Anti-CD19 CAR T-cell therapy for refractory lupus nephritis
KYSA-1: 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
This study is testing a new CAR T-cell therapy to see if it can help adults with tough-to-treat lupus nephritis feel better and improve their kidney function.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 32 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Kyverna Therapeutics Industry-sponsored |
| Drugs / interventions | CAR-T, immunotherapy, Chimeric Antigen Receptor, CAR T |
| Locations | 6 sites (Palo Alto, California and 5 other locations) |
| Trial ID | NCT05938725 on ClinicalTrials.gov |
What this trial studies
This study investigates the use of KYV-101, an anti-CD19 chimeric antigen receptor T-cell therapy, in adults with refractory lupus nephritis, a severe manifestation of systemic lupus erythematosus. The approach targets B cells, which play a crucial role in the disease's pathology, by utilizing CAR T-cells to deplete these cells from circulation and tissues. Participants will undergo a standard lymphodepletion regimen prior to receiving the CAR T-cell therapy. The study aims to evaluate the safety and efficacy of this innovative treatment in improving renal function and reducing disease activity.
Who should consider this trial
Good fit: Ideal candidates for this study are adults aged 18 and older with a clinical diagnosis of systemic lupus erythematosus and biopsy-proven proliferative lupus nephritis Class III or IV.
Not a fit: Patients with rapidly progressive glomerulonephritis or severe central nervous system lupus may not benefit from this study.
Why it matters
Potential benefit: If successful, this therapy could provide a new treatment option for patients suffering from refractory lupus nephritis, potentially improving their kidney function and overall quality of life.
How similar studies have performed: While CAR T-cell therapies have shown promise in treating various hematological malignancies, their application in autoimmune diseases like lupus nephritis is relatively novel and untested.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Palo Alto, California and 5 other locations
- Stanford University Medical Center — Palo Alto, California, United States (Recruiting)
- University of Colorado — Denver, Colorado, United States (Recruiting)
- University of Massachusetts Worcester — Worcester, Massachusetts, United States (Recruiting)
- Northwell Health — Great Neck, New York, United States (Recruiting)
- Ohio State University Wexner Medical Center — Columbus, Ohio, United States (Recruiting)
- University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)
Study contacts
- Study coordinator: Kyverna Therapeutics
- Email: Clinicaltrials@kyvernatx.com
- Phone: 510-925-2484
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.