KYSA-8: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD-19 CAR T) Therapy, in Subject With Treatment Refractory Stiff Person Syndrome

Phase 2

Recruiting

• Conditions: Stiff-Person Syndrome; SPS
• Interventions: Biological: Standard lymphodepletion regimen

• Registration Number: NCT06588491
• Lead Sponsor: Kyverna Therapeutics

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.

Study Timeline

• Study First Submitted: 2024-09-06
• Study First Submitted QC: 2024-09-06
• Study First Posted: 2024-09-19
• Study Start: 2024-09-25
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-31
• Last Update Posted: 2024-11-01
• Primary Completion: 2026-04
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 25

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.

Key

Read More

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%.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
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	Up to 16 weeks	Change in the Timed 25-Foot Walk (T25-FW) from baseline
To evaluate the safety of KYV-101	Up to 12 months	Incidence of adverse events and laboratory abnormalities

Secondary Outcome Measures

Name	Time	Method
To evaluate efficacy of KYV-101	Up to 12 months	36-Short form survey (SF-36). The SF-36 has eight scaled scores. Scores range from 0 - 100 with lower scores equating to more disability and higher scores equating to less disability.
To characterize the pharmacokinetics (PK)	Up to 12 months	Levels of KYV-101 CAR-positive T cells in the blood
To characterize the pharmacodynamics (PD)	Up to 12 months	Levels of systemic cytokine concentrations in serum
To evaluate the immunogenicity (humoral response) of KYV-101	Up to 12 months	Percentage of participants who develop anti-KYV-101 antibodies by immunoassays

Trial Locations

Locations (2)

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States