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Progressive Multiple SclerosisPhase 1/2NCT06675864

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)

A Phase 1/2 study testing rapcabtagene autoleucel (YTB323) in people with Progressive Multiple Sclerosis, run by Novartis Pharmaceuticals at 18 sites in 7 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is an open-label, multi-center, non-confirmatory study to assess the safety, disease progression, and cellular kinetics following YTB323 administration to 28 participants with non-active Progressive Multiple Sclerosis (PMS). Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Progressive Multiple Sclerosis
What is being tested?
rapcabtagene autoleucel (YTB323)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
18 sitesin 7 countries
Study dates
12 Dec 2024to 14 Jun 2030
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Male or female participants 18 to 60 years (inclusive) at screening.
  • Signed informed consent must be obtained prior to participation in the study.
  • 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.
  • Diagnosis of SPMS or PPMS according to the 2017 McDonald diagnostic criteria (Thompson et al 2018) as confirmed at screening visit.
  • Less than 15 years (inclusive) from onset of first MS symptoms as determined by the investigator during screening.
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  • Ambulatory Patients (EDSS 3 to 6.5 inclusive) at screening.
  • Evidence of recent (within 24 months) disease progression of ≥1.00 on the EDSS scale.
  • No relapse in the last 24 months at screening.
  • No Gd-enhancing lesion on brain or spinal cord MRI at screening.
  • 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.

Who cannot join

  • 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.
  • 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.
  • 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).
  • Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or neurological symptoms consistent with PML prior to or during screening.
  • 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.
  • Have donated blood or experienced a loss of blood > 400 mL within 3 months prior screening, or longer if required by local regulations.
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  • Any prior stem cell therapy or organ transplantation or gene therapy.
  • 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.
  • 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).
  • Pregnant or nursing (lactating) women.
  • Past surgical history of splenectomy.
  • 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).
  • 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.
  • 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).

Trial locations and contacts

18 sites in 7 countries.

18 sites in 7 countries

France4 sites

  • Novartis Investigative Site

    Bron, 69677

  • Novartis Investigative Site

    Montpellier, 34090

  • Novartis Investigative Site

    Nancy, 54035

  • Novartis Investigative Site

    Rennes, 35033

Other trials in France

Germany3 sites

  • Novartis Investigative Site

    Essen, 45147

  • Novartis Investigative Site

    Mainz, 55131

  • Novartis Investigative Site

    Ulm, 89081

Other trials in Germany

Spain3 sites

  • Novartis Investigative Site

    Barcelona, 08035

  • Novartis Investigative Site

    Madrid, 28222

  • Novartis Investigative Site

    Málaga, 29010

Other trials in Spain

Switzerland3 sites

  • Novartis Investigative Site

    Bern, 3010

  • Novartis Investigative Site

    Lausanne, 1011

  • Novartis Investigative Site

    Zurich, 8091

Other trials in Switzerland

Australia2 sites

  • Novartis Investigative Site

    Darlinghurst, New South Wales, 2010

  • Novartis Investigative Site

    Melbourne, Victoria, 3004

Other trials in Australia

Italy2 sites

  • Novartis Investigative Site

    Genova, GE, 16132

  • Novartis Investigative Site

    Milan, MI, 20132

Other trials in Italy

Canada1 site

  • Novartis Investigative Site

    Québec, Quebec, G1J 1Z4

Other trials in Canada

About this study

Official title: 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)

This is an open-label, multi-center, non-confirmatory study to assess the safety, disease progression, and cellular kinetics following YTB323 administration to 28 participants with non-active Progressive Multiple Sclerosis (PMS). The study design utilizes an ascending single dose design consisting of 3 sentinel cohorts followed by an expansion cohort.

Read the detailed description

All participants in this study will receive YTB323. Both the participant and the study doctor will know the participant is getting YTB323. Participants will be given one dose of YTB323. Different groups of participants may receive a higher dose of YTB323, if proven to be safe for every participant at the lower dose. Participants are in this study for 2 years and will be followed for an additional 13 years in a long-term follow up study. The main question this trial is designed to answer: Is YTB323 treatment safe for participants with progressive MS?

Being tested
rapcabtagene autoleucel (YTB323)
Keywords
Chimeric Antigen Receptor T cells, CAR-T, YTB323, Multiple Sclerosis, MS, Progressive Multiple Sclerosis, PMS, rapcabtagene autoleucel
Medical subject headings
Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rapcabtagene autoleucel (YTB323)Biological

    CAR-T cell suspension for intravenous infusion

Study groups in NCT06675864
Study groupRoleWhat they receive
YTB323 Cohort 1ExperimentalParticipants will receive one dose of YTB323
Receives: Biological: rapcabtagene autoleucel (YTB323)
YTB323 Cohort 2ExperimentalParticipants will receive one dose of YTB323
Receives: Biological: rapcabtagene autoleucel (YTB323)
YTB323 Cohort 3ExperimentalParticipants will receive one dose of YTB323
Receives: Biological: rapcabtagene autoleucel (YTB323)
YTB323 Cohort 4ExperimentalParticipants will receive one dose of YTB323
Receives: Biological: rapcabtagene autoleucel (YTB323)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with dose limiting toxicities (DLTs), Adverse Events (AEs), and Serious Adverse Events (SAEs)

    Occurrence, severity, and frequency of dose limiting toxicities (DLTs), AEs and SAEs, including changes in vital signs, electrocardiograms (ECGs), laboratory parameters, neurological status and magnetic resonance (MRI) of the brain and spinal cord qualifying and reported as AEs.

    Measured: Day 1 through Year 2

Secondary outcomes (14)

  1. Measure of Disability: Expanded Disability Status Scale (EDSS).

    EDSS is used to measure the change in disability level in participants using a scale from 0 to 10. The higher the score, the greater the degree of disability.

    Measured: Day 1 through Year 2

  2. Measure of Disability: Short Form Health Survey (SF-36 v2)

    The Short Form Health Survey (SF-36 v2) is a widely used and extensively studied instrument to measure health-related quality of life among healthy participants and participants with acute and chronic conditions. It consists of eight subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) also can be computed. The SF 36 has proven useful in monitoring general and specific populations, comparing the relative burden of different diseases, differentiating the health benefits produced by different treatments, and in screening individual participants.

    Measured: Day 1 through Year 2

  3. Measure of Disability: Timed 25 Foot Walk (T25FW)

    The T25FW is a mobility test based on a timed walk of 25 feet that is administered by a trained administrator. The participant is directed to walk the clearly marked 25-foot distance as quickly as possible. Longer completion time corresponds with decreased mobility.

    Measured: Day 1 through Year 2

  4. Measure of Disability: 9 Hole Peg Test (9HPT)

    The 9HPT is a finger dexterity test that is administered by a trained administrator. The participant is directed to put 9 pegs, one by one, onto and then off the holder board as quickly as possible starting with using only the dominant hand, and then repeated with the non-dominant hand. Longer completion times are associated with decreased finger dexterity.

    Measured: Day 1 through Year 2

  5. Measure of Disability: Symbol Digit Modalities Test (SDMT)

    The SDMT is a timed cognition test administered by a trained administrator. The test assesses sustained attention, processing speed, visual scanning, and motor speed to determine cognitive impairment. Participants are given a coding key which contains abstract symbols that correspond to specific numbers. Participants are timed how quickly and accurately they are able to substitute the symbols for the numbers and is scored by the number of correctly coded items.

    Measured: Day 1 through Year 2

  6. Modified Fatigue Impact Scale (MFIS)

    The MFIS is a questionnaire to assess fatigue-related symptoms in patients with MS.

    Measured: Day 1 through Year 2

  7. Whole Blood Pharmacokinetics (PK) of YTB323 - CMAX

    Measured by Cmax - The maximum plasma concentration of YTB323

    Measured: Day 1 through Year 2

  8. Whole Blood Pharmacokinetics (PK) of YTB323 - AUC

    Measured by AUC - Area under the curve of YTB323

    Measured: Day 1 Through Year 2

  9. Whole Blood Pharmacokinetics (PK) of YTB323 - Tmax

    Measured by Tmax - Time to Reach the Maximum Concentration After Drug Administration of YTB323

    Measured: Day 1 Through Year 2

  10. Whole Blood Pharmacokinetics (PK) of YTB323 - Clast

    Clast is defined as the Last observed (quantifiable) plasma concentration (Clast

    Measured: Day 1 Through Year 2

  11. Whole Blood Pharmacokinetics (PK) of YTB323 - Tlast

    Tlast is defined as Time of Last Measurable Concentration

    Measured: Day 1 through Year 2

  12. Humoral Immunogenicity of YTB323

    Incidence and prevalence of pre-existing and treatment induced humoral immunogenicity of YTB323

    Measured: Day 1 through Year 2

  13. Cellular Immunogenicity of YTB323

    Incidence and prevalence of pre-existing and treatment induced cellular immunogenicity of YTB323

    Measured: Day 1 through Year 2

  14. Safety data including dose limiting toxicities (DLTs), Adverse Events (AEs), and Serious Adverse Events (SAEs) from each dose level

    Safety data from each dose level will be used to assess safe dose-level(s) to be continued in phase 2 and later clinical studies

    Measured: Day 1 through Year 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2024
  2. Study start12 Dec 2024
  3. Primary completion14 Jun 2030 (estimated)
  4. Study completion14 Jun 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
28 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06675864
Sponsor's protocol ID
CYTB323r12101
Status last verified
Sep 2026
First submitted
4 Nov 2024
Last updated
4 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing rapcabtagene autoleucel (YTB323) in people with Progressive Multiple Sclerosis, run by Novartis Pharmaceuticals at 18 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in France, Germany, Spain, Switzerland, Australia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with dose limiting toxicities (DLTs), Adverse Events (AEs), and Serious Adverse Events (SAEs) (time frame: Day 1 through Year 2). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06675864.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.

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