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Cholangitis, SclerosingPhase 1/2MerlinNCT02997878

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

A Phase 1/2 study testing Orbcel-C in people with Cholangitis, Sclerosing and Hepatitis, Autoimmune, run by University of Birmingham at 1 site in United Kingdom.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Orbcel-C
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited Kingdom
Study dates
7 Dec 2018to 1 Oct 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

None listed.

Who cannot join

  • Patients who meet any of the following exclusion criteria are excluded from participating in the MERLIN trial
  • 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
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  • 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
  • Creatinine > 133 μmol/L or being treated with renal replacement therapy at the time of Visit 1
  • AST or ALT > 10 x ULN
  • ALP > 10 x ULN
  • Platelets < 50 x 10^9/L
  • Total Bilirubin > 2 x ULN
  • INR > 1.3 (in the absence of concomitant use of Warfarin or equivalent anti-coagulant therapy)
  • Albumin < 35 g/L
  • Haemoglobin < 10 g/dL
  • Past or present evidence of decompensated chronic liver disease:
  • Radiological or clinical evidence of ascites
  • Hepatic encephalopathy
  • Endoscopic evidence for portal hypertensive bleeding
  • Any active treatment with biologic therapy (monoclonal antibodies)
  • Clinically severe cardiovascular disease as evaluated by the Investigator
  • Pregnancy or breast-feeding
  • Women of child bearing potential who are unwilling to practice effective contraception (i.e. barrier, oral contraceptive pill, implanted contraception, or previous hysterectomy, bilateral oophorectomy) for the duration of the trial up to 90 days after the trial drug is administered. If using hormonal agents the same method must have been used for at least 1 month before trial dosing and patients must use a barrier method during that time period
  • Non-vasectomised men, sexually active with women of child bearing potential, who are not willing to practice effective contraception (condom with spermicide) for the duration of the trial up to 90 days after the trial drug is administered
  • Patients with a history of hepatitis C (present or past infection), known positivity for antibody to HIV or any evidence of current or past hepatitis B infection
  • Presence of an acute/chronic infection or illness that, at the discretion of the Investigator, might compromise the patient's health and safety in the trial
  • Any symptoms indicative of Covid-19; including fever, chronic/persistent cough, or loss of sense of taste or smell in the preceding two weeks.
  • Receipt of live vaccination within six weeks prior to Visit 1
  • Documented alternative aetiology for sclerosing cholangitis (i.e. secondary sclerosing cholangitis)
  • A dominant (as determined by Investigator) alternative chronic or active liver injury other than PSC at the time of Visit 1; Patients with possible overlap syndrome with AIH are excluded from the PSC cohort if the Investigator considers AIH as the dominant liver injury
  • UDCA dose modification within the last 90 days
  • ALP > 10 x ULN
  • Evidence of cholangitis within 90 days of Visit 1
  • Documented evidence of cholangitis by physician
  • Need for any antibiotics for presumed cholangitis
  • Any patient taking prophylactic antibiotics to combat recurrent cholangitis
  • Presence of percutaneous biliary drain, or internal biliary stent
  • Diagnosed hepatocellular carcinoma or cholangiocarcinoma or high clinical suspicion thereof
  • Dominant stricture clinically suspicious of cholangiocarcinoma (as determined by Investigator)
  • Unstable disease as evidenced by:
  • Documented clinically significant flare within 90 days of enrolment requiring any marked intensification of therapy from baseline maintenance (maintenance therapy = thiopurines, 5- aminosalicylates, or oral prednisolone < 10mg/day; biologics therapy is an exclusion criteria
  • Requirement for daily prednisolone > 10mg
  • Mayo Clinic Score ≥ 2 (see Appendix 1 for details) AND clinician assessment of active disease requiring up-titration of treatment; last colonoscopy within last year used for endoscopic component
  • Any colonoscopic evidence of clinically significant dysplasia at last colonoscopy
  • Patients who have not had their routine colonoscopy within 24 months prior to planned MSC infusion and are unable to have their screening colonoscopy examination as per standard care prior to Visit 3
  • A Mayo score/ Disease Activity Index for Ulcerative Colitis of ≥ 5 (https://www.mdcalc.com/mayo-score- disease-activity-index-dai-ulcerative-colitis)
  • A dominant (as determined by Investigator) alternative chronic or active liver injury other than AIH at the time of Visit 1; Patients with possible overlap syndrome with PSC are excluded from the AIH cohort if the Investigator considers PSC as the dominant liver injury
  • AST or ALT > 10 x ULN
  • Patients on a prednisolone dose of > 20 mg at the time of screening
  • Treatment with biologic therapy within 24 weeks of the time of screening
  • Patients with a history of poor compliance with medication
  • Diagnosed hepatocellular carcinoma or cholangiocarcinoma or high clinical suspicion thereof

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital

    Birmingham, West Midlands, B15 2TT

Other trials in United Kingdom

About this study

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

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

  1. 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™.

Read the detailed description

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

  1. 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
Being tested
Orbcel-C
Keywords
Autoimmune, AIH, PSC, Liver disease, Cholangitis
Medical subject headings
Cholangitis, Sclerosing, Hepatitis, Autoimmune, Liver Diseases, Cholangitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Orbcel-CBiological

    Selected Mesenchymal Stromal Cells derived from human umbilical cord

Study groups in NCT02997878
Study groupRoleWhat they receive
PSC patientsExperimentalSelected 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.
Receives: Biological: Orbcel-C
AIH patientsExperimentalSelected 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.
Receives: Biological: Orbcel-C

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Visit 3 to Visit 5 -14 days

  2. 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)

    Measured: Visit 3 to Visit 8 - 56 days

  3. 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)

    Measured: Baseline to Visit 8 - Approximately 80 days

  4. 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.

    Measured: Baseline to Visit 8 - Approximately 80 days

Secondary outcomes (9)

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

    Change from baseline at Visit 7, Visit 8 and throughout the trial period (up to Visit 8) following ORBCEL-C™ infusion in Phenotypic expression of TRegs as measured by flow cytometry (principal secondary outcome)

    Measured: Baseline to Visit 8 - Approximately 80 days

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

    Change from baseline at Visit 7, Visit 8 and throughout the trial period (up to Visit 8) following ORBCEL-C™ infusion in Individual markers of liver biochemistry and function including AST, ALP, GGT, bilirubin, albumin, INR and composite risk score (MELD)

    Measured: Baseline to Visit 8 - Approximately 80 days

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

    Change from baseline at Visit 7, Visit 8 and throughout the trial period (up to Visit 8) following ORBCEL-C™ infusion in marker of immune activation - immunoglobulin G concentrations

    Measured: Baseline to Visit 8 - Approximately 80 days

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

    Change from baseline at Visit 7, Visit 8 and throughout the trial period (up to Visit 8) following ORBCEL-C™ infusion in Non-invasive clinical markers of fibrosis - ELF and transient elastography (Fibroscan®)

    Measured: Baseline to Visit 8 - Approximately 80 days

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

    Change from baseline at Visit 7, Visit 8 and throughout the trial period (up to Visit 8) following ORBCEL-C™ infusion in QoL as measured by Pruritus Visual Analogue Scale, nine-point fatigue severity scale and SF-36v2

    Measured: Baseline to Visit 8 - Approximately 80 days

  6. All patients with Primary Sclerosing Cholangitis (PSC) - Secondary Outcome Measure 1

    Change from baseline at Visit 7, Visit 8 and throughout the trial period (up to Visit 8) following ORBCEL-C™ infusion in Phenotypic expression of TRegs as measured by flow cytometry (principal secondary outcome)

    Measured: Baseline to Visit 8 - Approximately 80 days

  7. All patients with Primary Sclerosing Cholangitis (PSC) - Secondary Outcome Measure 2

    Change from baseline at Visit 7, Visit 8 and throughout the trial period (up to Visit 8) following ORBCEL-C™ infusion in Individual markers of liver biochemistry and function including aspartate aminotransferase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), bilirubin, albumin, international normalised ratio [INR] and composite risk scores (Mayo PSC risk score and Model for End Stage Liver Disease [MELD])

    Measured: Baseline to Visit 8 - Approximately 80 days

  8. All patients with Primary Sclerosing Cholangitis (PSC) - Secondary Outcome Measure 3

    Change from baseline at Visit 7, Visit 8 and throughout the trial period (up to Visit 8) following ORBCEL-C™ infusion in Non-invasive clinical markers of fibrosis: Enhanced Liver Fibrosis (ELF) and transient elastography (Fibroscan®)

    Measured: Baseline to Visit 8 - Approximately 80 days

  9. All patients with Primary Sclerosing Cholangitis (PSC) - Secondary Outcome Measure 4

    Change from baseline at Visit 7, Visit 8 and throughout the trial period (up to Visit 8) following ORBCEL-C™ infusion in QoL as measured by Pruritus Visual Analogue Scale, nine-point fatigue severity scale and SF-36v2 Severity of IBD as measured by the non-endoscopic aspects of the Mayo IBD score - stool frequency, rectal bleeding, and physician's global assessment

    Measured: Baseline to Visit 8 - Approximately 80 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Dec 2016 (estimated)
  2. Study start7 Dec 2018
  3. Primary completion23 Nov 2023
  4. Study completion1 Oct 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02997878
Sponsor's protocol ID
RG-13-124
Acronym
Merlin
Status last verified
Jul 2024
First submitted
13 Dec 2016
Last updated
11 Jul 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Orbcel-C in people with Cholangitis, Sclerosing and Hepatitis, Autoimmune, run by University of Birmingham at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 55 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 11 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose finding and incidence of treatment emergent adverse events (safety and tolerability) in all PSC and AIH Patients (time frame: Visit 3 to Visit 5 -14 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02997878.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2024.

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