rapcabtagene autoleucel for Non-active progressive multiple sclerosis (PMS) | Secondary progressive multiple sclerosis | Primary progressive multiple sclerosis

Inclusion criteria

• {"criterion_text":"- Male or female participants 18 to 60 years (inclusive) at screening."}
• {"criterion_text":"- Signed informed consent must be obtained prior to participation in the study."}
• {"criterion_text":"- Able to communicate well with the investigator, to understand and comply with the requirements of the study including: Able to undergo LP, CSF collection, blood draws, tolerate brain and spinal MRIs, and able to participate and tolerate all study procedures at study visits."}
• {"criterion_text":"- Diagnosis of SPMS or PPMS according to the 2017 McDonald diagnostic criteria (Thompson et al 2018) as confirmed at screening visit."}
• {"criterion_text":"- Less than 15 years (inclusive) from onset of first MS symptoms as determined by the investigator during screening."}
• {"criterion_text":"- Ambulatory Patients (EDSS 3 to 6.5 inclusive) at screening."}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- Occurrence, severity and frequency of dose limiting toxicities (DLTs), Adverse Events (AEs) and change from baseline over 2 years in safety parameters including, but not limited to vital signs, laboratory, ECG, neurological status, and safety measures from brain and spinal cord MRIs.","definition_or_measurement_approach":"Assessment of DLTs and AEs, and change from baseline over 2 years in safety parameters (vital signs, laboratory tests, ECG, neurological status) and brain/spinal MRI safety measures."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline for clinical measures of disability (includes EDSS, T25FW, 9HPT, SDMT).","definition_or_measurement_approach":"Change from baseline measured using clinical disability scales: EDSS, Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), Symbol Digit Modalities Test (SDMT)."}
• {"endpoint_text":"- YTB323 transgene expression levels by qPCR over time in blood; cellular kinetics parameters (Cmax, AUC, Tmax, Clast, Tlast).","definition_or_measurement_approach":"Transgene expression measured by quantitative PCR in blood over time; cellular kinetics parameters including Cmax, AUC, Tmax, Clast, Tlast derived from qPCR data."}
• {"endpoint_text":"- Safety data from each dose level.","definition_or_measurement_approach":"Safety assessment stratified by dose level (adverse events, lab parameters, vital signs, imaging, etc.)."}
• {"endpoint_text":"- Pre-existing and treatment-induced immunogenicity (humoral, anti-YTB323 antibody; and cellular, presence of CAR19 specific CD4 and CD8 T cells measuring interferon gamma production).","definition_or_measurement_approach":"Assessment of humoral immunogenicity (anti-YTB323 antibodies) and cellular immunogenicity (presence of CAR19-specific CD4 and CD8 T cells measured via interferon-gamma production assays)."}

Germany

Earliest CTIS Part Ii Submission Date

25-03-2025

Latest Decision Or Authorization Date

04-12-2025

Processing Time Days

254

Number Of Sites

3

Number Of Participants

5

France

Earliest CTIS Part Ii Submission Date

23-03-2025

Latest Decision Or Authorization Date

24-12-2025

Processing Time Days

276

Number Of Sites

9

Number Of Participants

5

Spain

Earliest CTIS Part Ii Submission Date

15-04-2025

Latest Decision Or Authorization Date

24-12-2025

Processing Time Days

232

Number Of Sites

4

Number Of Participants

5

Italy

Earliest CTIS Part Ii Submission Date

21-01-2025

Latest Decision Or Authorization Date

16-01-2026

Processing Time Days

360

Number Of Sites

2

Number Of Participants

3

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Pharma Bio-Research Group

Responsibilities

Analysis of humoral IG

Name

Parexel International (IRL) Limited

Responsibilities

Ancillary supply management

Name

IQVIA Limited

Name

Syneos Health Inc.

Name

Icon Clinical Research Limited

Third parties

• {"country":"Netherlands","full_name":"Pharma Bio-Research Group","duties_or_roles":"Analysis of humoral IG","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Eurofins Genomics Europe AgriGenomics Products & Services A/S","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"COA licensing, formatting, and translations","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Opis S.r.l.","duties_or_roles":"TMF archive","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"Ancillary supply management","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"Analysis of cellular IG","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Neurorx Research Inc.","duties_or_roles":"Central imaging services","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Navigate Biopharma Services Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"Analysis of GFAP","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"EPL Pathology Archives LLC","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"","organisation_type":"Pharmaceutical company"}