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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Fistula, Pouch, Ileal

Intervention / Treatment
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* Drug: Ossium vBM-MSC
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria 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. 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. 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. Failed oral antibiotic therapy -any oral antibiotic that has been attempted and has not been effective for fistula closure. 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 Competent and able to provide written informed consent Ability to comply with protocol. Exclusion Criteria Change in medical management for CD in the previous 2 months or changes anticipated in the next 2 months Daily use of prednisone of greater than 20 mg per day 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. Specific exclusions; HIV Hepatitis B or C History of cancer including melanoma (with the exception of localized skin cancers) within 1 year prior to treatment Investigational drug within thirty (30) days of baseline Pregnant or breast feeding or trying to become pregnant Contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia Unwilling to agree to use acceptable contraception methods during participation in study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vertebral Bone Marrow Derived Mesenchymal Stem Cells (vBM-MSC)<br>Direct injection of vertebral bone marrow derived mesenchymal stem cells at a dose of 100 million cells into the ileal pouch fistula(s) at baseline with a possible repeat injection at 3 months if not completely healed from the first injection. | Drug: Ossium vBM-MSC<br>* Vertebral bone marrow derived mesenchymal stem cells<br>* Other names: Ossium Vertebral Bone Marrow Derived Mesenchymal Stem Cells;|
| Placebo Comparator: Placebo<br>Direct injection of normal saline. If not completely healed after 6 months, participants will then cross over to the treatment group to receive a direct injection of vertebral allogeneic bone marrow derived mesenchymal stem cells at a dose of 100 million cells into ileal pouch fistula(s). | Other: Placebo<br>* Normal Saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment related adverse events | Number of participants with treatment related adverse events post-injection of 100 million vertebral bone marrow derived MSC's for the treatment of medically refractory pouch fistulizing disease as assessed by protocol | Month 6 | 
| Complete clinical healing | Number of participants with complete clinical healing post-injection of 100 million allogeneic bone marrow derived MSC's for the treatment of medically refractory pouch fistulizing disease in the setting of Crohn's disease of the pouch. Complete Healing is defined as: Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 3 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain Clinical Healing: 100% cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening | Month 6 | 
| Complete clinical healing | Number of participants with complete clinical healing post-injection of 100 million allogeneic bone marrow derived MSC's for the treatment of medically refractory pouch fistulizing disease in the setting of Crohn's disease of the pouch. Complete Healing is defined as: Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 3 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain Clinical Healing: 100% cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening | Month 12 | 
| Partial healing | Number of participants with partial clinical healing,post-injection of 100 million allogeneic bone marrow derived MSC's for the treatment of medically refractory pouch fistulizing disease in the setting of Crohn's disease Partial Healing is defined as: Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 2 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain Clinical healing: Greater than or equal to 50 % cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening | Month 6 | 
| Partial healing | Number of participants with partial clinical healing,post-injection of 100 million allogeneic bone marrow derived MSC's for the treatment of medically refractory pouch fistulizing disease in the setting of Crohn's disease Partial Healing is defined as: Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 2 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain Clinical healing: Greater than or equal to 50 % cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening | Month 12 | 
| Lack of response | Number of participants with lack of response post-injection of 100 million allogeneic bone marrow derived MSC's for the treatment of medically refractory pouch fistulizing disease in the setting of Crohn's disease Lack of Response is defined as: Radiographic and Clinical healing which does not meet the threshold for Partial Healing | Month 6 | 
| Lack of response | Number of participants with lack of response post-injection of 100 million allogeneic bone marrow derived MSC's for the treatment of medically refractory pouch fistulizing disease in the setting of Crohn's disease Lack of Response is defined as: Radiographic and Clinical healing which does not meet the threshold for Partial Healing | Month 12 | 
| Worsening disease | Number of participants with worsening disease-injection of 100 million vertebral bone marrow derived MSC's for the treatment of medically refractory pouch fistulizing disease in the setting of Crohn's disease Worsening Disease is defined as: Radiographic: MRI with a fluid collection >2 cm in 2 of 3 dimensions, edema, inflammation or sign of active inflammatory response. An increased number of tracts may be seen, or increased branching from the primary tract, Clinical: Increased drainage per patient report and on clinical exam | Month 6 | 
| Worsening disease | Number of participants with worsening disease-injection of 100 million vertebral bone marrow derived MSC's for the treatment of medically refractory pouch fistulizing disease in the setting of Crohn's disease Worsening Disease is defined as: Radiographic: MRI with a fluid collection >2 cm in 2 of 3 dimensions, edema, inflammation or sign of active inflammatory response. An increased number of tracts may be seen, or increased branching from the primary tract, Clinical: Increased drainage per patient report and on clinical exam | Month 12 |