This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05938725
Recruitment Status : Recruiting
First Posted : July 10, 2023
Last Update Posted : April 18, 2024
Sponsor:
Information provided by (Responsible Party):
Kyverna Therapeutics

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Subjects With Refractory Lupus Nephritis

Condition or disease Intervention/treatment Phase
Lupus Nephritis Lupus Nephritis - World Health Organization (WHO) Class III Lupus Nephritis - WHO Class IV Biological: KYV-101 anti-CD19 CAR-T cell therapy Drug: Standard lymphodepletion regimen Phase 1 Phase 2

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : April 28, 2023
Estimated Primary Completion Date : August 2025
Estimated Study Completion Date : August 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 1)
Dosing with KYV-101 CAR T cells
 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
Experimental: KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 2)
Recommended Phase 2 Dose
 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


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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


Secondary Outcome Measures :
  1. 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

  2. To characterize the pharmacodynamics (PD) (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
    Levels of B cells in the blood

  3. To characterize the pharmacodynamics (PD) (Phase 1 and Phase 2) [ Time Frame: Up to 2 months ]
    Levels of cytokines in serum

  4. 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

  5. To evaluate disease related biomarkers (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
    Levels of complement C3, C4 in serum

  6. To evaluate efficacy (Phase 1 and Phase 2) [ Time Frame: 12, 24, and 52 weeks ]
    Complete renal response rates (CRR)

  7. To evaluate efficacy (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
    Time to Complete renal response rates (CRR)

  8. 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

  9. 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)

  10. 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

  11. 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

  12. 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

  13. 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

  14. To assess PRO after infusion of KYV-101 (Phase 1 and Phase 2) [ Time Frame: Up to 2 years ]
    Change from Baseline in WPAI

  15. To define the Recommended Phase 2 Dose (RP2D) (Phase 1) [ Time Frame: Up to 2 years ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05938725


Contacts
Layout table for location contacts
Contact: Kyverna Therapeutics 510-925-2484 medicalmonitor@kyvernatx.com

Locations
Layout table for location information
United States, California
Stanford University Medical Center Recruiting
Palo Alto, California, United States, 94305
Contact: Study Coordinator         
United States, Colorado
University of Colorado Recruiting
Denver, Colorado, United States, 80045
Contact: Study Coordinator         
United States, Massachusetts
University of Massachusetts Worcester Recruiting
Worcester, Massachusetts, United States, 01655
Contact: Study Coordinator         
United States, New York
Northwell Health Recruiting
Great Neck, New York, United States, 11021
Contact: Study Coordinator         
United States, Ohio
Ohio State University Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Study Coordinator         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Study Coordinator         
Sponsors and Collaborators
Kyverna Therapeutics
Investigators
Layout table for investigator information
Study Director: MD Kyverna Therapeutics
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications:

Layout table for additonal information
Responsible Party: Kyverna Therapeutics
ClinicalTrials.gov Identifier: NCT05938725    
Other Study ID Numbers: KYV101-001
First Posted: July 10, 2023    Key Record Dates
Last Update Posted: April 18, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Keywords provided by Kyverna Therapeutics:
KYV-101
glomerulonephritis
autoimmune disease
anti-CD19 CAR-T therapy
cellular therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Nephritis
Lupus Nephritis
Kidney Diseases
Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases
Glomerulonephritis
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
 Immune System Diseases
Cyclophosphamide
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists