A Phase I/II Safety and Tolerability Dose Escalation Study of Autologous Stem Cells to Patients With Liver Insufficiency

This is a prospective dose escalation study of the administration of expanded autologous adult human stem cells in patients with chronic liver insufficiency. Four groups of two patients will receive ascending doses of autologous adult human stem cells starting at a dose of 1 x 10[8] cells. The cells will be infused into either the hepatic artery or the portal vein of research participants. The consultant radiologist will review a duplex Doppler scan of the blood supply to the liver to determine the safest route for delivery of the cells.

The first patients (01 and 02) will receive 1 x 10[8] cells. If no adverse events are observed in either patient in the two-week period post stem cell administration, patient numbers 03 and 04 will receive 5 x 1[08] cells. This will continue through patients 05 and 06 receiving cells at 1 x 10[9] and 07 and 08 receiving 5 x 10[9] cells. If any patient in any cohort suffers adverse events considered to be treatment-related, the next group of patients will receive cells at a concentration one step down from that received by the patient suffering the adverse events.

At the completion of this first stage of the study, if no adverse treatment related events are seen, a further group of 10 patients will receive cells at a concentration of 5 x 10[9] cells.

It should be noted that if fewer cells are obtained at the end of the expansion period the re-infusion of the cells to the patient should nonetheless continue. This patient will be considered inevaluable and the next participant will be allocated their trial number.

The total period that each patient will be participating in the study is 12 weeks and the total duration of this clinical trial is expected to be approximately 12 months.

All patients will be assessed 4 weeks after coming off study (week 12), whether from completion of protocol or early withdrawal for whatever reason. They will also be monitored in the clinic for the remainder of their life.

Patients who are withdrawn due to issues of toxicity will be followed until the adverse event is resolved or the outcome is known. Patients will then be followed-up for four weeks after resolution and thereafter for life in the clinic.

Inclusion criteria

• Male or female patients aged from 20 to 65 years of age
• Evidence of chronic liver insufficiency
• The presence of abnormal serum albumin and/or bilirubin and/or prothrombin time
• Patient is unlikely to receive a liver transplant
• Has a World Health Organisation (WHO) performance score of less than 2
• Has a life expectancy of at least 3 months
• Ability to give written consent
• Women of childbearing potential may be included, but must use a reliable and appropriate contraceptive method

Exclusion criteria

• Patients below the age of 20 or above the age of 65 years
• Pregnant or lactating women
• Patients with recent recurrent GI bleeding or spontaneous bacterial peritonitis
• Patients with evidence of HIV or other life threatening infection
• Patients unable to give written consent
• Patients with a history of hypersensitivity to Granulocyte-Colony Stimulating Factor (F-CSF)
• Patients who have been included in any other clinical trial within the previous month