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.
MS clinical stability on disease modifying therapy.
Clinical relapse of MS in the 1 year prior to study entry.
Diseases other than MS to explain the first demyelinating event, including aquaporin 4 IgG or myelin oligodendrocyte glycoprotein-IgG seropositivity.
Prior treatment with CAR-T or gene therapy product directed at any target.
Sequential
TRX319
Biological/VaccineTRX319 is an investigational research cell therapy that may treat and provide long term relief to individuals suffering from Primary Progressive Multiple Sclerosis and/or Secondary Progressive Multiple Sclerosis.
Bendamustine
DrugAdministration of bendamustine prior to TRX319 infusion
6
Treatment groupsSee each treatment group below.
To assess the safety and tolerability of TRX319 infusion in subjects with Primary Progressive or Secondary Progressive Multiple Sclerosis.
* Number of participants with severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) * Rate of Adverse Events of Special Interest (AESIs) in participants * The safety of TRX319 determined by negative Replication Competent Lentivirus (RCL) at approximately 3-months, 6-months, and 12-months
To characterize target engagement via reduction of Oligoclonal bands (OCB) and/or normalization of cerebral spinal fluid (CSF) Immunoglobulin G (IgG) index
* Reduction of OCB in CSF * Reduction and/or normalization of CSF IgG index
To evaluate the effects of TRX319 on disease progression/reactivation by gadolinium-enhancing MRI
No increase in gadolinium-enhanced T1-weighted lesions and no new or enlarging T1- or T2-weighted lesions in brain and cervical spinal cord
To evaluate disease response, as measured by the Neurostatus Expanded Disability Status Scale (EDSS)
Measure of disease response based on change in disability and walking score at Weeks 12, 24, 36, and 48.
