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