A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Refractory Lupus Nephritis (KYSA-3)

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-3)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06342960
• Other study ID #: KYV101-003
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 1, 2022
• Est. completion date: January 2029

Study information

• Verified date: June 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: January 2029
• Est. primary completion date: October 2028
• 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/ 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:

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 therapy (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
Germany	Charite- Universitätsklinikum Berlin	Berlin
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg

Sponsors (1)

Lead Sponsor	Collaborator
Kyverna Therapeutics

Country where clinical trial is conducted

Germany, 

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 (Phase 1)		Up to 2 years
Secondary	To characterize the pharmacokinetics (PK) (Phase 1 and 2)	Levels of KYV-101 CAR-positive T cells in the blood	Up to 2 years
Secondary	To characterize the pharmacokinetics (PK) (Phase 1 and 2)	Levels of KYV-101 CAR Transgene	Up to 2 years
Secondary	To characterize the pharmacodynamics (PD) (Phase 1 and 2)	Levels of B cells in the blood	Up to 2 years
Secondary	To characterize the pharmacodynamics (PD) (Phase 1 and 2)	Levels of systemic cytokine concentrations in serum	Up to 2 months
Secondary	To evaluate disease related biomarkers (Phase 1 and 2)	Levels of anti-double stranded DNA (anti-dsDNA) in serum	Up to 2 years
Secondary	To evaluate disease related biomarkers (Phase 1 and 2)	Levels of complement C3, C4 in serum	Up to 2 years
Secondary	To evaluate efficacy of KYV-101 (Phase 1 and 2)	Complete renal response rates (CRR)	12, 24, and 52 weeks
Secondary	To evaluate efficacy of KYV-101 (Phase 1 and 2)	Time to Complete renal response (CRR)	Up to 2 years
Secondary	To evaluate efficacy of KYV-101 (Phase 1 and 2)	Time from first achieved Complete renal response (CRR) to disease worsening or end of study	Up to 2 years
Secondary	To evaluate the immunogenicity (humoral response) of KYV-101 (Phase 1 and 2)	Percentage of participants who develop anti-KYV-101 antibodies by immunoassays	Up to 2 years
Secondary	To access Patient Related Outcome (PRO) after infusion of KYV-101 (Phase 1 and 2)	Change from baseline in 36-Item Short Form Survey (SF-36)	Up to 2 years
Secondary	To access Patient Related Outcome (PRO) after infusion of KYV-101 (Phase 1 and 2)	Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F)	Up to 2 years
Secondary	To access Patient Related Outcome (PRO) after infusion of KYV-101 (Phase 1 and 2)	Change from baseline in Lupus Quality of Life (Qol) Questionnaire	Up to 2 years
Secondary	To access Patient Related Outcome (PRO) after infusion of KYV-101 (Phase 1 and 2)	Change from baseline in Work Productivity and Activity Impairment (WPAI)	Up to 2 years
Secondary	To define the recommended Phase 2 dose (Phase 1)		Up to 2 years