Efficacy and Safety of BMSCs (CG-BM1) for ACLF Patients

NCT06740149 | Recruiting Phase 1

• 1 other identifier: CGBM1-ACLF
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if CG-BM1 Allogeneic Human Bone Marrow Mesenchymal Stem Cell Injection (hereinafter referred to as CG-BM1) can treat acute-on-chronic liver failure (ACLF) patients. Main purposes of this clinical trial are:

• To evaluate the safety and tolerability of CG-BM1 for the treatment of adult patients with ACLF.
• To observe the preliminary effectiveness of CG-BM1 in treating adult ACLF patients, and to provide a basis for subsequent clinical trial protocol design.

Conditions

Acute-On-Chronic Liver Failure

Keywords

bone marrow mesenchymal stem cells; acute-on-chronic liver failure

Outcome Measures

Primary Outcomes (3)

• Phase I: Incidence of CG-BM1-related dose-limiting toxicity (DLT) events

  Incidence of CG-BM1-related DLT events.

  From first dose to 180 days after the first dose.

• Phase I: Adverse event related to CG-BM1 treatment

  Any adverse event related to CG-BM1 treatment that occurred during the study period.

  From first dose to 180 days after the first dose.

• Phase II: Liver transplant-free survival

  90-day liver transplant-free survival.

  90 day after the first dose.

Secondary Outcomes (34)

• Phase I: Liver transplant-free survival

  28 day, 90 day, and 180 days after the first dose.

• Phase I: Changes of aspartate aminotransferase (AST)

  Pre-treatment, 3 days, 7 days, 14 days, 21 days, 28 days, 90 days after the first dose.

• Phase I: Changes of alanine aminotransferase (ALT)

  Pre-treatment, 3 days, 7 days, 14 days, 21 days, 28 days, 90 days after the first dose.

• Phase I: Changes of albumin

  Pre-treatment, 3 days, 7 days, 14 days, 21 days, 28 days, 90 days after the first dose.

• Phase I: Changes of alkaline phosphatase (ALP)

  Pre-treatment, 3 days, 7 days, 14 days, 21 days, 28 days, 90 days after the first dose.

Study Arms (6)

Phase 2: Placebo Control

PLACEBO COMPARATOR

The control group received placebo + conventional treatment. Placebo was solubilizer of CG-BM1. Conventional treatment included hepatoprotection, antiviral therapy or other etiologic treatments, supplementation of plasma and albumin, supplementation of coagulation factors, treatment of complications, and nutritional support.

Drug: Solvent of CG-BM1

Phase 2: Low Dose Group

EXPERIMENTAL

Patients in low dose group receive CG-BM1 + conventional treatment. Administration procedure of CG-BM1 is 1.0×10\^6 cells/kg CG-BM1 once a week for a total of 4 administrations.

Drug: Bone marrow mesenchymal stem cells (low dose)

Phase 2: Medium Dose Group

EXPERIMENTAL

Patients in medium dose group receive CG-BM1 + conventional treatment. Administration procedure of CG-BM1 is 2.0×10\^6 cells/kg CG-BM1 once a week for a total of 4 administrations.

Drug: Bone marrow mesenchymal stem cells (medium dose)

Phase 1: Low Dose Group

EXPERIMENTAL

The trial group with a low dose (1.0×10\^6 cells/kg) will first enroll one subject, who will be infused with single dose CG-BM1 and then observed for at least 28 days. The clinical data of the first subject will be reviewed by the SRC. * If the first subject in the low-dose trial group experiences DLT, enrollment will be suspended. After discussion, recommendations will be made. If the trial is to continue, two additional subjects will be enrolled for observation. If no DLT occurs, the dose trial group will need to enroll three more subjects. * If the first subject in the dose trial group does not experience DLT after 28 days, - the remaining two subjects in that dose trial group will be enrolled. Once all subjects in the dose trial group have completed the infusion and have been observed for 28 days, the clinical data of all subjects will be submitted to the SRC. After a comprehensive evaluation, the SRC will provide recommendations for dose escalation.

Drug: Bone marrow mesenchymal stem cells (low dose)

Phase 1: Medium Dose Group

EXPERIMENTAL

The trial group with a low dose (2.0×10\^6 cells/kg) will first enroll one subject, who will be infused with single dose CG-BM1 and then observed for at least 28 days. The clinical data of the first subject will be reviewed by the SRC. * If the first subject in the low-dose trial group experiences DLT, enrollment will be suspended. After discussion, recommendations will be made. If the trial is to continue, two additional subjects will be enrolled for observation. If no DLT occurs, the dose trial group will need to enroll three more subjects. * If the first subject in the dose trial group does not experience DLT after 28 days, - the remaining two subjects in that dose trial group will be enrolled. Once all subjects in the dose trial group have completed the infusion and have been observed for 28 days, the clinical data of all subjects will be submitted to the SRC. After a comprehensive evaluation, the SRC will provide recommendations for dose escalation.

Drug: Bone marrow mesenchymal stem cells (medium dose)

Phase 1: High Dose Group

EXPERIMENTAL

The trial group with a low dose (4.0×10\^6 cells/kg) will first enroll one subject, who will be infused with single dose CG-BM1 and then observed for at least 28 days. The clinical data of the first subject will be reviewed by the SRC. * If the first subject in the low-dose trial group experiences DLT, enrollment will be suspended. After discussion, recommendations will be made. If the trial is to continue, two additional subjects will be enrolled for observation. If no DLT occurs, the dose trial group will need to enroll three more subjects. * If the first subject in the dose trial group does not experience DLT after 28 days, - the remaining two subjects in that dose trial group will be enrolled. Once all subjects in the dose trial group have completed the infusion and have been observed for 28 days, the clinical data of all subjects will be submitted to the SRC. After a comprehensive evaluation, the SRC will provide recommendations for dose escalation.

Drug: Bone marrow mesenchymal stem cells (high dose)

Interventions

Bone marrow mesenchymal stem cells (low dose) DRUG

Administered intravenously. For phase I: single infusion, 1.0×10\^6 cells/kg. For phase II: 1.0×10\^6 cells /kg once a week for a total of 4 times.

Also known as: CG-BM1

Phase 1: Low Dose Group; Phase 2: Low Dose Group

Solvent of CG-BM1 DRUG

Administered intravenously, once a week for a total of 4 doses.

Phase 2: Placebo Control

Bone marrow mesenchymal stem cells (medium dose) DRUG

Administered intravenously. For phase I: single infusion, 2.0×10\^6 cells /kg. For phase II: 2.0×10\^6 cells /kg once a week for a total of 4 times.

Phase 1: Medium Dose Group; Phase 2: Medium Dose Group

Bone marrow mesenchymal stem cells (high dose) DRUG

Administered intravenously. For phase I: single infusion, 4×10\^6 cells /kg.

Phase 1: High Dose Group

Eligibility Criteria

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

You may qualify if:

• Voluntarily participate in the clinical study. The patient or legal guardian fully understands and is informed about the study and signs an informed consent form. Willing to follow and be able to complete all trial procedures.
• Age ≥18 years old, male or female.
• Diagnostic criteria in accordance with the Guidelines for Diagnosis and Treatment of Liver Failure (2018 edition) issued by the Liver Failure and Artificial Liver Group of the Infectious Diseases Branch of the Chinese Medical Association and the Liver Disease Branch of the Chinese Medical Association Diagnostic criteria, specific indicators include 1) Suffering from the basis of chronic liver disease; 2) Serum TBIL 171 μ mol/l or mean daily rise ≥17.1 μmol/L; 3) Meeting any of the following three: i. Having a bleeding tendency; ii. Comorbid hepatic encephalopathy; iii. Comorbid hepatorenal syndrome.
• The cause of liver failure is unlimited.
• Model for End Stage Liver Disease (MELD) score under 30.
• No conception (or conception of sexual partner) during the study period (from signing of informed consent to the last visit) and within 6 months after the last cell infusion; and childbearing, or breastfeeding potential, including:
• Female subject with persistent spontaneous menopause \>12 months or who have undergone sterilization (e.g., tubal ligation or bilateral oophorectomy or hysterectomy).
• Non-menopausal female subject with a negative serum pregnancy test within 7 days prior to the first cellular infusion. Sign an informed consent and willingness to use one of the following effective methods of contraception, including intrauterine device (IUD), tubal ligation, double barrier method (condom, vaginal diaphragm, spermicide) and spermicide for the male partner, but does not include oral contraceptives, for a period of 6 months after the last cellular infusion.
• Male subjects who are willing to use one or more effective methods of contraception, including vasectomy, double-barrier methods, use of the pill by the female partner, intrauterine devices or tubal ligation from the time of the first infusion until 6 months after the last infusion.
• Male or non-menopausal female subjects who do not have, or are willing to not have sexual intercourse during the study and for 6 months after the last cell infusion.

You may not qualify if:

• Be allergic to known components of the drug (the main component of the product is bone marrow mesenchymal stem cells, excipients include dimethyl sulfoxide, human albumin) or other history of severe allergy.
• Patients with severe infections such as septic shock.
• Patients with gastrointestinal bleeding at the time of screening.
• Hepatic encephalopathy grade 4.
• Concurrent failure of 3 or more organs (liver failure defined as TBiL ≥12 mg/dl, renal failure defined as creatinine ≥2.0 mg/dl, coagulation failure defined as INR ≥2.5, cerebral failure defined as hepatic encephalopathy grades 3-4, circulatory failure defined by use of vasoactive drugs, and respiratory failure was defined as PaO2 /FiO2 ≤200 or SpO2 /FiO2 ≤214 or mechanical ventilation)
• Pregnancy or breastfeeding.
• Previous history of malignant tumors.
• Imaging suggestive of intrahepatic nodular space-occupying lesions.
• A history of immunodeficiency, including HIV-positive, or other acquired or congenital immunodeficiency diseases.
• Patients with previous liver transplantation.
• Deep vein thrombosis at screening or history of pulmonary embolism within 3 months prior to screening.
• Patients with pulmonary hypertension.
• History of myocardial infarction within 6 months.
• Previous stem cell therapy.
• Participation in another interventional clinical trial within 3 months or 5 half-lives (for experimental drug interventions only, whichever is longer) prior to infusion.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Guangzhou Cellgenes Biotechnology Co.,Ltd: collaborator

Study Sites (1)

Third Affliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510630, China

RECRUITING

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MeSH Terms

Conditions

Acute-On-Chronic Liver Failure

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Central Study Contacts

Bingliang Lin, MD

CONTACT

86-020-85253165; linbingl@mail.sysu.edu.cn

Junfeng Chen, MD

CONTACT

86-020-85253165; chenjf36@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: December 11, 2024
• First Posted: December 18, 2024
• Study Start: March 1, 2023
• Primary Completion: October 31, 2025
• Study Completion: January 31, 2026
• Last Updated: December 18, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)