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

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ClinicalTrials.gov Identifier: NCT05075811
Recruitment Status : Not yet recruiting
First Posted : October 13, 2021
Last Update Posted : October 13, 2021
Sponsor:
Collaborator:
Ossium Health, Inc.
Information provided by (Responsible Party):
Amy Lightner, The Cleveland Clinic

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.

Condition or disease Intervention/treatment Phase
Pouch, Ileal Fistula Drug: Ossium vBM-MSC Other: Placebo Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Crossover Assignment
Masking: Single (Participant)
Masking Description: Single
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : November 15, 2021
Estimated Primary Completion Date : November 15, 2024
Estimated Study Completion Date : November 15, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Ossium vBM-MSC
Vertebral bone marrow derived mesenchymal stem cells
Other Name: Ossium Vertebral Bone Marrow Derived Mesenchymal Stem Cells

Placebo Comparator: 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).
Other: Placebo
Normal Saline




Primary Outcome Measures :
  1. Treatment related adverse events [ Time Frame: Month 6 ]
    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

  2. Complete clinical healing [ Time Frame: Month 6 ]

    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


  3. Complete clinical healing [ Time Frame: Month 12 ]

    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


  4. Partial healing [ Time Frame: Month 6 ]

    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


  5. Partial healing [ Time Frame: Month 12 ]

    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


  6. Lack of response [ Time Frame: Month 6 ]

    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


  7. Lack of response [ Time Frame: Month 12 ]

    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


  8. Worsening disease [ Time Frame: Month 6 ]

    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


  9. Worsening disease [ Time Frame: Month 12 ]

    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




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05075811


Contacts
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Contact: Caroline Matyas, BS 216-212-0746 ibdstemcelltherapy@ccf.org
Contact: Alex VanDenBossche 216-379-0307 ibdstemcelltherapy@ccf.org

Locations
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United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Contact: Caroline Matyas         
Contact: Alex VanDenBossche         
Sponsors and Collaborators
Amy Lightner
Ossium Health, Inc.
Investigators
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Principal Investigator: Amy Lightner, MD The Cleveland Clinic
Publications:
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Responsible Party: Amy Lightner, Sponsor-Investigator, MD, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT05075811    
Other Study ID Numbers: CSP-5007
First Posted: October 13, 2021    Key Record Dates
Last Update Posted: October 13, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Crohn Disease
Fistula
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Pathological Conditions, Anatomical