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

NCT05075811 | Terminated Phase 1 FDA Drug

• 1 other identifier: 21-860
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Pouch, Ileal; Fistula

Outcome Measures

Primary Outcomes (9)

• 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

Study Arms (2)

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

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Ossium vBM-MSC DRUG

Vertebral bone marrow derived mesenchymal stem cells

Also known as: Ossium Vertebral Bone Marrow Derived Mesenchymal Stem Cells

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

Placebo OTHER

Normal Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Ossium Health, Inc.: collaborator
• Anthony Lembo: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Related Publications (6)

• 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.

  PMID: 23299522 BACKGROUND

• 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.

  PMID: 24468224 BACKGROUND

• 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.

  PMID: 19279412 BACKGROUND

• 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.

  PMID: 7634973 BACKGROUND

• 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.

  PMID: 9667712 BACKGROUND

• 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.

  PMID: 10816636 BACKGROUND

MeSH Terms

Conditions

Fistula

Condition Hierarchy (Ancestors)

Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Amy Lightner, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Single
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator, MD

Model Details: Crossover Assignment

Study Record Dates

• First Submitted: September 28, 2021
• First Posted: October 13, 2021
• Study Start: February 1, 2022
• Primary Completion: November 15, 2024
• Study Completion: November 15, 2024
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)