Clinical trial NCT03838250: Study to Evaluate Hepatic Artery Injection of Autologous Human Bone Marrow-Derived MSCs in Patients With Alcoholic LC
Official title: A Phase I, Open-Label, Single-Dose Study to Evaluate the Safety and Efficacy of Hepatic Artery Injection of Autologous Human Bone Marrow-Derived Mesenchymal Stem Cells (Cellgram™) in Patients With Alcoholic Liver Cirrhosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Alcoholic Liver Cirrhosis
Keywords: Alcoholic
Liver
Cirrhosis
Liver Disease
Lead sponsor: Pharmicell Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-02-12
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A single-dose injection of autologous bone marrow-derived mesenchymal stem cells (Cellgram™) will be administered to the patient by an experienced interventional radiologist.
Primary purpose: TREATMENT

Brief summary: This study is to evaluate the safety and efficacy of a single dose of Cellgram™ delivered via hepatic artery in patients with decompensated alcoholic liver cirrhosis.

Detailed description: After providing written informed consent, subjects will return to the study center for further evaluation and to have their Bone marrow harvested by an experienced hematologist or interventional radiologist.

Within approximately 1 month (30 ± 7 days) after Bone marrow aspiration, study participants will be admitted to the study center on Day 1.

At the study center, the participant will undergo hepatic artery catheterization by an interventional radiologist who will inject a single dose of Cellgram™. Participants will remain as in-patients and be observed for 24 hours post-infusion. Following discharge, participants will periodically return to the study center for study assessment visits over a period of 1 year.

When a suitable candidate is identified by the Investigator, the Investigator or designated healthcare professional will ask the patient about his/her willingness to be included in the clinical study. Following this, patients will be allowed sufficient time, in their own opinion, to consider study entry, and will be offered the opportunity to ask any further questions prior to signing the informed consent form.

Eligibility criteria: Inclusion Criteria:

1. Alcoholic liver cirrhosis as diagnosed by clinical, biochemical, radiological, or histological evidence.
2. Male or female, 18 to 70 years of age, inclusive.
3. Child-Pugh class B (7 to 9 points)
4. Capable, in the Investigators opinion, of undergoing hepatic artery catheterization.
5. No consumption of alcohol or other potentially hepatotoxic substances considered clinically relevant in the opinion of the Investigator, within 6 months prior to screening and throughout the study.
6. Provision of informed consent by the patient (or their legal representative) to participate in the clinical study.
7. Able, in the Investigator's opinion, to comply with the requirements of the protocol (including the follow-up period).
8. Females of childbearing potential must test negative on standard urine pregnancy test and must be willing to practice appropriate contraceptive methods for the duration of the study. Highly effective methods of birth control include hormonal birth control, intrauterine devices (IUDs), or any double-barrier method (sponges, female condoms) used by the woman in addition to contraception used by their male partner such as vasectomy or condom supplemented with spermicide.

Exclusion Criteria:

1. Current diagnosis of malignant hematologic disease (e.g., acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma).
2. Etiology other than alcohol for underlying liver cirrhosis.
3. Baseline creatinine \>1.7 mg/dL and/or estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m2
4. Clinical history of a solid cancer within 5 years prior to screening or current diagnosis of a solid cancer (including hepatocellular carcinoma assessed by ultrasonography and elevated AFP level) and currently receiving cancer treatment.

   Continuous use of a clinically relevant amount of steroids or antibiotics within 1 month prior to screening. Clinical relevance will be determined by the Investigator.
5. Model for End-Stage Liver Disease score \>20.
6. International normalized ratio \>3.0 and/or platelet counts \<30,000/mm3
7. Major operation within 3 months prior to screening.
8. Presence of extrahepatic biliary stricture.
9. Participant has undergone transjugular intrahepatic portosystemic shunt.
10. Active hepatic artery or portal vein thrombosis.
11. Presence of advanced hepatic encephalopathy Stages 3-4 (West Haven criteria) at the time of screening.
12. Active variceal bleeding during the last 6 months before screening.
13. Severe cardiac, renal, or respiratory failure.
14. Positive serological test results for human immunodeficiency virus (HIV), HCV, hepatitis B surface antigen (HBsAg) and/or syphilis.
15. Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to the EOS visit.
16. Positive urine pregnancy test at Screening.
17. Drug abuse within the past 2 years (as confirmed by patient disclosure or a urine drug screen conducted at Screening).
18. Participation in an interventional clinical study within 30 days prior to screening.

Primary outcomes:
measure: Incidence of Serious Adverse Events
timeFrame: 12 months
Secondary outcomes:
measure: Number of patients with Hepatocellular carcinoma (primary liver cancer) development
timeFrame: 12 months
measure: Incidence of Adverse Events
timeFrame: 12 months
measure: Liver stiffness measurement
timeFrame: 12 months
measure: How well the Liver is functioning
timeFrame: 12 months
measure: Chronic liver disease as assessed by the Child-Pugh score
timeFrame: 12 months
measure: Model for End-Stage Liver Disease (MELD) Score
timeFrame: 12 months
measure: Overall survival
timeFrame: 12 months
measure: Quality of life as assessed by 36-Item Short Form Survey (SF-36) Questionnaire
timeFrame: 12 months
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Utah
name: Juan Gallegos-Orozco, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: