Ignite Creation Date:
2025-12-24 @ 3:04 PM
Ignite Modification Date:
2025-12-28 @ 6:30 PM
Study NCT ID:
NCT06451159
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-01-20
First Post:
2024-06-03
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Study of KYV-101, a CD19 CAR T Cell Therapy, in Participants with Treatment Refractory Progressive Multiple Sclerosis
Sponsor:
Bruce Cree
Organization:
Study Overview
Official Title:
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
Status Verified Date:
2025-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
* 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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: