Treatment of Moderate to Severe Refractory Crohn's Disease

December 3, 2025 updated by: Tr1X, Inc.

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 research study is testing an investigational research product called TRX103 as a possible treatment for individuals suffering from Crohn's Disease (CD). The primary purpose of this study is to learn how safe and effective different doses of TRX103 are when administered to individuals with CD.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Please see our study website at https://www.cdclinicaltrial.com

Study Type

Interventional

Enrollment (Estimated)

39

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Recruiting
        • Mayo Clinic Arizona
        • Contact:
    • California
      • Sacramento, California, United States, 95817
        • Recruiting
        • University of California, Davis
        • Contact:
      • San Francisco, California, United States, 94158
        • Recruiting
        • University of California, San Francisco
        • Contact:
    • Florida
    • Illinois
      • Chicago, Illinois, United States, 60637
      • Chicago, Illinois, United States, 60611
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa
        • Contact:
    • Kentucky
      • Louisville, Kentucky, United States, 40202
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Contact:
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic Rochester
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University in St. Louis
        • Contact:
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Mount Sinai Health Systems
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1
Dose level 1
Biological: TRX103
TRX103 is an investigational research product that may treat and provide long term relief to individuals suffering from Crohn's Disease.
Experimental: Cohort 2
Dose level 2
Biological: TRX103
TRX103 is an investigational research product that may treat and provide long term relief to individuals suffering from Crohn's Disease.
Experimental: Cohort 3
Dose level 3
Biological: TRX103
TRX103 is an investigational research product that may treat and provide long term relief to individuals suffering from Crohn's Disease.
Experimental: Cohort 2A
Dose level 2 with conditioning
Biological: TRX103
TRX103 is an investigational research product that may treat and provide long term relief to individuals suffering from Crohn's Disease.
Drug: Cyclophosphamide
Low dose cyclophosphamide conditioning.
Experimental: Cohort 3A
Dose level 3 with conditioning
Biological: TRX103
TRX103 is an investigational research product that may treat and provide long term relief to individuals suffering from Crohn's Disease.
Drug: Cyclophosphamide
Low dose cyclophosphamide conditioning.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess the safety and tolerability of TRX103 infusion in subjects with moderate to severe treatment-refractory Crohn's Disease.
Time Frame: From baseline until 12 months post TRX103 infusion.

As measured by:

  • Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs), including CD flares (perforations, abscesses).
  • Incidence of infections, either bacterial, fungal or viral.
  • The safety of TRX103 determined by negative Replication Competent Lentivirus (RCL) at approximately 3-months, 6-months, and 12-months.
From baseline until 12 months post TRX103 infusion.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement of CD status.
Time Frame: From baseline to Week 12 post TRX103 infusion.
  • Clinical remission, defined as CD Activity Index (CDAI) ≤ 150 at Week 12.
  • Clinical response, defined as ≥ 100-point reduction in CDAI score from Baseline at Week 12.
  • Proportion of subjects who discontinue corticosteroid use and achieve clinical remission at all subsequent timepoints, in subjects taking corticosteroids at Baseline.
From baseline to Week 12 post TRX103 infusion.
Reduction in Fecal Calprotectin.
Time Frame: From baseline to Week 12 post TRX103 infusion.
  • Change from Baseline in fecal calprotectin at each timepoint.
  • Proportion of subjects with fecal calprotectin < 250 μg/mg at Week 12 or a decrease of 50% from Baseline.
From baseline to Week 12 post TRX103 infusion.
Reduction of highly sensitive C-reactive protein (hs-CRP).
Time Frame: From baseline until 12 months post TRX103 infusion.
Change from Baseline in hs-CRP at each timepoint.
From baseline until 12 months post TRX103 infusion.
Improvement in Patient Reported Outcomes (PRO).
Time Frame: From baseline until 12 months post TRX103 infusion.

Change from Baseline in Health-Related Quality-of-Life (HRQOL) Questionnaires scores:

  • Inflammatory Bowel Disease Questionnaire (IBDQ)
  • EuroQol Group - 5 Dimension - 5 Level (EQ-5D-5L) Questionnaire
From baseline until 12 months post TRX103 infusion.
Pharmacokinetics (PK) of TRX103.
Time Frame: From baseline until 12 months post TRX103 infusion.
TRX103 kinetics post infusion.
From baseline until 12 months post TRX103 infusion.
Level of Inflammation and mucosal damage
Time Frame: From baseline until 12 months post TRX103 infusion.
Change from baseline in histopathological scores by Global Histologic Disease Activity Score (GHAS) and Robarts Histopathology Index (RHI).
From baseline until 12 months post TRX103 infusion.
Improvement in Simple Endoscopic Score for Crohn's Disease (SES-CD Score).
Time Frame: From baseline to Week 12 post TRX103 infusion.

Endoscopic remission defined as:

- Participants with ileocolonic or isolated ileal CD: SES-CD ≤ 4 points and no sub-score > 1 point in any individual variable, as scored by central reviewer at Week 12.

OR

- Participants with isolated ileal disease: SES-CD of 0 - 2 points, as scored by central reviewer at Week 12.

Endoscopic response, defined as: Decrease in SES-CD ≥ 50% from Baseline at Week 12.
From baseline to Week 12 post TRX103 infusion.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tr1X, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 5, 2025

Primary Completion (Estimated)

January 30, 2026

Study Completion (Estimated)

January 30, 2027

Study Registration Dates

First Submitted

November 25, 2024

First Submitted That Met QC Criteria

December 3, 2024

First Posted (Actual)

December 6, 2024

Study Record Updates

Last Update Posted (Actual)

December 10, 2025

Last Update Submitted That Met QC Criteria

December 3, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRX103-02
  • RESTORE Study (Other Identifier: Tr1X, Inc.)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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