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

Plain English Summary

Treatment of Participants With Primary or Secondary Progressive Multiple Sclerosis is a Phase 2 clinical trial sponsored by Tr1X, Inc. studying Primary Progressive Multiple Sclerosis, Secondary Progressive Multiple Sclerosis (SPMS), Multiple Sclerosis, Multiple Sclerosis (MS) Primary Progressive, Multiple Sclerosis (MS) Secondary Progressive. This trial is testing a new treatment called TRX319 for people with primary or secondary progressive Multiple Sclerosis (MS). It is for individuals aged 18-65 with a confirmed diagnosis of progressive MS who have shown signs of worsening disability. Participants will receive up to three doses of TRX319, potentially after a pre-treatment with Bendamustine, and will undergo blood tests, MRI scans, and lumbar punctures for about a year. Alternative treatments for progressive MS are limited, with current options focusing on managing symptoms or slowing progression rather than reversing disability. The trial aims to enroll 39 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are between 18 and 65 years old and have been diagnosed with primary or secondary progressive MS. You must have experienced worsening disability in the last two years and have specific markers in your spinal fluid. You cannot join if you have had a recent MS relapse, certain other neurological conditions, or have received specific prior treatments like CAR-T therapy or certain MS medications recently. You must have a positive test for the chickenpox virus or be vaccinated at least 4 weeks before treatment. This trial is studying Primary Progressive Multiple Sclerosis, Secondary Progressive Multiple Sclerosis (SPMS), Multiple Sclerosis, Multiple Sclerosis (MS) Primary Progressive, Multiple Sclerosis (MS) Secondary Progressive, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how safe and well-tolerated TRX319 is, meaning it will assess if the treatment causes any serious problems and if patients can handle it. The specific primary outcome measures are: To assess the safety and tolerability of TRX319 infusion in subjects with Primary Progressive or Secondary Progressive Multiple Sclerosis. (From baseline until 12 months post TRX319 Infusion). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a significant unmet need for effective treatments for progressive forms of Multiple Sclerosis, which currently have limited therapeutic options. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Primary Progressive Multiple Sclerosis, Secondary Progressive Multiple Sclerosis (SPMS), Multiple Sclerosis, Multiple Sclerosis (MS) Primary Progressive, Multiple Sclerosis (MS) Secondary Progressive, where improved treatment options are needed.

Investor Insight

This trial represents an early-stage investment in a novel cell therapy for a large patient population with progressive MS, indicating potential for a significant market if successful. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if TRX319 is appropriate for your specific type of MS and if the potential benefits outweigh the risks. Understand that participation involves regular visits for tests, including blood draws, MRIs, and spinal taps, over approximately one year. Be prepared for potential side effects and the possibility of receiving pre-treatment with Bendamustine before TRX319. This trial is currently recruiting participants. The trial is being conducted at 2 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 39 participants

Interventions

• BIOLOGICAL: TRX319 — 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.
• DRUG: Bendamustine — Administration of bendamustine prior to TRX319 infusion

Primary Outcomes

• To assess the safety and tolerability of TRX319 infusion in subjects with Primary Progressive or Secondary Progressive Multiple Sclerosis. (From baseline until 12 months post TRX319 Infusion)

Secondary Outcomes

• 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)

Full 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.

Trial Locations

• University of Kansas Medical Center, Kansas City, Kansas, United States
• Washington University, St. Louis, St Louis, Missouri, United States

Frequently Asked Questions

Related Conditions

• Multiple Sclerosis
• Primary Progressive Multiple Sclerosis
• Secondary Progressive Multiple Sclerosis
• Relapsing-Remitting Multiple Sclerosis (as a comparator for disease progression)
• Neuromyelitis Optica Spectrum Disorder (as a differential diagnosis)
• Autoimmune Encephalitis
• Leukodystrophies
• Neuroinflammation
• Demyelinating Diseases
• Central Nervous System Disorders

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