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Assessing the safety and effects of YTB323 in patients with non-active Progressive Multiple Sclerosis

An Open-label, Multi-center, Phase I/II Study to Assess Safety, Disease Progression, and Cellular Kinetics Following YTB323 Administration in Participants With Non-active Progressive Multiple Sclerosis (PMS)

Phase1; Phase2 Interventional Novartis · NCT06675864

This study is testing a new treatment called YTB323 to see if it is safe for people with non-active Progressive Multiple Sclerosis and how it affects their condition over time.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment28 (estimated)
Ages18 Years to 60 Years
SexAll
SponsorNovartis Industry-sponsored
Locations17 sites (Darlinghurst, New South Wales and 16 other locations)
Trial IDNCT06675864 on ClinicalTrials.gov

What this trial studies

This open-label, multi-center study evaluates the safety, disease progression, and cellular kinetics of YTB323 in 28 participants diagnosed with non-active Progressive Multiple Sclerosis (PMS). Participants will receive a single dose of YTB323, with the possibility of escalating doses based on safety assessments. The study will last for 2 years, followed by a long-term follow-up period of 13 years to monitor ongoing effects. The primary aim is to determine the safety profile of YTB323 in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 60 with a diagnosis of non-active Progressive Multiple Sclerosis and recent evidence of disease progression.

Not a fit: Patients with relapsing multiple sclerosis or active Progressive Multiple Sclerosis may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with non-active Progressive Multiple Sclerosis.

How similar studies have performed: While this approach is novel in the context of non-active Progressive Multiple Sclerosis, similar CAR-T therapies have shown promise in other conditions.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

1. Male or female participants 18 to 60 years (inclusive) at screening.
2. Signed informed consent must be obtained prior to participation in the study.
3. Able to communicate well with the investigator, to understand and comply with the requirements of the study including:

   * Able to undergo lumbar puncture (LP), blood draws, tolerate brain and spinal MRI, and able to participate and tolerate all study procedures at study visits.
4. Diagnosis of SPMS or PPMS according to the 2017 McDonald diagnostic criteria (Thompson et al 2018) as confirmed at screening visit.
5. Less than 15 years (inclusive) from onset of first MS symptoms as determined by the investigator during screening.
6. Ambulatory Patients (EDSS 3 to 6.5 inclusive) at screening.
7. Evidence of recent (within 24 months) disease progression of ≥1.00 on the EDSS scale.
8. No relapse in the last 24 months at screening.
9. No Gd-enhancing lesion on brain or spinal cord MRI at screening.
10. Participants must receive or be current on all recommended vaccinations according to institutional, local, or global guidelines for immunocompromised patients at least 6 weeks prior to lymphodepletion.

Key Exclusion Criteria:

1. Diagnosis of relapsing multiple sclerosis (RMS) or active PMS according to the 2017 revision of the McDonald diagnostic criteria (Thompson et al 2018) at screening.
2. History of, or current, clinically significant CNS disease except MS (e.g. stroke, traumatic brain or spinal injury, history or presence of myelopathy, history of seizures or epilepsy) or neurological disorders which may mimic MS at screening.
3. Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, New York Heart Association Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 6 months prior to or during screening).
4. Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or neurological symptoms consistent with PML prior to or during screening.
5. Clinically significant, active, opportunistic, chronic or recurrent infection (including positive for hepatitis B or hepatitis C) confirmed by clinical evidence, imaging, or positive laboratory tests one month prior to leukapheresis.
6. Have donated blood or experienced a loss of blood \> 400 mL within 3 months prior screening, or longer if required by local regulations.
7. Any prior stem cell therapy or organ transplantation or gene therapy.
8. Any contraindications to LP, including but not limited to:

   * Known or suspected structural abnormality of the lumbar spine that, in the opinion of the Investigator, may interfere with the performance of the LP, or increase the risk of the procedure for the participant.
   * Presence of risk for increased or uncontrolled bleeding (including but not limited to vascular abnormalities or neoplasms at or near the LP site, disorders of the coagulation cascade, platelet function, or platelet count).
   * Participants on anticoagulants (e.g., warfarin) or antiplatelets \[except for low-dose aspirin (100 mg/day or lower) and low-dose nonsteroidal anti-inflammatory drugs such as ibuprofen (600 mg/day or lower) which are allowed\], are not eligible to participate.
9. Not willing or able to have MRI scans as per protocol e.g. due to claustrophobia, or absolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator).
10. Pregnant or nursing (lactating) women.
11. Past surgical history of splenectomy.
12. Evidence of active or latent tuberculosis (TB) infection by QuantiFERON® TB-Gold assay (or equivalent) performed at Screening by central lab. In case of unclear or indeterminate test results, the Investigator should consult with an infectious disease expert to exclude the diagnosis of active or latent TB infection and document this in the source data. Participant should be excluded if they have any signs of active TB observed in available lung imaging (e.g., X-ray or HRCT).
13. Any psychiatric, pulmonary (including, history of or active severe respiratory disease, including Chronic Obstructive Pulmonary Disease, interstitial lung disease or pulmonary fibrosis), renal, hepatic, endocrine, metabolic (e.g. severe hypoproteinemia due to nephrotic syndrome), hematological disorders or gastrointestinal disease that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant, prior to or during screening.
14. Grade 2 or higher thromboembolic event in the past 4 weeks prior to or during Screening or evidence of disorders of coagulation or platelet function including subjects that require chronic use of anticoagulation or antiplatelet drugs (please refer to the key exclusion criteria no. 8 for the exceptions).

Where this trial is running

Darlinghurst, New South Wales and 16 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Progressive Multiple SclerosisChimeric Antigen Receptor T cellsCAR-TYTB323Multiple SclerosisMSPMSrapcabtagene autoleucel
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.