Study of Mesenchymal Stem Cells for the Treatment of Medically Refractory Crohn's Colitis

Prior treatment

• Clinically significant medical conditions within the six months before administration of MSCs: e.g. myocardial infarction, active angina, congestive heart failure or other conditions that would, in the opinion of the investigators, compromise the safety of the patient.
• Investigational drug within one year of study enrollment
• Fulminant colitis requiring emergency surgery
• Concurrent active clostridium difficile infection of the colon
• Concurrent CMV infection of the colon
• Three or more prior small bowel resections
• Unable to wean off corticosteroids
• Patients with a known allergy to DMSO, porcine and/or bovine proteins. Control patients will have additional criteria that need to be met prior to the patients' crossing over to receive treatment.
• Given oral and intravenous steroids for a colitis flare
• Desires exclusion from the study to pursue escalation in medical management or surgery

Other illness

• History of cancer including melanoma (with the exception of localized skin cancers) within 5 years of study enrollment
• Evidence of colonic perforation
• Massive hemorrhage from the colon requiring emergent surgery
• Active or latent tuberculosis
• Has a colonic perforation that requires surgery
• Has colonic bleeding that requires surgery

Lab values

• Specific exclusions;
  • HIV
  • Hepatitis B or C
  • Abnormal AST or ALT at screening defined as > 3x upper limit of normal?

Other

• Inability to give informed consent.
• Pregnant or breast feeding.
• If patient is of reproductive capacity, unwilling to use adequate birth control measures while they are in the study
• Ulcerative colitis or indeterminate colitis
• Neoplasia of the colon on preoperative biopsy
• Presence of an ostomy
• Colonic stricture that unable to pass an adult colonoscope
• Patients with primary sclerosing cholangitis
• Required repeat hospitalization for a colitis flare
• Had worsening abdominal pain frequency of bowel movements, blood in stool

• Males and Females 18-75 years of age.
• Crohn's colitis of at least 6 months duration with medically refractory symptoms who has failed one anti-TNF therapy, with a next step of subtotal colectomy or escalation in medical management.
• Exposure to corticosteroids, 5-ASA drugs, thiopurines, methotrexate, anti-TNF therapy, anti-integrin and anti-interleukin in the past are permitted but a washout period of 4 weeks for any monoclonal antibody is necessary.
  • If receiving conventional immunomodulators (ie, AZA, 6-MP, or MTX), must have been taking them for ≥12 weeks, and on a stable dose for at least 4 weeks.
  • If AZA, 6-MP, or MTX has been recently discontinued, it must have been stopped for at least 4 weeks.
  • If receiving oral 5-ASA compounds, the dose must have been stable for at least 4 weeks.If receiving oral corticosteroids, the dose must be ≤20 mg/day prednisone or its equivalent and must have been stable for at least 4 weeks.
  • If receiving budesonide, the dose must have been stable for at least 2 weeks.
  • If oral 5-ASA compounds or oral corticosteroids (including budesonide) have been recently discontinued, they must have been stopped for at least 2 weeks.
• The following medications/therapies must have been discontinued before first administration of study agent:
  • TNF-antagonist therapy (eg, infliximab, etanercept, certolizumab, adalimumab, golimumab), vedolizumab, ustekinumab for at least 4 weeks.
  • Cyclosporine, tacrolimus, or sirolimus, for at least 4 weeks.
  • 6-thioguanine (6-TG) must have been discontinued for at least 4 weeks.
  • Rectal corticosteroids (ie, corticosteroids [including budesonide] administered to the
  • rectum or sigmoid colon via foam or enema or suppository) for at least 2 weeks.
  • Rectal 5-ASA compounds (ie, 5-ASAs administered to the rectum or sigmoid colon viafoam or enema or suppository) for at least 2 weeks.
  • Parenteral corticosteroids for at least 2 weeks.
  • Total parenteral nutrition (TPN) for at least 2 weeks.
  • Antibiotics for the treatment of UC (eg, ciprofloxacin, metronidazole, or rifaximin) for atleast 2 weeks.
• No colonic dysplasia and malignancy as ruled out by colonoscopy within 30 days of MSC delivery
• Ability to comply with protocol
• Competent and able to provide written informed consent
• Must have lost response to at least one monoclonal antibody (anti-TNF, anti-interleukin, or anti- integrin therapy), or tofacitinib, or have a contra-indication to biologic therapy
• Received placebo at the point of first injection
• Completed all study visits to date
• Clinical status has remained the same or improved, not worsened