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

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.

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