KYSA-1: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Refractory Lupus Nephritis

NCT ID: NCT05938725

Last Updated: 2025-10-29

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-28
• Study Completion Date: 2027-08-31

Brief Summary

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

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.

Conditions

Lupus Nephritis; Lupus Nephritis - World Health Organization (WHO) Class III; Lupus Nephritis - WHO Class IV

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 1)

Dosing with KYV-101 CAR T cells

Group Type: EXPERIMENTAL

KYV-101 anti-CD19 CAR-T cell therapy

Intervention Type: BIOLOGICAL

KYV-101 anti-CD19 CAR-T cell therapy

Standard lymphodepletion regimen

Intervention Type: DRUG

Standard lymphodepletion regimen

KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 2)

Recommended Phase 2 Dose

Group Type: EXPERIMENTAL

KYV-101 anti-CD19 CAR-T cell therapy

Intervention Type: BIOLOGICAL

KYV-101 anti-CD19 CAR-T cell therapy

Standard lymphodepletion regimen

Intervention Type: DRUG

Standard lymphodepletion regimen

Interventions

KYV-101 anti-CD19 CAR-T cell therapy

KYV-101 anti-CD19 CAR-T cell therapy

Intervention Type: BIOLOGICAL

Standard lymphodepletion regimen

Standard lymphodepletion regimen

Intervention Type: DRUG

Other Intervention Names

Cyclophosphamide; Fludarabine

Eligibility Criteria

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 (COVID-19)/ severe acute respiratory syndrome coronavirus 2 (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 immunotherapy (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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kyverna Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Kyverna Therapeutics

Locations

Stanford University Medical Center

Palo Alto, California, United States

University of Colorado

Denver, Colorado, United States

University of Massachusetts Worcester

Worcester, Massachusetts, United States

Northwell Health

Great Neck, New York, United States

Ohio State University Wexner Medical Center

Columbus, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 31959992 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 36109639 (View on PubMed)

Other Identifiers

KYV101-001

Identifier Type: OTHER

Identifier Source: secondary_id

KYSA-1

Identifier Type: -

Identifier Source: org_study_id