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

Overview

About this study

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

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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%.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 11/14/2024. Questions regarding updates should be directed to the study team contact.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Anastasia Zekeridou, M.D., Ph.D.

Contact us for the latest status

Contact information:

Morgan Mohler

(507) 293-9803

Mohler.Morgan@mayo.edu

More information

Publications

  • Stiff person syndrome (SPS), stiff limb syndrome, jerking SPS and progressive encephalomyelitis with rigidity and myoclonus (PERM) are a family of rare, insidiously progressive diseases of the central nervous system. They all share the core clinical features of appendicular and axial rigidity caused by continuous involuntary motor unit activity, and superimposed stimulus-sensitive spasms. There is good evidence for a primary auto-immune aetiology. Anti-glutamic acid decarboxylase (anti-GAD) antibodies, specifically to the GAD65 isoform, are present in serum or cerebrospinal fluid of 60-80% of patients with SPS and its variants. A paraneoplastic form of SPS is recognized in about 5%, associated with a different profile of auto-antibodies. Repeated intravenous immunoglobulin is the mainstay of disease-modifying therapy in SPS. Rigidity and spasms may be treated symptomatically with benzodiazepines, baclofen, tiagabine and levetiracetam. After an initial progressive phase, patients with SPS generally stabilize over a period of months to years. However, 10% will require prolongedadmission to intensive care at some stage during the disease. Sudden death has been reported in asmany as 10% of patients because of unexplained metabolic acidosis or autonomic crises. The prognosis in paraneoplastic SPS, jerking SPS and PERM, in terms of mortality, is generally worse than in primary SPS. Read More on PubMed
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CLS-20577201

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