KYSA-8: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Treatment Refractory Stiff Person Syndrome

NCT ID: NCT06588491

Last Updated: 2025-12-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-25
• Study Completion Date: 2026-12-31

Brief Summary

A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Subjects with Treatment Refractory Stiff Person Syndrome

Detailed Description

Stiff person syndrome (SPS) is a rare progressive immune-mediated disorder of the central nervous system (CNS) that is characterized by progressive rigidity and painful spasms of predominantly axial and proximal limb muscles. The condition gradually worsens over time and left untreated, it can lead to permanent disability and in some cases, mortality.

B cells contribute to systemic autoimmunity and development of disease in several ways, most notably via cytokine production, antigen presentation and complement activation (via autoantibody production). In SPS, B cell involvement is supported by the presence of antibodies against glutamic acid decarboxylase (GAD), which is widely expressed within the CNS, catalyzing the conversion of the excitatory neurotransmitter l-glutamate to the inhibitory GABA.

CAR-T therapy such as KYV-101 may be an effective treatment for SPS, by targeting these autoreactive B cells. Using chimeric antigen receptor (CAR) T-cell technology, engineered T cells with receptors are designed to recognize and eliminate B cells, including those that produce GAD autoantibodies. This approach aims to intervene at the root of the autoimmune response, offering a precise and potentially transformative treatment for SPS. CAR-T cell therapy holds promise as a targeted and effective intervention, addressing the autoimmune component directly and potentially halting disease progression.

Conditions

Stiff-Person Syndrome; SPS

Keywords

SPS; Stiff-Person Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• 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

Standard lymphodepletion regimen

Intervention Type: BIOLOGICAL

Standard lymphodepletion regimen

Interventions

Standard lymphodepletion regimen

Standard lymphodepletion regimen

Intervention Type: BIOLOGICAL

Other Intervention Names

Cyclophosphamide; Fludarabine

Eligibility Criteria

Inclusion Criteria

• Subject must have been diagnosed SPS per the following criteria:

• Rigidity of limb and axial (trunk) muscles prominent in the abdominal and thoracolumbar paraspinal areas and making bending difficult
• Clinical or electrophysiological evidence of continuous contraction of agonist and antagonist muscles
• Episodic spasms precipitated by unexpected noises, tactile stimuli, or emotional upset
• Absence of any other neurologic disease that could explain the stiffness and rigidity
• High titer serum anti-GAD65 antibodies shown at screening -OR- seropositive for anti-glycine antibodies. If anti-GAD65 antibodies are lower than the high titer threshold peripherally but positive in the cerebrospinal fluid (CSF), the subject can be included. A prior documented high titer anti-GAD65 antibody level may be acceptable subject to sponsor review.
• Active symptoms with inadequate response to at least one immunomodulatory therapy.
• Stiffness index ≥2.
• At least 20 of the 25 enrolled subjects should be ambulatory.

Exclusion Criteria

• Bedridden subjects for more than 3 months.
• History of CNS or spinal cord tumor, metabolic or infectious cause of myelopathy, genetically inherited progressive CNS disorder, sarcoidosis, non-SPS progressive neurologic condition or progressive multifocal leukoencephalopathy (PML).
• History of stroke, seizure, dementia, Parkinson's disease, cerebellar diseases, psychosis, aphasia, and any other neurologic disorder that is of a nature and severity that the investigator considers would increase the risk for the subject.
• Cardiac ejection fraction ≤ 40%.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 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

Locations

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Mayo Clinic

Rochester, Minnesota, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Countries

United States

References

Dalakas MC. Therapies in Stiff-Person Syndrome: Advances and Future Prospects Based on Disease Pathophysiology. Neurol Neuroimmunol Neuroinflamm. 2023 Apr 14;10(3):e200109. doi: 10.1212/NXI.0000000000200109. Print 2023 May.

Reference Type: BACKGROUND

PMID: 37059468 (View on PubMed)

Duddy ME, Baker MR. Stiff person syndrome. Front Neurol Neurosci. 2009;26:147-165. doi: 10.1159/000212375. Epub 2009 Apr 6.

Reference Type: BACKGROUND

PMID: 19349711 (View on PubMed)

Other Identifiers

KYV101-008

Identifier Type: OTHER

Identifier Source: secondary_id

KYSA-8

Identifier Type: -

Identifier Source: org_study_id