Mesenchymal Stem Cells (MSCs) for Perianal Fistula

Study Overview
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Brief Summary
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OSSM-001 will be evaluated in a double blind, randomized phase I safety study of a single injection of 100 and 300 million bone marrow derived MSCs in 16 patients with refractory perianal fistulas in the setting of Crohn's disease. There will be 2 cohorts (100M and 300M MSCs); 8 subjects in each cohort; 6 subjects receiving the investigational product and 2 subjects receiving placebo (normal saline) in each cohort.

Official Title
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A Phase I Safety Study of Allogeneic Bone Marrow Derived MSCs for Refractory Perianal Fistulizing Crohn's Disease

Conditions
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Rectal Fistula

Intervention / Treatment
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* Biological: OSSM-001
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and Women 18-75 years of age with a diagnosis of unhealing perianal fistulas in the setting of Crohn's disease and must be on maximal standard of care therapy (e.g., antibiotics, 5-ASA, and immunomodulator, anti-TNF, anti-integrin, and anti-interleukin therapies) for at least six months duration. Presence of perianal fistula with maximum of two internal fistula tracts and a maximum of three external openings based on clinical assessment and MRI. Fistula must have been draining for at least 6 weeks prior to the screening visit. Medically refractory perianal fistulizing Crohn's disease (i.e., standard of care such as antibiotics, immunosuppressives) Have no contraindications to MR evaluations: e.g., pacemaker or magnetically active metal fragments, claustrophobia Ability to comply with protocol Competent and able to provide written informed consent Concurrent Crohn's-related therapies with stable doses corticosteroids, 5- ASA drugs, immunomodulators, anti-TNF therapy, anti-integrin and anti-interleukin therapies are permitted. A female participant and of childbearing potential must have a negative serum or urine pregnancy test at time of screening, and must not plan to become pregnant during the study. Exclusion Criteria: Inability to give informed consent. Clinically significant medical conditions within the six months before administration of 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 patient. Specific exclusions: Hepatitis B or C, HIV, Abnormal AST or ALT at screening History of cancer including melanoma (with the exception of localized skin cancers) in the past five years Received treatment with an investigational drug or device within 60 days of randomization or have not completed 5 half-life washout (whichever is later) for drugs or biologics. If the half-life of the product is not known, then subjects cannot be randomized within 6 months of investigation drug treatment. Participated in a cell therapy-based trial within 6 months before randomization Participated in Crohn's/ulcerative colitis or any fistulizing Crohn's study within 6 months before randomization Pregnant or breast feeding or trying to become pregnant. Presence of a rectovaginal or perineal body fistula Change in Crohn's immunosuppressive regimen prior to enrollment. Subjects should be on stable, maximal medical therapy for 4 months prior to enrollment. Uncontrolled intestinal Crohn's disease which will require escalation for medical therapy or surgery within 3 months of enrollment Severe anal canal disease that is stenotic and requires dilation or severe proctitis making difficult to the surgery A female or male participant unwilling to agree to use acceptable contraception methods during participation in study. Acceptable contraception methods include: Implants, injectables, combined oral contraceptives, an intrauterine device, a bilateral tubal ligation, a vasectomy, a vasectomized partner for female participant, double-barrier methods, and physical barrier if male participant is not vasectomized Associated perianal abscess(es). Laboratory exclusions: Serum creatinine levels >1.5 times the upper limit of normal (ULN). Total bilirubin >1.5 × ULN. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5.0 × ULN. Hemoglobin <10.0 g/dL for females or <11.0 g/dL for males. Platelets <75.0 × 109/L. Any contraindications to MRI or surgical or anesthetic procedure(s) Any major GI surgery or major perianal local surgery within 6 months of randomization

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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100M of OSSM-001<br>Single injection of mesenchymal stem cells at dose of 100M | Biological: OSSM-001<br>* Single injection of OSSM-001 at dose of 100M or 300M cells<br>|
| Experimental: 300M of OSSM-001<br>Single injection of mesenchymal stem cells at dose of 300M | Biological: OSSM-001<br>* Single injection of OSSM-001 at dose of 100M or 300M cells<br>|
| Placebo Comparator: Placebo<br>Single injection of normal saline | Other: Placebo<br>* Single injection of placebo (saline)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OSSM-001 (100M dose) related adverse events as assessed by CTCAE v5.0 | To determine the safety of a single injection of 100M allogeneic bone marrow MSCs for the treatment of refractory perianal fistulizing Crohn's disease by assessing OSSM-001 related adverse events as assessed by CTCAE v5.0. | 12 weeks | 
| OSSM-001 (300M dose) related adverse events as assessed by CTCAE v5.0 | To determine the safety of a single injection of 300M allogeneic bone marrow MSCs for the treatment of refractory perianal fistulizing Crohn's disease by assessing OSSM-001 related adverse events as assessed by CTCAE v5.0. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fistula healing assessed by radiographic (MRI) assessments for OSSM-001 (100M dose) | To assess fistula healing induced by the delivery of a single injection of 100M allogeneic bone marrow derived MSCs on refractory perianal fistulizing Crohn's disease using radiographic assessment (MRI) assessments. Complete healing defined as MRI with an absence of a fluid collection >2cm in 3 of 3 dimensions, lack of edema, inflammation, or sign of active inflammatory response. A remnant of scar of a fistula tract may remain. Partial healing defined as MRI with an absence of a fluid collection >2cm in 2 of 3 dimensions, lack of edema, inflammation, or sign of active inflammatory response. A remnant of scar of a fistula tract may remain. Lack of response defined as healing which does not meet the threshold for partial healing. Worsening disease defined as MRI with fluid collection >2cm 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. | 12 weeks | 
| Fistula healing assessed by clinical assessments for OSSM-001 (100M dose) | To assess fistula healing induced by the delivery of a single injection of 100M allogeneic bone marrow derived MSCs on refractory perianal fistulizing Crohn's disease using clinical assessments. Complete healing defined as 100% cessation of drainage on clinical exam and with gentle finger compression. Partial healing defined as greater than or equal to 50% cessation of drainage on clinical exam with gentle finger compression. Lack of response defined as healing which does not meet the threshold for partial healing. Worsening disease defined as increased drainage on clinical exam. | 12 weeks | 
| Fistula healing assessed by radiographic (MRI) assessments for OSSM-001 (300M dose) | To assess fistula healing induced by the delivery of a single injection of 300M allogeneic bone marrow derived MSCs on refractory perianal fistulizing Crohn's disease using radiographic assessment (MRI) assessments. Complete healing defined as MRI with an absence of a fluid collection >2cm in 3 of 3 dimensions, lack of edema, inflammation, or sign of active inflammatory response. A remnant of scar of a fistula tract may remain. Partial healing defined as MRI with an absence of a fluid collection >2cm in 2 of 3 dimensions, lack of edema, inflammation, or sign of active inflammatory response. A remnant of scar of a fistula tract may remain. Lack of response defined as healing which does not meet the threshold for partial healing. Worsening disease defined as MRI with fluid collection >2cm 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. | 12 weeks | 
| Fistula healing assessed by clinical assessments for OSSM-001 (300M dose) | To assess fistula healing induced by the delivery of a single injection of 300M allogeneic bone marrow derived MSCs on refractory perianal fistulizing Crohn's disease using clinical assessments. Complete healing defined as 100% cessation of drainage on clinical exam and with gentle finger compression. Partial healing defined as greater than or equal to 50% cessation of drainage on clinical exam with gentle finger compression. Lack of response defined as healing which does not meet the threshold for partial healing. Worsening disease defined as increased drainage on clinical exam. | 12 weeks |