An Open-label Study to Assess the Safety, Efficacy, and Cellular Kinetics of YTB323 in Relapsing Multiple Sclerosis

NCT06617793 | Recruiting Phase 1 DMC

• 2 other identifiers: CYTB323N121012024-512714-18
• Study Type: interventional
• Target: 28
• Locations: 6 countries
• Sites: 18

Brief Summary

This is an open-label, multi-center, non-confirmatory study to assess the safety, efficacy, and cellular kinetics of YTB323 in approximately 28 participants with Relapsing Multiple Sclerosis (RMS) with breakthrough disease activity during previous treatment with a highly efficacious therapy (BD-HET). The study design utilizes an ascending single dose design consisting of 3 sentinel cohorts followed by an expansion cohort.

Conditions

Relapsing Multiple Sclerosis

Keywords

Chimeric Antigen Receptor T cells; CAR-T; YTB323; Multiple Sclerosis; MS; Relapsing Multiple Sclerosis; RMS; breakthrough disease activity during previous treatment with a highly efficacious therapy; BD-HET

Outcome Measures

Primary Outcomes (1)

• Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Incidence 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 (15)

• 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:

• Signed informed consent, and able to communicate well with the investigator and comply with the requirements of the study
• Adequate renal, hepatic, cardiac, hematological, and pulmonary function
• Male or female participants, ≥18 years to ≤60 years at screening, with diagnosis of RMS according to the 2017 McDonald diagnostic criteria Evidence of recent (i.e. within 1 year) breakthrough disease activity while at least 6 months on a highly efficacious therapy (any of the following): rituximab (Rituxan®), ocrelizumab (Ocrevus®), natalizumab (Tysabri®), ofatumumab (Kesimpta®), ublituximab (Briumvi®) or evidence of breakthrough disease activity within 2 years after the latest alemtuzumab infusion (Lemtrada®).
• Evidence of breakthrough disease activity is defined as one or more of the following:
• Confirmed Clinical MS relapse
• Persistent radiological activity defined by one of the following:
• ≥2 T1 gadolinium-enhancing lesions on a single MRI scan
• ≥1 T1 gadolinium-enhancing lesions on two or more separate MRI scans
• ≥2 new T2 lesions compared to a previous scan within a period ≤1 year
• Ambulatory patients (EDSS of 3 to 6 points, inclusive assessed outside of relapse)
• Disease duration less than 15 years
• 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 primary progressive multiple sclerosis (PPMS) according to the 2017 revision of the McDonald diagnostic criteria at screening
• History of or current clinically significant CNS disease (e.g. stroke, traumatic brain or spinal injury, history or presence of myelopathy) or neurological disorders which may mimic MS or ICANS at screening
• Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 6 months prior to screening), neurological disorders other than MS (including seizure disorders even when well controlled), 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 screening
• 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 \[except for low-dose aspirin (100 mg/day or lower) and low-dose ibuprofen (600 mg/day or lower) which are allowable\], are not eligible to participate
• Participants not willing or able to take MRI scans as per protocol. Unable to undergo MRI due to for example claustrophobia, or presents absolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (18)

Novartis Investigative Site

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

Novartis Investigative Site

Melbourne, Victoria, 3004, Australia

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

Bochum, 44791, Germany

RECRUITING

Novartis Investigative Site

Essen, 45147, Germany

RECRUITING

Novartis Investigative Site

Mainz, 55131, 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, 08035, Spain

RECRUITING

Novartis Investigative Site

Córdoba, 14004, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28034, Spain

RECRUITING

Novartis Investigative Site

Valencia, 46026, Spain

RECRUITING

Novartis Investigative Site

Bern, 3010, Switzerland

RECRUITING

Novartis Investigative Site

Lausanne, 1011, Switzerland

RECRUITING

Novartis Investigative Site

Zurich, 8091, Switzerland

RECRUITING

MeSH Terms

Conditions

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

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

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: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2024
• First Posted: September 27, 2024
• Study Start: February 24, 2025
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

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