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

NCT07795151 | Not Yet Recruiting Phase 1

• 1 other identifier: KY-2026-7-120-1
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II clinical trial evaluates human umbilical cord-derived mesenchymal stromal cell (hUC-MSC) injection in patients with primary biliary cholangitis (PBC). The phase I component uses a 3+3 dose-escalation design with separate single-dose and multiple-dose stages to assess safety and tolerability, establish the maximum tolerated dose and recommended phase II dose, while monitoring adverse events, vital signs, laboratory parameters, and immunogenicity, and to explore preliminary efficacy signals. The phase II component is a randomized, double-blind, placebo-controlled trial with the primary endpoint of composite response of alkaline phosphatase and bilirubin at 12 weeks to evaluate efficacy, alongside continuous safety surveillance. Systematic measurements of liver function, cholestasis, immune markers, quality of life, and pruritus scores are incorporated to investigate mechanisms and potential biomarkers, aiming to generate robust clinical evidence that supports future development and clinical translation of hUC-MSC therapy for PBC.

Conditions

Primary Biliary Cholangitis

Outcome Measures

Primary Outcomes (4)

• Incidence of Dose-Limiting Toxicity (DLT) in Phase I

  Occurrence of DLT during the DLT observation period (single-dose cohort: 7 days after infusion; multiple-dose cohort: 28 days after first infusion), graded by CTCAE v6.0.

  Up to Day 7 (single-dose) or up to Day 28 (multiple-dose).

• Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events (Phase I)

  Safety and tolerability assessed by monitoring TEAEs, SAEs, and clinically significant changes in vital signs, physical examination, laboratory parameters, and 12-lead ECG.

  Up to Day 7 (single-dose) or up to Day 28 (multiple-dose).

• Maximum Tolerated Dose (MTD) of hUC-MSC in PBC Patients (Phase I)

  Determination of MTD based on DLT occurrence in the 3+3 dose-escalation phase I; MTD is the highest dose with ≤1/6 participants experiencing DLT.

  At completion of phase I dose escalation (after DLT evaluation).

• Composite Biochemical Response at Week 12 (Phase II)

  Proportion of participants achieving all three: ALP \< 1.67×ULN, ALP reduction ≥15% from baseline, and total bilirubin ≤ ULN at Week 12.

  Week 12

Secondary Outcomes (23)

• Proportion with ALP <1.67×ULN or ALP Reduction ≥15% or TB ≤ULN at Week 12 (Phase I)

  Week 12

• Change from Baseline in Alkaline Phosphatase (ALP) (Phase I)

  Baseline, Day 3, Week 1, 2, 4, 12, 24, 48, 72, 96

• Change from Baseline in Total Bilirubin (TB) (Phase I)

  Baseline, Day 3, Week 1, 2, 4, 12, 24, 48, 72, 96

• Change from Baseline in Direct Bilirubin (DBIL) (Phase I)

  Baseline, Day 3, Week 1, 2, 4, 12, 24, 48, 72, 96

• Change from Baseline in Alanine Aminotransferase (ALT) (Phase I)

  Baseline, Day 3, Week 1, 2, 4, 12, 24, 48, 72, 96.

Other Outcomes (4)

• Change from Baseline in Immunoglobulins (IgG, IgM) - (Phase I)

  Baseline, Day 3, Week 1, 2, 4, 12, 24, 48.

• Change from Baseline in Lymphocyte Subsets (Phase II)

  Baseline, Day 3, Week 1, 2, 4, 12, 24, 48.

• Change from Baseline in Cytokines (Phase II)

  Baseline, Day 3, Week 1, 2, 4, 12, 24, 48.

Study Arms (3)

Placebo Group

PLACEBO COMPARATOR

Participants receive placebo infusions via peripheral intravenous infusion once weekly for 3 consecutive weeks (at Week 0, Week 1, and Week 2), in addition to background therapy as per inclusion criteria (i.e., continued stable UDCA for patients on prior UDCA, or no UDCA for those intolerant to UDCA).

Drug: Standard background therapy; Drug: Placebo

hUC-MSC Dose Level 1 (planned 1.5×10⁸ cells, final dose TBD)

EXPERIMENTAL

Participants receive human umbilical cord-derived mesenchymal stromal cells (hUC-MSC) at a planned dose of 1.5×10⁸ cells per infusion (final dose to be confirmed based on the maximum tolerated dose / recommended phase II dose determined from phase I results) via peripheral intravenous infusion once weekly for 3 consecutive weeks (at Week 0, Week 1, and Week 2), in addition to background therapy as per inclusion criteria (continued stable UDCA for prior users, or no UDCA for intolerant patients).

Drug: Standard background therapy; Biological: hUC-MSC Dose Level 1

hUC-MSC Dose Level 2 (planned 2.0×10⁸ cells, final dose TBD)

EXPERIMENTAL

Participants receive hUC-MSC at a planned dose of 2.0×10⁸ cells per infusion (final dose to be confirmed based on the MTD/RP2D from phase I) via peripheral intravenous infusion once weekly for 3 consecutive weeks (at Week 0, Week 1, and Week 2), in addition to background therapy as per inclusion criteria (continued stable UDCA for prior users, or no UDCA for intolerant patients).

Drug: Standard background therapy; Biological: hUC-MSC Dose Level 2

Interventions

Standard background therapy DRUG

UDCA capsule 250 mg, orally, 13-15 mg/kg/day, taken with a small amount of water. This background therapy is administered only to participants who have been on a stable dose of UDCA for at least 6 months prior to enrollment (and stable for ≥3 months before screening). Participants who are intolerant to UDCA (and have not used UDCA for ≥3 months before enrollment) do not receive UDCA during the study.

Placebo Group; hUC-MSC Dose Level 1 (planned 1.5×10⁸ cells, final dose TBD); hUC-MSC Dose Level 2 (planned 2.0×10⁸ cells, final dose TBD)

Placebo DRUG

Matching placebo solution (e.g., 5% human serum albumin in 0.9% saline) administered via peripheral intravenous infusion at Week 0, Week 1, and Week 2 (once weekly for 3 infusions).

Placebo Group

hUC-MSC Dose Level 1 BIOLOGICAL

Human umbilical cord-derived mesenchymal stromal cells, planned at 1.5×10⁸ cells per infusion (final dose subject to confirmation based on phase I MTD/RP2D). Administered via peripheral intravenous infusion at Week 0, Week 1, and Week 2 (once weekly for 3 infusions).

hUC-MSC Dose Level 1 (planned 1.5×10⁸ cells, final dose TBD)

hUC-MSC Dose Level 2 BIOLOGICAL

Human umbilical cord-derived mesenchymal stromal cells, planned at 2.0×10⁸ cells per infusion (final dose subject to confirmation based on phase I MTD/RP2D). Administered via peripheral intravenous infusion at Week 0, Week 1, and Week 2 (once weekly for 3 infusions).

hUC-MSC Dose Level 2 (planned 2.0×10⁸ cells, final dose TBD)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• ×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.

You may not qualify if:

• 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.
• 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).
• 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.
• 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.
• 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.
• Received any other investigational drug or participated in another interventional clinical trial within 3 months before screening; prior use of elafibranor or seladelpar.
• History of drug or alcohol abuse within 1 year before screening.
• 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.
• Co-infection with HIV or syphilis.
• Known allergy to any component of the study drug.

Sponsors & Collaborators

• Beijing 302 Hospital: lead

Study Sites (1)

Beijing 302 Hospital

Beijing, Beijing Municipality, China

Location

Related Publications (18)

• Phang MWL, Hisam NSM, Supandi F, Cheng PG, Lim SH, Lim LW, Wong KH. The Tiger Milk Medicinal Mushroom Lignosus rhinocerus (Agaricomycetes) Mitigates Oxidative Damage in a Cellular Model Mimicking Friedreich's Ataxia. Int J Med Mushrooms. 2025;27(11):63-87. doi: 10.1615/IntJMedMushrooms.2025059734.

  PMID: 40752029 BACKGROUND

• Chen W, Lin F, Feng X, Yao Q, Yu Y, Gao F, Zhou J, Pan Q, Wu J, Yang J, Yu J, Cao H, Li L. MSC-derived exosomes attenuate hepatic fibrosis in primary sclerosing cholangitis through inhibition of Th17 differentiation. Asian J Pharm Sci. 2024 Feb;19(1):100889. doi: 10.1016/j.ajps.2024.100889. Epub 2024 Feb 12.

  PMID: 38419761 RESULT

• Zheng X, Tian S, Li T, Zhang S, Zhou X, Liu Y, Su R, Zhang M, Li B, Qi C, Guo G, Ma S, Sun K, Yang F, Hu Y, Yang C, Cui L, Shang Y, Guo C, Jin B, Guan L, Wang J, Ning W, Han Y. Host FSTL1 defines the impact of stem cell therapy on liver fibrosis by potentiating the early recruitment of inflammatory macrophages. Signal Transduct Target Ther. 2025 Mar 7;10(1):81. doi: 10.1038/s41392-025-02162-6.

  PMID: 40050288 RESULT

• Ye Y, Zhang X, Su D, Ren Y, Cheng F, Yao Y, Shi G, Ji Y, Chen S, Shi P, Dai L, Su X, Deng H. Therapeutic efficacy of human adipose mesenchymal stem cells in Crohn's colon fibrosis is improved by IFN-gamma and kynurenic acid priming through indoleamine 2,3-dioxygenase-1 signaling. Stem Cell Res Ther. 2022 Sep 8;13(1):465. doi: 10.1186/s13287-022-03157-8.

  PMID: 36076306 RESULT

• Wang L, Han Q, Chen H, Wang K, Shan GL, Kong F, Yang YJ, Li YZ, Zhang X, Dong F, Wang Q, Xu D, Hu ZJ, Wang SH, Keating A, Bi YL, Zhang FC, Zhao RC. Allogeneic bone marrow mesenchymal stem cell transplantation in patients with UDCA-resistant primary biliary cirrhosis. Stem Cells Dev. 2014 Oct 15;23(20):2482-9. doi: 10.1089/scd.2013.0500. Epub 2014 Jul 16.

  PMID: 24835895 RESULT

• Shokati A, Nikbakht M, Sahraian MA, Saeedi R, Asadollahzadeh E, Rezaeimanesh N, Chahardouli B, Gharaylou Z, Mousavi SA, Ai J, Naser Moghadasi A. Cell therapy with placenta-derived mesenchymal stem cells for secondary progressive multiple sclerosis patients in a phase 1 clinical trial. Sci Rep. 2025 May 8;15(1):16005. doi: 10.1038/s41598-025-00590-6.

  PMID: 40341605 RESULT

• Shi L, Zhang Z, Mei S, Wang Z, Xu Z, Yao W, Liu L, Yuan M, Pan Y, Zhu K, Liu K, Meng F, Sun J, Liu W, Xie X, Dong T, Huang L, Meng F, Fu JL, Li Y, Zhang C, Fan X, Shi M, Zhang Y, Li Y, Xie WF, Zhang P, Wang FS. Dose-escalation studies of mesenchymal stromal cell therapy for decompensated liver cirrhosis: phase Ia/Ib results and immune modulation insights. Signal Transduct Target Ther. 2025 Jul 29;10(1):238. doi: 10.1038/s41392-025-02318-4.

  PMID: 40721581 RESULT

• Li L, He Y, Zhao J, Yin H, Feng X, Fan X, Wu W, Lu Q. Mesenchymal Stromal Cell-Based Therapy: A Promising Approach for Autoimmune Diseases. Clin Rev Allergy Immunol. 2025 Feb 21;68(1):21. doi: 10.1007/s12016-025-09030-9.

  PMID: 39982546 RESULT

• Hoang DM, Pham PT, Bach TQ, Ngo ATL, Nguyen QT, Phan TTK, Nguyen GH, Le PTT, Hoang VT, Forsyth NR, Heke M, Nguyen LT. Stem cell-based therapy for human diseases. Signal Transduct Target Ther. 2022 Aug 6;7(1):272. doi: 10.1038/s41392-022-01134-4.

  PMID: 35933430 RESULT

• Gholamrezanezhad A, Mirpour S, Bagheri M, Mohamadnejad M, Alimoghaddam K, Abdolahzadeh L, Saghari M, Malekzadeh R. In vivo tracking of 111In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis. Nucl Med Biol. 2011 Oct;38(7):961-7. doi: 10.1016/j.nucmedbio.2011.03.008. Epub 2011 Jun 22.

  PMID: 21810549 RESULT

• Wang Y, Chen X, Cao W, Shi Y. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol. 2014 Nov;15(11):1009-16. doi: 10.1038/ni.3002.

  PMID: 25329189 RESULT

• Ankrum JA, Ong JF, Karp JM. Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol. 2014 Mar;32(3):252-60. doi: 10.1038/nbt.2816. Epub 2014 Feb 23.

  PMID: 24561556 RESULT

• Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999 Apr 2;284(5411):143-7. doi: 10.1126/science.284.5411.143.

  PMID: 10102814 RESULT

• Galipeau J, Sensebe L. Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities. Cell Stem Cell. 2018 Jun 1;22(6):824-833. doi: 10.1016/j.stem.2018.05.004.

  PMID: 29859173 RESULT

• You H, Ma X, Efe C, Wang G, Jeong SH, Abe K, Duan W, Chen S, Kong Y, Zhang D, Wei L, Wang FS, Lin HC, Yang JM, Tanwandee T, Gani RA, Payawal DA, Sharma BC, Hou J, Yokosuka O, Dokmeci AK, Crawford D, Kao JH, Piratvisuth T, Suh DJ, Lesmana LA, Sollano J, Lau G, Sarin SK, Omata M, Tanaka A, Jia J. APASL clinical practice guidance: the diagnosis and management of patients with primary biliary cholangitis. Hepatol Int. 2022 Feb;16(1):1-23. doi: 10.1007/s12072-021-10276-6. Epub 2022 Feb 4. No abstract available.

  PMID: 35119627 RESULT

• Levy C, Manns M, Hirschfield G. New Treatment Paradigms in Primary Biliary Cholangitis. Clin Gastroenterol Hepatol. 2023 Jul;21(8):2076-2087. doi: 10.1016/j.cgh.2023.02.005. Epub 2023 Feb 19.

  PMID: 36809835 RESULT

• Galoosian A, Hanlon C, Zhang J, Holt EW, Yimam KK. Clinical Updates in Primary Biliary Cholangitis: Trends, Epidemiology, Diagnostics, and New Therapeutic Approaches. J Clin Transl Hepatol. 2020 Mar 28;8(1):49-60. doi: 10.14218/JCTH.2019.00049. Epub 2020 Jan 29.

  PMID: 32274345 RESULT

• Rodrigues PM, Perugorria MJ, Santos-Laso A, Bujanda L, Beuers U, Banales JM. Primary biliary cholangitis: A tale of epigenetically-induced secretory failure? J Hepatol. 2018 Dec;69(6):1371-1383. doi: 10.1016/j.jhep.2018.08.020. Epub 2018 Sep 5.

  PMID: 30193962 RESULT

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Fu-Sheng Wang, MD, PhD

  The Fifth Medical Center of PLAGeneral Hospital

  STUDY CHAIR

Central Study Contacts

Lei Shi, MD, PhD

CONTACT

86-10-66949623; shilei302@126.com

Fu-Sheng Wang, MD, PhD

CONTACT

86-10-66933332; fswang302@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases

Model Details: The phase I dose-escalation stage (3+3 design) is conducted first to determine the recommended phase II dose; after that, the phase II randomized, double-blind, placebo-controlled stage is initiated with three parallel arms.

Study Record Dates

• First Submitted: August 24, 2026
• First Posted: August 31, 2026
• Study Start: August 31, 2026
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): August 31, 2030
• Last Updated: August 31, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)