Multiple Sclerosis, Primary Progressive, Multiple Sclerosis, Secondary Progressive, Multiple Sclerosis, MS
Conditions
Keywords
KYV-101, multiple sclerosis, autoimmune disease, anti-CD19 CAR-T therapy, cellular therapy, MS
Brief summary
A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects with Refractory Primary and Secondary Progressive Multiple Sclerosis
Detailed description
Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease in which lymphocytes at first attack the myelin sheaths within the central nervous system (CNS), accompanied or later followed by axonal damage. B cells play a central and multifunctional role in the immunopathogenesis of MS. B cells present antigen to T cells in stimulating a pro-inflammatory immune cascade, secrete pathogenic cytokines, moderate T cell and myeloid cell functions, form structural B cell meningeal follicles within the human central nervous system and produce pathogenic antibodies upon evolution to plasma cells. 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 refractory primary and secondary progressive multiple sclerosis.
Interventions
Sponsors
Kyverna Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Subject must have a history of diagnosis of primary progressive or secondary progressive MS. 2. History of treatment with anti-CD20 mAb with continuing evidence of worsening physical disability over a period of ≥6 months, with documented clinical disability progression within the 2 years prior to inclusion. Key
Exclusion criteria
1. Monophasic disease, radiologically isolated syndrome, clinically isolated syndrome, progressive solitary sclerosis or relapsing-remitting disease as defined by the 2017 McDonald criteria. 2. History of CNS or spinal cord tumor, metabolic or infectious cause of myelopathy, genetically inherited progressive CNS disorder, sarcoidosis, non-MS progressive neurologic condition or PML. 3. Prior treatment with cellular therapy (CAR-T) or gene therapy product directed at any target 4. History of allogeneic or autologous stem cell transplant 5. Evidence of active hepatitis B or hepatitis C infection 6. Positive serology for HIV 7. Primary immunodeficiency 8. History of splenectomy 9. 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 10. Impaired cardiac function or clinically significant cardiac disease 11. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate efficacy of KYV-101 | at least 12 weeks | Confirmed disability Progression on the EDSS scale. The EDSS scale ranges from 0 to 10 in 0.5- unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To characterize the safety and tolerability of KYV-101 | Up to 2 years | Incidence and severity of adverse events (AEs) |
| To evaluate efficacy of KYV-101 | up to 12 weeks | Composite Confirmed Disability Progression (CCPD) |
| To characterize the pharmacokinetics (PK) | Up to 2 years | Levels of Chimeric antigen receptor positive (CAR-positive) T cell counts |
| To characterize the Pharmacodynamics (PD) | Up to 2 years | Levels of B cell in the blood |
| To evaluate the immunogenicity (humoral response) of KYV-101 | Up to 2 years | Percentage of participants who develop anti-KYV-101 antibodies by immunoassays) |
Countries
United States
Outcome results
None listed