Clinical trial NCT06400303: KYSA-5: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Systemic Sclerosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: Kyverna Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-05-06
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of adverse events and laboratory abnormalities (Phase 1)
timeFrame: Up to 2 years
measure: Frequency of Dose-Limiting Toxicities (DLTs) at each dose level (Phase 1)
timeFrame: Up to 2 years
measure: To evaluate efficacy of KYV-101(Phase 2)
timeFrame: 52 weeks
Secondary outcomes:
measure: To evaluate pharmacodynamics (PK) of KYV-101 in blood (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: To evaluate pharmacodynamics (PD) of KYV-101 in blood (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: To evaluate pharmacodynamics (PD) of KYV-101 in blood (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: To evaluate efficacy of KYV-101 (Phase 1 and Phase 2)
timeFrame: 12, 24, 52 weeks
measure: To evaluate immunogenicity (humoral response) of KYV-101 (Phase 1 and Phase 2)
timeFrame: Up to 2 years
measure: To define the Recommended Phase 2 Dose (RP2D) (Phase 1)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Great Neck
country: United States
facility: Northwell Health
state: New York
Study officials:
affiliation: Kyverna Therapeutics, Inc.
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.