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

Sponsor

Kyverna Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05938725

Collaborator

(none)

Enrollment

Locations

Arm

39.1

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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

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

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 28, 2023

Anticipated Primary Completion Date :

Aug 1, 2025

Anticipated Study Completion Date :

Aug 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: KYV-101 CAR-T cells with lymphodepletion conditioning 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

Arm

Intervention/Treatment

Experimental: KYV-101 CAR-T cells with lymphodepletion conditioning

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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