MSC Intratissular Injection in Crohn Disease Patients

Study Overview
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Brief Summary
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The main objective is to assess the efficacy of local injection of MSC on the healing of refractory intestinal and perianal lesions in crohn disease. The second co-primary endpoint is safety.

Official Title
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Treatment of Refractory Crohn's Disease Lesions by Local Injection of Mesenchymal Stem Cells

Conditions
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Efficacy and Safety

Intervention / Treatment
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* Biological: Mesenchymal Stromal Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years of age Signing the informed consent Diagnosis of Crohn Disease for more than 6 months Presence of at least one Crohn Disease lesion refractory to conventional therapies (azathioprine, 6-mercaptopurine or methotrexate) and to biologic treatments (anti-Tumor Necrosis Factor therapies, vedolizumab, or ustekinumab). Refractory lesion defined by (1) a stricture with a length of 2 to 5cm of the colon or the ileum accessible by ileocolonoscopy (i.e. a lesion identified during a colonoscopy with a lumen narrowing non passable by the colonoscope), (2) unhealed deep ulcer of the colon or the ileum accessible to ileocolonoscopy, or (3) actively draining perianal fistula(s). Twenty patients with stricture(s), 20 patients with unhealed deep ulcer(s), and 20 patients with an actively draining perianal fistula(s) will be included Exclusion Criteria: Indication for immediate luminal surgery Intestinal obstruction Intra-abdominal fistulas or abscess Intestinal/colonic stricture or deep unhealed ulcer not accessible to ileocolonoscopy Undrained peri-anal abscess Pregnant women or planning pregnancy within one year Positive stool culture/toxin for clostridium difficile pathogen or other pathogens Renal failure (anuria, serious fluid overload, Glomerular Filtration Rate < 30 ml/min, dialysis) or hepatic failure (Fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin >3 mg/dL) documented human immunodeficiency virus infection; active hepatitis B, C, or tuberculosis an opportunistic infection within 6 months before screening or a serious infection in the previous 3 months malignancy within the past 5 years; or a history of lymphoproliferative disease

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Interventional Model Description: Non-controlled, non-randomized, open label study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal Stromal Cells<br> | Biological: Mesenchymal Stromal Cells<br>* Suspension of mesenchymal stromal cells for intratissular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with deep ulcer healing | Complete deep ulcer healing is defined by the disappearance of the ulcer; partial healing is defined by a decrease in the depth or the diameter of the ulcer. | Week 12 | 
| Proportion of patients with stricture healing | Complete stricture healing is defined by the ability to pass the ileocolonoscope through the stricture; partial healing is defined by the increase in the diameter of the stricture. | Week 12 | 
| Proportion of patients with complex perianal fistula healing | Complete complex perianal fistula healing is defined by the complete closure of the external fistula opening, no drainage upon gentle pressure, no abscess. And by looking at the size of the fistulous track, presence of collection, and gadolinium enhancement by MRI | Week 12 | 
| Safety assessed by the incidence of treatment-emergent adverse events during the study period | Assessment of the incidence of adverse and serious adverse events over the 48 weeks study period. Toxicity grade of adverse events is determined using the Common Terminology Criteria for Adverse Events (version 4.0). Relationship to the therapeutic procedure will systematically be assessed. | from week 0 to week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution of clinical disease activity index | Assess disease activity in Crohn's disease over 7 days using the Crohn's disease activity index | week 0, 12 and 48 | 
| Evolution of Short health scale (quality of life) | min : 0 - max : 10 (worse) | week 0, 12 and 48 | 
| Evolution of the Lemann Index (measuring cumulated intestinal damage in Crohn's disease) | which incorporates clinical, surgical, endoscopic, and imaging findings from all segments of the digestive tract into one composite score | week 0, 12 and 48 | 
| Evolution of the  Group of Therapeutic Study of Inflammatory Disorders of the Digestive Tube obstructive score for Crohn Disease strictures | Grade : from 0 to higher value 6 | weeks 0, 12 and 48 |