KYSA-7: A Study of Anti-CD19 CAR T-Cell Therapy, in Subjects With Refractory Primary and Secondary Progressive Multiple Sclerosis

NCT ID: NCT06384976

Last Updated: 2025-01-13

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-20
• Study Completion Date: 2029-01-31

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.

Conditions

Multiple Sclerosis, Primary Progressive; Multiple Sclerosis, Secondary Progressive; Multiple Sclerosis; MS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

KYV-101 CAR-T cells with lymphodepletion conditioning

Dosing with KYV-101 CAR T cells

Group Type: EXPERIMENTAL

KYV-101

Intervention Type: BIOLOGICAL

Anti-CD19 CAR-T cell therapy

Standard lymphodepletion regimen

Intervention Type: DRUG

CYC/FLU

Anti- CD20 mAb

Dosing with anti-CD20 mAb

Group Type: ACTIVE_COMPARATOR

Anti-CD20 mAB

Intervention Type: DRUG

Anti-CD20 mAB

Interventions

KYV-101

Anti-CD19 CAR-T cell therapy

Intervention Type: BIOLOGICAL

Standard lymphodepletion regimen

CYC/FLU

Intervention Type: DRUG

Anti-CD20 mAB

Anti-CD20 mAB

Intervention Type: DRUG

Eligibility Criteria

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.

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kyverna Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Kyverna Therapeutics, Inc.

Locations

Stanford University Medical Center

Palo Alto, California, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 33636613 (View on PubMed)

Other Identifiers

KYV101-007

Identifier Type: OTHER

Identifier Source: secondary_id

KYSA-7

Identifier Type: -

Identifier Source: org_study_id