KYSA-1: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Refractory Lupus Nephritis

NCT05938725 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: KYSA-1KYV101-001
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 6

Brief Summary

A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Subjects With Refractory Lupus Nephritis

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Incidence adverse events (AEs) and laboratory abnormalities (Phase 1 and Phase 2)

  Up to 2 years

• Frequency of dose limiting toxicities at each dose level (Phase 1)

  Up to 2 years

• To Evaluate efficacy (Phase 2)

  Complete renal response rates (CRR)

  Up to 52 Weeks

Secondary Outcomes (15)

• To characterize the pharmacokinetics (PK) (Phase 1 and Phase 2)

  Up to 2 years

• To characterize the pharmacodynamics (PD) (Phase 1 and Phase 2)

  Up to 2 years

• To characterize the pharmacodynamics (PD) (Phase 1 and Phase 2)

  Up to 2 months

• To evaluate disease related biomarkers (Phase 1 and Phase 2)

  Up to 2 years

• To evaluate disease related biomarkers (Phase 1 and Phase 2)

  Up to 2 years

Study Arms (2)

KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 1)

EXPERIMENTAL

Dosing with KYV-101 CAR T cells

Biological: KYV-101 anti-CD19 CAR-T cell therapy; Drug: Standard lymphodepletion regimen

KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 2)

EXPERIMENTAL

Recommended Phase 2 Dose

Biological: KYV-101 anti-CD19 CAR-T cell therapy; Drug: Standard lymphodepletion regimen

Interventions

KYV-101 anti-CD19 CAR-T cell therapy BIOLOGICAL

KYV-101 anti-CD19 CAR-T cell therapy

KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 1); KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 2)

Standard lymphodepletion regimen DRUG

Standard lymphodepletion regimen

Also known as: Cyclophosphamide, Fludarabine

KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 1); KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (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

You may not qualify if:

• Rapidly progressive glomerulonephritis; history of or currently active severe central nervous system (CNS) lupus, including cerebritis, cerebrovascular accident, and seizures
• Prior treatment with cellular immunotherapy (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

Sponsors & Collaborators

• Kyverna Therapeutics: lead

Study Sites (6)

Stanford University Medical Center

Palo Alto, California, 94305, United States

Location

University of Colorado

Denver, Colorado, 80045, United States

Location

University of Massachusetts Worcester

Worcester, Massachusetts, 01655, United States

Location

Northwell Health

Great Neck, New York, 11021, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related 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.

  PMID: 31959992 BACKGROUND

• 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.

  PMID: 36109639 BACKGROUND

MeSH Terms

Conditions

Lupus Nephritis; Glomerulonephritis; Autoimmune Diseases

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• MD

  Kyverna Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2022
• First Posted: July 10, 2023
• Study Start: April 28, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: October 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)