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

• Register: ClinicalTrials.gov
• Last refreshed on: 21 November 2022
• Main ID: NCT02997878
• Date of registration: 13/12/2016
• Prospective Registration: Yes
• Primary sponsor: University of Birmingham
• Public title: Selected Mesenchymal Stromal Cells to Reduce Inflammation in Patients With PSC and AIH Merlin
• Scientific 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
• Date of first enrolment: December 7, 2018
• Target sample size: 18
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT02997878
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United Kingdom

Contacts

• Name: Senior Trial Coordinator

• Name: Phillip N Newsome, Prof
• Affiliation: University of Birmingham

Key inclusion & exclusion criteria

Inclusion Criteria - Patients with Primary Sclerosing Cholangitis (PSC):

1. Age = 18 at Visit 1

2. Diagnosis of PSC at Visit 1 as evidenced clinically by:

1. 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

2. Radiological AND/OR histological evidence of clinically documented PSC

3. Serum ALP = 1.5 x ULN at Visit 1

4. 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.

5. At Visit 2 (and Visit 2a if applicable), it should be confirmed that a patient does
not meet any of the exclusion criteria

Inclusion Criteria - Patients with Autoimmune Hepatitis (AIH):

1. Age = 18 at Visit 1

2. 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

3. Active AIH defined by ALT = 1.5 x ULN

4. Serum ALT must be above = 1.5 x ULN at both Visit 1 and Visit 2

5. At Visit 2, it should be confirmed that a patient does not meet any of the exclusion
criteria

6. Patients must be on standard-of-care AIH treatment for = 24 weeks -this includes any
AIH therapy except biologics

7. Stable doses of immunosuppression for a minimum period of 4 weeks (28 days) at the
time of Visit 1.

Exclusion Criteria - Patients with PSC and AIH:

Patients who meet any of the following exclusion criteria are excluded from participating
in the MERLIN trial

1. Refusal or lacks capacity to give informed consent to participate in trial

2. Patient who is unable to participate in follow-up assessment

3. Participation actively, or within 5 half-lives, of another interventional clinical
trial

4. Known hypersensitivity to the investigational product or any of its formulation
excipients

5. Evidence of active malignancy (within 3 years of Visit 1), other than non-melanomatous
skin cancer and cervical dysplasia in situ

6. Major surgical procedure within 30 days at Visit 1

7. Prior organ transplantation

8. Active harmful alcohol consumption as evaluated and documented by the Investigator

9. Poor venous access, therefore unable to support a 22G needle for infusion

10. Creatinine > 133 µmol/L or being treated with renal replacement therapy at the time of
Visit 1

11. AST or ALT > 10 x ULN

12. ALP > 10 x ULN

13. Platelets < 50 x 10^9/L

14. Total Bilirubin > 2 x ULN

15. INR > 1.3 (in the absence of concomitant use of Warfarin or equivalent anti-coagulant
therapy)

16. Albumin < 35 g/L

17. Haemoglobin < 10 g/dL

18. Past or present evidence of decompensated chronic liver disease:

1. Radiological or clinical evidence of ascites

2. Hepatic encephalopathy

3. Endoscopic evidence for portal hypertensive bleeding

19. Any active treatment with biologic therapy (monoclonal antibodies)

20. Clinically severe cardiovascular disease as evaluated by the Investigator

21. Pregnancy or breast-feeding

22. 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

23. 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

24. 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

25. 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

26. Any symptoms indicative of Covid-19; including fever, chronic/persistent cough, or
loss of sense of taste or smell in the preceding two weeks.

27. Receipt of live vaccination within six weeks prior to Visit 1

Exclusion Criteria Specific to Patients with PSC:

1. Documented alternative aetiology for sclerosing cholangitis (i.e. secondary sclerosing
cholangitis)

2. 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

3. UDCA dose modification within the last 90 days

4. ALP > 10 x ULN

5. Evidence of cholangitis within 90 days of Visit 1

1. Documented evidence of cholangitis by physician

2. Need for any antibiotics for presumed cholangitis

6. Any patient taking prophylactic antibiotics to combat recurrent cholangitis

7. Presence of percutaneous biliary drain, or internal biliary stent

8. Diagnosed hepatocellular carcinoma or cholangiocarcinoma or high clinical suspicion
thereof

9. Dominant stricture clinically suspicious of cholangiocarcinoma (as determined by
Investigator)

Exclusion Criteria for PSC patients with IBD:

1. Unstable disease as evidenced by:

1. 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

2. Re


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cholangitis, Sclerosing

Hepatitis, Autoimmune

Intervention(s)

Biological: Orbcel-C

Primary Outcome(s)

Activity at the Highest Safe Dose (HSD) of ORBCEL-C in AIH patients, by measure of change in Alanine Aminotransferase (ALT) [Time Frame: Baseline to Visit 8 - Approximately 80 days]

Activity and Safety at the Highest Safe Dose (HSD) of ORBCEL-C in PSC patients, by measure of change in Alkaline Phosphatase (ALP) [Time Frame: Baseline to Visit 8 - Approximately 80 days]

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]

Incidence of treatment emergent adverse events (safety and tolerability) for PSC and AIH patients treated at the Highest Safe Dose (HSD) only [Time Frame: Visit 3 to Visit 8 - 56 days]

Secondary Outcome(s)

All patients with Autoimmune Hepatitis (AIH) - Secondary Outcome Measure 2 [Time Frame: Baseline to Visit 8 - Approximately 80 days]

All patients with Primary Sclerosing Cholangitis (PSC) - Secondary Outcome Measure 1 [Time Frame: Baseline to Visit 8 - Approximately 80 days]

All patients with Primary Sclerosing Cholangitis (PSC) - Secondary Outcome Measure 3 [Time Frame: Baseline to Visit 8 - Approximately 80 days]

All patients with Autoimmune Hepatitis (AIH) - Secondary Outcome Measure 3 [Time Frame: Baseline to Visit 8 - Approximately 80 days]

All patients with Primary Sclerosing Cholangitis (PSC) - Secondary Outcome Measure 2 [Time Frame: Baseline to Visit 8 - Approximately 80 days]

All patients with Autoimmune Hepatitis (AIH) - Secondary Outcome Measure 4 [Time Frame: Baseline to Visit 8 - Approximately 80 days]

All patients with Autoimmune Hepatitis (AIH) - Secondary Outcome Measure 1 [Time Frame: Baseline to Visit 8 - Approximately 80 days]

All patients with Autoimmune Hepatitis (AIH) - Secondary Outcome Measure 5 [Time Frame: Baseline to Visit 8 - Approximately 80 days]

All patients with Primary Sclerosing Cholangitis (PSC) - Secondary Outcome Measure 4 [Time Frame: Baseline to Visit 8 - Approximately 80 days]

Secondary ID(s)

RG-13-124

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

NHS Blood and Transplant