory, urinary, neurological, psychiatric disorders (including substance/alcohol abuse), immunodeficiency, or severe autoimmune diseases, or any condition that may limit life expectancy to \<2 years, or judged by the investigator as unsuitable for participation.

Other

• Pregnant, planning pregnancy, or women of childbearing potential unwilling to use effective contraception (≥1 method) during the study and for 30 days after last dose; breastfeeding women.
• Psychologically unstable or incapacitated, unable to provide valid informed consent or comply with study procedures.

• Voluntary participation and signed informed consent.
• Age 18 to 75 years, both genders.
• Diagnosis of PBC per the 2025 PBC Guideline of the National Health Commission of China, meeting at least 2 of the following 3 criteria:
  • Biochemical evidence of cholestasis (predominantly elevated ALP and GGT) with imaging excluding extrahepatic or intrahepatic large bile duct obstruction;
  • Positive for anti-mitochondrial antibody (AMA)/AMA-M2, or other PBC-specific autoantibodies (anti-gp210, anti-sp100);
  • Histological evidence of non-suppurative destructive cholangitis and small bile duct destruction.
• Inadequate response to UDCA prior to enrollment, defined as ALP ≥1.67×ULN after at least 6 months of UDCA therapy (with stable dose for ≥3 months before screening).
• 1.67×ULN ≤ ALP \< 10×ULN and total bilirubin ≤ 3×ULN at screening.
• If taking colchicine, stable dose for ≥3 months before screening.
• If taking medications for pruritus (e.g., cholestyramine, rifampicin, naltrexone, sertraline), stable dose for ≥3 months before screening.
• If taking statins or ezetimibe, stable dose for ≥2 months before screening.