Comparison of B-cell Depletion by Rituximab and Anti-CD 19 CAR-T Therapy in Patients With Rheumatoid Arthritis

A regiszterben nem jelölt feltételek

• Main Inclusion Criteria:
• Understand and voluntarily sign an informed consent form
• Male or female, age ≥ 18 and ≤ 80 years at time of consent
• Able to adhere to the study visits and protocol
• Fulfilment of the 2010 ACR-EULAR RA classification criteria
• ACPA positivity (cut off 20 mU/ml) at screening
• Disease Activity Score DAS28-ESR>3.2 at screening
• Failure (defined as inadequate response after at least 3 months of therapy) of at least one conventional DMARD and at least two tsDMARD/bDMARDs
• At least one swollen joint with Power Doppler activity of at least grade 1 or B-mode activity of at least grade 2 at screening
• Willingness to participate in a synovial puncture and biopsy
• Male subjects unless surgically sterile, must agree to use two accepta-ble 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 or rituximab
• Females of childbearing potential (FCBP) must have a negative serum 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 or rituximab
• Updated vaccination record according to the STIKO recommendations for immunocompromised patients
  • Main Exclusion Criteria:
• ANC < 1.000/mm3, ALC < 500/mm3 or hemoglobin < 8g/dl, absolute CD3+T cell count < 100/µl
• Severely impaired renal (eGFR ≤ 30 ml/min/m2), liver (Child Pugh B or C), or heart andor pulmonary (NYHA III or IV, blood oxygenation <92%) function
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to partici-pate in the study or confounds the ability to interpret data from the study
• Prior treatment with anti-CD19 antibody therapy, adoptive T cell thera-py or any prior gene therapy product (e.g. CAR T cell therapy)
• Only in phase II: Prior treatment of rituximab < 7 months before base-line OR ≥ 7 months before baseline and B cell level < 0.1/nl
• History of bone marrow/ hematopoietic stem cell or solid organ trans-plantation
• csDMARD other than MTX at baseline
• Any concomitant severe active infection, e.g. HIV, hepatitis B or C, SARS-CoV-2 (COVID-19), or active tuberculosis as defined by a posi-tive Quantiferon TB-test. If presence of latent tuberculosis is estab-lished then treatment according to local guidelines must have been ini-tiated prior to enrollment
• Pregnant or lactating females
• Females who are intending to conceive during the study
• Known hypersensitivity to any drug components
• Malignancy in the last 5 years before screening (except basal or squamous cell skin cancer)
• Requirement for immunization with live vaccine during the study peri-od or within 14 days preceding leukapheresis,
• Subjects who are younger than 18 years or are incapable to under-stand the aim, importance and consequences of the study and to give legal informed consent (according to § 40 Abs. 4 and § 41 Abs. 2 and Abs. 3 AMG),
• Subject who Hhave a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the Investigator, may in-crease the risks associated with study participation or study agent ad-ministration, or may interfere with interpretation of results,
• Subjects who possibly are dependent on the Sponsor, the Principal In-vestigator or Investigator (e.g. family members).
• Subjects who are institutionalized by order of court or public authority
• Subjects participating in another clinical trial with an investigational medicinal product or medical device (3 months before this trial)