A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Subjects with Treatment Refractory Stiff Person Syndrome
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Standard lymphodepletion regimen
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
Mayo Clinic
Rochester, Minnesota, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
To evaluate efficacy of KYV-101
Change in the Timed 25-Foot Walk (T25-FW) from baseline
Time frame: Up to 12 months
To evaluate the safety of KYV-101
Incidence of adverse events and laboratory abnormalities
Time frame: 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.
Time frame: Up to 12 months
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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 12 months
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