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

NCT06475495 | Active Not Recruiting Phase 1

• 2 other identifiers: CCM-RNT-2024012024-514955-13-00
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Rheumatoid Arthritis

Keywords

treatment refractory; ACPA-positive; difficult-to-treat

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (26)

• Clinical secondary endpoint (1)

  from week 7 to week 52

• Clinical secondary endpoint (2)

  from week 7 to week 52

• Clinical secondary endpoint (3)

  up to 52 weeks

• Clinical secondary endpoint (4)

  up to 52 weeks

• Clinical secondary endpoint (5)

  up to 52 weeks

Study Arms (2)

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.

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.

Drug: Rituximab (active comparator)

Interventions

KYV101 DRUG

an autologous fully-human anti-CD19 CAR T-cell immunotherapy

KYV101

Rituximab (active comparator) DRUG

anti CD20 monoclonal antibody

Rituximab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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,

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Kyverna Therapeutics: collaborator

Study Sites (1)

Charité - Universitätsmedizin Berlin

Berlin, State of Berlin, 10117, Germany

Location

Related Publications (15)

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• 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.

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  PMID: 37748491 BACKGROUND

• 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.

  PMID: 15201414 BACKGROUND

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MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David Simon, Professor Dr. med.

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med. David Simon

Model Details: 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

Study Record Dates

• First Submitted: June 13, 2024
• First Posted: June 26, 2024
• Study Start: December 4, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)