Clinical trial NCT06296095: To Evaluate the Clinical Study of CUD005 Injection in Patients With Cirrhosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
Conditions: Cirrhosis, Liver
Keywords: Cirrhosis
cell therapy
PBMC
safety
tolerability
MTD
DLT
dose escalation
Lead sponsor: Anhui Provincial Hospital
Sponsor class: OTHER_GOV
First posted: 2024-03-06
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: DLT,MTD
timeFrame: 28 days
Secondary outcomes:
measure: fibrosis staging and inflammatory grading
timeFrame: 180 days
measure: All-cause mortality
timeFrame: 1 year
measure: TE（Transient elastography）
timeFrame: 1 year
Other outcomes:
measure: MELD（Model for End-stage Liver Disease）
timeFrame: 1 year
Locations:
city: Hefei
country: China
facility: Anhui province hospital
state: Anhui
Study officials:
affiliation: Anhui Provincial Hospital
name: Lianxin LX Liu, Professor
role: PRINCIPAL_INVESTIGATOR
References: