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

NCT06400303 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: KYSA-5KYV101-005
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

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

Keywords

KYV-101; systemic sclerosis; autoimmune disease; anti-CD19 CAR-T therapy; cellular therapy; Scleroderma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• To evaluate pharmacodynamics (PK) of KYV-101 in blood (Phase 1 and Phase 2)

  Up to 2 years

• To evaluate pharmacodynamics (PD) of KYV-101 in blood (Phase 1 and Phase 2)

  Up to 2 years

• To evaluate pharmacodynamics (PD) of KYV-101 in blood (Phase 1 and Phase 2)

  Up to 2 years

• To evaluate efficacy of KYV-101 (Phase 1 and Phase 2)

  12, 24, 52 weeks

• To evaluate immunogenicity (humoral response) of KYV-101 (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; Drug: Standard lymphodepletion regimen

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

EXPERIMENTAL

Recommended Phase 2 Dose

Biological: KYV-101; Drug: Standard lymphodepletion regimen

Interventions

KYV-101 BIOLOGICAL

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:

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

You may not qualify if:

• Clinically significant ILD
• Prior treatment with cellular therapy (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 (2)

Stanford University Medical Center

Palo Alto, California, 94305, United States

Location

Northwell Health

Great Neck, New York, 11021, United States

Location

Related Publications (1)

• 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.

  PMID: 29669578 BACKGROUND

MeSH Terms

Conditions

Scleroderma, Systemic; Scleroderma, Diffuse; Autoimmune Diseases

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin 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, Inc.

  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: August 29, 2023
• First Posted: May 6, 2024
• Study Start: August 6, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: October 8, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)