RAPCABTAGENE AUTOLEUCEL for Relapsing multiple sclerosis

Inclusion criteria

• {"criterion_text":"- Signed informed consent, and able to communicate well with the investigator and comply with the requirements of the study"}
• {"criterion_text":"- Adequate renal, hepatic, cardiac, hematological, and pulmonary function (see definitions in Section 5.1)"}
• {"criterion_text":"- Male or female participants, ≥18 years to ≤60 years at screening, with diagnosis of RMS according to the 2017 McDonald diagnostic criteria (Thompson et al 2018b)"}
• {"criterion_text":"- XX of recent (i.e. within 1 year) breakthrough disease activity while XX. XX of breakthrough disease activity is defined as one or more of the following: a. XX"}
• {"criterion_text":"- Ambulatory patients (EDSS 3 to 6 inclusive assessed outside of relapse)"}
• {"criterion_text":"- Disease duration less than 15 years"}

Exclusion criteria

• {"criterion_text":"- Diagnosis of primary progressive multiple sclerosis (PPMS) according to the 2017 revision of the McDonald diagnostic criteria (Thompson et al 2018b) at screening"}
• {"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) or neurological disorders which may mimic MS or ICAN 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 [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"}
• {"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 ibuprofen (600 mg/day or lower) which are allowable], are not eligible to participate"}
• {"criterion_text":"- Patients 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)"}

Primary endpoints

• {"endpoint_text":"- Change in safety parameters including, but not limited to severity and frequency dose limiting toxicities (DLTs) of Adverse Events (AEs) and findings in vital signs, laboratory, ECG, neurological status, and safety MRIs of the brain and spinal cord","definition_or_measurement_approach":"Measured by severity and frequency of dose limiting toxicities (DLTs) and AEs, plus assessments of vital signs, laboratory tests, ECG, neurological status evaluations, and safety MRIs of brain and spinal cord."}

Secondary endpoints

• {"endpoint_text":"- Clinical measures for relapses and disability (includes EDSS, XX, T25FW, 9HPT, SDMT, XX) and MRI changes in disease activity (including new and enlarging T2 lesions and Gd-enhancing T1 lesions)","definition_or_measurement_approach":"Clinical scales and tests (EDSS, T25FW, 9HPT, SDMT, etc.) to evaluate relapses and disability; MRI assessments for new/enlarging T2 lesions and gadolinium-enhancing T1 lesions."}
• {"endpoint_text":"- YTB323 transgene expression levels by qPCR over time in blood; cellular kinetics parameters (Cmax, AUC, Tmax, Clast, Tlast)","definition_or_measurement_approach":"Quantitative PCR measurement of transgene expression in blood over time; calculation of cellular kinetics parameters including Cmax, AUC, Tmax, Clast, Tlast."}
• {"endpoint_text":"- Safety data from each dose level","definition_or_measurement_approach":"Safety assessments (AEs, labs, vital signs, ECG, imaging, neurological exams) summarized by dose level."}
• {"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":"Humoral immunogenicity assessed by anti-YTB323 antibody assays; cellular immunogenicity assessed by detection of CAR19-specific CD4+ and CD8+ T cells via interferon-gamma production assays."}

Italy

Earliest CTIS Part Ii Submission Date

26-02-2025

Latest Decision Or Authorization Date

16-01-2026

Processing Time Days

324

Number Of Sites

2

Number Of Participants

3

France

Earliest CTIS Part Ii Submission Date

03-03-2025

Latest Decision Or Authorization Date

15-01-2026

Processing Time Days

318

Number Of Sites

9

Number Of Participants

4

Germany

Earliest CTIS Part Ii Submission Date

03-03-2025

Latest Decision Or Authorization Date

19-01-2026

Processing Time Days

322

Number Of Sites

4

Number Of Participants

4

Spain

Earliest CTIS Part Ii Submission Date

26-02-2025

Latest Decision Or Authorization Date

19-01-2026

Processing Time Days

327

Number Of Sites

4

Number Of Participants

4

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Parexel International (IRL) Limited

Responsibilities

Ancillary supply management

Name

Syneos Health Inc.

Name

Icon Clinical Research Limited

Name

IQVIA Limited

Third parties

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