NCT06451159

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

Phase 1, Open-Label, Single Center Study of KYV-101, an Autologous Fully-Human Anti-CD19 Chimeric Antigen Receptor T Cell (CD19 CAR T) Therapy, in Participants With Treatment Refractory Progressive Multiple Sclerosis

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Bruce Cree · Academic / Other
• Sex: All
• Age: 25 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The goal of this study is to test a drug called KYV-101 in people who have progressive multiple sclerosis (MS) and who have not responded to standard therapies to slow disease progression. The main questions it aims to answer are: * What is the highest therapy dose that can be given without causing harm? * Can this therapy enter the central nervous system? Participants will be asked to: * Attend 14 visits plus an 8-day inpatient hospital stay over the course of 58 weeks. * Complete apheresis and chemotherapy treatments in preparation for KVY-101 therapy. * Undergo medical and research testing such as physical and neurological exams, MRI, lumbar puncture, blood draws, questionnaires, and vision assessments.

Detailed description

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.

Conditions

• Progressive Multiple Sclerosis

Interventions

Type	Name	Description
BIOLOGICAL	KYV-101 (Biological) - 0.33 ×10^8 cells	KYV-101 is a type of treatment called CAR T-cell therapy. It uses cells from your own immune system, called T-cells, to attack cells that cause inflammation. T-cells are a type of white blood cell.
BIOLOGICAL	KYV-101 (Biological) - 1 ×10^8 cells	KYV-101 is a type of treatment called CAR T-cell therapy. It uses cells from your own immune system, called T-cells, to attack cells that cause inflammation. T-cells are a type of white blood cell.
DRUG	Chemotherapy: cyclophosphamide (CYC)	Participants will receive one 3-day cycle of lymphodepletion with CYC 300 mg/m2 prior to administration of KYV-101.
DRUG	Chemotherapy: fludarabine (FLU)	Participants will receive one 3-day cycle of lymphodepletion with FLU 30 mg/m2 prior to administration of KYV-101.

Timeline

• Start date: 2024-06-20
• Primary completion: 2026-02-01
• Completion: 2027-02-01
• First posted: 2024-06-11
• Last updated: 2026-01-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study