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

Lupus Nephritis Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05938725
• Other study ID #: KYV101-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• 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
• 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

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

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