New treatment for moderate to severe Crohn's Disease

A Phase 1/2a, Open Label, Dose Escalation Study to Evaluate the Safety and Preliminary Efficacy of TRX103 in Subjects With Moderate to Severe Treatment-Refractory Crohn's Disease

This study is testing a new treatment called TRX103, combined with another medication, to see if it can help people with moderate to severe Crohn's Disease feel better and reduce their symptoms.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Tr1X, Inc. (industry)
• Drugs / interventions: prednisone
• Locations: 13 sites (Scottsdale, Arizona and 12 other locations)
• Trial ID: NCT06721962 on ClinicalTrials.gov

What this trial studies

This clinical trial is evaluating the safety and effectiveness of an investigational product called TRX103 for individuals with moderate to severe refractory Crohn's Disease. Participants will receive different doses of TRX103, along with Cyclophosphamide, to assess how well these treatments work in managing their condition. The study aims to gather data on the drug's impact on bowel inflammation and overall disease symptoms. Eligible participants must have a documented history of Crohn's Disease and meet specific clinical criteria.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 with moderate to severe active Crohn's Disease and specific clinical indicators of inflammation.

Not a fit: Patients with mild Crohn's Disease or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new option for patients suffering from difficult-to-treat Crohn's Disease.

How similar studies have performed: Other studies have shown promise in treating Crohn's Disease with novel approaches, but the specific use of TRX103 is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Male and females ≥ 18 and ≤ 65 years of age at time of consent.
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 for ilealcolonic or ≥ 4 isolated ileal disease by central reader)
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;
   * CDAI 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 Failure of therapies are defined as either non-response (primary failure), complete loss of response (secondary failure) or intolerant to therapy at a dose indicated for CD.
   * Primary failure is defined as:

     * When a subject does not achieve a response after having received the induction doses of a CD approved drug per prescribing information. Induction period is defined as 12-weeks.
     * A response is defined as CDAI score that reduces by ≥ 100-point from Baseline or by Physician assessment.
   * Secondary failure, or relapse defined as:

     * Subjects who respond to the therapy or achieves remission after an induction regimen per prescribing information, but subsequently lose response or relapses during maintenance treatment.
     * Relapse is defined as an increase in the CDAI score from maintenance of ≥ 100 points and a CDAI score \> 220, and/or SES-CD score ≥ 6 (or ≥ 4 if isolated ileal disease) or by Physician assessment.
   * Intolerant to therapy, defined as:

     * When a subject is unable to cope with the side effects or mechanism of actions of the treatment and/or experiences unacceptable side effects when dosed at appropriate therapeutic levels.
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.

Exclusion Criteria:

1. Prior organ transplant, or allogeneic bone marrow, peripheral blood, or cord blood stem cell transplant. Note: Blood transfusion are not exclusionary if it occurred ≥ 3 years (- 3 months) of TRX103 infusion.
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.
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) - abscess with no evidence of pus when pressed upon are permitted,
    * impassable fibrotic strictures - Patients with strictures passable by dilation are permitted,
    * symptomatic bowel strictures - must be confirmed via endoscopy and/or radiologically,
    * fulminant colitis,
    * toxic megacolon,
    * ostomy or ileoanal pouch - previous temporary ostomy pouch, followed by a reversal is permitted,
    * 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. Note: Surgery for temporary use of an ostomy bag or reconnection of the gut post colostomy use is not considered exclusionary, nor considered as part of the surgical resection if during the reconnection removal of tissue is required to facilitate reattachment.
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 or by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation \< 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.

Where this trial is running

Scottsdale, Arizona and 12 other locations

• Mayo Clinic Arizona — Scottsdale, Arizona, United States (RECRUITING)
• University of California, Davis — Sacramento, California, United States (RECRUITING)
• University of California, San Francisco — San Francisco, California, United States (RECRUITING)
• University of Florida — Gainesville, Florida, United States (RECRUITING)
• Northwestern — Chicago, Illinois, United States (RECRUITING)
• University of Chicago — Chicago, Illinois, United States (RECRUITING)
• University of Iowa — Iowa City, Iowa, United States (RECRUITING)
• University of Louisville — Louisville, Kentucky, United States (RECRUITING)
• University of Michigan — Ann Arbor, Michigan, United States (RECRUITING)
• Mayo Clinic Rochester — Rochester, Minnesota, United States (RECRUITING)
• Washington University in St. Louis — St Louis, Missouri, United States (RECRUITING)
• Mount Sinai Health Systems — New York, New York, United States (RECRUITING)
• Cleveland Clinic — Cleveland, Ohio, United States (RECRUITING)

Study contacts

• Study coordinator: Tr1X Clinical Trials Tr1X Clinical Trials

Conditions: Crohns Disease, Tr1X, RESTORE, Crohns, autoimmune, IBD, CD, chronic inflammation