∙ Are 18 to 65 years of age, inclusive, at enrollment date.

‣ Have a diagnosis of CD that has been endoscopically or radiographically confirmed. A colonoscopy will be required at baseline to document mucosal disease activity. SES-CD will be obtained with minimum score of 7.

‣ Have active CD symptoms as defined by a CDAI score between 220 and 350 and demonstrate active symptoms as defined by continued weight loss, abdominal pain and/or diarrhea not controlled by standard therapy.

‣ The participant must have active CD symptoms and therefore have had an inadequate response to, loss of response to, or intolerance to at least 1 of the following agent groups in control of their disease (as defined below for each individual agent group: Corticosteroids or Immunomodulators or TNF-alpha sign antagonists or Anti-integrin antibodies)

∙ a. Corticosteroids

∙ i. 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 greater than or equal to 30 mg PO once daily (QD) for 2 weeks or intravenously (IV) for 1 week OR

∙ ii. One failed attempt to taper corticosteroids to below a dose equivalent to prednisone 10 mg PO QD or to taper to below a dose

∙ of 9 mg of budesonide OR

∙ iii. History of intolerance of corticosteroids at the discretion of the principal investigator (PI) (including but not limited to Cushing s

∙ syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, or infection)

∙ b. Immunomodulators

∙ i. Signs and symptoms of persistently active disease despite a history of at least one 12-week regimen of oral azathioprine (AZA) (greater than or equal to 2.5 mg/kg/Day) or 6-MP (greater than or equal to 1.5 mg/kg/Day) OR

∙ ii. Signs and symptoms of persistently active disease despite a history of at least one 12-week regimen of MTX (greater than or equal to 25 mg/week) OR

∙ iii. History of intolerance of at least one immunomodulator (including but not limited to nausea/vomiting leading to discontinuation,

∙ abdominal pain, pancreatitis, liver function test abnormalities, lymphopenia, thiopurine methyltransferase genetic mutation, or

∙ serious infection)

∙ c. TNF-alpha sign antagonists with signs and symptoms of persistently active disease despite a history of receiving infliximab, adalimumab, or certolizumab at a dose approved for the treatment of CD and:

∙ i. Patient had an inadequate response after completing the full induction regimen, per approved product labeling

∙ ii. Responded initially but then lost response with continued therapy

∙ iii. Patient had a significant adverse event response which precluded further use including but not exclusion of infusion reaction, serum

∙ sickness and/or lupus-like rash.

∙ d. Anti-integrin antibodies: with signs and symptoms of persistently active disease despite a history of receiving an anti-integrin antibody agent (natalizumab or vedolizumab) at a dose approved for the treatment of CD and:

∙ i. Patient had an inadequate response after completing the full induction regimen, per approved product labeling

∙ ii. Responded initially but then lost response with continued therapy

∙ iii. Patient had a significant adverse event response which precluded further use including but not exclusion of infusion reaction, serum

∙ sickness and/or lupus-like reaction.

‣ At the discretion of the PI, concomitant medications will be permitted if the following conditions are met prior to baseline assessment (Day-1):

∙ a. 5-aminosalicylic acid (ASA)-based compounds are permissible if:

∙ i. Oral 5-ASA-based compounds must be at a stable dose for at least 3 weeks prior to baseline or

∙ ii. Recently discontinued oral 5-ASA-based compounds must have been discontinued at least 3 weeks prior to baseline or

∙ iii. Rectal 5-ASA-based compounds are not permissible during the study and must have been discontinued at least 3 weeks prior to baseline.

∙ b. Corticosteroids (e.g., prednisone, budesonide) are permissible if:

∙ i. Oral corticosteroids must be at a prednisone-equivalent dose of less than or equal to 40 mg/day, or 9 mg/day of budesonide, and have been at a stable dose for at least 3 weeks prior to baseline or

∙ ii. Discontinuation of oral corticosteroids must have been completed at least 3 weeks prior to baseline or

∙ iii. Parenteral (subcutaneous, intramuscular, or IV) or rectal corticosteroids are not permitted during the study and must not have been used within a 3-week period prior to baseline

∙ c. CD-specific antibiotics are permissible if using an antibiotic for treatment of CD ( a CD-specific antibiotic i.e., metronidazole, ciprofloxacin, rifaximin, ampicillin, sulfonamide and tetracycline)

∙ i. Participants must have been using the antibiotic for at least 3 weeks before baseline at a stable dose or

∙ ii. If not currently using a CD-specific antibiotic, the stop date must have been at least 3 weeks prior to baseline.

∙ d. Immunomodulators are permissible if:

∙ i. Participants receiving chronic (i.e., greater than or equal to 12 weeks) treatment with AZA, 6-MP, or MTX prior to baseline must be on a stable dose for at least 6- 8 weeks prior to baseline and must continue on this same dose during the study. OR

∙ ii. Participants who have discontinued therapy with AZA, 6-MP, or MTX must have stopped the medication at least 4 weeks prior to baseline. OR

∙ iii. Participants must not have received therapy with other known immunomodulators (e.g., cyclosporine, tacrolimus, sirolimus, pentoxifylline, or mycophenolate mofetil) or experimental agents (e.g., granulocyte- or macrophage colony stimulating factor) for at least

• 8 weeks or 5 half-lives of agent from baseline, whichever is longer.

• e. The use of Anti-TNF and Anti-integrin therapy or other biological therapy listed below will not be permitted and the following washout period will be required in order for participant to be eligible:

• i. Three months washout prior to baseline for certolizumab or natalizumab.

• ii. Two months washout prior to baseline for adalimumab, infliximab, and vedolizumab.

• iii. 8 week washout prior to baseline for cyclosporine, pimecrolimus, tacrolimus, and any other systemic immunosuppressant.

• 6\. Participants must agree to have samples of their blood and tissue stored for potential future research use.

• 7\. Participants must have a primary medical care provider.

• 8\. Male participants must agree to employ birth control measures to prevent pregnancy in female partners from start of treatment, and continuing through 3 months post treatment.

• 9\. Females of childbearing potential must not be breast-feeding, possibly or actually pregnant, must not have had unprotected intercourse for one month prior to dosing, and must agree not to become pregnant beginning from enrollment in the study to at least 6 months after the end of treatment. Participants must remain completely abstinent of potentially reproductive sexual intercourse (e.g. due to a committed lifestyle) or to consistently use BOTH a barrier method with a spermicide (male or female condom) AND ALSO one of the below listed methods of birth control:

⁃ Continuous/daily hormonal methods including oral contraceptive pills, patch, implant/injection, etc.

⁃ Surgical sterilization of either partner, of sufficient duration to be effective, and NOT known to have failed.

⁃ Intrauterine device.