A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Refractory Lupus Nephritis

• ClinicalTrials.gov Identifier: NCT05938725
• Recruitment Status: Recruiting
• First Posted: July 10, 2023
• Last Update Posted: May 7, 2024
• Sponsor: Kyverna Therapeutics
• Information provided by (Responsible Party): Kyverna Therapeutics

Tracking Information

• First Submitted Date: October 11, 2022
• First Posted Date: July 10, 2023
• Last Update Posted Date: May 7, 2024
• Actual Study Start Date: April 28, 2023
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 16, 2024)

• Incidence adverse events (AEs) and laboratory abnormalities (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
• Frequency of dose limiting toxicities at each dose level (Phase 1) [ Time Frame: Up to 2 years ]
• To Evaluate efficacy (Phase 2) [ Time Frame: Up to 52 Weeks ]
  Complete renal response rates (CRR)

Original Primary Outcome Measures (submitted: July 7, 2023)

• Incidence adverse events (AEs) and laboratory abnormalities [ Time Frame: Up to 24 months ]
• Frequency of dose limiting toxicities at each dose level [ Time Frame: Up to 24 months ]

Current Secondary Outcome Measures (submitted: April 16, 2024)

• To characterize the pharmacokinetics (PK) (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
  Levels of KYV-101 CAR-positive T cells in the blood
• To characterize the pharmacodynamics (PD) (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
  Levels of B cells in the blood
• To characterize the pharmacodynamics (PD) (Phase 1 and Phase 2) [ Time Frame: Up to 2 months ]
  Levels of cytokines in serum
• To evaluate disease related biomarkers (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
  Levels of anti-double stranded DNA (anti-dsDNA) in serum
• To evaluate disease related biomarkers (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
  Levels of complement C3, C4 in serum
• To evaluate efficacy (Phase 1 and Phase 2) [ Time Frame: 12, 24, and 52 weeks ]
  Complete renal response rates (CRR)
• To evaluate efficacy (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
  Time to Complete renal response rates (CRR)
• To evaluate efficacy (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
  Time from first achieved CRR to disease worsening or end of study
• To evaluate efficacy (Phase 2) [ Time Frame: Up to 52 weeks ]
  Duration of CRR to Week 52 but no less than 12 weeks (duration of remission)
• To evaluate the immunogenicity (humoral response) of KYV-101 (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
  Percentage of participants who develop anti-KYV-101 antibodies by immunoassays
• To assess PRO after infusion of KYV-101 (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
  Change from Baseline in SF-36
• To assess PRO after infusion of KYV-101 (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
  Change from Baseline in FACIT-F
• To assess PRO after infusion of KYV-101 (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
  Change from Baseline in Lupus QoL Questionnaire
• To assess PRO after infusion of KYV-101 (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
  Change from Baseline in WPAI
• To define the Recommended Phase 2 Dose (RP2D) (Phase 1) [ Time Frame: Up to 2 years ]

Original Secondary Outcome Measures (submitted: July 7, 2023)

• To characterize the pharmacokinetics (PK) [ Time Frame: Up to 2 years ]
  Levels of KYV-101 CAR-positive T cells in the blood
• To characterize the pharmacodynamics (PD) [ Time Frame: Up to 2 years ]
  Levels of B cells in the blood
• To characterize the pharmacodynamics (PD) [ Time Frame: Up to 2 months ]
  Levels of cytokines in serum
• To evaluate disease related biomarkers [ Time Frame: Up to 2 years ]
  Levels of anti-double stranded DNA (anti-dsDNA) in serum
• To evaluate disease related biomarkers [ Time Frame: Up to 2 years ]
  Levels of complement C3, C4 in serum
• To evaluate efficacy [ Time Frame: 12, 24, and 52 weeks ]
  Complete renal response rates (CRR)
• To evaluate efficacy [ Time Frame: Up to 2 years ]
  Time to CRR
• To evaluate efficacy [ Time Frame: Up to 2 years ]
  Time from first achieved CRR to disease worsening or end of study
• To evaluate the immunogenicity (humoral response) of KYV-101 [ Time Frame: Up to 2 years ]
  Percentage of participants who develop anti-KYV-101 antibodies by immunoassays

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Refractory Lupus Nephritis
• Official Title: 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)
• 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.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Lupus Nephritis
• Lupus Nephritis - World Health Organization (WHO) Class III
• Lupus Nephritis - WHO Class IV

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
  Other Names:

  • Cyclophosphamide
  • Fludarabine

Study Arms

• Experimental: KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 1)
  Dosing with KYV-101 CAR T cells
  Interventions:

  • Biological: KYV-101 anti-CD19 CAR-T cell therapy
  • Drug: Standard lymphodepletion regimen
• Experimental: KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 2)
  Recommended Phase 2 Dose
  Interventions:

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

Publications *

• 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.
• 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;:

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 16, 2024): 32
• Original Estimated Enrollment (submitted: July 7, 2023): 12
• Estimated Study Completion Date: August 2026
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Kyverna Therapeutics; 510-925-2484; Clinicaltrials@kyvernatx.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05938725
• Other Study ID Numbers: KYV101-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Kyverna Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Kyverna Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Kyverna Therapeutics

• PRS Account: Kyverna Therapeutics
• Verification Date: April 2024