Rheumatoid ArthritisPhase 1/2COMPARENCT06475495

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

A Phase 1/2 study testing KYV101 and Rituximab (active comparator) in people with Rheumatoid Arthritis, run by Charite University, Berlin, Germany at 1 site in Germany.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Rheumatoid Arthritis
What is being tested?: KYV101 and Rituximab (active comparator)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 1 siteGermany
Study dates: 4 Dec 2024to Jun 2027
Phase: Phase 1/2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

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)

Trial locations and contacts

1 site in 1 country.

Germany1 site

Charité - Universitätsmedizin Berlin
Berlin, State of Berlin, 10117

Other trials in Germany

About this study

Official title: 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

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.

Read the detailed description

This study aims to investigate the use of either rituximab as an established therapy or KYV101 (a fully human anti-CD19 CAR T cell therapy) in ACPA-positive RA patients who are refractory to previous treatments. This study is designed to determine and compare (i) the safety of these two B-cell targeted therapies, (ii) their clinical efficacy, (iii) their impact on the immunological status of the patient and in particular on ACPA positivity, and (iv) their ability to induce long-term (deep) clinical and molecular remission and drug-free survival.

The investigational product (IMP), KYV-101, is an autologous fully-human anti-CD19 CAR T-cell immunotherapy. . Before IMP infusion, patients will receive a premedication of 4 mg Dimetindenmaleat iv or equivalent antihistamine and 1000 mg oral acetaminophene. Prophylactic doses of acyclovir of 400mg 2x daily as well as cotrimoxazole 960mg 3x weekly will be administered orally following CAR T cell infusion until week 24. Tocilizumab 8mg/kg will be administered intravenously when required for treatment of IMP-related cytokine release syndrome. Dexamethasone as needed will be administered intravenously when required for treatment of neurological adverse event (ICANS).

In the control arm in phase II, rituximab will be administered. Rituximab, a chimeric monoclonal antibody targeting CD20, induces B cell depletion and is authorized for treatment of RA. A dose of 1000 mg will be administered intravenously at baseline and at day 14 as per summary of product characteristics. The need for further courses will be evaluated 24 weeks after baseline where retreatment of 1000 mg rituximab may be initiated if residual disease activity remains.

Follow-up time (both arms) is 52 weeks with regular visits at the site.

Conditions: Rheumatoid Arthritis
Being tested: KYV101, Rituximab (active comparator)
Keywords: treatment refractory, ACPA-positive, difficult-to-treat
Medical subject headings: Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

KYV101Drug
an autologous fully-human anti-CD19 CAR T-cell immunotherapy
Rituximab (active comparator)Drug
anti CD20 monoclonal antibody

Study groups in NCT06475495
Study group	Role	What they receive
KYV101	Experimental	Participants in this arm will receive a single dose of KYV-101 i.v., an autologous fully-human anti-CD19 CAR T-cell immunotherapy. Receives: Drug: KYV101
Rituximab	Active comparator	In the Comparator group patients will receive 2x1 g Rituximab i.v. (Day 0 and Day 14). Retreatment of 1000 mg rituximab i.v. may be initiated at week 24 if residual disease activity remains, otherwise retreatment should be delayed until disease activity returns. A DAS-28-CRP > 3.2 will be used as a non-binding guidance for the re-treatment decision. Receives: Drug: Rituximab (active comparator)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: up to 52 weeks
Efficacy Phase II
Percentage of subjects with ACPA seroconversion = ACPA level <20 mU/ml at week 16.
Measured: visit week 16
Safety Phase II (1)
AE due to IMP and rituximab throughout the whole study
Measured: up to 52 weeks
Safety Phase II (2)
SAE due to IMP and rituximab throughout the whole study
Measured: up to 52 weeks

Secondary outcomes (26)

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
Measured: from week 7 to week 52
Clinical secondary endpoint (2)
Time to relapse/flare
Measured: from week 7 to week 52
Clinical secondary endpoint (3)
ACR 20/50/70 response
Measured: up to 52 weeks
Clinical secondary endpoint (4)
DAS28-CRP remission
Measured: up to 52 weeks
Clinical secondary endpoint (5)
DAS28-CRP<3.2
Measured: up to 52 weeks
Clinical secondary endpoint (6)
SDAI remission
Measured: up to 52 weeks
Clinical secondary endpoint (7)
Boolean 2.0 remission
Measured: up to 52 weeks
Clinical secondary endpoint (8)
Change in Disease Activity Score 28-CRP (DAS28-CRP)
Measured: up to 52 weeks
Clinical secondary endpoint (9)
Change in American College of Rheumatology (ACR) score components
Measured: up to 52 weeks
Clinical secondary endpoint (10)
Change in Simplified Disease Activity Index (SDAI)
Measured: up to 52 weeks
Clinical secondary endpoint (11)
Change in Clinical Disease Activity Index (CDAI)
Measured: up to 52 weeks
Clinical secondary endpoint (12)
Number of flares
Measured: 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
Measured: visit week 24
cellular and humoral response (2)
Duration of persistence of CAR T cells in the peripheral blood
Measured: up to 52 weeks
cellular and humoral response (3)
Duration of B cell depletion in the peripheral blood
Measured: up to 52 weeks
cellular and humoral response (4)
Expansion of CAR T cells in the patient over time
Measured: up to 52 weeks
cellular and humoral response (5)
Change in Anti-citrullinated protein antibody (ACPA) levels (mU/ml) over time
Measured: up to 52 weeks
cellular and humoral response (6)
Change in Rheumatoid Factor (RF) levels (U/ml) over time
Measured: 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
Measured: up to 52 weeks
cellular and humoral response (8)
Change in levels of Anti-citrullinated protein antibody (ACPA) isotypes at week over time
Measured: up to 52 weeks
cellular and humoral response (9)
Change in levels of IgG subclasses at week over time
Measured: up to 52 weeks
cellular and humoral response (10)
Change in IgM immunoglobulins over time
Measured: up to 52 weeks
cellular and humoral response (11)
Change in total IgA immunoglobulins over time
Measured: up to 52 weeks
cellular and humoral response (12)
Change in IgG immunoglobulins subclasses over time
Measured: up to 52 weeks
cellular and humoral response (13)
Change in total IgG immunoglobulins over time
Measured: 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
Measured: up to 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Dec 2024Jun 2027

First posted26 Jun 2024
Study start4 Dec 2024
Primary completionJun 2027 (estimated)
Study completionJun 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (16)Papers the sponsor has linked to this study.
Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: 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
Masking: None (open label)
Enrolment: 13 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06475495
Sponsor's protocol ID: CCM-RNT-202401
Other IDs: 2024-514955-13-00
Acronym: COMPARE
Status last verified: Mar 2026
First submitted: 13 Jun 2024
Last updated: 5 Mar 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: results will be published anonymized and summarized

Publications

van Vollenhoven RF, Fleischmann RM, Furst DE, Lacey S, Lehane PB. Longterm Safety of Rituximab: Final Report of the Rheumatoid Arthritis Global Clinical Trial Program over 11 Years. J Rheumatol. 2015 Oct;42(10):1761-6. doi: 10.3899/jrheum.150051. Epub 2015 Aug 15.
PubMed 26276965
Stemmler F, Simon D, Liphardt AM, Englbrecht M, Rech J, Hueber AJ, Engelke K, Schett G, Kleyer A. Biomechanical properties of bone are impaired in patients with ACPA-positive rheumatoid arthritis and associated with the occurrence of fractures. Ann Rheum Dis. 2018 Jul;77(7):973-980. doi: 10.1136/annrheumdis-2017-212404. Epub 2018 Feb 23.
PubMed 29475856
Tedder TF. CD19: a promising B cell target for rheumatoid arthritis. Nat Rev Rheumatol. 2009 Oct;5(10):572-7. doi: 10.1038/nrrheum.2009.184.
PubMed 19798033
Greco R, Alexander T, Del Papa N, Muller F, Saccardi R, Sanchez-Guijo F, Schett G, Sharrack B, Snowden JA, Tarte K, Onida F, Sanchez-Ortega I, Burman J, Castilla Llorente C, Cervera R, Ciceri F, Doria A, Henes J, Lindsay J, Mackensen A, Muraro PA, Ricart E, Rovira M, Zuckerman T, Yakoub-Agha I, Farge D. Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee. EClinicalMedicine. 2024 Feb 10;69:102476. doi: 10.1016/j.eclinm.2024.102476. eCollection 2024 Mar.
PubMed 38361991
Brudno JN, Lam N, Vanasse D, Shen YW, Rose JJ, Rossi J, Xue A, Bot A, Scholler N, Mikkilineni L, Roschewski M, Dean R, Cachau R, Youkharibache P, Patel R, Hansen B, Stroncek DF, Rosenberg SA, Gress RE, Kochenderfer JN. Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma. Nat Med. 2020 Feb;26(2):270-280. doi: 10.1038/s41591-019-0737-3. Epub 2020 Jan 20.
PubMed 31959992
Kastbom A, Strandberg G, Lindroos A, Skogh T. Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project). Ann Rheum Dis. 2004 Sep;63(9):1085-9. doi: 10.1136/ard.2003.016808.
PubMed 15308517
Mackensen A, Muller F, Mougiakakos D, Boltz S, Wilhelm A, Aigner M, Volkl S, Simon D, Kleyer A, Munoz L, Kretschmann S, Kharboutli S, Gary R, Reimann H, Rosler W, Uderhardt S, Bang H, Herrmann M, Ekici AB, Buettner C, Habenicht KM, Winkler TH, Kronke G, Schett G. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022 Oct;28(10):2124-2132. doi: 10.1038/s41591-022-02017-5. Epub 2022 Sep 15.
PubMed 36109639
Schett G, Mackensen A, Mougiakakos D. CAR T-cell therapy in autoimmune diseases. Lancet. 2023 Nov 25;402(10416):2034-2044. doi: 10.1016/S0140-6736(23)01126-1. Epub 2023 Sep 22.
PubMed 37748491
Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004 Jun 17;350(25):2572-81. doi: 10.1056/NEJMoa032534.
PubMed 15201414
Muller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Volkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schafer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Kronke G, Mackensen A, Schett G. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med. 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917.
PubMed 38381673
Mougiakakos D, Kronke G, Volkl S, Kretschmann S, Aigner M, Kharboutli S, Boltz S, Manger B, Mackensen A, Schett G. CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2021 Aug 5;385(6):567-569. doi: 10.1056/NEJMc2107725. No abstract available.
PubMed 34347960
Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, Keystone EC, Loveless JE, Burmester GR, Cravets MW, Hessey EW, Shaw T, Totoritis MC; REFLEX Trial Group. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006 Sep;54(9):2793-806. doi: 10.1002/art.22025.
PubMed 16947627
Hilliquin S, Herrou J, Gutermann L, Goulvestre C, Avouac J, Henry J, Hilliquin P, Dougados M, Molto A. Changes of anti-citrullinated peptide antibodies titers after biologic treatment in patients with rheumatoid arthritis: a systematic literature review and retrospective study. Clin Exp Rheumatol. 2023 Jul;41(7):1417-1426. doi: 10.55563/clinexprheumatol/1h6h71. Epub 2022 Dec 7.
PubMed 36533995
Teng YK, Wheater G, Hogan VE, Stocks P, Levarht EW, Huizinga TW, Toes RE, van Laar JM. Induction of long-term B-cell depletion in refractory rheumatoid arthritis patients preferentially affects autoreactive more than protective humoral immunity. Arthritis Res Ther. 2012 Mar 12;14(2):R57. doi: 10.1186/ar3770.
PubMed 22409963
Zhang B, Wang Y, Yuan Y, Sun J, Liu L, Huang D, Hu J, Wang M, Li S, Song W, Chen H, Zhou D, Zhang X. In vitro elimination of autoreactive B cells from rheumatoid arthritis patients by universal chimeric antigen receptor T cells. Ann Rheum Dis. 2021 Feb;80(2):176-184. doi: 10.1136/annrheumdis-2020-217844. Epub 2020 Sep 30.
PubMed 32998865

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT06475495
Acronym / sponsor ID: COMPARE / CCM-RNT-202401
Conditions: Rheumatoid Arthritis
Keywords: treatment refractory, ACPA-positive, difficult-to-treat
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 13 participants (estimated)
Lead sponsor: Charite University, Berlin, GermanyUniversity, hospital or other
Collaborators: Kyverna Therapeutics
Study start: 4 Dec 2024 (actual)
Primary completion: Jun 2027 (estimated)
Study completion: Jun 2027 (estimated)
First posted: 26 Jun 2024 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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)

Follow-up time (both arms) is 52 weeks with regular visits at the site.

Detailed description

Follow-up time (both arms) is 52 weeks with regular visits at the site.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: 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

Arm	Type	Receives
KYV101	Experimental	Drug: KYV101Participants in this arm will receive a single dose of KYV-101 i.v., an autologous fully-human anti-CD19 CAR T-cell immunotherapy.
Rituximab	Active comparator	Drug: Rituximab (active comparator)In the Comparator group patients will receive 2x1 g Rituximab i.v. (Day 0 and Day 14). Retreatment of 1000 mg rituximab i.v. may be initiated at week 24 if residual disease activity remains, otherwise retreatment should be delayed until disease activity returns. A DAS-28-CRP > 3.2 will be used as a non-binding guidance for the re-treatment decision.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
KYV101an autologous fully-human anti-CD19 CAR T-cell immunotherapy	Drug	KYV101
Rituximab (active comparator)anti CD20 monoclonal antibody	Drug	Rituximab

Primary outcome

Safety Phase I (1) Safety
Time frame: up to week 52
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.
Safety Phase I (2) Safety
Time frame: up to 52 weeks
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.
Safety Phase I (3) Safety
Time frame: up to 52 weeks
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.
Safety Phase I (4) Safety
Time frame: up to 52 weeks
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.
Efficacy Phase II
Time frame: visit week 16
Percentage of subjects with ACPA seroconversion = ACPA level <20 mU/ml at week 16.
Safety Phase II (1)
Time frame: up to 52 weeks
AE due to IMP and rituximab throughout the whole study
Safety Phase II (2)
Time frame: up to 52 weeks
SAE due to IMP and rituximab throughout the whole study

26 secondary outcomes

Clinical secondary endpoint (1)
Time frame: from week 7 to week 52
Clinical secondary endpoint (2)
Time frame: from week 7 to week 52
Clinical secondary endpoint (3)
Time frame: up to 52 weeks
Clinical secondary endpoint (4)
Time frame: up to 52 weeks
Clinical secondary endpoint (5)
Time frame: up to 52 weeks
Clinical secondary endpoint (6)
Time frame: up to 52 weeks
Clinical secondary endpoint (7)
Time frame: up to 52 weeks
Clinical secondary endpoint (8)
Time frame: up to 52 weeks
Clinical secondary endpoint (9)
Time frame: up to 52 weeks
Clinical secondary endpoint (10)
Time frame: up to 52 weeks
Clinical secondary endpoint (11)
Time frame: up to 52 weeks
Clinical secondary endpoint (12)
Time frame: up to 52 weeks
cellular and humoral response (1)
Time frame: visit week 24
cellular and humoral response (2)
Time frame: up to 52 weeks
cellular and humoral response (3)
Time frame: up to 52 weeks
cellular and humoral response (4)
Time frame: up to 52 weeks
cellular and humoral response (5)
Time frame: up to 52 weeks
cellular and humoral response (6)
Time frame: up to 52 weeks
cellular and humoral response (7)
Time frame: up to 52 weeks
cellular and humoral response (8)
Time frame: up to 52 weeks
cellular and humoral response (9)
Time frame: up to 52 weeks
cellular and humoral response (10)
Time frame: up to 52 weeks
cellular and humoral response (11)
Time frame: up to 52 weeks
cellular and humoral response (12)
Time frame: up to 52 weeks
cellular and humoral response (13)
Time frame: up to 52 weeks
cellular and humoral response (14)
Time frame: up to 52 weeks

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2026.
Background: PubMed 26276965van Vollenhoven RF, Fleischmann RM, Furst DE, Lacey S, Lehane PB. Longterm Safety of Rituximab: Final Report of the Rheumatoid Arthritis Global Clinical Trial Program over 11 Years. J Rheumatol. 2015 Oct;42(10):1761-6. doi: 10.3899/jrheum.150051. Epub 2015 Aug 15.
Background: PubMed 29475856Stemmler F, Simon D, Liphardt AM, Englbrecht M, Rech J, Hueber AJ, Engelke K, Schett G, Kleyer A. Biomechanical properties of bone are impaired in patients with ACPA-positive rheumatoid arthritis and associated with the occurrence of fractures. Ann Rheum Dis. 2018 Jul;77(7):973-980. doi: 10.1136/annrheumdis-2017-212404. Epub 2018 Feb 23.
Background: PubMed 19798033Tedder TF. CD19: a promising B cell target for rheumatoid arthritis. Nat Rev Rheumatol. 2009 Oct;5(10):572-7. doi: 10.1038/nrrheum.2009.184.
Background: PubMed 38361991Greco R, Alexander T, Del Papa N, Muller F, Saccardi R, Sanchez-Guijo F, Schett G, Sharrack B, Snowden JA, Tarte K, Onida F, Sanchez-Ortega I, Burman J, Castilla Llorente C, Cervera R, Ciceri F, Doria A, Henes J, Lindsay J, Mackensen A, Muraro PA, Ricart E, Rovira M, Zuckerman T, Yakoub-Agha I, Farge D. Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee. EClinicalMedicine. 2024 Feb 10;69:102476. doi: 10.1016/j.eclinm.2024.102476. eCollection 2024 Mar.
Background: PubMed 31959992Brudno JN, Lam N, Vanasse D, Shen YW, Rose JJ, Rossi J, Xue A, Bot A, Scholler N, Mikkilineni L, Roschewski M, Dean R, Cachau R, Youkharibache P, Patel R, Hansen B, Stroncek DF, Rosenberg SA, Gress RE, Kochenderfer JN. Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma. Nat Med. 2020 Feb;26(2):270-280. doi: 10.1038/s41591-019-0737-3. Epub 2020 Jan 20.
Background: PubMed 15308517Kastbom A, Strandberg G, Lindroos A, Skogh T. Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project). Ann Rheum Dis. 2004 Sep;63(9):1085-9. doi: 10.1136/ard.2003.016808.
Background: PubMed 36109639Mackensen A, Muller F, Mougiakakos D, Boltz S, Wilhelm A, Aigner M, Volkl S, Simon D, Kleyer A, Munoz L, Kretschmann S, Kharboutli S, Gary R, Reimann H, Rosler W, Uderhardt S, Bang H, Herrmann M, Ekici AB, Buettner C, Habenicht KM, Winkler TH, Kronke G, Schett G. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022 Oct;28(10):2124-2132. doi: 10.1038/s41591-022-02017-5. Epub 2022 Sep 15.
Background: PubMed 37748491Schett G, Mackensen A, Mougiakakos D. CAR T-cell therapy in autoimmune diseases. Lancet. 2023 Nov 25;402(10416):2034-2044. doi: 10.1016/S0140-6736(23)01126-1. Epub 2023 Sep 22.
Background: PubMed 15201414Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004 Jun 17;350(25):2572-81. doi: 10.1056/NEJMoa032534.
Background: PubMed 38381673Muller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Volkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schafer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Kronke G, Mackensen A, Schett G. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med. 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917.
Background: PubMed 34347960Mougiakakos D, Kronke G, Volkl S, Kretschmann S, Aigner M, Kharboutli S, Boltz S, Manger B, Mackensen A, Schett G. CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2021 Aug 5;385(6):567-569. doi: 10.1056/NEJMc2107725. No abstract available.
Background: PubMed 16947627Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, Keystone EC, Loveless JE, Burmester GR, Cravets MW, Hessey EW, Shaw T, Totoritis MC; REFLEX Trial Group. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006 Sep;54(9):2793-806. doi: 10.1002/art.22025.
Individual participant dataSharing planned: No. results will be published anonymized and summarized

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David Simon, Professor Dr. med. principal investigator

Charite University, Berlin, Germany

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing KYV101 and Rituximab (active comparator) in people with Rheumatoid Arthritis, run by Charite University, Berlin, Germany at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety Phase I (1) Safety (time frame: up to week 52). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06475495, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2026; AzTrials last refreshed its copy on 8 Nov 2026.