Selected Mesenchymal Stromal Cells to Reduce Inflammation in Patients With PSC and AIH — Merlin  

Hepatitis, Autoimmune Clinical Trial

Official title: An Adaptive, Multicentre, Phase IIa, Multi-disease Trial Investigating the Safety & Activity of a Single Infusion of Selected Mesenchymal Stromal Cells in the Treatment of Patients With Primary Sclerosing Cholangitis & Autoimmune Hepatitis

Status Recruiting

Clinical Trial Summary

MERLIN is an adaptive, single arm, multi-centre, phase IIa multi-disease clinical trial. It is designed to:

i) Determine dose safety of ORBCEL-C™ (selected Mesenchymal stromal cells derived from human umbilical cord) ii) Evaluate treatment activity through assessment of biomarkers (for patients treated at the highest safe dose only (HSD))

This trial will determine the Highest Safe Dose (HSD) that can be administered by observing for occurrence of dose limiting toxicity (DLT).

Upon completion of this trial we hope to be able to justify and conduct separate, larger scale trials using ORBCEL-C™.

Clinical Trial Description

MERLIN is an adaptive, single arm, multi-centre, phase IIa multi-disease clinical trial. It is designed to:

i) Determine dose safety of ORBCEL-C™ (selected Mesenchymal stromal cells derived from human umbilical cord) ii) Evaluate treatment activity through assessment of biomarkers

This trial will determine the HSD* that can be administered by observing for occurrence of dose limiting toxicity (DLT).

• An investigated dose level is determined to be safe if we see 0 DLTs in 3 patients or ((in the instance where a cohort is expanded to 6 patients due to occurrence of a DLT in the first 3 patients treated at a cohort) < 2 DLTs in 6 patients. The HSD is the highest such dose which fulfils these criteria and will be ascertained via dose-escalation using 3+3 methodology.

Further safety and activity outcomes will be determined on patients treated at the HSD only. Upon completion of this trial we hope to be able to justify and conduct separate, larger scale trials using ORBCEL-C™.

OBJECTIVES

For Both Primary Sclerosing Cholangitis (PSC) and Autoimmune Hepatitis (AIH) patients:

The primary objective for all patients is:

• To determine the highest safe single intravenous infusion dose of ORBCEL-C™ over a 14 day (Visit 3 to Visit 5) reporting period.

For patients treated at HSD only, there is an additional co-primary objective:

• To investigate whether a single intravenous infusion of ORBCEL-C™ in patients with PSC and AIH treated at the HSD is safe and tolerated over the period of trial follow-up (up to Visit 8)

For PSC patients only:

• Reduces serum alkaline phosphatase (ALP) in patients with PSC. This is a non- invasive biochemical surrogate of clinical outcomes in PSC

For AIH patients only:

• Reduces serum alanine aminotransferase (ALT) in patients with AIH. This is a non- invasive biochemical surrogate marker of hepatic inflammatory activity and outcomes in AIH.

The secondary objectives are to investigate whether a single intravenous infusion of ORBCEL-C™ elicits a change over the duration of the trial after treatment in all patients with PSC and AIH on:

• Circulating inflammatory cells profile as measured by flow cytometry (key secondary outcome)

• Liver biochemistry and function, immunoglobulin G concentrations (in AIH patients) and composite risk scores

• Non-invasive clinical markers of fibrosis

• Patient Quality of Life (QoL)

• Severity of co-existent Inflammatory Bowel Disease (IBD) in patients with PSC

Further exploratory research objectives of the trial determine whether MSC infusion modulates the immune response by measuring whether treatment elicits a change in all patients with PSC and AIH:

• Markers of immune activation including immunoglobulin values and C-reactive protein (CRP) concentration

• Markers of biliary injury including total bile acid levels

• Endothelial cell activation markers such as VAP-1 and ICAM1

• Serum cytokine, chemokine, ribonucleic acid (RNA) and micro-RNA expression profiles ;

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Hepatitis
• Hepatitis, Autoimmune

• NCT number: NCT02997878
• Study type: Interventional
• Source: University of Birmingham
• Contact: Senior Trial Coordinator
• Phone: 01213718198
• Email: merlin@trials.bham.ac.uk
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 7, 2018
• Completion date: December 2023