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

Phase 2

Recruiting

• Conditions: Multiple Sclerosis, Primary Progressive; Multiple Sclerosis, Secondary Progressive; Multiple Sclerosis; MS
• Interventions: Drug: Anti-CD20 mAB; Biological: KYV-101; Drug: Standard lymphodepletion regimen

• Registration Number: NCT06384976
• Lead Sponsor: Kyverna Therapeutics

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.

Study Timeline

• Study First Submitted: 2023-11-21
• Study First Submitted QC: 2024-04-23
• Study First Posted: 2024-04-25
• Status Verified: 2024-09
• Study Start: 2024-09
• Last Update Submitted: 2024-09-27
• Last Update Posted: 2024-10-01
• Primary Completion: 2027-04
• Study Completion: 2029-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anti- CD20 mAb	Anti-CD20 mAB	Dosing with anti-CD20 mAb
KYV-101 CAR-T cells with lymphodepletion conditioning	KYV-101	Dosing with KYV-101 CAR T cells
KYV-101 CAR-T cells with lymphodepletion conditioning	Standard lymphodepletion regimen	Dosing with KYV-101 CAR T cells

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
To evaluate the immunogenicity (humoral response) of KYV-101	Up to 2 years	Percentage of participants who develop anti-KYV-101 antibodies by immunoassays)
To characterize the safety and tolerability of KYV-101	Up to 2 years	Incidence and severity of serious adverse events (SAEs)
To evaluate efficacy of KYV-101	up to 12 weeks	Composite Confirmed Disability Progression (CCPD)
To characterize the Pharmacodynamics (PD)	Up to 2 years	Serum cytokines will be measured by multiplexed mesoscale discovery (MSD) assay and will include cytokines historically associated with potential CAR T toxicity (CRS and ICANS) such as gamma interferon (IFNg) and interleukin 6 (IL-6).
To characterize the pharmacokinetics (PK)	Up to 2 years	Levels of CAR Transgene levels

Trial Locations

Locations (1)

Stanford University Medical Center; 🇺🇸 Palo Alto, California, United States