KYSA-3: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Refractory Lupus Nephritis

KYSA-3: A Phase 1/2, Open-Label, Multicenter Study of KYV-101, an Autologous Fully-Human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Refractory Lupus Nephritis

A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Subjects With Refractory Lupus Nephritis

Study Overview

• Status: Active, not recruiting
• Conditions: Lupus Nephritis; Lupus Nephritis - WHO Class IV; Lupus Nephritis - WHO Class III
• Intervention / Treatment: Biological: KYV-101 anti-CD19 CAR-T cell therapy; Drug: Standard lymphodepletion regimen

Detailed Description

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a wide spectrum of organ involvement and disease severity. Renal involvement (categorized as lupus nephritis [LN]) may occur in approximately 50% of SLE patients and is marked by proteinuria, microscopic hematuria, and varying degrees of renal insufficiency. B cells play a central role in the pathogenesis of SLE and LN, with autoantibodies developing as an early finding, and local, tissue resident B cells producing pathogenic autoantibodies and driving inflammation and tissue damage over time. CD19-targeted chimeric antigen receptor (CAR) T cells harness the ability of cytotoxic T cells to directly and specifically lyse target cells to effectively deplete B cells in the circulation and in lymphoid and potentially non-lymphoid tissues. KYV-101, a fully human anti-CD19 CAR T-cell therapy, will be investigated in adult subjects with refractory lupus nephritis.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Charite- Universitätsklinikum Berlin
  • Dresden, Germany
    • Universitatsklinikum Carl Gustav Carus Dresden
  • Düsseldorf, Germany
    • Universitatsklinikum Dusseldorf
  • Erlangen, Germany
    • Universitatsklinikum Erlangen
  • Frankfurt, Germany
    • Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP
  • Hamburg, Germany
    • Universitatsklinikum Hamburg-Eppendorf

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years
2. Clinical diagnosis of SLE according to 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria
3. Biopsy-proven proliferative LN Class III or IV according to 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria
4. Positive anti-nuclear antibody (ANA) (titer ≥1:80 ), anti-dsDNA (≥30 IU/mL on enzyme-linked immunosorbent assay [ELISA]), or anti-Smith at screening or by documented medical history
5. Up to date on recommended vaccinations, including against coronavirus disease 2019/ severe acute respiratory syndrome coronavirus 2 (Covid-19/SARS-Cov-2), per Centers for Disease Control and Prevention (CDC) or institutional guidelines for immune compromised individuals

Exclusion Criteria:

1. Rapidly progressive glomerulonephritis; history of or currently active severe central nervous system (CNS) lupus, including cerebritis, cerebrovascular accident, and seizures
2. Prior treatment with cellular therapy (CAR-T) or gene therapy product directed at any target
3. History of allogeneic or autologous stem cell transplant
4. Evidence of active hepatitis B or hepatitis C infection
5. Positive serology for HIV
6. Primary immunodeficiency
7. History of splenectomy
8. History of stroke, seizure, dementia, Parkinson's disease, coordination movement disorder, cerebellar diseases, psychosis, paresis, aphasia, and any other neurologic disorder investigator considers would increase the risk for the subject.
9. Impaired cardiac function or clinically significant cardiac disease

10. Previous or concurrent malignancy with the following exceptions:

    1. Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to screening)
    2. In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening
    3. A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 5 years prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 1); Dosing with KYV-101 CAR T cells	Biological: KYV-101 anti-CD19 CAR-T cell therapy; KYV-101 anti-CD19 CAR-T cell therapy; Drug: Standard lymphodepletion regimen; Standard lymphodepletion regimen; Other Names: Cyclophosphamide; Fludarabine
Experimental: KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 2); Recommended Phase 2 Dose	Biological: KYV-101 anti-CD19 CAR-T cell therapy; KYV-101 anti-CD19 CAR-T cell therapy; Drug: Standard lymphodepletion regimen; Standard lymphodepletion regimen; Other Names: Cyclophosphamide; Fludarabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence adverse events (AEs) and laboratory abnormalities (Phase 1 and Phase 2)	Up to 2 years
Frequency of dose limiting toxicities (Phase 1)	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterize the pharmacokinetics (PK) (Phase 1 and 2)	Levels of KYV-101 CAR-positive T cells in the blood	Up to 2 years
To characterize the pharmacokinetics (PK) (Phase 1 and 2)	Levels of KYV-101 CAR Transgene	Up to 2 years
To characterize the pharmacodynamics (PD) (Phase 1 and 2)	Levels of B cells in the blood	Up to 2 years
To characterize the pharmacodynamics (PD) (Phase 1 and 2)	Levels of systemic cytokine concentrations in serum	Up to 2 months
To evaluate disease related biomarkers (Phase 1 and 2)	Levels of anti-double stranded DNA (anti-dsDNA) in serum	Up to 2 years
To evaluate disease related biomarkers (Phase 1 and 2)	Levels of complement C3, C4 in serum	Up to 2 years
To evaluate efficacy of KYV-101 (Phase 1 and 2)	Complete renal response rates (CRR)	12, 24, and 52 weeks
To evaluate efficacy of KYV-101 (Phase 1 and 2)	Time to Complete renal response (CRR)	Up to 2 years
To evaluate efficacy of KYV-101 (Phase 1 and 2)	Time from first achieved Complete renal response (CRR) to disease worsening or end of study	Up to 2 years
To evaluate the immunogenicity (humoral response) of KYV-101 (Phase 1 and 2)	Percentage of participants who develop anti-KYV-101 antibodies by immunoassays	Up to 2 years
To access Patient Related Outcome (PRO) after infusion of KYV-101 (Phase 1 and 2)	Change from baseline in 36-Item Short Form Survey (SF-36)	Up to 2 years
To access Patient Related Outcome (PRO) after infusion of KYV-101 (Phase 1 and 2)	Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F)	Up to 2 years
To access Patient Related Outcome (PRO) after infusion of KYV-101 (Phase 1 and 2)	Change from baseline in Lupus Quality of Life (Qol) Questionnaire	Up to 2 years
To access Patient Related Outcome (PRO) after infusion of KYV-101 (Phase 1 and 2)	Change from baseline in Work Productivity and Activity Impairment (WPAI)	Up to 2 years
To define the recommended Phase 2 dose (Phase 1)		Up to 2 years

Collaborators and Investigators

• Sponsor: Kyverna Therapeutics
• Investigators: Study Director: MD, Kyverna Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: March 27, 2024
• First Submitted That Met QC Criteria: March 27, 2024
• First Posted (Actual): April 2, 2024

Study Record Updates

• Last Update Posted (Estimated): October 29, 2025
• Last Update Submitted That Met QC Criteria: October 27, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: SLE; Systemic lupus erythematosus; cellular therapy; glomerulonephritis; autoimmune disease; KYV-101; anti-CD19 CAR-T therapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Immune System Diseases; Nephritis; Skin and Connective Tissue Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis; Glomerulonephritis; Autoimmune Diseases; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: KYSA-3; KYV101-003 (Other Identifier: Kyverna Therapeutics)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes