Clinical trial NCT06384976: KYSA-7: A Study of Anti-CD19 CAR T-Cell Therapy, in Subjects With Refractory Primary and Secondary Progressive Multiple Sclerosis
Official title: KYSA-7: A Phase 2, Open-Label, Randomized, Multicenter Study of KYV-101, an Autologous Fully Human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Refractory Primary and Secondary Progressive Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Multiple Sclerosis, Primary Progressive
Multiple Sclerosis, Secondary Progressive
Multiple Sclerosis
MS
Keywords: KYV-101
multiple sclerosis
autoimmune disease
anti-CD19 CAR-T therapy
cellular therapy
MS
Lead sponsor: Kyverna Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-04-25
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: To evaluate efficacy of KYV-101
timeFrame: at least 12 weeks
Secondary outcomes:
measure: To characterize the safety and tolerability of KYV-101
timeFrame: Up to 2 years
measure: To characterize the safety and tolerability of KYV-101
timeFrame: Up to 2 years
measure: To characterize the safety and tolerability of KYV-101
timeFrame: Up to 2 years
measure: To evaluate efficacy of KYV-101
timeFrame: up to 12 weeks
measure: To characterize the pharmacokinetics (PK)
timeFrame: Up to 2 years
measure: To characterize the pharmacokinetics (PK)
timeFrame: Up to 2 years
measure: To characterize the Pharmacodynamics (PD)
timeFrame: Up to 2 years
measure: To characterize the Pharmacodynamics (PD)
timeFrame: Up to 2 years
measure: To evaluate the immunogenicity (humoral response) of KYV-101
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
Study officials:
affiliation: Kyverna Therapeutics, Inc.
name: MD
role: STUDY_DIRECTOR
References:
citation: Silva BA, Miglietta E, Ferrari CC. Insights into the role of B cells in the cortical pathology of Multiple sclerosis: evidence from animal models and patients. Mult Scler Relat Disord. 2021 May;50:102845. doi: 10.1016/j.msard.2021.102845. Epub 2021 Feb 16.