Evaluation of PROCHYMAL® Adult Human Stem Cells for Treatment-resistant Moderate-to-severe Crohn's Disease

• Disease improvement (Reduction by at least 100 points in CDAI) [ Time Frame: 28 days ]
• Improvement in quality of life (IBDQ) [ Time Frame: 28 days ]
• Reduction in number of draining fistulas [ Time Frame: 28 days ]

A significant number of individuals with Crohn's disease do not find relief with existing steroidal, immunosuppressive, or biologic therapies, and are forced to seek surgery or other drastic measures for treatment.

PROCHYMAL® adult human stem cells are manufactured from healthy, volunteer donors, extensively tested, and are stored to be available as needed. Human and animal studies have shown that the cells do not require any donor-recipient matching. The cells may have both immunosuppressive and healing benefits in Crohn's disease. The cells naturally migrate specifically to sites of inflammation, so their effects are believed to be local and self-limiting rather than systemic.

Protocol 603 is enrolling subjects to evaluate the ability of PROCHYMAL to induce remission in subjects with moderate-to-severe disease (Crohn's disease activity index -- CDAI -- of between 250 and 450, inclusive) who have failed or been intolerant of at least one drug in each of the steroid, immunosuppressant, and biologic classes.

• Drug: adult human mesenchymal stem cells
  Intravenous infusion of suspension of adult human mesenchymal stem cells, total of 1200 million (high dose) or 600 million (low dose) cells infused in four visits over two weeks.
• Drug: Placebo
  Placebo

• Placebo Comparator: 1
  Placebo
  Intervention: Drug: Placebo
• Active Comparator: 2
  Low dose (600 million cells total over four infusions in two weeks)
  Intervention: Drug: adult human mesenchymal stem cells
• Active Comparator: 3
  High dose (1200 million cells delivered in four infusions over two weeks)
  Intervention: Drug: adult human mesenchymal stem cells

Inclusion Criteria:

• failed (within last 2 yr) or intolerant of at least one steroid AND at least one immunosuppressant AND at EXACTLY one biologic
• CDAI between 250 and 450, inclusive
• endoscopically or radiographically confirmed Crohn's disease of ileus or colon or both
• CRP of at least 5 mg/l (0.5 mg/dl)*OR* CDAI of at least 300
• weight between 40 and 150 kg, inclusive
• adequate renal function
• negative PPD test (or evaluated low risk of TB activation)

Exclusion Criteria:

• HIV or hepatitis infection active
• allergy to CT contrast agents, or to bovine or porcine products
• symptomatic fibrostenotic Crohn's disease
• permanent ostomy
• biologic therapy within past 90 d
• prednisone greater than 20 mg/d within past month
• short-bowel syndrome
• total parenteral nutrition
• abnormal liver function
• malignancy active within past 5 years (except completely resected basal or squamous cell carcinoma of skin)
• enteric pathogens, including C. difficile
• history of colonic mucosal dysplasia
• current or prior evidence of TB (unless risk of activation or re-activation deemed low)