A Phase 1/2 Study to Evaluate TRX319 in Subjects with Progressive Multiple Sclerosis
Study Description
The goal of this clinical trial is to treat male and female participants with two types of Multiple Sclerosis (MS) called primary progressive or secondary progressive MS.
The main questions the trial aims to answer are the following:
Is TRX319 safe when administered to patients with progressive forms of MS?
At what dose does TRX319 work the best to treat participants with primary and or secondary progressive MS?
Is pre-conditioning (with Bendamustine) needed to allow TRX319 to better treat participants with primary and/or secondary progressive MS?
Participants will be asked to be on study for up 1 year and may receive up to 3 total administrations of TRX319. While on study, participants will have blood tests and other assessments (MRI scans and lumbar punctures) done to understand the safety of TRX319 and how it may benefit their multiple sclerosis.
Eligibility
INCLUSION CRITERIA
Age 18-65 at the time of consent.
Diagnosed with primary progressive MS (PPMS) or secondary progressive MS (SPMS) according to the 2025 McDonald criteria.
Disability score (EDSS) of 2.5-6.5.
Evidence that MS-related disability has worsened within the past 2 years.
Spinal fluid testing shows at least one required marker: oligoclonal bands found only in spinal fluid, an elevated IgG index, or kappa free light chains.
Adequate organ function based on study testing.
Negative pregnancy test at screening for participants who can become pregnant.
All participants must follow study contraception requirements.
Able to understand the study, provide informed consent, and complete all required procedures and visits.
Blood testing shows antibodies to varicella zoster virus, which causes chickenpox and shingles. Participants without these antibodies must complete vaccination at least 4 weeks before the TRX319 infusion.
Willing to avoid donating blood for 1 year after the TRX319 infusion.
EXCLUSION CRITERIA
MS is clinically stable while taking disease-modifying treatment.
An MS relapse within the year before study entry.
Another disease could explain the first episode of damage to the protective covering of nerves, including a positive aquaporin-4 IgG or MOG-IgG antibody test.
Previous CAR-T treatment or gene therapy directed at any target.
Treatment with mitoxantrone, cladribine, other chemotherapy, or alemtuzumab within 2 years before TRX319.
Treatment with a CD20-depleting antibody within 3 months, or a BTK inhibitor or S1P modulator within 1 month, before TRX319.
Received or plans to receive a live, weakened vaccine within 4 weeks before TRX319, or another vaccine within 2 weeks before TRX319.
Blood tests showing active hepatitis B or C infection, or a positive HIV test.
History of progressive multifocal leukoencephalopathy (PML), a serious brain infection.
Untreated active tuberculosis (TB), latent TB, or previously treated active TB without a chest X-ray confirming no active disease.
An inherited disorder causing an immune deficiency.
Previous removal of the spleen.
Reduced heart function or significant heart disease.
Current or previous cancer.
Previous organ transplant or donor stem cell transplant, or receipt of peripheral blood products within 3 years before TRX319.
Major surgery within 4 weeks before TRX319, or planned within 4 weeks afterward.
Another neurological disorder or medical condition that the study doctor believes would increase risk, including a seizure disorder.
Life-threatening allergy, hypersensitivity, or documented intolerance to ingredients in TRX319.
Pregnant, breastfeeding, or planning to become pregnant during the study. Participants must agree to use highly effective contraception.
Any serious or uncontrolled medical condition that the study doctor believes would make participation unsafe, interfere with study procedures or results, or prevent following study requirements.
This is a summary. The study team will review all detailed eligibility requirements.
