Study of Ossium Mesenchymal Stem Cells for the Treatment of Pouch Fistulas in the Setting of Crohn's Disease

A Phase IB/IIA Study of Ossium Vertebral Bone Marrow Derived Mesenchymal Stem Cells (vBM-MSC) for the Treatment of Ileal Anal Anastomosis and Ileal Pouch Fistulas in the Setting of Crohn's Disease of the Pouch

The purpose of this study is to determine the safety and feasibility of using Ossium vertebral Bone Marrow Derived Mesenchymal Stem Cells (vBM-MSC) to treat people with an ileal pouch anal anastomosis (IPAA) who develop a fistula in the setting of Crohn's disease of the pouch.

Proctocolectomy with ileal pouch anal anastomosis (IPAA) remains the procedure of choice for patients with ulcerative colitis (UC). IPAA allows at risk tissue to be removed with restoration of intestinal continuity while maintaining favorable long-term functional outcomes and quality of life.1 2 While less than 30% of patients experience short-term postoperative morbidity following IPAA,3-5 up to 15% of pouches will ultimately fail due to technical or inflammatory complications, the majority of which manifest as a fistula from the pouch to the perianal or vaginal locations.1,2,6-8 Pouch failure due to a fistula tract is notoriously difficult to treat. Despite immunosuppressive medications and attempts at local repair, most patients will end up with a pouch excision and permanent ostomy. This can be a devastating outcome in some patients as it impacts body image and quality of life.1

Given the high safety profile, and relative success in treating perianal disease, we sought to use a GMP grade allogeneic bone marrow derived MSCs to establish safety and secondarily monitor for healing in patients with ileal anal anastomosis and ileal pouch fistulas. This trial will use allogeneic bone marrow derived mesenchymal stem cells (MSCs) to produce regenerative signals.

This study will enroll adult men and women who have undergone IPAA at least six months prior and now have a peri-pouch fistula related to Crohn's disease of the pouch. Subjects who are refractory to conventional medical therapy will be considered. Subjects enrolled will be those that meet current indications.

Inclusion Criteria

1. Men and women 18-75 years of age who have undergone an ileal pouch anal anastomosis at least 6 months prior who have developed a clinical diagnosis of Crohn's disease of the pouch as determined by a combination of clinical symptoms, pouchoscopy with biopsy, enterography.

2. Single and multi-tract (up to 2 internal and 3 external openings) fistula tract arising from the ileal pouch, ileal anal anastomosis, or anal canal distal to anastomosis that travels to the perianal skin, perineal body, or vagina. Subjects with fistulas that arise from the pouch, anastomosis, or anal canal distal to the anastomosis will both be included in enrollment. a. Acceptable internal openings and tract locations for the fistula to arise from include the ileal pouch body, the pouch anal anastomosis, and the anal canal distal to the anastomosis.

   b. Acceptable external openings and tract locations for the fistula to arise from include the perianal skin, perineal body, and/or the vaginal wall.

3. Concurrent Crohn's related therapies with stable doses (>3 months) corticosteroids, 5-ASA drugs, immunomodulators, anti-TNF therapy, anti-integrin and anti-interleukin are permitted.

4. Failed oral antibiotic therapy -any oral antibiotic that has been attempted and has not been effective for fistula closure.

5. Have failed conventional medical therapies described above, defined as a lack of response to systemic immune suppression (e.g. azathioprine, methotrexate, 6-mercaptopurine) or biologic (e.g. anti-TNF, anti-integrin, anti-interleukin) therapies to treat fistulizing CD for at least 3 months

6. Competent and able to provide written informed consent

7. Ability to comply with protocol.

Exclusion Criteria

1. Change in medical management for CD in the previous 2 months or changes anticipated in the next 2 months

2. Daily use of prednisone of greater than 20 mg per day

3. Clinically significant medical conditions within the six months before administration of vBM-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 subject.

4. Specific exclusions;

   • HIV
   • Hepatitis B or C

5. History of cancer including melanoma (with the exception of localized skin cancers) within 1 year prior to treatment

6. Investigational drug within thirty (30) days of baseline

7. Pregnant or breast feeding or trying to become pregnant

8. Contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia

9. Unwilling to agree to use acceptable contraception methods during participation in study