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

NCT ID: NCT06400303

Last Updated: 2025-10-08

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-06
• Study Completion Date: 2027-03-31

Brief Summary

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

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.

Conditions

Systemic Sclerosis; Systemic Sclerosis - Diffuse Cutaneous; Systemic Sclerosis - 2013 ACR/EULAR Classification Criteria

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Dosing with KYV-101 CAR T cells

Group Type: EXPERIMENTAL

KYV-101

Intervention Type: BIOLOGICAL

Anti-CD19 CAR-T cell therapy

Standard lymphodepletion regimen

Intervention Type: DRUG

Standard lymphodepletion regimen

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

Recommended Phase 2 Dose

Group Type: EXPERIMENTAL

KYV-101

Intervention Type: BIOLOGICAL

Anti-CD19 CAR-T cell therapy

Standard lymphodepletion regimen

Intervention Type: DRUG

Standard lymphodepletion regimen

Interventions

KYV-101

Anti-CD19 CAR-T cell therapy

Intervention Type: BIOLOGICAL

Standard lymphodepletion regimen

Standard lymphodepletion regimen

Intervention Type: DRUG

Other Intervention Names

Cyclophosphamide; Fludarabine

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kyverna Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Kyverna Therapeutics, Inc.

Locations

Stanford University Medical Center

Palo Alto, California, United States

Northwell Health

Great Neck, New York, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 29669578 (View on PubMed)

Other Identifiers

KYV101-005

Identifier Type: OTHER

Identifier Source: secondary_id

KYSA-5

Identifier Type: -

Identifier Source: org_study_id