Liver Cirrhosis MedDRA version: 20.0 Level: LLT Classification code 10024667 Term: Liver cirrhosis System Organ Class: 100000004871
Conditions
Interventions
Product Name: Autologous Macrophage Cell Product
Product Code: MATCH
Pharmaceutical Form: Dispersion for infusion
Concentration type: up to
Sponsors
University of Edinburgh
NHS Lothian
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: INCLUSION CRITERIA 1. 18= AGE =75 at screening 2. Aetiology: one or more of: • Alcohol Related Liver Disease (ALD) No active alcohol misuse =6 calendar months prior to screening. Features of chronic liver disease with a compatible history of alcohol excess (>80g/day), in the absence of other causes of chronic liver disease. Participants with other aetiologies of liver disease may drink alcohol within current recommended limits (14 units per week for females and for males) • Primary Biliary Cirrhosis (PBC) 2 out of: Cholestatic LFTs Positive AMA (>1:40) Compatible Histology If already receiving Ursodeoxycholic Acid must be established on current dose >3 months prior to enrolment • Non-Alcoholic Fatty Liver Disease (NAFLD) Either: Histological evidence of steatosis in the absence of other liver diseases Or: Imaging compatible with NAFLD (eg Fatty infiltration of liver) and one or more risk factors (e.g. elevated BMI, T2DM, Hypertriglyceridaemia, Hypertension) And: The absence of significant alcohol consumption (60%, Ferritin >400), Genotype (Homozygous C282Y or H63D, Compound Heterozygote) or Histology • Alpha-1 anti-trypsin deficiency Diagnosis based on compatible genetic, phenotypic or histological testing. • Previous Hepatitis C (sustained viral response ie. undetectable HCV RNA 24 weeks after completion of treatment.) 3. Diagnosis of Cirrhosis – invasive or non-invasive; Cirrhosis, defined as one of: • Previous liver biopsy confirming histological features of cirrhosis • Transient Elastography (Fibroscan) >15 kPa • Clinical and radiological features that in the opinion of the investigator correlate with a diagnosis of cirrhosis 4. 10>/MELD score=65 years) yes F.1.3.1 Number of subjects for this age range 74
Exclusion criteria
Exclusion criteria: EXCLUSION CRITERIA • Refusal or inability to give informed consent to participate in the study • Other cause of chronic liver disease / cirrhosis not included in listed aetiologies – this is left to the clinical judgement of the investigator based on previous investigations and trial screening • Portal Hypertensive Bleeding; active episode of bleeding requiring hospitalisation in the last 3 months • Ascites unless, in the opinion of the investigator, the ascites is minimal and well controlled with no increase to diuretic therapy in last 3 months • Encephalopathy; current or requiring hospitalisation for treatment in last 3 months • Hepatocellular Carcinoma – uncertain cases to be discussed at local hepatobiliary Multidisciplinary meeting, dysplastic or indeterminate nodules to be excluded, regenerative or other nodules to be included at discretion of MDM • Previous diagnosis of Hepatocellular Carcinoma • Previous organ Transplant or previous recipient of tissue • Listed for Liver Transplantation • Any situation that in the Investigators opinion may interfere with optimal study participation such as alcohol or drug abuse, domicile too distant from study site, potential non-compliance or inability to co-operate • Presence of clinically relevant acute illness that in the opinion of the investigator might compromise the participant’s safe participation in the study • Presence or history of cancer within past 5 years with exception of adequately treated localised skin carcinoma, in situ cervical cancer or solid malignancy surgically excised in total without recurrence for 5 years • Pregnancy or Breastfeeding • Allergy to steroids - Active infection on the mandatory microbiology blood tests - Immunosuppressants eg Azathioprine - Current enrolment in an interventional study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I (dose escalation study): The primary objective of this study is to demonstrate safety and the maximum tolerated dose of autologous monocyte derived macrophages in participants with advanced liver cirrhosis. Phase II (repeat dosing study): The primary objective of the repeat dosing study is to demonstrate an improvement in the severity of liver disease over 3 months. ;Secondary Objective: Secondary objectives are to demonstrate improvement in markers of liver fibrosis, improved disease related quality of life, reduced liver related clinical events and improved transplant free survival.;Primary end point(s): Phase I (dose escalation study) The primary endpoints are the safety and feasibility and to establish the maximum safe dose of infusion of autologous macrophages to cirrhotic participants Phase II (repeat dosing study) The change in MELD (Model for End Stage Liver Disease) score (delta MELD) at 3 months from the 1st infusion of macrophages ;Timepoint(s) of evaluation of this end point: phase I endpoint once all patients in dose escalation have completed all treatment and reached 14 days safety visit. all patients will be monitored for 1 year post infusion phase II endpoint 3 months post infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints are changes in the ELF (Enhanced Liver Fibrosis) panel, Protein Fingerprint Biomarkers, Fibroscan, Chronic Liver Disease Quality of Life, UKELD (United Kingdom Model for End Stage Liver disease), blood parameters, number of clinical events and transplant free survival;Timepoint(s) of evaluation of this end point: base line to 90 days changes in our secondary endpoint measures, all patients will be monitored for 1 year post infusion | — |
Countries
United Kingdom
Contacts
Public ContactProfessor Stuart Forbes
University of Edinburgh
Outcome results
None listed