Anti-CD 19 CAR-T Cell Therapy in Patients With ANCA Vasculitis

Prior treatment

• Prior treatment with anti-CD19 antibody therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR T cell therapy)
• Any concomitant severe active infection, e.g. HIV, hepatitis B or C, 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 guide-lines must have been initiated prior to enrollment
• Requirement for immunization with live vaccine during the study period or within 14 days preceding leukapheresis,
• Subjects participating in another clinical trial with an investigational medicinal product or medical device (3 months before this trial).

Other illness

• Clinically relevant rapidly progressive glomerulonephritis or pulmonary alveolar hemorrhage
• History of bone marrow/ hematopoietic stem cell or solid organ transplantation
• Known hypersensitivity to any drug components
• Malignancy in the last 5 years before screening (except adequately treated basal or squamous cell skin cancer)
• 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 participa-tion or study agent administration, or may interfere with interpretation of results,

Lab values

• ANC less than 500/µl, ALC less than 100/µl or hemoglobin less than 8g/dl, absolute CD3+T cell count less than 100/µl at screening
• Severely impaired renal (eGFR ≤ 30 ml/min/m2), liver (Child Pugh C), or heart or pulmonary (NYHA IV, blood oxygenation less than 92%) function
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study

Age

• 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 (accord-ing to § 40 Abs. 4 and § 41 Abs. 2 and Abs. 3 AMG),

Other

• Pregnant or lactating females
• Females who are intending to conceive during the study
• Subjects who possibly are dependent on the Sponsor, the Principal Investigator or Investigator (e.g. family members).
• Subjects who are institutionalized by order of court or public authority,

• Understand and voluntarily sign an informed consent form
• Male or female, age ≥ 18 and ≤ 75 years at ti me of consent
• Able to adhere to the study visits and protocol
• Fulfilment of
• EITHER both of the following
  • 2022 ACR-EULAR classification criteria for granulomatosis with polyangiitis (GPA)
  • detectable anti-PR3 antibodies (≥ 20 AU/ml in CLIA) at screening
• OR both of the following
  • 2022 ACR/EULAR classification criteria for microscopic polyangiitis (MPA)
  • detectable anti-MPO antibodies (≥ 10 AU/ml in CLIA) at screening
• Active disease, defined as Clinical activity (BVAS ≥ 3) at screening
• Insufficient response or intolerance/contraindication to glucocorticoids and to at least one of the following treatments: rituximab, mycophenolate mofetil, azathioprine, methotrexate, cyclophosphamide, avacopan. Insufficient response is defined as having disease activity based on the definition explained in the previous bullet point
• 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
• 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 less than 1) starting from the time of signing the ICF and for 12 months after dosing of the IMP
• Updated vaccination record according to the STIKO recommendations for immuno-compromised patients