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

NCT02997878 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: RG-13-124
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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™.

Conditions

Cholangitis, Sclerosing; Hepatitis, Autoimmune

Keywords

Autoimmune; AIH; PSC; Liver disease; Cholangitis

Outcome Measures

Primary Outcomes (4)

• Dose finding and incidence of treatment emergent adverse events (safety and tolerability) in all PSC and AIH Patients

  Occurrence of Dose Limiting Toxicity (DLT) over 14 day (Visit 3 to Visit 5) reporting period after ORBCEL-C infusion

  Visit 3 to Visit 5 -14 days

• Incidence of treatment emergent adverse events (safety and tolerability) for PSC and AIH patients treated at the Highest Safe Dose (HSD) only

  Determine safety and tolerability by occurrence of Dose Limiting Toxicity (DLT) (Visit 3 to Visit 5 only), Serious Adverse Events (SAEs) and Adverse Events (AEs) throughout trial period (up to Visit 8)

  Visit 3 to Visit 8 - 56 days

• Activity and Safety at the Highest Safe Dose (HSD) of ORBCEL-C in PSC patients, by measure of change in Alkaline Phosphatase (ALP)

  Change in Alkaline Phosphatase (ALP) after ORBCEL-C infusion - Examination of change in ALP at Day 28 from Baseline and changes over multiple time-points before and after infusion (Visit 1 to Visit 8)

  Baseline to Visit 8 - Approximately 80 days

• Activity at the Highest Safe Dose (HSD) of ORBCEL-C in AIH patients, by measure of change in Alanine Aminotransferase (ALT)

  Change in Alanine Aminotransferase (ALT) trend after ORBCEL-C infusion. Measurements of ALT will be taken at multiple time points from Visit 1 to Visit 8.

  Baseline to Visit 8 - Approximately 80 days

Secondary Outcomes (9)

• All patients with Autoimmune Hepatitis (AIH) - Secondary Outcome Measure 1

  Baseline to Visit 8 - Approximately 80 days

• All patients with Autoimmune Hepatitis (AIH) - Secondary Outcome Measure 2

  Baseline to Visit 8 - Approximately 80 days

• All patients with Autoimmune Hepatitis (AIH) - Secondary Outcome Measure 3

  Baseline to Visit 8 - Approximately 80 days

• All patients with Autoimmune Hepatitis (AIH) - Secondary Outcome Measure 4

  Baseline to Visit 8 - Approximately 80 days

• All patients with Autoimmune Hepatitis (AIH) - Secondary Outcome Measure 5

  Baseline to Visit 8 - Approximately 80 days

Other Outcomes (5)

• All patients with PSC and AIH - Exploratory Research Outcome 1

  Up to Visit 8 (56 days)

• All patients with PSC and AIH - Exploratory Research Outcome 2

  Up to Visit 8 (56 days)

• All patients with PSC and AIH - Exploratory Research Outcome 3

  Up to Visit 8 (56 days)

Study Arms (2)

PSC patients

EXPERIMENTAL

Selected Mesenchymal Stromal Cells (dose selection and efficacy) - Orbcel-C. dose selection, combination of 0.5, 1.0,2.5 million cells/kg (3 dose levels). IV single-infusion.

Biological: Orbcel-C

AIH patients

EXPERIMENTAL

Selected Mesenchymal Stromal Cells (dose selection and efficacy) - Orbcel-C. dose selection, combination of 0.5, 1.0,2.5 million cells/kg (3 dose levels). IV single-infusion.

Biological: Orbcel-C

Interventions

Orbcel-C BIOLOGICAL

Selected Mesenchymal Stromal Cells derived from human umbilical cord

AIH patients; PSC patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 at Visit 1
• Diagnosis of PSC at Visit 1 as evidenced clinically by:
• Chronic biochemical cholestasis (elevated serum alkaline phosphatase (ALP) above the upper limit of normal (ULN) and/or gamma-glutamyl transpeptidase (GGT) above the ULN) ≥6 months duration AND
• Radiological AND/OR histological evidence of clinically documented PSC
• Serum ALP ≥ 1.5 x ULN at Visit 1
• Any serum ALP value change is \<40% using two sets of laboratory values obtained during screening:
• If a participant fails to confirm an ALP at Visit 2 that is within 40% of the ALP at Visit 1, a further screening ALP (Visit 2a) can be arranged, so long as the variation in ALP was \<50%, and the Principal Investigator has no other clinical reason to suggest the participant is clinically unstable. If the ALP is within 40% variance at Visit 2a as compared to visit 1, Trial registration is permitted.

You may not qualify if:

• Age ≥ 18 at Visit 1
• Established pre-existing clinical diagnosis of AIH confirmed by clinical expert review consistent with the simplified IAIHG criteria (http://www.mdcalc.com/simplified-scoring-autoimmune-hepatitis-aih/) and must include history of a liver biopsy reported compatible with AIH
• Active AIH defined by ALT ≥ 1.1 x ULN
• Serum ALT must be above ≥ 1.1 x ULN at both Visit 1 and Visit 2
• Patients must be on standard-of-care AIH treatment for ≥ 24 weeks -this includes any AIH therapy except biologics
• Stable doses of immunosuppression for a minimum period of 4 weeks (28 days) at the time of Visit 1.
• Refusal or lacks capacity to give informed consent to participate in trial
• Patient who is unable to participate in follow-up assessment
• Participation actively, or within 5 half-lives, of another interventional clinical trial
• Known hypersensitivity to the investigational product or any of its formulation excipients
• Evidence of active malignancy (within 3 years of Visit 1), other than non-melanomatous skin cancer and cervical dysplasia in situ
• Major surgical procedure within 30 days at Visit 1
• Prior organ transplantation
• Active harmful alcohol consumption as evaluated and documented by the Investigator
• Poor venous access, therefore unable to support a 22G needle for infusion

Sponsors & Collaborators

• University of Birmingham: lead
• NHS Blood and Transplant: collaborator

Study Sites (1)

University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital

Birmingham, West Midlands, B15 2TT, United Kingdom

Location

MeSH Terms

Conditions

Cholangitis, Sclerosing; Hepatitis, Autoimmune; Liver Diseases; Cholangitis

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Hepatitis, Chronic; Hepatitis; Autoimmune Diseases; Immune System Diseases

Study Officials

• Phillip N Newsome, Prof

  University of Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2016
• First Posted: December 20, 2016
• Study Start: December 7, 2018
• Primary Completion: November 23, 2023
• Study Completion: October 1, 2025
• Last Updated: July 11, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)