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

Systemic Sclerosis Clinical Trial

Official title:

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 (KYSA-5)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06400303
• Other study ID #: KYV101-005
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: May 2024
• Est. completion date: March 2027

Study information

• Verified date: May 2024
• Source: Kyverna Therapeutics
• Contact: Kyverna Therapeutics, Inc.
• Phone: 510-925-2484
• Email: Clinicaltrials[@]kyvernatx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 21
• Est. completion date: March 2027
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

Biological:
• KYV-101
Anti-CD19 CAR-T cell therapy

Drug:
• Standard lymphodepletion regimen
Standard lymphodepletion regimen

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Kyverna Therapeutics

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events and laboratory abnormalities (Phase 1)		Up to 2 years
Primary	Frequency of Dose-Limiting Toxicities (DLTs) at each dose level (Phase 1)		Up to 2 years
Primary	To evaluate efficacy of KYV-101(Phase 2)	via revised Composite Response Index in Systemic Sclerosis (rCRISS) 30/5	52 weeks
Secondary	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
Secondary	To evaluate pharmacodynamics (PD) of KYV-101 in blood (Phase 1 and Phase 2)	Levels of B-cells in blood	Up to 2 years
Secondary	To evaluate pharmacodynamics (PD) of KYV-101 in blood (Phase 1 and Phase 2)	Levels of cytokines in serum	Up to 2 years
Secondary	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
Secondary	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
Secondary	To define the Recommended Phase 2 Dose (RP2D) (Phase 1)		Up to 2 years