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

NCT ID: NCT05075811

Last Updated: 2022-04-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-01
• Study Completion Date: 2024-11-15

Brief Summary

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

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.

Conditions

Pouch, Ileal; Fistula

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Vertebral Bone Marrow Derived Mesenchymal Stem Cells (vBM-MSC)

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.

Group Type: EXPERIMENTAL

Ossium vBM-MSC

Intervention Type: DRUG

Vertebral bone marrow derived mesenchymal stem cells

Placebo

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Normal Saline

Interventions

Ossium vBM-MSC

Vertebral bone marrow derived mesenchymal stem cells

Intervention Type: DRUG

Placebo

Normal Saline

Intervention Type: OTHER

Other Intervention Names

Ossium Vertebral Bone Marrow Derived Mesenchymal Stem Cells

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ossium Health, Inc.

INDUSTRY

Sponsor Role: collaborator

Amy Lightner

OTHER

Sponsor Role: lead

Responsible Party

Amy Lightner

Sponsor-Investigator, MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Amy Lightner, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cleveland Clinic

Cleveland, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Allison Bayles, AA

Role: CONTACT

ibdstemcelltherapy@ccf.org

216-444=0887

Alex VanDenBossche

Role: CONTACT

ibdstemcelltherapy@ccf.org

216-379-0307

Facility Contacts

Allison Bayles

Role: primary

Alex VanDenBossche

Role: backup

References

Fazio VW, Kiran RP, Remzi FH, Coffey JC, Heneghan HM, Kirat HT, Manilich E, Shen B, Martin ST. Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707 patients. Ann Surg. 2013 Apr;257(4):679-85. doi: 10.1097/SLA.0b013e31827d99a2.

Reference Type: BACKGROUND

PMID: 23299522 (View on PubMed)

Ozdemir Y, Kiran RP, Erem HH, Aytac E, Gorgun E, Magnuson D, Remzi FH. Functional outcomes and complications after restorative proctocolectomy and ileal pouch anal anastomosis in the pediatric population. J Am Coll Surg. 2014 Mar;218(3):328-35. doi: 10.1016/j.jamcollsurg.2013.11.019. Epub 2013 Nov 26.

Reference Type: BACKGROUND

PMID: 24468224 (View on PubMed)

Remzi FH, Fazio VW, Kirat HT, Wu JS, Lavery IC, Kiran RP. Repeat pouch surgery by the abdominal approach safely salvages failed ileal pelvic pouch. Dis Colon Rectum. 2009 Feb;52(2):198-204. doi: 10.1007/DCR.0b013e31819ad4b6.

Reference Type: BACKGROUND

PMID: 19279412 (View on PubMed)

Foley EF, Schoetz DJ Jr, Roberts PL, Marcello PW, Murray JJ, Coller JA, Veidenheimer MC. Rediversion after ileal pouch-anal anastomosis. Causes of failures and predictors of subsequent pouch salvage. Dis Colon Rectum. 1995 Aug;38(8):793-8. doi: 10.1007/BF02049833.

Reference Type: BACKGROUND

PMID: 7634973 (View on PubMed)

Meagher AP, Farouk R, Dozois RR, Kelly KA, Pemberton JH. J ileal pouch-anal anastomosis for chronic ulcerative colitis: complications and long-term outcome in 1310 patients. Br J Surg. 1998 Jun;85(6):800-3. doi: 10.1046/j.1365-2168.1998.00689.x.

Reference Type: BACKGROUND

PMID: 9667712 (View on PubMed)

Farouk R, Pemberton JH, Wolff BG, Dozois RR, Browning S, Larson D. Functional outcomes after ileal pouch-anal anastomosis for chronic ulcerative colitis. Ann Surg. 2000 Jun;231(6):919-26. doi: 10.1097/00000658-200006000-00017.

Reference Type: BACKGROUND

PMID: 10816636 (View on PubMed)

Other Identifiers

21-860

Identifier Type: -

Identifier Source: org_study_id