UPCC 03023 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 (KYSA-1) (ACC-RELEVANT)

Investigating the Use of Investigational CAR T-Cell Therapy in Refractory Lupus Nephritis

Administratively Closed
18 years or above
All
Phase 1/2
6 participants needed
1 Location

Brief description of study

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

Detailed description of study

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.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Lupus Nephritis, Lupus Nephritis - World Health Organization (WHO) Class III, Lupus Nephritis - WHO Class IV
  • Age: 18 years or above
  • Gender: All

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

This study investigates the use of investigational CAR T-cell therapy in adults with refractory lupus nephritis. The investigational therapy aims to target and reduce the B cells that contribute to the disease.

Participants in the study will receive an investigational CAR T-cell therapy, which includes using modified T cells to target and destroy B cells involved in lupus nephritis. This approach uses the body's own immune cells to potentially reduce inflammation and damage caused by the disease. The study will monitor the effects of this treatment on participants' kidney function and overall health.

  • Who can participate: Adults aged 18 and older with a clinical diagnosis of systemic lupus erythematosus and biopsy-proven lupus nephritis Class III or IV can participate. Participants must have specific antibody markers and be up to date on vaccinations.
  • Study details: Participants will receive an investigational CAR T-cell therapy, which involves using modified immune cells to target and destroy specific B cells in the body. This approach aims to reduce inflammation and damage caused by lupus nephritis.
Updated on 28 Jul 2026. Study ID: 23-0843

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