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

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.

Timeline

Start

2026-08-31

Primary completion

2029-08-31

Completion

2030-08-31

Publications

• Background 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.
• Results 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.

Drugs

Indications