To Evaluate the Clinical Study of CUD005 Injection in Patients With Cirrhosis

A Single-center, Single-arm, Open-label, Dose-escalation Clinical Study Evaluating the Safety, Tolerability, and Initial Efficacy of CUD005 Injection in Patients With Cirrhosis

The study is a single-center, single-arm, open-label, dose-escalation clinical study, to evaluate the tolerability, safety and preliminary efficacy of CUD005 injection in patients with cirrhosis

Study Overview

• Status: Enrolling by invitation
• Conditions: Cirrhosis, Liver
• Intervention / Treatment: Biological: Cell therapy

Detailed Description

The study was designed according to the 3+3 principle, with a total of 3 dose levels and dose escalation.

Low-dose group: 5.0×107 cells/time; Medium-dose group: 1.5×108 cells/time; High-dose group: 5.0×108 cells/time. Subjects were sequentially placed in 3 different dose groups administered as a single peripheral intravenous dose.

According to the enrollment restriction design, a total of a minimum of 9 subjects are expected to be enrolled, and the final sample size depends on the number of DLT, the number of dose groups ascended before DLT is observed, and the MTD is determined.

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Anhui Province Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. BMI≤30 kg/m2
2. The results of liver histopathological examination were consistent with the Ishak stage of liver fibrosis ≥3 points；
3. Consent to liver histopathological examination before and after cell therapy (The subject is exempted from liver histopathological examination during the screening period, if he has been performed liver histopathological examination within 2 months before signing the informed consent)；
4. Subjects were able to communicate well with the investigator, cooperate with follow-up work, and understand and comply with the requirements of the study.

Exclusion Criteria:

1. Subjects who were Allergic to cell therapy, steroids, and related drugs used in the study；
2. Have malignant tumors, history of organ transplantation or tissue regeneration therapy, active, known or suspected autoimmune diseases, idiopathic pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-induced pneumonia, active pneumonia, heart disease that is not well controlled, hypertension, etc;
3. Subjects with stage III or IV hepatic encephalopathy within 3 months before apheresis or currently diagnosed；
4. Virology shows anti-HCV antibodies, HIV-positive, or syphilis antibodies during the screening period；
5. Subjects were HBV surface antigen positive and HBV-DNA titer was ≥ 20 IU/mL during the screening period；
6. Subjects with clinically symptomatic ascites or pleural effusions requiring puncture drainage. Or who had received thoracic and ascites drainage within 2 weeks prior to treatment, had may only show a small amount of ascites or pleural effusions on imaging, except in those without clinical symptoms；
7. According to the judgment of the investigator, the subjects had other factors that may cause the study to be terminated halfway, such as other serious concomitant diseases (such as severe diabetes, mental illness, drug use, etc.), serious laboratory abnormalities, accompanied by family or social factors, which will affect the safety of the subject, or the collection of data and samples.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm; cell therapy	Biological: Cell therapy; Subjects were placed sequentially into three different dose groups, 5.0×107 cells/time (low-dose group), 1.5×108 cells/time (medium-dose group), and 5.0×108 cells/time (high-dose group) for dose escalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT,MTD	Dose-limiting toxicity（DLT）: frequency of occurrence, level of dose of DLT toxicity;Maximum tolerated dose (MTD)	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fibrosis staging and inflammatory grading	Histological changes in liver biopsy at day 180 after cell therapy.Methods: A small amount of liver tissue was taken from the liver by percutaneous puncture, and its histological changes were observed directly under the microscope. According to the pathological results, the Ishak scoring system for liver fibrosis (which includes fibrosis stage and inflammation grade evaluation criteria) was used to evaluate liver fibrosis, in which 0 was the best and 6 was the worst.	180 days
All-cause mortality	the ratio of the total number of deaths due to various factors over 1 year of cell therapy to the number of people in this population for the same period	1 year
TE（Transient elastography）	Changes in transient elastography.Methods: A special probe was used to generate an instantaneous low-frequency pulse to cause instantaneous displacement and shear wave in the liver tissue. The shear wave was tracked and collected to obtain the elastic modulus of the tissue, and the degree of liver fibrosis was evaluated by liver stiffness measurement (LSM). The higher the shear wave velocity, the higher the LSM value, and the stiffer the liver tissue in the detection area.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
MELD（Model for End-stage Liver Disease）	Changes in the Model of End-Stage Liver Disease.Methods: Creatinine, international normalized ratio (INR), and bilirubin combined with the etiology of liver cirrhosis were used to evaluate liver function reserve and prognosis in patients with chronic liver disease. Formula: MELD=3.78×ln [T-BiL(mg/dl)]+11.2×ln[INR]+9.57×ln[Cr (mg/dl)]+ 6.43× cause (0 for cholestatic and alcoholic cirrhosis, 1 for cirrhosis due to other causes such as viruses)	1 year

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital
• Investigators: Principal Investigator: Lianxin LX Liu, Professor, Anhui Provincial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2023
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: July 17, 2023
• First Submitted That Met QC Criteria: March 4, 2024
• First Posted (Estimated): March 6, 2024

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: tolerability; safety; cell therapy; Cirrhosis; dose escalation; MTD; DLT; PBMC
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: KDS-CUD-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No