Comparison of B-cell Depletion by Rituximab and Anti-CD 19 CAR-T Therapy in Patients With Rheumatoid Arthritis
NCT Number: NCT06475495
Acronym: COMPARE
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Rheumatoid Arthritis
Interventions: DRUG: KYV101|DRUG: Rituximab (active comparator)
Sponsor: Charite University, Berlin, Germany
Collaborators: Kyverna Therapeutics
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 13
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-11
Completion Date: 2027-03

Summary:
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.

Primary Outcome Measures: Safety Phase I (1) Safety, Incidence and grading of severity (graded 0-4) of Cytokine Release Syndrome (CRS) due to IMP within the first 4 weeks after anti-CD19 CAR T cell therapy., up to week 52|Safety Phase I (2) Safety, Incidence and grading of severity (graded 0-4) of Immune Cell Associated Neurotoxicity Syn-drome (ICANS) due to IMP within the first 4 weeks after anti-CD19 CAR T cell therapy., up to 52 weeks|Safety Phase I (3) Safety, Incidence and grading of severity (graded 0-4) of Adverse Events (AE) due to IMP within the first 4 weeks after anti-CD19 CAR T cell therapy., up to 52 weeks|Safety Phase I (4) Safety, Incidence and grading of severity (graded 0-4) of Serious Adverse Events (SAE) due to IMP within the first 4 weeks after anti-CD19 CAR T cell therapy., up to 52 weeks|Efficacy Phase II, Percentage of subjects with ACPA seroconversion = ACPA level \<20 mU/ml at week 16., visit week 16|Safety Phase II (1), AE due to IMP and rituximab throughout the whole study, up to 52 weeks|Safety Phase II (2), SAE due to IMP and rituximab throughout the whole study, up to 52 weeks
Secondary Outcome Measures: Clinical secondary endpoint (1), Drug free survival time (beginning of immunosuppression for RA treatment except for stable dosage of MTX in the control arm) from week 7 to 52, from week 7 to week 52|Clinical secondary endpoint (2), Time to relapse/flare, from week 7 to week 52|Clinical secondary endpoint (3), ACR 20/50/70 response, up to 52 weeks|Clinical secondary endpoint (4), DAS28-CRP remission, up to 52 weeks|Clinical secondary endpoint (5), DAS28-CRP\<3.2, up to 52 weeks|Clinical secondary endpoint (6), SDAI remission, up to 52 weeks|Clinical secondary endpoint (7), Boolean 2.0 remission, up to 52 weeks|Clinical secondary endpoint (8), Change in Disease Activity Score 28-CRP (DAS28-CRP), up to 52 weeks|Clinical secondary endpoint (9), Change in American College of Rheumatology (ACR) score components, up to 52 weeks|Clinical secondary endpoint (10), Change in Simplified Disease Activity Index (SDAI), up to 52 weeks|Clinical secondary endpoint (11), Change in Clinical Disease Activity Index (CDAI), up to 52 weeks|Clinical secondary endpoint (12), Number of flares, up to 52 weeks|cellular and humoral response (1), Percentage of subjects with Anti-citrullinated protein antibody (ACPA) seroconversion = ACPA level \<20 mU/ml at week 24 and 52, visit week 24|cellular and humoral response (2), Duration of persistence of CAR T cells in the peripheral blood, up to 52 weeks|cellular and humoral response (3), Duration of B cell depletion in the peripheral blood, up to 52 weeks|cellular and humoral response (4), Expansion of CAR T cells in the patient over time, up to 52 weeks|cellular and humoral response (5), Change in Anti-citrullinated protein antibody (ACPA) levels (mU/ml) over time, up to 52 weeks|cellular and humoral response (6), Change in Rheumatoid Factor (RF) levels (U/ml) over time, up to 52 weeks|cellular and humoral response (7), Change in Anti-citrullinated protein antibody (ACPA) levels (mU/ml) in HLA-defined subgroups over time, up to 52 weeks|cellular and humoral response (8), Change in levels of Anti-citrullinated protein antibody (ACPA) isotypes at week over time, up to 52 weeks|cellular and humoral response (9), Change in levels of IgG subclasses at week over time, up to 52 weeks|cellular and humoral response (10), Change in IgM immunoglobulins over time, up to 52 weeks|cellular and humoral response (11), Change in total IgA immunoglobulins over time, up to 52 weeks|cellular and humoral response (12), Change in IgG immunoglobulins subclasses over time, up to 52 weeks|cellular and humoral response (13), Change in total IgG immunoglobulins over time, up to 52 weeks|cellular and humoral response (14), Change in the number of plasmablasts, B cell and T cell numbers over time in peripheral blood, up to 52 weeks