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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05938725
Other study ID # KYV101-001
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date April 28, 2023
Est. completion date August 2026

Study information

Verified date April 2024
Source Kyverna Therapeutics
Contact Kyverna Therapeutics
Phone 510-925-2484
Email Clinicaltrials@kyvernatx.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 32
Est. completion date August 2026
Est. primary completion date August 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
KYV-101 anti-CD19 CAR-T cell therapy
KYV-101 anti-CD19 CAR-T cell therapy
Drug:
Standard lymphodepletion regimen
Standard lymphodepletion regimen

Locations

Country Name City State
United States Ohio State University Wexner Medical Center Columbus Ohio
United States University of Colorado Denver Colorado
United States Northwell Health Great Neck New York
United States Stanford University Medical Center Palo Alto California
United States University of Pennsylvania Philadelphia Pennsylvania
United States University of Massachusetts Worcester Worcester Massachusetts

Sponsors (1)

Lead Sponsor Collaborator
Kyverna Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. Erratum In: Nat Med. 2020 May;26(5):803. — View 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. Erratum In: Nat Med. 2022 Nov 3;: — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence adverse events (AEs) and laboratory abnormalities (Phase 1 and Phase 2) Up to 2 years
Primary Frequency of dose limiting toxicities at each dose level (Phase 1) Up to 2 years
Primary To Evaluate efficacy (Phase 2) Complete renal response rates (CRR) Up to 52 Weeks
Secondary To characterize the pharmacokinetics (PK) (Phase 1 and Phase 2) Levels of KYV-101 CAR-positive T cells in the blood Up to 2 years
Secondary To characterize the pharmacodynamics (PD) (Phase 1 and Phase 2) Levels of B cells in the blood Up to 2 years
Secondary To characterize the pharmacodynamics (PD) (Phase 1 and Phase 2) Levels of cytokines in serum Up to 2 months
Secondary To evaluate disease related biomarkers (Phase 1 and Phase 2) Levels of anti-double stranded DNA (anti-dsDNA) in serum Up to 2 years
Secondary To evaluate disease related biomarkers (Phase 1 and Phase 2) Levels of complement C3, C4 in serum Up to 2 years
Secondary To evaluate efficacy (Phase 1 and Phase 2) Complete renal response rates (CRR) 12, 24, and 52 weeks
Secondary To evaluate efficacy (Phase 1 and Phase 2) Time to Complete renal response rates (CRR) Up to 2 years
Secondary To evaluate efficacy (Phase 1 and Phase 2) Time from first achieved CRR to disease worsening or end of study Up to 2 years
Secondary To evaluate efficacy (Phase 2) Duration of CRR to Week 52 but no less than 12 weeks (duration of remission) Up to 52 weeks
Secondary To evaluate the immunogenicity (humoral response) of KYV-101 (Phase 1 and Phase 2) Percentage of participants who develop anti-KYV-101 antibodies by immunoassays Up to 2 years
Secondary To assess PRO after infusion of KYV-101 (Phase 1 and Phase 2) Change from Baseline in SF-36 Up to 2 years
Secondary To assess PRO after infusion of KYV-101 (Phase 1 and Phase 2) Change from Baseline in FACIT-F Up to 2 years
Secondary To assess PRO after infusion of KYV-101 (Phase 1 and Phase 2) Change from Baseline in Lupus QoL Questionnaire Up to 2 years
Secondary To assess PRO after infusion of KYV-101 (Phase 1 and Phase 2) Change from Baseline in WPAI Up to 2 years
Secondary To define the Recommended Phase 2 Dose (RP2D) (Phase 1) Up to 2 years
See also
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