Primary sclerosing cholangitis, rheumatoid arthritis, lupus nephritis, Crohn’s disease Not Applicable Cholangitis, Rheumatoid arthritis, unspecified, Systemic lupus erythematosus with organ or system involvement, Crohn disease [regional enteritis]
Conditions
Interventions
Mesenchymal stromal cells (MSC) have been safely used in over 100 clinical trials, and have been shown to be effective at potentially treating a number of inflammatory conditions. The aim of this stud
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 02/07/2024: Inclusion criteria for ALL patients: 1. Age =18 years at Visit 1/1a (screening) 2. In this clinical trial, for all cohorts, only participants with severe active disease and refractory to the standard of care treatment (and biologic-refractory for Rheumatoid Arthritis and Crohn’s Disease cohort) can be included (where a standard of care therapy is available*) 3. Active, uncontrolled, or partially controlled inflammatory disease despite receiving standard-of-care therapy (where a standard-of-care therapy is available*) 4. On an approved therapy if indicated and available, unless the patient is intolerant of, or has refused, the standard of care therapy *For patients with PSC, no ‘standard of care treatment’ or standard definition for ‘uncontrolled/partially controlled disease’ is available. Patients must have severe active disease to be included. Inclusion criteria specific to patients with primary sclerosing cholangitis (PSC): 1. Diagnosis of PSC at Visit 1a (screening) as evidenced clinically by Radiological AND/OR histological evidence. Individuals with small duct PSC may be included, only if they have concomitant inflammatory bowel disease 2. Serum ALP = 1.5 x ULN at Visit 1a and 1b (screening) 3. Serum ALP value at Visit 1b within ± 40% of ALP value at Visit 1a as per the formula below: 3.1. ((ALPVisit 1b - ALPVisit 1a) / ALPVisit 1a) x 100 = 40% 4. At Visit 1b, it should be confirmed that a patient does not meet any of the exclusion criteria Inclusion criteria specific to patients with rheumatoid arthritis (RA): 1. Patients fulfilling 2010 ACR/EULAR criteria or 1987 ACR criteria for a diagnosis of RA for = 6 months 2. Previous failure (inefficacy according to investigator judgement) to at least one biologic therapy or targeted synthetic Disease-Modifying Anti-Rheumatic Drug (tsDMARD) 3. DAS28 ESR = 3.2 with at least three swollen joints 4. Willing to have a synovial biopsy Inclusion criteria specific to patients with lupus nephritis (LN) (updated 07/02/2025: please note this cohort is closed to recruitment): 1. Has received induction of remission therapy for new diagnosis OR relapse of LN within 36 months of Visit 1 (screening) with corticosteroids AND mycophenolate mofetil OR azathioprine OR cyclophosphamide OR rituximab 2. Renal biopsy with evidence of active LN within 36 months of Visit 1 (screening). Biopsy-proven active LN for the purposes of eligibility is defined as LN class III, IV or V with evidence of activity. Concurrent evidence of chronic damage is permitted (Priority will be given to the recruitment of patients with biopsy-proven evidence of active LN within 36 months of the screening date. Patients that have had a renal biopsy with evidence of active lupus nephritis prior to 36 months of Visit 1 [screening] may be recruited following discussion with the coordinating centre as long as they have received induction of remission therapy within 36 months of Visit 1 [screening], as per inclusion criterion 1) 3. Ongoing proteinuria with uACR = 50 mg/mmol 4. If the patient is on mycophenolate mofetil or azathioprine, stable or reducing dose of the drug for the last three months prior to Visit 1 (screening) Main inclusion criteria specific to patients with Crohn’s disease (CD) (updated 07/02/2025: please note this cohort is closed to recruitment): 1. Confirmed diagnosis of CD as per standard clinical criteria 2. Colonoscopic detection of post-operative disease recur
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 02/07/2024: Exclusion criteria for ALL patients 1. Refusal or lacks the capacity to give informed consent to participate in the POLARISE Trial 2. Patient who is unable to participate in follow-up assessment 3. Participation actively or within five half-lives of Investigational Medicinal Product (IMP) and/or Advanced Therapy Investigational Medicinal Product (ATIMP) in another clinical trial 4. Known hypersensitivity to the ATIMP 5. Evidence of active malignancy (within three years of Visit 1/1a [screening]), other than non-melanoma skin cancer and cervical dysplasia in situ 6. Major surgical procedure within 30 days of Visit 1/1a (screening) 7. Prior organ transplantation (with the exception of a corneal transplant = three months prior to Visit 1/1a [screening]) 8. Active harmful alcohol consumption as evaluated and documented by the Investigator (as defined by NICE [3]) 9. Any active treatment on biologic therapy (monoclonal antibodies), or within the washout period for previous biologic therapy at the time of screening (Visit 1/1a); Updated 07/02/2025: 9. Any active treatment on biologic therapy (monoclonal antibodies) or targeted synthetic DMARDs, or within the washout period (two half-lives for previous biologic therapy and 4 weeks for previous targeted synthetic DMARDs) at time of screening (Visit 1/1a) 10. Received oral corticosteroids > 10 mg (prednisolone or equivalent) in the four weeks prior to Visit 2 (first ORBCEL-C™ administration) 11. Clinically severe cardiovascular disease as evaluated by the Investigator 12. Pregnancy or breast-feeding 13. Women of childbearing potential (see Appendix 1 for definition) who are unwilling to practise effective contraception (see Appendix 2 for further detail) for the duration of the trial and up to 90 days after the last trial drug is administered. If using hormonal agents the same method must have been used for at least one month before the trial dosing and patients must use a barrier method during that time period 14. Non-vasectomised men, sexually active with women of childbearing potential, who are not willing to practise effective contraception (i.e. condom with spermicide) for the duration of the trial and up to 90 days after the last trial drug is administered 15. Any evidence of current (surface antigen positive) hepatitis B infection 16. Patients with active hepatitis C infection (Polymerase Chain Reaction (PCR) positive) 17. Known positivity for antibody to HIV 18. 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 19. Receipt of live vaccination within six weeks prior to Visit 1/1a (screening) 20. Any symptoms indicative of COVID-19 21. Renal impairment defined as an eGFR 10 x ULN at Visit 1a (screening) 5. Evidence of cholangitis within 90 days of Visit 1a (screening), i.e. documented evidence of cholangitis by a doctor 6. Need for any sys
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 02/07/2024: The relative proportion of M1- and M2-like monocyte/macrophage cells in peripheral blood, determined from cell counts quantified using flow cytometry, after ORBCEL-C™ administration: PSC patients: at Visits 2, 3, 4, 5, 6 & 7 RA patients: at Visits 2, 3, 4, 5, 6 & 7 LN patients: at Visits 2, 3, 4, 5, 6, 7 & 8 CD patients: at Visits 2, 3, 4, 5, 6, 7 & 8 Previous primary outcome measure: The relative proportion of M1- and M2-like monocyte/macrophage cells in peripheral blood, determined from cell counts quantified using flow cytometry, after ORBCEL-C™ administration: PSC patients: at Visits 2, 3, 4, 5, 6 & 7 RA patients: at Visits 2, 3, 4, 5, 6 & 7 LN patients: at Visits 2, 3, 4, 5, 6, 7 & 8 CD patients: at Visits 2, 3, 4, 5, 6, 7 & 8a | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 02/07/2024: Secondary outcome measures for all patients: Any change in the secondary outcome measures after ORBCEL-C™ administration: 1. Quality of life measured by Euroqol 5D-5L (EQ-5D-5L), Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) & Fatigue Severity Scale (FSS): 1.1. PSC patients: at Visits 2, 4, 6, 7, 7a, 8, Month 18 and Month 24 1.2. RA patients: at Visits 2, 4, 6, 7, 7a, 8, Month 18 and Month 24 1.3. LN patients: at Visits 2, 4, 6, 7, 7a, 8, 9, Month 18 and Month 24 1.4. CD patients: at Visits 2, 4, 6, 7, 8, 9, Month 18 and Month 24 2. Inflammatory markers measured by C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR): 2.1. PSC patients: at Visits 1a, 1b, 2, 3, 4, 5, 6, 7, 7a, 8, Month 18 and Month 24 2.2. RA patients: at Visits 1, 2, 3, 4, 5, 6, 7, 7a, 8, Month 18 and Month 24 2.3. LN patients: at Visits 1, 2, 3, 4, 5, 6, 7, 7a, 8, 9, Month 18 and Month 24 2.4. CD patients: at Visits 1, 2, 3, 4, 5, 6, 7, 8, 9, Month 18 and Month 24 3. Adverse events (AEs) measured by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 throughout the trial, commencing from the date of consent until Month 24 4. Patient-reported AEs measured by PRO-CTCAE™ Version 1.0 (where applicable) at Visit 2 and thereafter every 7 days. After Visit 7, it will be measured: 4.1. PSC patients: at Visit 7a, 8, Month 18 and Month 24 4.2. RA patients: at Visit 7a, 8, Month 18 and Month 24 4.3. LN patients: at Visit 7a, 8, 9, Month 18 and Month 24 4.4. CD patients: at Visit 8, 9, Month 18 and Month 24 Where necessary, patients can also complete ad hoc questionnaires. 5. Patient-reported global tolerability of treatment measured by FACT-G GP5 Version 4.0 (where applicable) at Visit 2 and thereafter every 7 days. After Visit 7, it will be measured: 5.1. PSC patients: at Visit 7a, 8, Month 18 and Month 24 5.2. RA patients: at Visit 7a, 8, Month 18 and Month 24 5.3. LN patients: at Visit 7a, 8, 9, Month 18 | — |
Countries
England, United Kingdom
Outcome results
None listed