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

NCT06588491 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: KYSA-8KYV101-008
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Stiff-Person Syndrome; SPS

Keywords

SPS; Stiff-Person Syndrome

Outcome Measures

Primary Outcomes (2)

• To evaluate efficacy of KYV-101

  Change in the Timed 25-Foot Walk (T25-FW) from baseline

  Up to 12 months

• To evaluate the safety of KYV-101

  Incidence of adverse events and laboratory abnormalities

  Up to 12 months

Secondary Outcomes (4)

• To evaluate efficacy of KYV-101

  Up to 12 months

• To evaluate efficacy of KYV-101

  Up to 12 months

• To evaluate efficacy of KYV-101

  Up to 12 months

• To evaluate efficacy of KYV-101

  Up to 12 months

Other Outcomes (8)

• To evaluate efficacy of KYV-101

  Up to 12 months

• To evaluate efficacy of KYV-101

  Up to 12 months

• To evaluate efficacy of KYV-101

  Up to 12 months

Study Arms (1)

KYV-101 CAR-T cells with lymphodepletion conditioning

EXPERIMENTAL

Dosing with KYV-101 CAR T cells

Biological: Standard lymphodepletion regimen

Interventions

Standard lymphodepletion regimen BIOLOGICAL

Standard lymphodepletion regimen

Also known as: Cyclophosphamide, Fludarabine

KYV-101 CAR-T cells with lymphodepletion conditioning

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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%.

Sponsors & Collaborators

• Kyverna Therapeutics: lead

Study Sites (3)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (2)

• 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.

  PMID: 37059468 BACKGROUND

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

  PMID: 19349711 BACKGROUND

MeSH Terms

Conditions

Stiff-Person Syndrome

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Autoimmune Diseases of the Nervous System; Nervous System Diseases; Spinal Cord Diseases; Central Nervous System Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• MD

  Kyverna Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2024
• First Posted: September 19, 2024
• Study Start: September 25, 2024
• Primary Completion: April 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)