Prochymal™ Adult Human Mesenchymal Stem Cells for Treatment of Moderate-to-severe Crohn's Disease

A Phase II, Open-label, Randomized Study to Evaluate the Safety and Efficacy of PROCHYMAL™ IBD (ex Vivo Cultured Adult Human Mesenchymal Stem Cells) Intravenous Infusion for the Treatment of Subjects Experiencing Moderate-to-severe Crohn's Disease That is Refractory to Steroids and Immune Suppressants

Human mesenchymal stem cells (MSCs), derived from healthy adult volunteer human donors, can be obtained from bone marrow donation and cultured in the laboratory. MSCs have shown the ability to find injured tissue, reduce and control inflammation, and assist in tissue repair.

Prochymal™ MSCs will be infused into patients with moderate-to-severe Crohn's disease. Infusions will occur on two separate days, 7-10 days apart. Patients will be monitored for reduced Crohn's disease symptoms.

Human mesenchymal stem cells (MSCs), derived from healthy adult volunteer human donors, can be obtained from bone marrow donation and cultured in the laboratory. MSCs have shown the ability to find injured tissue, reduce and control inflammation, and assist in tissue repair.

Prochymal™ MSCs will be infused into patients with moderate-to-severe Crohn's disease. Infusions will occur on two separate days, 7-10 days apart. Patients will be monitored for reduced Crohn's disease symptoms. Patients will receive high or low dose. Study is open label.

Inclusion Criteria:

1. Subject must be 18 to 70 years of age, inclusive.

2. If female and of child-bearing age, subject must be non-pregnant, non-breast-feeding, and use adequate contraception. If male, subject must use adequate contraception.

3. Subject must have endoscopically or radiographically active Crohn's disease

4. Subject must have a Crohn's disease activity index (CDAI) of at least 220.

5. Subject must have a C-reactive protein (CRP) of at least 5 mg/l.

6. Subject must have ileocolitis, colitis, or ileitis.

7. At some time during the course of the subject's Crohn's disease (CD), subject must have received both steroids and immunosuppressive agents (for example, azothioprine, 6-mercaptopurine, or methotrexate) which did not control the CD.

8. Subject may be receiving antibiotics, 5-aminosalicylic acid, azathioprine, 6-mercaptopurine, methotrexate, prednisone, or any similar drugs at the time of enrollment.

   • The dose of 5-aminosalicylic acid (5-ASA) must have been stable for at least 4 weeks prior to enrollment.
   • The dose of steroids must have been stable for at least 4 weeks prior to enrollment.
   • The dose of antibiotics must have been stable for at least 4 weeks prior to enrollment.
   • The dose of immunosuppressants (for example, azathioprine, 6-mercaptopurine [6-MP], or methotrexate) must have been stable for at least 8 weeks prior to enrollment and the subject on therapy for at least three months prior to enrollment.

9. Subject must have adequate renal function as defined by a calculated creatinine clearance of greater than 30 ml/min using the Cockcroft-Gault equation, and a serum creatinine concentration of less than 2.0 mg/dl.

10. Subject must be available for all specified assessments at the study site through day 30.

11. Subject must provide a written informed consent form (ICF) and authorization for use of and disclosure of personal health information (PHI).

Exclusion Criteria:

1. Subject has any alcohol or substance abuse within 6 months of randomization.
2. Subject has evidence of fibrostenotic obstructive Crohn's disease.
3. Subject has an active infection with HIV or hepatitis B or C.
4. Subject has had surgery or trauma within 28 d prior to enrollment.
5. Subject has a known allergy to computed tomography (CT) contrast agents.
6. Subject has a known allergy to bovine or porcine products.
7. Subject has body mass greater than 150 kg.
8. Subject has had a stricture of the bowel requiring hospitalization within 6 months prior to enrollment.
9. Subject has had bowel surgery other than perianal (for example, fistulotomy, seton placement, or abscess drainage) within 6 months prior to enrollment.
10. Subject has received infliximab; adalimumab; or other antibody, protein, or biological therapy not specifically approved by the United States Food and Drug Administration (FDA) for Crohn's disease for 90 days (d) prior to enrollment in study.
11. Subject has received prednisone greater than 20 mg/d at any time 28 d prior to enrollment in study.
12. Subject has a permanent colostomy or ileostomy.
13. Subject has aspartate aminotransferase (AST), alkaline phosphatase (ALP), or alanine transaminase (ALT) more than 2.5 times the upper limit of normal at screening.
14. Subject has evidence of active malignancy other than resected basal or squamous cell carcinoma of the skin, or prior history of active malignancy that has not been in remission for at least 5 years.
15. Subject has history of bacteremia or other serious bacterial or fungal infection in past 3 months other than a treated urinary tract infection or drained perianal abscess.
16. Subject has received an investigational agent (IA)-an agent or device not approved by FDA for marketed use in any indication-within 90 d (or 5 half-lives, whichever is longer) of randomization.
17. Subject has cardiopulmonary disease that, in the opinion of the Investigator, is either unstable or severe enough to justify exclusion from this study.
18. Subject has any underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would make participation in the study unsafe.
19. Subject has any underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the subject. Such excluding conditions might include, for example, uncontrolled infection, right heart failure, pulmonary hypertension.
20. Subject has unstable arrhythmia.
21. Subject is unwilling or unable to adhere to requirements of protocols.