KYSA-5: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Systemic Sclerosis

KYSA-5: A Phase 1/2, Open-Label, Multicentre Study of KYV 101, an Autologous Fully Human Anti-CD19 Chimeric Antigen Receptor T Cell (CD19 CAR T) Therapy, in Subjects With Systemic Sclerosis

A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Subjects with Systemic Sclerosis

Study Overview

• Status: Active, not recruiting
• Conditions: Systemic Sclerosis; Systemic Sclerosis - Diffuse Cutaneous; Systemic Sclerosis - 2013 ACR/EULAR Classification Criteria
• Intervention / Treatment: Drug: Standard lymphodepletion regimen; Biological: KYV-101

Detailed Description

SSc is an immune-mediated rheumatic disease that is characterized by fibrosis of the skin and internal organs and vasculopathy. B-cells play a role in SSc, and the disease is characterized by the presence of autoantibodies such as anti-Scl-70 and anti-RNAP III antibodies. 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 systemic sclerosis.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94305
      • Stanford University Medical Center
  • New York
    • Great Neck, New York, United States, 11021
      • Northwell Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria

1. Clinical diagnosis of SSc according to 2013 ACR/EULAR classification
2. Clinical disease as follows: Classified as diffuse cutaneous SSc; ≤ 6 years since first non-Raynaud's sign or symptom; active disease
3. Up to date on all recommended vaccinations per CDC or institutional guidelines for immune-compromised individuals

Key Exclusion Criteria

1. Clinically significant ILD
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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 1); Dosing with KYV-101 CAR T cells	Drug: Standard lymphodepletion regimen; Standard lymphodepletion regimen; Other Names: Cyclophosphamide; Fludarabine; Biological: KYV-101; Anti-CD19 CAR-T cell therapy
Experimental: KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 2); Recommended Phase 2 Dose	Drug: Standard lymphodepletion regimen; Standard lymphodepletion regimen; Other Names: Cyclophosphamide; Fludarabine; Biological: KYV-101; Anti-CD19 CAR-T cell therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events and laboratory abnormalities (Phase 1)		Up to 2 years
Frequency of Dose-Limiting Toxicities (DLTs) at each dose level (Phase 1)		Up to 2 years
To evaluate efficacy of KYV-101(Phase 2)	via revised Composite Response Index in Systemic Sclerosis (rCRISS) 30/5	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To define the Recommended Phase 2 Dose (RP2D) (Phase 1)		Up to 2 years
To evaluate pharmacodynamics (PK) of KYV-101 in blood (Phase 1 and Phase 2)	Chimeric antigen receptor-positive (CAR-positive) T-cell counts in blood	Up to 2 years
To evaluate pharmacodynamics (PD) of KYV-101 in blood (Phase 1 and Phase 2)	Levels of B-cells in blood	Up to 2 years
To evaluate pharmacodynamics (PD) of KYV-101 in blood (Phase 1 and Phase 2)	Levels of cytokines in serum	Up to 2 years
To evaluate efficacy of KYV-101 (Phase 1 and Phase 2)	revised Composite Response Index in Systemic Sclerosis (rCRISS) 30/5 response rate	12, 24, 52 weeks
To evaluate 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

Collaborators and Investigators

• Sponsor: Kyverna Therapeutics
• Investigators: Study Director: MD, Kyverna Therapeutics, Inc.

Publications and helpful links

General Publications

• Bosello S, Angelucci C, Lama G, Alivernini S, Proietti G, Tolusso B, Sica G, Gremese E, Ferraccioli G. Characterization of inflammatory cell infiltrate of scleroderma skin: B cells and skin score progression. Arthritis Res Ther. 2018 Apr 18;20(1):75. doi: 10.1186/s13075-018-1569-0.

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: August 29, 2023
• First Submitted That Met QC Criteria: May 1, 2024
• First Posted (Actual): May 6, 2024

Study Record Updates

• Last Update Posted (Estimated): October 8, 2025
• Last Update Submitted That Met QC Criteria: October 6, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: cellular therapy; systemic sclerosis; autoimmune disease; Scleroderma; KYV-101; anti-CD19 CAR-T therapy
• Additional Relevant MeSH Terms: Connective Tissue Diseases; Immune System Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: KYSA-5; KYV101-005 (Other Identifier: Kyverna Therapeutics)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No