An Australian Study of Mesenchymal Stromal Cells for Crohn's Disease

Study Overview
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Brief Summary
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Despite the advent of newer biologic therapies such as infliximab for Crohn's disease, a form of autoimmune inflammatory bowel disease, a proportion of patients are refractory to such therapy and require surgery. The hypothesis is that mesenchymal stromal cell therapy using third party human cultured cells will be safe and effective

Official Title
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A Multicentre Australian Phase 2 Study to Evaluate Safety and Efficacy of Mesenchymal Stromal Cells for Treating Biologic Refractory Crohn's Disease

Conditions
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Crohn Disease

Intervention / Treatment
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* Drug: Mesenchymal stromal cells (MSC) for infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Colonic or small bowel Crohn's disease based on endoscopic appearances and histology Refractory to induction with infliximab or adalimumab; or have lost response to these agents; or have had side effects precluding their further use Where there has been loss of response to one of these agents, the other must be tried before being eligible Crohn's disease activity score (CDAI) 250 or more. C-reactive protein >10mg/L Surgery must have been offered to the subject (if appropriate) and declined Signed informed consent Exclusion Criteria: Active sepsis, perforating disease. Coexistent perianal fistulous disease is permitted, providing no co-existent infection within previous 4 weeks Chronic stricturing disease in isolation Coexistent CMV disease Prior history of malignancy Pregnant or unwilling to practice contraceptive therapy or breast feeding females Last biologic therapy must be greater than 4 weeks prior, must be on stable corticosteroid dose for 14 days prior, during therapy and for 14 days after therapy, must be on stable immunomodulator dose (eg, azathioprine) for 14 days prior, during therapy and for 14 days after.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal stromal cells<br>Mesenchymal stromal cells administered weekly for 4 weeks | Drug: Mesenchymal stromal cells (MSC) for infusion<br>* MSC 2X10E6/kg recipient weight are infused over 15 minutes intravenously weekly for 4 weeks<br>* Other names: No other names;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response to MSC: Reduction of Crohn's disease Activity score by 100 points or more at six weeks post start of therapy | Colonoscopy and biopsy as well as clinical parameters used for the Crohn's disease acivity (www.ibdaustralia.org/cdai/) will be undertaken at screening pre-therapy and at 6 weeks after start of therapy. | Six weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of infusional toxicity | Subjects will receive mesenchymal stromal cell therapy, 2X10E6/kg weekly by IV infusion for 4 weeks and will be assessed for 4 hours post infusion | Six weeks | 
| Induction of remission | Crohn's disease activity index assessed as below 150 | Six weeks | 
| Improved quality of life | Increase in IBDQ and SF-36 scores measured at six weeks | Six weeks | 
| Endoscopic improvement. | Crohn's disease endoscopic improvement score will be measured at repeat endoscopy six weeks after start of treatment | Six weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ileitis, mesenchymal stromal cells, colitis