Ignite Creation Date:
2024-06-16 @ 11:52 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06451159
Status:
RECRUITING
Last Update Posted:
2024-06-13
First Post:
2024-06-03
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:
University of California San Francisco
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:
RECRUITING
Status Verified Date:
2024-06
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 andor normalization of immunoglobulin G IgG IgG index and to characterize a preliminary safety profile of KYV-101 in treatment-refractory MS
Pharmacodynamics PDPharmacokinetics 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
PharmacodynamicsPharmacokinetics 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 CARchimeric antigen receptor PDpharmacodynamics PKpharmacokinetics
SafetyAdverse 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
SafetyAdverse 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 depressionanxiety including Columbia Suicide Severity Rating Scale C-SSRS
Abbreviations RCLreplication competent lentivirus VSV-G qPCRvesicular stomatitis virus G glycoprotein quantitative polymerase chain reaction PROpatient reported outcomes C-SSRSColumbia 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 PDPharmacokinetics 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
PharmacodynamicsPharmacokinetics 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 CARchimeric antigen receptor PDpharmacodynamics PKpharmacokinetics
SafetyAdverse 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
SafetyAdverse 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 depressionanxiety including Columbia Suicide Severity Rating Scale C-SSRS
Abbreviations RCLreplication competent lentivirus VSV-G qPCRvesicular stomatitis virus G glycoprotein quantitative polymerase chain reaction PROpatient reported outcomes C-SSRSColumbia 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:
None
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?:
None
Is an FDA AA801 Violation?:
None