RAPCABTAGENE AUTOLEUCEL for Systemic lupus erythematosus | Lupus nephritis

Inclusion criteria

• {"criterion_text":"-Signed informed consent.\n-Adequate renal, hepatic, cardiac, hematological and pulmonary function.\n-Men and women with SLE, aged ≥18 years and ≤65 years at screening, fulfilling the 2019 European League Against Rheumatism EULAR/ACR classification criteria for SLE.\n-Patient must be positive for at least one of the following autoantibodies at screening: antinuclear antibodies (ANA) at a titer of ≥1:80, or anti dsDNA (above the ULN); or anti-Sm (above the ULN).\n-Active (severe) disease as defined by SLEDAI-2K ≥8 (not including the SLEDAI-2K domains of lupus headache, cerebrovascular accident, organic brain syndrome*) AND at least one of the following significant SLE related organ involvements that can result in debilitating and permanent damage or may represent a life-threatening condition as judged by the investigator and defined by: - Renal - At least moderate or severe peri/myocarditis - At least moderate or severe pleuritis or other lung involvement - Vasculitis\n-000000000000000000"}

Exclusion criteria

• {"criterion_text":"-Clinically significant active, opportunistic, chronic or recurrent infection confirmed by clinical evidence, imaging, or positive laboratory tests (e.g., blood cultures, PCR for DNA/RNA, such as COVID-19 etc.) one month prior to or during screening. Patients who have had at least one severe infection that required prolonged hospitalization in the intensive care setting within 5 years prior to screening and/or at least one severe infection that required prolonged hospitalization within one year prior to screening.\n-Sexually active males unwilling to use a condom during intercourse from the time enrollment for at least 12 months after YTB323 administration and until CAR-T cells are no longer present by qPCR on two consecutive tests.\n-Any acute, severe lupus related 0000000 during screening that needs immediate treatment and/or makes the immunosuppressive washout impossible; thus, makes the patient ineligible for CD19 CAR-T therapy as judged by the Investigator,00000000000\n-000000000000.\n-Uncontrolled diabetes mellitus, lung diseases or any other illness that are not related to SLE that in the opinion of the Investigator would jeopardize the ability of the patient to tolerate lymphodepletion and CD19 CAR T cell therapy.\n-Prior history of malignancy except for localized basal cell or squamous skin cancer. Other malignancies for which the patient is judged to be cured for at least 5 years by local surgical therapy, such as head and neck cancer, or stage I breast cancer will be considered on an individual basis.\n-Any patients requiring medications prohibited by the protocol.\n-Any psychiatric condition or disability compliance with treatment or informed consent impossible.\n-Prior treatment with anti-CD19 therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR-T cell therapy).\n-History of bone marrow/hematopoietic stem cell or solid organ transplantation.\n-Female participants who are pregnant or breastfeeding or intending to conceive during the course of the study.\n-Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using a highly effective method of contraception starting from the time of enrollment to at least 12 months (24 months in the US) after the YTB323 administration (unless local regulations mandate a longer duration) and until CAR-T cells are no longer present by qPCR on two consecutive tests."}

Primary endpoints

• {"endpoint_text":"-Safety parameters include vital signs, adverse events, laboratory parameters and ECG evaluation.","definition_or_measurement_approach":"Safety parameters include vital signs, adverse events, laboratory parameters and ECG evaluation."}

Secondary endpoints

• {"endpoint_text":"-YTB323 transgene concentration by qPCR over time in peripheral blood; cellular kinetics parameters (Cmax, AUC, Tmax, T1/2, Clast, Tlast).","definition_or_measurement_approach":"YTB323 transgene concentration measured by qPCR over time in peripheral blood; cellular kinetics parameters (Cmax, AUC, Tmax, T1/2, Clast, Tlast)."}
• {"endpoint_text":"-Pre-existing and treatment induced immunogenicity (cellular, humoral) of YTB323.","definition_or_measurement_approach":"Assessment of cellular and humoral immunogenicity pre-existing and treatment-induced for YTB323."}
• {"endpoint_text":"-Manufacture success (defined as meeting release specification and at or above the planned target dose).","definition_or_measurement_approach":"Manufacture success defined as meeting release specifications and at or above planned target dose."}
• {"endpoint_text":"-At various timepoints: - SLEDAI-2K - Physician's global assessment - LLDAS - Remission (DORIS)","definition_or_measurement_approach":"Disease activity and clinical status measured at various timepoints using SLEDAI-2K, Physician's global assessment, LLDAS, and DORIS remission criteria."}
• {"endpoint_text":"-UPCR at various timepoints.","definition_or_measurement_approach":"Urine protein-to-creatinine ratio (UPCR) measured at various timepoints."}
• {"endpoint_text":"-Complete Renal Response (CRR) at various timepoints.","definition_or_measurement_approach":"Assessment of complete renal response (CRR) at various timepoints according to protocol definitions."}

Germany

Earliest CTIS Part Ii Submission Date

07-02-2024

Latest Decision Or Authorization Date

27-05-2024

Processing Time Days

110

Number Of Sites

2

Number Of Participants

5

Spain

Earliest CTIS Part Ii Submission Date

07-02-2024

Latest Decision Or Authorization Date

22-05-2024

Processing Time Days

105

Number Of Sites

2

Number Of Participants

6

France

Earliest CTIS Part Ii Submission Date

07-02-2024

Latest Decision Or Authorization Date

24-05-2024

Processing Time Days

107

Number Of Sites

8

Number Of Participants

8

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Iqvia Rds Inc.

Responsibilities

Review and evaluation of endpoint data related to BILAG, SLEDAI-2K, and PhGA.

Name

Icon Clinical Research Limited

Responsibilities

code 1

Name

Syneos Health Clinical Spain S.L.

Responsibilities

code 1

Name

Rps Research Iberica S.L.

Responsibilities

code 1

Name

Parexel International (IRL) Limited

Responsibilities

code 12

Name

IQVIA RDS Spain S.L.

Responsibilities

code 1

Third parties

• {"country":"United States","full_name":"Iqvia Rds Inc.","duties_or_roles":"Review and evaluation of endpoint data related to BILAG, SLEDAI-2K, and PhGA.","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Syneos Health Clinical Spain S.L.","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Rps Research Iberica S.L.","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Medidata Solutions International Limited","duties_or_roles":"code 7","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"code 12","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"PRO licensing, formatting and translations.","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"Ancillary supplies for Leukapheresis and Infusion kits.","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"IQVIA RDS Spain S.L.","duties_or_roles":"code 1","organisation_type":"Pharmaceutical company"}