Treatment for Stiff Person Syndrome using CAR T-Cell Therapy

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

This study is testing a new CAR T-cell therapy for people with Stiff Person Syndrome who haven't found relief from other treatments, to see if it can reduce their muscle stiffness and spasms.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Kyverna Therapeutics (Industry-sponsored)
• Drugs / interventions: Chimeric Antigen Receptor, CAR-T
• Locations: 3 sites (Aurora, Colorado and 2 other locations)
• Trial ID: NCT06588491 on ClinicalTrials.gov

What this trial studies

This study investigates the use of anti-CD19 chimeric antigen receptor T-cell therapy for patients with treatment refractory Stiff Person Syndrome (SPS), a rare autoimmune disorder characterized by muscle rigidity and painful spasms. The approach involves engineering T cells to target and eliminate autoreactive B cells that contribute to the disease, particularly those producing antibodies against glutamic acid decarboxylase (GAD). By addressing the underlying autoimmune response, this therapy aims to halt disease progression and improve patient outcomes. Participants will undergo a standard lymphodepletion regimen prior to receiving the CAR T-cell therapy.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals diagnosed with Stiff Person Syndrome who have not responded adequately to at least one immunomodulatory therapy.

Not a fit: Patients with other neurological diseases that could explain their symptoms or those without high titer serum anti-GAD65 antibodies may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a targeted treatment option that significantly improves symptoms and quality of life for patients with Stiff Person Syndrome.

How similar studies have performed: While CAR T-cell therapy has shown promise in other autoimmune conditions, this specific application for Stiff Person Syndrome is novel and has not been extensively tested in prior studies.

Eligibility criteria

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%.

Where this trial is running

Aurora, Colorado and 2 other locations

• University of Colorado Anschutz Medical Campus — Aurora, Colorado, United States (Recruiting)
• Mayo Clinic — Rochester, Minnesota, United States (Recruiting)
• Thomas Jefferson University Hospital — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Study coordinator: Kyverna Therapeutics

Conditions Stiff-Person Syndrome; SPS