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

KYSA-8: A Phase 2 Open-Label, Single-Arm, Multicenter Study of KYV-101, an Autologous Fully Human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Treatment Refractory Stiff Person Syndrome

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

Study Overview

• Status: Completed
• Conditions: Stiff-Person Syndrome; SPS
• Intervention / Treatment: Biological: Standard lymphodepletion regimen

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 Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Key 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 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%.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

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: Standard lymphodepletion regimen; Standard lymphodepletion regimen; Other Names: Cyclophosphamide; Fludarabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety of KYV-101	Incidence of adverse events and laboratory abnormalities	Up to 12 months
To evaluate efficacy of KYV-101	Change in the Timed 25-Foot Walk (T25-FW) from baseline	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate efficacy of KYV-101	Change in the scores of the distribution-of-stiffness index from baseline. Distribution of Stiffness Index: Scoring is from 0 to 6. A higher score indicates a worse outcome.	Up to 12 months
To evaluate efficacy of KYV-101	Change in Hauser Ambulation Index. Hauser Ambulation Index: Scoring is from 0 to 9. A higher score indicates a worse outcome.	Up to 12 months
To evaluate efficacy of KYV-101	Change in Heightened sensitivity scale. Heightened Sensitivity Scale: Scoring is from 0 to 7. A higher score indicates a worse outcome.	Up to 12 months
To evaluate efficacy of KYV-101	Change in Modified Rankin Scale from baseline Modified Rankin Scale: Scoring is from 0 (no symptoms) to 6 (death). A higher score indicates a worse outcome.	Up to 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate efficacy of KYV-101	6-minute walk test	Up to 12 months
To evaluate efficacy of KYV-101	Change in anti-GAD-65 antibody levels	Up to 12 months
To evaluate efficacy of KYV-101	Change in anti-glycine receptor antibodies	Up to 12 months
To evaluate efficacy of KYV-101	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.	Up to 12 months
To characterize the pharmacokinetics (PK)	Levels of KYV-101 CAR-positive T cells in the blood	Up to 12 months
To characterize the pharmacodynamics (PD)	Levels of B cells in the blood	Up to 12 months
To characterize the pharmacodynamics (PD)	Levels of systemic cytokine concentrations in serum	Up to 12 months
To evaluate the immunogenicity (humoral response) of KYV-101	Percentage of participants who develop anti-KYV-101 antibodies by immunoassays	Up to 12 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• Duddy ME, Baker MR. Stiff person syndrome. Front Neurol Neurosci. 2009;26:147-165. doi: 10.1159/000212375. Epub 2009 Apr 6.
• Piquet AL, et al. Miv-cel CD19 CAR T-cell therapy shows efficacy and safety in stiff person syndrome in a pivotal, multicenter, phase 2 study (KYSA-8). Presented at: American Academy of Neurology (AAN) Annual Meeting; April 18-21, 2026; Chicago, IL. Late Breaking Science Abstract 008.

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2024
• Primary Completion (Actual): June 25, 2026
• Study Completion (Actual): June 25, 2026

Study Registration Dates

• First Submitted: September 6, 2024
• First Submitted That Met QC Criteria: September 6, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): July 24, 2026
• Last Update Submitted That Met QC Criteria: July 22, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: SPS; Stiff-Person Syndrome
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Spinal Cord Diseases; Stiff-Person Syndrome; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: KYSA-8; KYV101-008 (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