Comparison of B-cell Depletion by Rituximab and Anti-CD 19 CAR-T Therapy in Patients With Rheumatoid Arthritis. Two-stage Interventional, Prospective, Randomized, Controlled, Open Label, Parallel-group Phase I/II Trial in Patients With Active, ACPA-positive and Treatment Refractory Rheumatoid Arthritis

CCM-RNT-202401

The goal of this phase I/II clinical trial is to compare B-cell depletion by rituximab and anti-CD 19 CAR-T therapy in patients with rheumatoid arthritis. The main questions it aims to answer are: * To assess the safety of anti-CD19 CAR T cell therapy in subjects with active, ACPA positive and treatment refractory RA (Phase-I) * To assess the safety of anti-CD19 CAR T cell therapy and of rituximab in subjects with active, ACPA positive and treatment refractory RA (Phase-II) * To assess ACPA seroconversion after anti-CD19 CAR T cell or rituximab therapy in subjects with active, ACPA positive and treatment refractory RA (Phase-II) Participants in the test-arm will receive a single dose of KYV-101 i.v., an autologous fully-human anti-CD19 CAR T-cell immunotherapy. In the comparator group patients will receive 2x1 g Rituximab i.v. Follow-up time (both arms) is 52 weeks with regular visits at the site.

2024-11-01

2027-03-01

2027-03-01

Not yet recruiting

Early phase I

13

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)

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Two-stage interventional, prospective, randomized, controlled, open label, parallel-group phase I/II trial in patients with active, ACPA-positive and treatment refractory rheumatoid arthritis', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 13, 'type': 'ESTIMATED'}}

2024-06-26