Mesenchymal Stem Cells (MSCs) for Perianal Fistula

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

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.

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