Macrophage Therapy For Acute Liver Injury (MAIL) trial: a phase I randomised, open-label, dose-escalation study to evaluate safety, tolerability, and activity of allogeneic alternatively activated macrophages (AAM) in patients with paracetamol-induced acute liver injury.
Acute liver injury (paracetamol-induced)
Participants will receive a single infusion of allogeneic alternatively activated macrophages (AAM). The first patient will be dosed with 10e6 macrophages; if there are no safety concerns, the highest dose in this trial will be up to 10e9 cells. Patients will be dosed in 5 cohorts with dose escalation decisions being guided by an independent Data Monitoring Committee. In dose cohorts 3-5, the dose of AAM will be randomised using a centralised online randomisation system. Participants will be followed-up for 30 days following the infusion.
1. Serum ALT activity > 1000U/L at screening. 2. History of paracetamol overdose within 5 days of ALT>1000. Overdoses of paracetamol alone and mixed overdoses are eligible. 3. Other causes of ALT increase excluded based on previous investigations and trial screening. This will be documented in the patient’s medical notes. 4. Provision of written informed consent. 5. Adult male or female (16 yrs old or above). 6. Deemed safe for hospital discharge from a mental health perspective after full mental health assessment by a mental health professional. This will be documented in the patient’s medical notes. 7. Patients with child bearing potential must have a negative urine or serum pregnancy test at screening. If the patient is of child bearing potential, or is a male with a female partner with child bearing potential, the patient, and their partner(s), must agree to use a highly effective method of contraception throughout the trial period and for 90 days post study completion.
1. Patients who do not have the capacity to consent. 2. Any situation that in the Investigator’s opinion may interfere with optimal study participation such as alcohol or drug abuse, potential non-compliance or inability to co-operate. 3. Patients with known viral hepatitis infection or known COVID-19 infection. 4. Patients who are pregnant, or are planning on becoming pregnant during the study, or are breastfeeding and wish to continue breastfeeding. Patients of childbearing potential, or male patients with a female partner of childbearing potential, must agree to use a highly effective method of contraception as detailed above. 5. Patients who have previously participated in this study or another ATMP. 6. Potentially life-threatening liver injury with an immediate need for transplantation as documented in the patient’s medical notes. 7. Patients listed for any organ transplant. 8. Patients with stage 4 or 5 chronic kidney disease. 9. Any history of or suspected hypersensitivity to the cell product, excipients, or possible residual components used in manufacture. 10. Patients who are currently enrolled in another ATMP or Clinical Trial of an Investigational Medicinal Product (CTIMP).