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)

NCT06675864 | Recruiting Phase 1 DMC

• 1 other identifier: CYTB323r12101
• Study Type: interventional
• Target: 28
• Locations: 7 countries
• Sites: 17

Brief 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). The study design utilizes an ascending single dose design consisting of 3 sentinel cohorts followed by an expansion cohort.

Conditions

Progressive Multiple Sclerosis

Keywords

Chimeric Antigen Receptor T cells; CAR-T; YTB323; Multiple Sclerosis; MS; Progressive Multiple Sclerosis; PMS; rapcabtagene autoleucel

Outcome Measures

Primary Outcomes (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.

  Day 1 through Year 2

Secondary Outcomes (14)

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

  Day 1 through Year 2

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

  Day 1 through Year 2

• Measure of Disability: Timed 25 Foot Walk (T25FW)

  Day 1 through Year 2

• Measure of Disability: 9 Hole Peg Test (9HPT)

  Day 1 through Year 2

• Measure of Disability: Symbol Digit Modalities Test (SDMT)

  Day 1 through Year 2

Study Arms (4)

YTB323 Cohort 1

EXPERIMENTAL

Participants will receive one dose of YTB323

Biological: rapcabtagene autoleucel (YTB323)

YTB323 Cohort 2

EXPERIMENTAL

Participants will receive one dose of YTB323

Biological: rapcabtagene autoleucel (YTB323)

YTB323 Cohort 3

EXPERIMENTAL

Participants will receive one dose of YTB323

Biological: rapcabtagene autoleucel (YTB323)

YTB323 Cohort 4

EXPERIMENTAL

Participants will receive one dose of YTB323

Biological: rapcabtagene autoleucel (YTB323)

Interventions

rapcabtagene autoleucel (YTB323) BIOLOGICAL

CAR-T cell suspension for intravenous infusion

YTB323 Cohort 1; YTB323 Cohort 2; YTB323 Cohort 3; YTB323 Cohort 4

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (17)

Novartis Investigative Site

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

Novartis Investigative Site

Melbourne, Victoria, 3004, Australia

RECRUITING

Novartis Investigative Site

Québec, Quebec, G1J 1Z4, Canada

RECRUITING

Novartis Investigative Site

Bron, 69677, France

RECRUITING

Novartis Investigative Site

Montpellier, 34090, France

RECRUITING

Novartis Investigative Site

Nancy, 54035, France

RECRUITING

Novartis Investigative Site

Rennes, 35033, France

RECRUITING

Novartis Investigative Site

Essen, 45147, Germany

RECRUITING

Novartis Investigative Site

Ulm, 89081, Germany

RECRUITING

Novartis Investigative Site

Genova, GE, 16132, Italy

RECRUITING

Novartis Investigative Site

Milan, MI, 20132, Italy

RECRUITING

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

RECRUITING

Novartis Investigative Site

Majadahonda, Madrid, 28222, Spain

RECRUITING

Novartis Investigative Site

Málaga, 29010, Spain

RECRUITING

Novartis Investigative Site

Bern, 3010, Switzerland

ACTIVE NOT RECRUITING

Novartis Investigative Site

Lausanne, 1011, Switzerland

RECRUITING

Novartis Investigative Site

Zurich, 8091, Switzerland

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis

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

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

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: November 4, 2024
• First Posted: November 5, 2024
• Study Start: December 12, 2024
• Primary Completion (Estimated): June 14, 2030
• Study Completion (Estimated): June 14, 2030
• Last Updated: November 20, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

AU (2); CA (1); ES (3); CH (3); FR (4); DE (2); IT (2)