Treatment of Moderate to Severe Refractory Crohn's Disease

Eligibility Criteria

• 1. Male and females ≥ 18 and ≤ 65 years of age at time of Screening
• 2. Weight of ≥ 40 kg
• 3. Medical history and biological evidence of active bowel inflammation documented by:
• * Minimum of approximate 1 year of Crohn's disease diagnosis confirmed through Endoscopy, and;
• * Endoscopic evidence of CD diagnosis at least 3 months prior to and/or at Screening (SES-CD ≥ 6 by central reader), and;
• * Highly sensitive C-reactive protein (hs-CRP) \> 5 mg/L at Screening.
• 4. Active disease defined as moderate to severe active CD at Screening defined by all of the following:
• * Evidence of mucosal inflammation, defined as SES-CD ≥ 6 (≥ 4 for subjects with isolated ileal disease), and;
• * Average daily very soft or liquid stool frequency (SF) ≥ 4 and/or average daily abdominal pain (AP) score ≥ 2 (values represent the unweighted daily averages of the corresponding sub-scores from the CDAI and total scores
• * 220).
• 5. Subject on treatment with corticosteroids may be included if they meet the following:
• * prednisone or equivalent dose ≤ 20 mg/day; or
• * budesonide ≤ 9 mg/day; or
• * has been on a stable dose for at least 7 days prior to TRX103 dose.
• 6. Advanced therapy-refractory disease defined by:
• * Failure of two or more advanced approved therapies. Prior therapies may be inclusive of any combination of the following:
• * TNF-alpha inhibitors
• * IL-12/23 inhibitors
• * Anti-integrins
• * JAK inhibitors
• * OR
• * Non-response (primary failure), complete loss of response (secondary failure) or intolerant to therapy at a dose indicated for CD.
• 7. Absence of uncontrolled bacterial, viral, or fungal infection at time of enrollment.
• 8. Subjects must be able to understand and sign informed consent and be willing and able to complete all specified procedures and visits.
• 1. Prior organ transplant, or allogeneic bone marrow, peripheral blood, or cord blood stem cell transplant.
• 2. Received another investigational agent or therapy, within 28 days of planned TRX103 infusion (or 5 half-lives, whichever is longer) and/or have not recovered from treatment related toxicities.
• 3. Received any approved treatment for CD within the designated washout period (including off-label use of approved therapies) as per the protocol (see Table 4).
• 4. Strictures, active fistulae (including perianal), or abscess by computed tomography (CT) or magnetic resonance enterography (MRE) or Endoscopy within 6 months of Screening.
• 5. Positive serology for HIV.
• 6. Positive hepatitis-B surface antigen. Subject may be included if they are HBV PCR negative.
• 7. Hepatitis C virus (HCV RNA detectable in any subject with anti-HCV antibodies).
• 8. Subject with active or chronic recurring infections or untreated latent Tuberculosis (TB).
• 9. Current diagnosis of ulcerative colitis (UC), indeterminate colitis or CD isolated to colon only (the colitis must be related to CD and inclusive of ileal with or without colonic involvement).
• 10. Subjects with the following known complications of Crohn's Disease
• * active diverticulitis,
• * active fistulae or abscess,
• * abscess (abdominal or perianal),
• * impassable fibrotic strictures,
• * symptomatic bowel strictures,
• * fulminant colitis,
• * toxic megacolon,
• * ostomy or ileoanal pouch,
• * diagnosed with short gut or short bowel syndrome,
• * or any other manifestation that might require surgery while enrolled in the study.
• 11. Subject with surgical bowel resection within the past 3 months prior to Screening, or a history of \> 2 bowel resections.
• 12. Subjects that are pregnant, breast feeding, or aim to become pregnant during the 12 month study period. (Subjects, males and females, must agree to use a highly effective method of contraception).
• 13. Screening laboratory and other analyses show any of the following abnormal results:
• * Serum aspartate transaminase or alanine transaminase \> 3.0 × upper limit of normal;
• * Total white blood cell count \< 2,000/μL;
• * Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula \< 40 mL/min/1.73 m2;
• * Hemoglobin \< 8 g/dL;
• * Bilirubin ≥ 2 x ULN;
• * Platelet count \< 100,000/μL;
• * Absolute neutrophil count \< 1,200/μL;
• * Absolute lymphocytes count \< 750/μL.
• 14. Any subject with a history of significant renal, hepatic, pulmonary, or cardiac dysfunction, or on treatment to support cardiac dysfunction.
• 15. Any serious illness, uncontrolled inter-current illness, psychiatric illness, active or uncontrolled infection, or other medical condition or history, including laboratory results, which, in the Investigator's opinion:
• * places the subject at increased risk during participation in the study, and/or;
• * interferes with the subject's capacity to provide informed consent and their participation in the study, and/or;
• * interferes with the interpretation of the results.