Clinical trial NCT06588491: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Stiff-Person Syndrome
SPS
Keywords: SPS
Stiff-Person Syndrome
Lead sponsor: Kyverna Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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%.

Primary outcomes:
measure: To evaluate efficacy of KYV-101
timeFrame: Up to 16 weeks
measure: To evaluate the safety of KYV-101
timeFrame: Up to 12 months
Secondary outcomes:
measure: To evaluate efficacy of KYV-101
timeFrame: Up to 16 weeks
measure: To evaluate efficacy of KYV-101
timeFrame: Up to 12 months
measure: To evaluate efficacy of KYV-101
timeFrame: Up to 12 months
measure: To evaluate efficacy of KYV-101
timeFrame: Up to 12 months
measure: To evaluate efficacy of KYV-101
timeFrame: Up to 12 months
measure: To evaluate efficacy of KYV-101
timeFrame: Up to 12 months
measure: To evaluate efficacy of KYV-101
timeFrame: Up to 12 months
measure: To evaluate efficacy of KYV-101
timeFrame: Up to 12 months
measure: To characterize the pharmacokinetics (PK)
timeFrame: Up to 12 months
measure: To characterize the pharmacodynamics (PD)
timeFrame: Up to 12 months
measure: To characterize the pharmacodynamics (PD)
timeFrame: Up to 12 months
measure: To evaluate the immunogenicity (humoral response) of KYV-101
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
Study officials:
affiliation: Kyverna Therapeutics
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Duddy ME, Baker MR. Stiff person syndrome. Front Neurol Neurosci. 2009;26:147-165. doi: 10.1159/000212375. Epub 2009 Apr 6.