Treatment of Participants With Primary or Secondary Progressive Multiple Sclerosis

NCT07477639 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TRX319-01
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Primary Progressive Multiple Sclerosis; Secondary Progressive Multiple Sclerosis (SPMS); Multiple Sclerosis; Multiple Sclerosis (MS) Primary Progressive; Multiple Sclerosis (MS) Secondary Progressive

Keywords

TRX319-01; IMPACT-MS; Tr1X; Multiple Sclerosis; MS; Autoimmune; Impact MS; PPMS; SPMS; Primary Progressive; Secondary Progressive

Outcome Measures

Primary Outcomes (1)

• 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

  From baseline until 12 months post TRX319 Infusion

Secondary Outcomes (3)

• To characterize target engagement via reduction of Oligoclonal bands (OCB) and/or normalization of cerebral spinal fluid (CSF) Immunoglobulin G (IgG) index

  From baseline until 12 months post TRX319 Infusion

• To evaluate the effects of TRX319 on disease progression/reactivation by gadolinium-enhancing MRI

  From baseline until 12 months post TRX319 Infusion

• To evaluate disease response, as measured by the Neurostatus Expanded Disability Status Scale (EDSS)

  From baseline to approximately 12 months post TRX319 infusion

Study Arms (6)

Cohort 1

EXPERIMENTAL

Dose Level 1

Biological: TRX319

Cohort 1A

EXPERIMENTAL

Dose Level 1 with pre-conditioning

Biological: TRX319; Drug: Bendamustine

Cohort 2

EXPERIMENTAL

Dose level 2

Biological: TRX319

Cohort 2A

EXPERIMENTAL

Dose Level 2 with pre-conditioning

Biological: TRX319; Drug: Bendamustine

Cohort 3

EXPERIMENTAL

Dose Level 3

Biological: TRX319

Cohort 3A

EXPERIMENTAL

Dose level 3 with pre-conditioning

Biological: TRX319; Drug: Bendamustine

Interventions

TRX319 BIOLOGICAL

TRX319 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.

Cohort 1; Cohort 1A; Cohort 2; Cohort 2A; Cohort 3; Cohort 3A

Bendamustine DRUG

Administration of bendamustine prior to TRX319 infusion

Cohort 1A; Cohort 2A; Cohort 3A

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Prior treatment with mitoxantrone, cladribine (or other chemotherapies), or alemtuzumab within 2 years prior to TRX319 dose.
• 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.
• 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.
• Serologic status reflecting active hepatitis B or C infection.
• Positive serology for human immunodeficiency virus (HIV).
• History of progressive multifocal leukoencephalopathy.
• 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.
• Primary immunodeficiency as defined by a known genetic disorder.
• History of splenectomy.
• Impaired cardiac function or clinically significant cardiac disease.
• Previous or concurrent malignancy.

Sponsors & Collaborators

• Tr1X, Inc.: lead

Study Sites (2)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

Washington University, St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis

Interventions

Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Tr1X Clinical Trials

CONTACT

858-283-7879; Tr1xClinicalTrials@Tr1x.bio

Study Team

CONTACT

Tr1xClinicalTrials@Tr1x.bio

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2026
• First Posted: March 17, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)