A Study of KYV-101, a CD19 CAR T Cell Therapy, in Participants With Treatment Refractory Progressive Multiple Sclerosis

This study will treat up to 10 participants. The primary objective is to characterize central nervous system (CNS) penetration of KYV-101 and its effectiveness of target engagement via elimination of oligoclonal bands (OCB) and/or normalization of immunoglobulin G (IgG) IgG index and to characterize a preliminary safety profile of KYV-101 in treatment-refractory MS. Pharmacodynamics (PD)/Pharmacokinetics (PK) Objectives * To characterize the PK and PD of KYV 101 in blood. * To evaluate changes in PD and disease-related biomarkers. * To assess the immunophenotype of Chimeric Antigen Receptor (CAR) T cells. Pharmacodynamics/Pharmacokinetics Endpoints * CAR-positive T cell counts, CAR transgene level, B-cell counts over time, systemic cytokine concentrations. * Immunophenotype B and T cells through flow cytometry (including non-CAR T cell and B-cell subsets, if detectable), serum proteins and gene expression analysis. * CAR T cell phenotypic composition as defined by markers of activation, proliferation, differentiation, and exhaustion (prior to and post infusion). Abbreviations: CAR=chimeric antigen receptor; PD=pharmacodynamics; PK=pharmacokinetics Safety/Adverse Event Objectives * To evaluate for disease re-activation. * To evaluate the immunogenicity (humoral response) of KYV-101. * To evaluate the immunogenicity (cellular response) of KYV-101. * To determine whether RCL is present in participants who receive KYV-101. * To evaluate changes in long-term humoral response after KYV-101. * To assess mood patient-reported outcomes (PROs) after infusion of KYV-101. Safety/Adverse Event Endpoints * Disease reactivation as defined by the presence of new T2 hyperintense or gadolinium (GAD) enhancing lesions on MRI brain at 8 weeks post-infusion of KYV-101. * Incidence of detectable anti-KYV-101 antibodies in peripheral blood. * Incidence of detectable T cells specific to KYV-101 drug product in peripheral blood. * Detectable replication competent lentivirus (RCL) as measured by surrogate assay (VSV-G qPCR). * Persistence of IgG antibody titers to common vaccine-related antigens (varicella, measles, mumps, rubella, tetanus). * Change from baseline in depression/anxiety including Columbia Suicide Severity Rating Scale (C-SSRS). Abbreviations: RCL=replication competent lentivirus; VSV-G qPCR=vesicular stomatitis virus G glycoprotein quantitative polymerase chain reaction; PRO=patient reported outcomes; C-SSRS=Columbia Suicide severity rating scale The safety and tolerability of KYV-101 will be evaluated by reported adverse events (AEs), physical examination findings, vital sign measurements, neurological assessment, and laboratory analyses.