None listed
Conditions
Brief summary
We propose a first-in-man clinical trial of human amnion epithelial cells (hAEC), a type of stem cell obtained from the placenta, The placenta is normally discarded after delivery so the use of hAEC does not pose any ethical issues. In laboratory studies we have shown that these cells can reduce liver fibrosis (scar tissue in the liver) and stimulate regeneration of liver cells.. Worldwide, cirrhosis is the sixth most common cause of death and liver transplantation remains the only chance for survival for some people with cirrhosis. In this study we will assess the safety and tolerability of giving hAEC to patients with stable liver cirrhosis. Our long-term goal is to develop hAEC as a clinically useful therapy to reduce the need for liver transplantation.
Interventions
This is a pilot study to examine the safety of human amnion epithelial cells administered to patients with compensated cirrhosis. To determine whether patients have compensated cirrhosis and to avoid including patients with decompensated cirrhosis, the hepatic venous pressure gradient will be measured, which is the most accurate way to make this determination. Human amnion epithelial cells ( hAEC) are derived from the placenta, specifically the amnion epithelium that lines the sac in which the
This is a pilot study to examine the safety of human amnion epithelial cells administered to patients with compensated cirrhosis. To determine whether patients have compensated cirrhosis and to avoid including patients with decompensated cirrhosis, the hepatic venous pressure gradient will be measured, which is the most accurate way to make this determination. Human amnion epithelial cells ( hAEC) are derived from the placenta, specifically the amnion epithelium that lines the sac in which the fetus develops, We have shown that hAEC have intrinsic immune modulating characteristics that can induce hepatic fibrosis regression and stimulate liver regeneration. We have developed a method to isolate the cells that is free of animal products and compliant for clinical use. Once isolated, the cells are frozen until ready for infusion, i.e. they do not undergo any further manipulation or expansion. Twelve patients in total will be studied. They will be divided into four cohorts and each cohort will include three patients. In Cohort 1, three patients will receive hAEC (500,000 cells/kg) as a single intravenous injection. If no serious adverse events (SAE) occur within 5 days, a further three patients will be enrolled in Cohort 2 and receive hAEC (1,000,000 cells/kg) as a single IV injection. If no SAE occur within 5 days, a further three patients will be enrolled in Cohort 3 and receive hAEC (1,000,000 cells/kg) as a single IV injection at 0 and 30 days. If no SAE occur within 5 days, a further three patients will be enrolled in Cohort 4 and receive hAEC (1,000,000 cells/kg) as a single IV injection at days 0, 30 and 60. The hAEC will be administered by peripheral intravenous infusion over 30 minutes at a concentration of 250,000 cells/ml. The number of cells infused and the number of infusions will be determined by the specific cohort. The cell infusions will be done by trained nurses in the Clinical Trial Centre of the Monash Health Translational Research Facility. Patients will be monitored for 24 hours after the infusion in the Clinical Trial Centre by nursing and medical personnel. .The CTC has direct access to Monash Medical Centre.
Sponsors
Monash Health
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Adult female or male patients, age 18 years to 70 years Liver disease due to non-alcoholic fatty liver disease, alcohol related liver disease (must be abstinent for at least 3 months), hepatitis C virus infection (treated or not treated), hepatitis B virus infection (on nucleoside analogues with normal ALT and HBV DNA viral load) or inactive phase, HIV co-infection with HCV/HBV with virological suppression >12 months, cryptogenic cirrhosis, haemochromatosis (on maintenance venesection) Cirrhosis, defined as one of: liver biopsy confirming cirrhosis, transient elastography (Fibroscan) with a liver stiffness measurement (LSM) >12.5 kPa, FIB 4 >3.25, or clinical and radiological features that in the opinion of the investigator are consistent with a diagnosis of cirrhosis. Compensated cirrhosis will be defined as a hepatic venous pressure gradient between 6 - 10 mmHg.
Exclusion criteria
Patients will be excluded from the study if they have current or previous episodes of decompensated liver disease, including variceal haemorrhage, hepatic encephalopathy, ascites, are listed for liver transplantation, have primary biliary cholangitis, autoimmune hepatitis or other active autoimmune disease (IgG >2xULN), renal insufficiency (eGFR < 70mL/min/1.73m2), HIV infection (untreated or uncontrolled viraemia), HBV DNA >200 IU/mL, fulminant hepatitis (severe acute hepatitis withencephalopathy), primary sclerosing cholangitis, portal/hepatic vein thrombosis, significant comorbidity (chronic heart failure, COAD, pulmonary hypertension, diabetes or other in the investigator’s opinion), pregnancy, fibrotic liver disease other than cirrhosis (nodular regenerative hyperplasia), inability or unwillingness to provide informed consent
Outcome results
None listed