Back to resultsA Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Refractory Lupus Nephritis
Primary Purpose
Lupus Nephritis, Lupus Nephritis - World Health Organization (WHO) Class III, Lupus Nephritis - WHO Class IV
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
KYV-101 anti-CD19 CAR-T cell therapy
Standard lymphodepletion regimen
Sponsored by
About this trial
This is an interventional treatment trial for Lupus Nephritis focused on measuring KYV-101, glomerulonephritis, autoimmune disease, anti-CD19 CAR-T therapy, cellular therapy
Eligibility Criteria
Inclusion Criteria: Age ≥18 years Clinical diagnosis of SLE according to 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria Biopsy-proven proliferative LN Class III or IV according to 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria 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 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: Rapidly progressive glomerulonephritis; history of or currently active severe central nervous system (CNS) lupus, including cerebritis, cerebrovascular accident, and seizures Prior treatment with cellular therapy (CAR-T) or gene therapy product directed at any target History of allogeneic or autologous stem cell transplant Evidence of active hepatitis B or hepatitis C infection Positive serology for HIV Primary immunodeficiency History of splenectomy 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 Impaired cardiac function or clinically significant cardiac disease Previous or concurrent malignancy with the following exceptions: Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to screening) In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 5 years prior to screening
Sites / Locations
- University of ColoradoRecruiting
- Northwell HealthRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
KYV-101 CAR-T cells with lymphodepletion conditioning
Arm Description
Dosing with KYV-101 CAR T cells
Outcomes
Primary Outcome Measures
Incidence adverse events (AEs) and laboratory abnormalities
Frequency of dose limiting toxicities at each dose level
Secondary Outcome Measures
To characterize the pharmacokinetics (PK)
Levels of KYV-101 CAR-positive T cells in the blood
To characterize the pharmacodynamics (PD)
Levels of B cells in the blood
To characterize the pharmacodynamics (PD)
Levels of cytokines in serum
To evaluate disease related biomarkers
Levels of anti-double stranded DNA (anti-dsDNA) in serum
To evaluate disease related biomarkers
Levels of complement C3, C4 in serum
To evaluate efficacy
Complete renal response rates (CRR)
To evaluate efficacy
Time to CRR
To evaluate efficacy
Time from first achieved CRR to disease worsening or end of study
To evaluate the immunogenicity (humoral response) of KYV-101
Percentage of participants who develop anti-KYV-101 antibodies by immunoassays
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05938725
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, 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
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 28, 2023 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kyverna Therapeutics
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
KYV-101 CAR-T cells with lymphodepletion conditioning
Arm Type
Experimental
Arm Description
Dosing with KYV-101 CAR T cells
Intervention Type
Biological
Intervention Name(s)
KYV-101 anti-CD19 CAR-T cell therapy
Intervention Description
KYV-101 anti-CD19 CAR-T cell therapy
Intervention Type
Drug
Intervention Name(s)
Standard lymphodepletion regimen
Other Intervention Name(s)
Cyclophosphamide, Fludarabine
Intervention Description
Standard lymphodepletion regimen
Primary Outcome Measure Information:
Title
Incidence adverse events (AEs) and laboratory abnormalities
Time Frame
Up to 24 months
Title
Frequency of dose limiting toxicities at each dose level
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
To characterize the pharmacokinetics (PK)
Description
Levels of KYV-101 CAR-positive T cells in the blood
Time Frame
Up to 2 years
Title
To characterize the pharmacodynamics (PD)
Description
Levels of B cells in the blood
Time Frame
Up to 2 years
Title
To characterize the pharmacodynamics (PD)
Description
Levels of cytokines in serum
Time Frame
Up to 2 months
Title
To evaluate disease related biomarkers
Description
Levels of anti-double stranded DNA (anti-dsDNA) in serum
Time Frame
Up to 2 years
Title
To evaluate disease related biomarkers
Description
Levels of complement C3, C4 in serum
Time Frame
Up to 2 years
Title
To evaluate efficacy
Description
Complete renal response rates (CRR)
Time Frame
12, 24, and 52 weeks
Title
To evaluate efficacy
Description
Time to CRR
Time Frame
Up to 2 years
Title
To evaluate efficacy
Description
Time from first achieved CRR to disease worsening or end of study
Time Frame
Up to 2 years
Title
To evaluate the immunogenicity (humoral response) of KYV-101
Description
Percentage of participants who develop anti-KYV-101 antibodies by immunoassays
Time Frame
Up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥18 years
Clinical diagnosis of SLE according to 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria
Biopsy-proven proliferative LN Class III or IV according to 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria
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
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:
Rapidly progressive glomerulonephritis; history of or currently active severe central nervous system (CNS) lupus, including cerebritis, cerebrovascular accident, and seizures
Prior treatment with cellular therapy (CAR-T) or gene therapy product directed at any target
History of allogeneic or autologous stem cell transplant
Evidence of active hepatitis B or hepatitis C infection
Positive serology for HIV
Primary immunodeficiency
History of splenectomy
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
Impaired cardiac function or clinically significant cardiac disease
Previous or concurrent malignancy with the following exceptions:
Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to screening)
In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening
A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 5 years prior to screening
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kyverna Therapeutics
Phone
510-626-8708
Email
ClinicalTrials@kyvernatx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Kyverna Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
University of Colorado
City
Denver
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Facility Name
Northwell Health
City
Great Neck
State/Province
New York
ZIP/Postal Code
11021
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31959992
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. Erratum In: Nat Med. 2020 May;26(5):803.
Results Reference
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PubMed Identifier
36109639
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;:
Results Reference
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A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Refractory Lupus Nephritis
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