Clinical Trials

Subjects are eligible to be included in the study only if all the following criteria apply:

Disease Characteristics

Inclusion Criteria:

• Clinical diagnosis of MS with evidence of PPMS or SPMS according to 2025 McDonald criteria.

• EDSS range ≥ 2.5 to ≤ 6.5.

• Evidence of clinical disability progression within 2 years prior to enrollment as determined by one of the following:

  • Progression of EDSS of at least 1.0-point increase sustained for at least 6 months if inclusion EDSS is from 2.5 to 5.5 or at least 0.5-point increase sustained for at least 6 months if inclusion EDSS is from 6.0 to 6.5; or

  • Increase of T25-FW by at least 20% sustained for at least 6 months; or

  • Other well-documented objective worsening despite at least 1 year of prior treatment for progressive forms of MS (including S1P receptor modulators and/or anti-B-lymphocyte antigen [CD20] mAb, e.g., ocrelizumab).

• Documented presence of CSF-restricted OCBs and/or elevated IgG index and/or κ free light chain (centrally confirmed at screening).

Baseline Characteristics

• Males and females ≥ 18 and ≤ 65 years of age at time of consent.

• Evidence of adequate organ function as determined by all of the following:

  • Hemoglobin > 8 g/dL.

  • Platelet count > 50,000/μL.

  • ANC > 1,000/ μL (prior growth factor support is permitted but must be without support within 7 days prior to the laboratory test).

  • ALC > 500/μL.

  • Immunoglobulin G (IgG) > 600 mg/dL.

  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2 × upper limit

  • of normal (ULN).

  • Total bilirubin ≤ 1.5 mg/dL (not applicable for subjects with Gilbert's syndrome).

  • Estimated glomerular filtration rate (eGFR) > 45 mL/min/1.73 m2, measured by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 2021) equation or by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula.

• Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and prior to any study treatment. Refer to Section 12.3, Appendix 3 for the definition of WOCBP.

• Contraceptive use by subjects and subjects’ partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies (refer to Section 12.3, Appendix 3 for details on contraceptive guidance).

  • WOCBP, or male subjects with partners of childbearing potential, must agree to use a highly effective method of birth control (failure rate of < 1% per year when used consistently and correctly) from the time of signing the ICF until 12 months after the TRX319 infusion.

  • Women must refrain from donating eggs, and male subjects must refrain from donating sperm, during this same period.

Informed Consent

• Subjects must be able to understand, consent, and be willing and able to complete all specified procedures and visits.

Other Inclusion Criteria

• Positive varicella zoster virus titer. Subjects who test seronegative for varicella zoster virus IgG antibodies need to complete vaccination ≥ 4 weeks prior to TRX319 infusion.

• Subjects must be willing to refrain from donating blood for 1 year after TRX319 infusion.

Exclusion Criteria:

Disease Characteristics

• 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/Concomitant Therapy

• 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.

Medical Conditions/Other Exclusion Criteria

• 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.

  • Subjects should be up to date on recommended vaccinations, including against varicella zoster, coronavirus disease of 2019 (COVID-19)/ severe acute respiratory syndrome (SARS), and coronavirus 2 (CoV-2), per Centers for Disease Control and Prevention or institutional guidelines for immune-compromised individuals.

• Serologic status reflecting active hepatitis B or C infection.

  • Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. PCR positive subjects will be excluded.

  • Subjects who are positive for hepatitis B core antibody will be required to remain on appropriate prophylactic antiviral therapy (e.g., with entecavir) for the duration of the study. These patients will be regularly monitored throughout the study for HBV DNA by PCR as part of clinically indicated Infectious Disease Monitoring.

• 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 (defined by skin reaction and interferon-gamma [IFN] production) without a negative chest X-ray that shows no evidence of active tuberculosis. CDC-recommended treatment for latent tuberculosis should be initiated at least 4 weeks prior to TRX319 dosing (https://www.cdc.gov/tb/topic/treatment/pdf/LTBITreatmentRegimens. pdf).

• Primary immunodeficiency as defined by a known genetic disorder.

• History of splenectomy.

• Impaired cardiac function or clinically significant cardiac disease including:

  • Unstable angina or myocardial infarction or coronary artery bypass graft within 6 months prior to treatment with TRX319.

  • Stage III or IV congestive heart failure.

  • History of clinically significant cardiac arrhythmia (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular block, or QT prolongation.

  • Inadequate cardiac function defined as left ventricular ejection fraction (LVEF) < 40% as assessed by echocardiogram within 12 weeks of screening. Repeat testing may occur at Investigator's discretion.

• Previous or concurrent malignancy with the following exceptions: a. Adequately treated basal cell or squamous cell carcinoma of the skin (adequate wound healing is required prior to screening). b. In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening. c. A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 5 years prior to screening.

• Prior organ transplant, or allogeneic hematopoietic stem cell transplantation or recipient of peripheral blood products < 3 years prior to TRX319 infusion.

• Major surgery within 4 weeks prior or planned within 4 weeks after TRX319 administration. For surgery planned after 4 weeks post TRX319 administration, discuss with the Investigator.

• History of any other neurologic disorder or medical condition the Investigator considers would increase the risk for the participant, including seizure disorders

• Life-threatening allergies, hypersensitivity, or documented intolerance to TRX319 drug product excipients.

• Pregnant or breastfeeding or planning to become pregnant or breastfeed from the time of signing the ICF until 12 months after the TRX319 infusion.

• 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, such as:

  • Active, uncontrolled, viral, bacterial, or systemic fungal infection.

  • Chronic viral, bacterial, or systemic fungal infection that may be reactivated during treatment.

  • Requirement of supplemental oxygen to maintain oxygen saturation.

  • Clinical evidence of dementia.

  • A thromboembolic event within 6 months prior to TRX319 infusion.

  • Uncontrolled diabetes mellitus or uncontrolled hypertension.

  • Any other uncontrolled medical condition per Investigator judgement.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 12/3/2025. Questions regarding updates should be directed to the study team contact.