TRX319 treatment for people with primary or secondary progressive multiple sclerosis

A Phase 1/2a, Open-Label, Dose-Escalation Study to Evaluate the Safety and Preliminary Efficacy of TRX319 in Subjects With Primary or Secondary Progressive Multiple Sclerosis

This trial will test whether the experimental therapy TRX319, given with or without a short bendamustine pre-conditioning, is safe and can slow or improve disability in adults with primary or secondary progressive MS.

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: alemtuzumab, CAR-T
• Locations: 2 sites (Kansas City, Kansas and 1 other locations)
• Trial ID: NCT07477639 on ClinicalTrials.gov

What this trial studies

This phase 1/2 trial will enroll adults with primary or secondary progressive MS who meet criteria including EDSS 2.5–6.5, recent clinical progression, and CSF markers of immune activity. Participants may receive up to three administrations of TRX319 over a one-year period, with some randomized or assigned to receive bendamustine pre-conditioning to see if it enhances treatment effect. Safety, optimal dose, and biological activity will be monitored using blood tests, MRI scans, and lumbar punctures. The trial is being conducted at the University of Kansas Medical Center and Washington University in St. Louis.

Who should consider this trial

Good fit: Ideal candidates are adults 18–65 with clinically diagnosed primary or secondary progressive MS, EDSS 2.5–6.5, documented recent progression, and CSF evidence of intrathecal immune activity who can complete MRI and lumbar puncture procedures.

Not a fit: People with relapsing-only MS, EDSS scores outside 2.5–6.5, lacking the required CSF findings, or with contraindications to bendamustine or study procedures are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, TRX319 could provide a new option to slow or reduce disability progression in people with progressive MS.

How similar studies have performed: Early-phase immune-modulating and cell-based approaches for progressive MS have shown mixed results and no definitive cure, so this approach is experimental but builds on prior immunotherapy research.

Eligibility criteria

Inclusion Criteria:

1. Clinical diagnosis of MS with evidence of PPMS or SPMS according to 2025 McDonald criteria.
2. Expanded Disability Status Scale (EDSS) range ≥ 2.5 to ≤ 6.5.
3. Evidence of clinical disability progression within 2 years prior to enrollment.
4. Documented presence of CSF-restricted OCBs and/or elevated IgG index and/or κ free light chain.
5. Males and females ≥ 18 and ≤ 65 years of age at time of consent.
6. Evidence of adequate organ function
7. Women of child bearing potential have a negative pregnancy test at screening.
8. Contraceptive use by all participants while on study.
9. Participants must be able to understand, consent, and be willing and able to complete all specified procedures and visits.
10. Positive varicella zoster virus titer. Participants who test seronegative for varicella zoster virus IgG antibodies need to complete vaccination ≥ 4 weeks prior to TRX319 infusion.
11. Participants must be willing to refrain from donating blood for 1 year after TRX319 infusion.

Exclusion Criteria:

1. MS clinical stability on disease modifying therapy.
2. Clinical relapse of MS in the 1 year prior to study entry.
3. Diseases other than MS to explain the first demyelinating event, including aquaporin 4 IgG or myelin oligodendrocyte glycoprotein-IgG seropositivity.
4. Prior treatment with CAR-T or gene therapy product directed at any target.
5. Prior treatment with mitoxantrone, cladribine (or other chemotherapies), or alemtuzumab within 2 years prior to TRX319 dose.
6. Prior treatment with CD20-depleting antibodies within 3 months and prior treatment with Bruton's tyrosine kinase inhibitor (BTKi) and sphingosine 1 phosphate (S1P) modulators within 1 month of TRX319 dose.
7. Plan to or have received live, attenuated vaccines less than 4 weeks (28 days) prior to TRX319 infusion, and other vaccines less than 2 weeks (14 days) prior to TRX319 infusion.
8. Serologic status reflecting active hepatitis B or C infection.
9. Positive serology for human immunodeficiency virus (HIV).
10. History of progressive multifocal leukoencephalopathy.
11. Untreated active, or active with documented completed treatment but without a negative chest X-ray that shows no evidence of active tuberculosis, or latent tuberculosis.
12. Primary immunodeficiency as defined by a known genetic disorder.
13. History of splenectomy.
14. Impaired cardiac function or clinically significant cardiac disease.
15. Previous or concurrent malignancy.
16. Prior organ transplant, or allogeneic hematopoietic stem cell transplantation or recipient of peripheral blood products \< 3 years prior to TRX319 infusion.
17. Major surgery within 4 weeks prior or planned within 4 weeks after TRX319 administration.
18. History of any other neurologic disorder or medical condition the Investigator considers would increase the risk for the participant, including seizure disorders.
19. Life-threatening allergies, hypersensitivity, or documented intolerance to TRX319 drug product excipients.
20. Subjects that are pregnant, breast feeding or aim to become pregnant during the study period (Subjects must agree to use a highly effective method of contraception).
21. Serious and/or uncontrolled medical condition that, in the Investigator's judgment, would cause unacceptable safety risk, interfere with study procedures or results, or compromise compliance with the protocol.

Where this trial is running

Kansas City, Kansas and 1 other locations

• University of Kansas Medical Center — Kansas City, Kansas, United States (RECRUITING)
• Washington University, St. Louis — St Louis, Missouri, United States (RECRUITING)

Study contacts

• Study coordinator: Tr1X Clinical Trials

Conditions: Primary Progressive Multiple Sclerosis, Secondary Progressive Multiple Sclerosis, Multiple Sclerosis, Multiple Sclerosis Primary Progressive, Multiple Sclerosis Secondary Progressive, TRX319-01, IMPACT-MS, Tr1X