Autologous T-cells transduced with lentiviral vector expressing a chimeric antigen receptor directed against CD19 for Refractory systemic autoimmune diseases|Systemic lupus erythematosus (SLE)|Systemic sclerosis (SSc)|Dermatomyositis/Polymyositis (DM/PM)|ANCA-associated vasculitis (AAV)

Inclusion criteria

• {"criterion_text":"- General a) Subjects must understand and voluntarily sign an informed consent form including writ- ten consent for data protection;\n- b) Adults aged ≥ 18 years and ≤ 80 years at time of consent;\n- c) Male subjects unless surgically sterile, must agree to use two acceptable methods for contraception (e.g., spermicide and condom) during the trial and refrain from fathering a child starting from the time of signing the Informed Consent Form (ICF) until 12 months after dosing of the IMP;\n- d) Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening and must agree to use a highly effective contraceptive method (Pearl index <1) starting from the time of signing the ICF and for 12 months after dosing of the IMP;\n- e) Must be able to adhere to the study visit schedule and other protocol requirements;\n- f) Double vaccination (2 doses of vaccine)against SARS-CoV-2 or SARS-CoV-2 within the last 6 months."}

Exclusion criteria

• {"criterion_text":"- Clinically suitability for a less burdensome and/or approved therapeutic approach, as judged by the investigator;\n- ANC < 1.000/mm3, ALC < 500/mm3 or hemoglobin < 8 g/dl, absolute CD3+ T cell count ≤100/μl;\n- Evidence of significant and uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results.\n- Relevant cardiovascular disease: recent history of myocardial infarction, cardiac angioplasty or stenting, unstable angina, significant arrhythmia, congestive heart failure or left ventricular ejection fraction < 50%, as determined by echocardiography\n- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she was to participate in the study or confounds the ability to interpret data from the study;\n- Impaired renal function, i.e., eGFR < 30 ml/min;\n- Patients with evidence on thorax CT of advanced fibrotic interstitial lung disease and whose latest pulmonary function test showed a Forced Vital Capacity (FVC) < 40% of predicted or a Diffusing Capacity for Carbon Monoxide (DLCO) < 30% of predicted\n- Any concomitant severe active infection, including, HIV (even with negative viral load), active hepatitis B (either positive for Hepatitis B core antibody [HBcAb] or positive hepatitis B surface antigen [HBsAg] and NAT tests) and/or C (<12 weeks between achievement of a sustained virological response to the specific treatment and apheresis) according to the American Association for the Study of Liver Diseases guidelines, SARS-CoV 2 (COVID 19), or active tuberculosis as defined by a positive Quantiferon TB-test. If presence of latent tuberculosis is established then treatment according to local guidelines must have been initiated prior to enrolment;\n- Pregnant or lactating females;\n- Known hypersensitivity to either any drug components or any auxiliary medicinal products scheduled during trial participation, including during lymphodepletion;;\n- Malignancy in the last 5 years before screening.The inclusion of patients with previously completely resected carcinoma in situ who have not required treatment other than surgery is allowed.\n- Previous CAR T cell administration;\n- A therapeutic schedule not compatible with the wash-out requirements for the leukapheresis procedure (section 5.8.1) and the medications permitted during the study (section 7.11);\n- Concurrent treatment with other investigational agents or participation in other investigational trials.\n- Treatment, as part of an investigational clinical trial, with an experimental product with definite or potential effect on T or B-cells in the previous 2 years.\n- Requirement for immunization with live vaccine during the study period or within 14 days preceding leukapheresis;\n- Subjects who are younger than 18 years or are incapable to understand the aim, importance and consequences of the study and to give legal informed consent;\n- Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the Investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results;\n- Subjects who possibly are dependent on the Sponsor, the Principal Investigator or Investigator (e.g., family members)"}

Primary endpoints

• {"endpoint_text":"- Incidence and grading of severity (graded 0-4) of Cytokine Release Syndrome (CRS) and of CAR T cell Associated Neurotoxicity Syndrome (ICANS) within the first 4 weeks after ATMP administration.","definition_or_measurement_approach":"Grading of CRS and ICANS severity using a 0-4 scale; assessed within the first 4 weeks after ATMP administration."}
• {"endpoint_text":"- Incidence and severity of infections and leukopenia and/or hypogammaglobulinemia during the entire study period.","definition_or_measurement_approach":"Incidence and severity recorded throughout the entire study period; specific measurement methods not detailed in the provided record."}

Secondary endpoints

• {"endpoint_text":"- Duration of B cell depletion in the peripheral blood: CD19+ B cells assessed by fluorescence- activated cell sorting (FACS) equal to 0 up to week 24 and long-term FU.","definition_or_measurement_approach":"CD19+ B cells measured by FACS; duration defined by time with CD19+ B cells = 0, assessed up to week 24 and during long-term follow-up."}
• {"endpoint_text":"- Duration of persistence of CAR T cells in the peripheral blood: CAR+ CD3+ cells assessed by FACS > 0 up to week 24 and long-term FU.","definition_or_measurement_approach":"CAR+ CD3+ cells measured by FACS; persistence measured as presence >0, assessed up to week 24 and during long-term follow-up."}
• {"endpoint_text":"- Changes in the levels of disease-associated serum autoantibodies at week 24 including incidence of seroconversion (anti-dsDNA < LLN; ANA <1.100; all others “negative”) o SLE","definition_or_measurement_approach":"Serum autoantibody levels measured at week 24; seroconversion defined by thresholds (anti-dsDNA < LLN; ANA <1.100; others negative) as stated."}

Italy

Earliest CTIS Part Ii Submission Date

19-07-2024

Latest Decision Or Authorization Date

10-10-2025

Processing Time Days

448

Number Of Sites

2

Number Of Participants

8

Primary sponsor

Full Name

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy