Bone Marrow Stromal Cells for Inflammatory Bowel Diseases

Inclusion Criteria

• •Subjects who meet ALL of the following criteria will be considered for enrollment into this study:
• •1. Be 18 to 65 years of age, inclusive, as of the date of enrollment.
• •2. Be willing to take appropriate measures to avoid pregnancy during the study period. Subject to the judgment and discretion of the PI, participants who meet ANY of the criteria listed immediately below, as well as male participants who are in a monogamous relationship with a woman who meets ANY of the criteria below, may not be required to take any pregnancy avoidance measures (e.g. barrier methods). Such participants will be counseled on risks at the time of consent and at appropriate points (e.g. when pregnancy testing occurs) during the study:
• •1. Females who have had their uterus, and/or BOTH ovaries removed
• •2. Females who have had BOTH fallopian tubes surgically tied or removed
• •3. Females who have undergone other permanent birth control procedures, such as endometrial ablation or sterilization (such as Essure or Novasure), and have had any required follow up testing to confirm the effectiveness of the permanent birth control procedure.
• •4. Females who are above the age of 50 and have spontaneously had no menses at any point during the past 12 or more consecutive months (i.e. have reached menopause).
• •5. Females who, in the conservative and reasonable judgment of the PI (e.g. due to sexual orientation, or serious life choice), from the time of enrollment until
• •12 weeks after the last BMSC infusion, will NOT participate in any potentially reproductive sexual contact (i.e. sexual intercourse with a male partner).
• •6. Males who have had a vasectomy and have had the follow-up testing confirming zero sperm count in their semen.
• •3. Any subject who does NOT meet the criteria listed in #2 above, will be appropriately counseled on reproductive risks and pregnancy avoidance, and will be required to adhere to the following measures, as agreed upon by the subject and the PI until at least 12 weeks after the last BMSC infusion:
• •1. A highly effective hormonal method to prevent pregnancy \[e.g. CONSISTENT, CONTINUOUS use of contraceptive pill, patch, ring, implant or injection\], and/or IUD or equivalent.
• •IN ADDITION TO
• •2. A barrier method to be used at the time of potentially reproductive sexual activity (e.g. \[male/female condom, cap, or diaphragm\] + spermicide).
• •3. Male participants will be appropriately counseled on risks and must agree to consistently use effective contraception with female sexual partners through the Day 112 study visit to avoid a pregnancy that could be affected by the study drug. Appropriate measures to avoid pregnancy and trial related risks in sexual partners, per the PI s judgment, must be agreed to and practiced.
• •NOTE: Most of the above interventions to prevent pregnancy must be implemented at a particular time in the menstrual cycle, and may not be immediately effective. Trial activity that may pose a reproductive risk may NOT occur until the above contraceptive measures are fully effective and must continue until at least 12 weeks after the last BMSC infusion.
• •4. Have a diagnosis of CD or UC that has been endoscopically or radiographically confirmed at least 6 months prior to screening.
• •5. Have either active CD symptoms as defined by a CDAI score between 220 and 450, inclusive, as measured for 7 consecutive days during screening, or active UC as defined by a SCCAI score greater than or equal to 6.
• •6. The patient must have demonstrated an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents as defined below:
• •* Corticosteroids
• •* Signs and symptoms of persistently active disease despite a history of at least one 4-week induction regimen that included a dose equivalent to prednisone 30 mg daily orally for 2 weeks or intravenously for 1 week OR
• •* Two failed attempts to taper corticosteroids to below a dose equivalent to prednisone 10 mg daily orally on 2 separate occasions OR
• •* History of intolerance of corticosteroids (including, but not limited to Cushing s syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, infection)
• •* Immunomodulators
• •* Signs and symptoms of persistently active disease despite a history of at least one 8 week regimen of oral azathioprine (greater than or equal to 1.5 mg/kg) or 6-mercaptopurine mg/kg (greater than or equal to 0.75 mg/kg) OR
• •* Signs and symptoms of persistently active disease despite a history of at least one 8 week regimen of methotrexate (greater than or equal to 12.5 mg/week) OR
• •* History of intolerance of at least one immunomodulator (including, but not limited to nausea/vomiting, abdominal pain, pancreatitis, LFT abnormalities, lymphopenia, TPMT genetic mutation, infection)
• •* TNF alpha antagonists
• •* Signs and symptoms of persistently active disease despite a history of at least one 4 week induction regimen of 1 of the following agents
• •* Infliximab: 5 mg/kg IV, 2 doses at least 2 weeks apart
• •* Adalimumab: one 80 mg SC dose followed by one 40 mg dose at least 2 weeks apart
• •* Certolizumab pegol: 400 mg SC, 2 doses at least 2 weeks apart OR
• •* Recurrence of symptoms during scheduled maintenance dosing following prior clinical benefit (discontinuation despite clinical benefit does not qualify) OR
• •* History of intolerance of at least 1 TNF antagonist (including, but not limited to infusion-related reaction, demyelination, congestive heart failure, infection)
• •7. May be receiving a therapeutic dose of the following drugs:
• •* Oral 5-ASA compounds provided that the dose has been stable for the 2 weeks immediately prior to enrollment
• •* Oral corticosteroid therapy (prednisone at a stable dose less than or equal to 30 mg/day, budesonide at a stable dose less than or equal to 9 mg/day, or equivalent steroid) provided that the dose has been stable for the 4 weeks immediately prior to enrollment if corticosteroids have just been initiated, or for the 2 weeks immediately prior to enrollment if corticosteroids are being tapered
• •* Probiotics (e.g., Culturelle, Saccharomyces boulardii) provided that the dose has been stable for the 2 weeks immediately prior to enrollment
• •* Antidiarrheals (e.g., loperamide, diphenoxylate with atropine) for control of chronic diarrhea
• •* Azathioprine or 6-mercaptopurine provided that the dose has been stable for the 8 weeks immediately prior to enrollment
• •* Methotrexate provided that the dose has been stable for the 8 weeks immediately prior to enrollment
• •* Antibiotics used for the treatment of CD (i.e., ciprofloxacin, metronidazole) provided that the dose has been stable for the 2 weeks immediately prior to enrollment
• •8. Subjects must agree to have samples of their blood and tissue samples stored for potential future research use.
• •9. Be willing to take appropriate measures to avoid pregnancy until at least 12 weeks after the last BMSC infusion. All subjects will be informed of the potential risks of BMSC during pregnancy and counseled on pregnancy avoidance appropriate to the subject s circumstances (e.g. fertility status, medical contraindications to hormonal birth control, and/or personal or religious beliefs regarding pregnancy avoidance). Subject to thejudgement and discretion of the PI, some subjects may not need to take pregnancy avoidance measures.
• •10. Subjects must have a primary medical care provider.