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

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

A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects with Refractory Primary and Secondary Progressive Multiple Sclerosis

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis; Multiple Sclerosis, Secondary Progressive; MS; Multiple Sclerosis, Primary Progressive
• Intervention / Treatment: Biological: KYV-101; Drug: Standard lymphodepletion regimen; Drug: Anti-CD20 mAB

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 Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94305
      • Stanford University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KYV-101 CAR-T cells with lymphodepletion conditioning; Dosing with KYV-101 CAR T cells	Biological: KYV-101; Anti-CD19 CAR-T cell therapy; Drug: Standard lymphodepletion regimen; CYC/FLU
Active Comparator: Anti- CD20 mAb; Dosing with anti-CD20 mAb	Drug: Anti-CD20 mAB; Anti-CD20 mAB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate efficacy of KYV-101	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.	at least 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterize the safety and tolerability of KYV-101	Incidence and severity of adverse events (AEs)	Up to 2 years
To characterize the safety and tolerability of KYV-101	Incidence and severity of adverse events of special interests (AESIs)	Up to 2 years
To characterize the safety and tolerability of KYV-101	Incidence and severity of serious adverse events (SAEs)	Up to 2 years
To evaluate efficacy of KYV-101	Composite Confirmed Disability Progression (CCPD)	up to 12 weeks
To characterize the pharmacokinetics (PK)	Levels of Chimeric antigen receptor positive (CAR-positive) T cell counts	Up to 2 years
To characterize the pharmacokinetics (PK)	Levels of CAR Transgene levels	Up to 2 years
To characterize the Pharmacodynamics (PD)	Levels of B cell in the blood	Up to 2 years
To characterize the Pharmacodynamics (PD)	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).	Up to 2 years
To evaluate the immunogenicity (humoral response) of KYV-101	Percentage of participants who develop anti-KYV-101 antibodies by immunoassays)	Up to 2 years

Collaborators and Investigators

• Sponsor: Kyverna Therapeutics
• Investigators: Study Director: MD, Kyverna Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: November 21, 2023
• First Submitted That Met QC Criteria: April 23, 2024
• First Posted (Actual): April 25, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 10, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: MS; multiple sclerosis; cellular therapy; autoimmune disease; KYV-101; anti-CD19 CAR-T therapy
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Neoplastic Processes; Multiple Sclerosis; Sclerosis; Neoplasm Metastasis; Multiple Sclerosis, Chronic Progressive
• Other Study ID Numbers: KYSA-7; KYV101-007 (Other Identifier: Kyverna Therapeutics)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No