RAPCABTAGENE AUTOLEUCEL for Myasthenia gravis (treatment-resistant, generalized)

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":"- Male or female participants 18-65 years of age with adequate renal, hepatic, cardiac, hematological, and pulmonary function (see definitions in Section 5.1)"}
• {"criterion_text":"- Confirmed gMG diagnosis with documented positive AChR antibodies or MuSK antibodies at screening AND has one of the following: history of abnormal neuromuscular transmission test demonstrated by repetitive nerve stimulation or single-fiber electromyography OR history of positive acetylcholinesterase test OR improvement in MG signs on an oral acetylcholinesterase inhibitor as assessed by the treating physician"}
• {"criterion_text":"- Generalized myasthenia gravis classified as MGFA Class III-IVa at screening"}
• {"criterion_text":"- Treatment-resistant gMG as defined by: MG-ADL score ≥6 at screening despite adequate treatment trials with at least two different non-steroidal immunosuppressive drugs given at adequate doses and duration of therapy. Specifically, they must have failed treatment with at least one oral immunomodulatory or steroid-sparing drug (e.g., azathioprine, mycophenolate mofetil, tacrolimus) AND EITHER one approved anti-C5 complement antibody (e.g., eculizumab, ravulizumab) OR an approved FcRn antagonist OR rituximab, OR required two or more rescue therapies (plasma exchange/immunoadsorption or IVIg) for myasthenic worsening/crisis in the 12 months before screening"}
• {"criterion_text":"- If on chronic corticosteroids, ability and willingness to taper to a maximum dose at least one week before leukapheresis"}

Exclusion criteria

• {"criterion_text":"- Exclusively ocular myasthenia gravis (MGFA I), mild symptoms (MGFA II), or severe bulbar disease or MG crisis, MGFA Class IVb or V (at time of screening)"}
• {"criterion_text":"- Clinically significant active, opportunistic, chronic or recurrent infection (including positive for hepatitis B or hepatitis C, HIV or TB)"}
• {"criterion_text":"- History of malignancy of any organ system (other than complete resection of localized basal cell carcinoma of the skin or in situ cervical cancer or non-invasive malignant polyps that have been removed), treated or untreated, within the past 5 years"}
• {"criterion_text":"- Known thymic neoplasm or history of thymectomy within 12 months prior to screening"}
• {"criterion_text":"- Prior treatment with anti-CD19 therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR-T cell therapy)"}
• {"criterion_text":"- Hypersensitivity and/or contraindications to any product (including its ingredients) to be given to the participant as per the study protocol (e.g., YTB323, tocilizumab, lymphodepleting agents, etc.) or any condition that, in the Investigator's opinion, precludes lymphodepleting chemotherapy"}

Primary endpoints

• {"endpoint_text":"- Occurrence, severity, and frequency of Adverse Events (AEs) (including CRS and ICANs) and change from baseline in safety parameters including, but not limited to: Vital signs, laboratory parameters, ECG, and neurological status","definition_or_measurement_approach":"Assessment of occurrence, severity and frequency of AEs (including cytokine release syndrome [CRS] and immune cell-associated neurotoxicity syndrome [ICANs]); change from baseline in safety parameters assessed by vital signs, laboratory parameters, ECG, and neurological status as recorded during study visits."}

Secondary endpoints

• {"endpoint_text":"- YTB323 transgene levels by qPCR over time in peripheral blood; cellular kinetics parameters (Cmax, AUC, Tmax, Clast, Tlast)","definition_or_measurement_approach":"Quantitative PCR measurement of YTB323 transgene levels in peripheral blood over time; calculation of cellular kinetics parameters including Cmax, AUC, Tmax, Clast, and Tlast."}
• {"endpoint_text":"- Pre-existing and treatment induced immunogenicity (cellular, humoral, neutralizing antibodies) of YTB323","definition_or_measurement_approach":"Assessment of immunogenicity via cellular and humoral assays including measurement of neutralizing antibodies and other relevant immunogenicity assays to characterize pre-existing and treatment-induced responses."}
• {"endpoint_text":"- At various timepoints: •\tChange from BL of MG-ADL score •\tChange from BL of QMG total score •\tWhether or not patient achieves a ≥3-point reduction of QMG total score sustained for 6 months post BL •\tWhether or not patient achieves a ≥2-point reduction of MG-ADL score sustained for 6 months post BL •\tWhether or not a patient achieves MGFA Post intervention Status (PIS) of minimal manifestations (MM) or better and sustained for 6 months post BL","definition_or_measurement_approach":"Clinical efficacy assessments at scheduled timepoints using MG-ADL and QMG scales to measure change from baseline; binary assessments of achieving specified reductions (≥3-point QMG, ≥2-point MG-ADL) sustained for 6 months post baseline; assessment of MGFA Post Intervention Status (PIS) for minimal manifestations or better sustained for 6 months."}

France

Earliest CTIS Part Ii Submission Date

03-02-2025

Latest Decision Or Authorization Date

07-01-2026

Processing Time Days

338

Number Of Sites

12

Number Of Participants

3

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

code 1

Name

IQVIA Limited

Responsibilities

code 1

Name

Syneos Health Inc.

Responsibilities

code 1

Name

Parexel International (IRL) Limited

Responsibilities

code 12; Ancillary supplies for leukapheresis and infusion

Name

Navigate Biopharma Services Inc.

Responsibilities

code 4

Third parties

• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"Analysis of cellular IG; code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"PRO translation services","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Navigate Biopharma Services Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Pharma Bio-Research Group","duties_or_roles":"Analysis of humoral IG; code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Navigate Biopharma Services Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"code 12","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"Ancillary supplies for leukapheresis and infusion","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Eurofins Genomics Europe AgriGenomics Products & Services A/S","duties_or_roles":"Pharmacogenetics; code 4","organisation_type":"Pharmaceutical company"}