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

Primary Purpose

Pouch, Ileal, Fistula

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Ossium vBM-MSC

Placebo

About this trial

This is an interventional treatment trial for Pouch, Ileal

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Cleveland ClinicRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

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

Placebo

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

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

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

Complete clinical healing

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

Partial healing

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

Lack of response

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

Worsening disease

Secondary Outcome Measures

Full Information

NCT ID

NCT05075811

First Posted

September 28, 2021

Last Updated

April 1, 2022

Sponsor

Amy Lightner

Collaborators

Ossium Health, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT05075811

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Recruiting

Study Start Date

February 1, 2022 (Actual)

Primary Completion Date

November 15, 2024 (Anticipated)

Study Completion Date

November 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Amy Lightner

Collaborators

Ossium Health, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pouch, Ileal, Fistula

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Crossover Assignment

Model Description

Crossover Assignment

Masking

Participant

Masking Description

Single

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ossium vBM-MSC

Other Intervention Name(s)

Ossium Vertebral Bone Marrow Derived Mesenchymal Stem Cells

Intervention Description

Vertebral bone marrow derived mesenchymal stem cells

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Normal Saline

Primary Outcome Measure Information:

Title

Treatment related adverse events

Description

Time Frame

Month 6

Title

Complete clinical healing

Description

Time Frame

Month 6

Title

Complete clinical healing

Description

Time Frame

Month 12

Title

Partial healing

Description

Time Frame

Month 6

Title

Partial healing

Description

Time Frame

Month 12

Title

Lack of response

Description

Time Frame

Month 6

Title

Lack of response

Description

Time Frame

Month 12

Title

Worsening disease

Description

Time Frame

Month 6

Title

Worsening disease

Description

Time Frame

Month 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Allison Bayles, AA

Phone

216-444=0887

ibdstemcelltherapy@ccf.org

First Name & Middle Initial & Last Name or Official Title & Degree

Alex VanDenBossche

Phone

216-379-0307

ibdstemcelltherapy@ccf.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Amy Lightner, MD

Organizational Affiliation

The Cleveland Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cleveland Clinic

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Allison Bayles

First Name & Middle Initial & Last Name & Degree

Alex VanDenBossche

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

23299522

Citation

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.

Results Reference

background

PubMed Identifier

24468224

Citation

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.

Results Reference

background

PubMed Identifier

19279412

Citation

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.

Results Reference

background

PubMed Identifier

7634973

Citation

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.

Results Reference

background

PubMed Identifier

9667712

Citation

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.

Results Reference

background

PubMed Identifier

10816636

Citation

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.

Results Reference

background

Learn more about this trial

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

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