mesenchymal stem cells (mscs) for perianal fistula

Conditions: Rectal Fistula

Summary: 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.


Eligibility criteria:
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