Systemic Sclerosis, Systemic Sclerosis - Diffuse Cutaneous, Systemic Sclerosis - 2013 ACR/EULAR Classification Criteria
Conditions
Keywords
KYV-101, systemic sclerosis, autoimmune disease, anti-CD19 CAR-T therapy, cellular therapy, Scleroderma
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.
Interventions
BIOLOGICALKYV-101
Anti-CD19 CAR-T cell therapy
Standard lymphodepletion regimen
Sponsors
Kyverna Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 52 weeks | via revised Composite Response Index in Systemic Sclerosis (rCRISS) 30/5 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate immunogenicity (humoral response) of KYV-101 (Phase 1 and Phase 2) | Up to 2 years | Percentage of participants who develop anti-KYV-101 antibodies by immunoassays |
| To evaluate pharmacodynamics (PK) of KYV-101 in blood (Phase 1 and Phase 2) | Up to 2 years | Chimeric antigen receptor-positive (CAR-positive) T-cell counts in blood |
| To define the Recommended Phase 2 Dose (RP2D) (Phase 1) | Up to 2 years | — |
| To evaluate pharmacodynamics (PD) of KYV-101 in blood (Phase 1 and Phase 2) | Up to 2 years | Levels of B-cells in blood |
| To evaluate efficacy of KYV-101 (Phase 1 and Phase 2) | 12, 24, 52 weeks | revised Composite Response Index in Systemic Sclerosis (rCRISS) 30/5 response rate |
Countries
United States
Outcome results
None listed