Clinical trial NCT05938725: KYSA-1: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Refractory Lupus Nephritis
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Lupus Nephritis
Lupus Nephritis - World Health Organization (WHO) Class III
Lupus Nephritis - WHO Class IV
Keywords: KYV-101
glomerulonephritis
autoimmune disease
anti-CD19 CAR-T therapy
cellular therapy
Lead sponsor: Kyverna Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-07-10
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence adverse events (AEs) and laboratory abnormalities (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: Frequency of dose limiting toxicities at each dose level (Phase 1)
timeFrame: Up to 2 years
measure: To Evaluate efficacy (Phase 2)
timeFrame: Up to 52 Weeks
Secondary outcomes:
measure: To characterize the pharmacokinetics (PK) (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: To characterize the pharmacodynamics (PD) (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: To characterize the pharmacodynamics (PD) (Phase 1 and Phase 2)
timeFrame: Up to 2 months
measure: To evaluate disease related biomarkers (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: To evaluate disease related biomarkers (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: To evaluate efficacy (Phase 1 and Phase 2)
timeFrame: 12, 24, and 52 weeks
measure: To evaluate efficacy (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: To evaluate efficacy (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: To evaluate efficacy (Phase 2)
timeFrame: Up to 52 weeks
measure: To evaluate the immunogenicity (humoral response) of KYV-101 (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: To assess PRO after infusion of KYV-101 (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: To assess PRO after infusion of KYV-101 (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: To assess PRO after infusion of KYV-101 (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: To assess PRO after infusion of KYV-101 (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: To define the Recommended Phase 2 Dose (RP2D) (Phase 1)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Worcester
country: United States
facility: University of Massachusetts Worcester
state: Massachusetts
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Kyverna Therapeutics
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.