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

Multiple Sclerosis Clinical Trial

Official title:

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 (KYSA-7)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06384976
• Other study ID #: KYV101-007
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 2024
• Est. completion date: January 2029

Study information

• Verified date: April 2024
• Source: Kyverna Therapeutics
• Contact: Kyverna Therapeutics, Inc.
• Phone: 510-925-2484
• Email: medicalmonitor[@]kyvernatx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: January 2029
• Est. primary completion date: April 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Multiple Sclerosis, Primary Progressive
• Multiple Sclerosis, Secondary Progressive
• Neoplasm Metastasis
• Sclerosis

Intervention

Biological:
• KYV-101
Anti-CD19 CAR-T cell therapy

Drug:
• Standard lymphodepletion regimen
CYC/FLU
• Anti-CD20 mAB
Anti-CD20 mAB

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Kyverna Therapeutics

References & Publications (1)

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. — View Citation

Outcome

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