Lupus Nephritis, Lupus Nephritis - WHO Class III, Lupus Nephritis - WHO Class IV
Conditions
Keywords
KYV-101, glomerulonephritis, autoimmune disease, anti-CD19 CAR-T therapy, cellular therapy, SLE, Systemic lupus erythematosus
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.
Interventions
BIOLOGICALKYV-101 anti-CD19 CAR-T cell therapy
KYV-101 anti-CD19 CAR-T cell therapy
Standard lymphodepletion regimen
Sponsors
Kyverna Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| To characterize the pharmacodynamics (PD) (Phase 1 and 2) | Up to 2 years | Levels of B cells in the blood |
| To evaluate disease related biomarkers (Phase 1 and 2) | Up to 2 years | Levels of anti-double stranded DNA (anti-dsDNA) in serum |
| To evaluate efficacy of KYV-101 (Phase 1 and 2) | 12, 24, and 52 weeks | Complete renal response rates (CRR) |
| To access Patient Related Outcome (PRO) after infusion of KYV-101 (Phase 1 and 2) | Up to 2 years | Change from baseline in 36-Item Short Form Survey (SF-36) |
| To define the recommended Phase 2 dose (Phase 1) | Up to 2 years | — |
| To evaluate the immunogenicity (humoral response) of KYV-101 (Phase 1 and 2) | Up to 2 years | Percentage of participants who develop anti-KYV-101 antibodies by immunoassays |
| To characterize the pharmacokinetics (PK) (Phase 1 and 2) | Up to 2 years | Levels of KYV-101 CAR-positive T cells in the blood |
Countries
Germany
Outcome results
None listed