Stiff-Person Syndrome

Stiff Person Syndrome (SPS) is a rare autoimmune disorder, characterized by: a) incapacitating diffuse muscle stiffness prominent in the axial, abdominal and thoracolumbar paraspinal muscles leading to hyperlordosis, difficulty turning and bending; b) painful muscle spasms precipitated by external stimuli with difficulty performing routine daily activities; and c) slow freezing gait with frequent falls and need for walking aids leading to disability. SPS is due to impaired inhibitory GABAergic neurotransmission associated with high-titer IgG antibodies against Glutamic Acid Decarboxylase (GAD), the rate-limiting enzyme for the synthesis of the inhibitory gammaaminobutyric acid (GABA). Although SPS patients respond to IVIg based on the PI's controlled study (NEJM 2001), several patients do not improve, or their response is modest and declines over time, as documented in a longitudinal study of 36 patients followed in our Jefferson clinic; because another controlled study we performed with Rituximab was negative and SPS is a progressive disease, new therapies are needed. Efgartigimod is an FcRn inhibitor that enhances the catabolism of circulating IgG; its subcutaneous, self-administered form, HYTRULO, has been effective and FDA-approved in patients with myasthenia gravis or CIDP poorly responding to IVIg. There is evidence that patients with myasthenia who also had SPS, Hytrulo not only helped their myasthenia but the SPS also impressively improved. The present study is an investigator- initiated, double-blind, placebo controlled, cross-over, trial in 26 GAD-positive SPS patients poorly responding to available therapies. Patients will be recruited from the large number of patients seen and referred to the PI who is known for his work in SPS and has conducted the 2 previous controlled trials. Although Hytrulo is approved as selfadministered subcutaneous drug with pre-refilled syringes, in this study will be given by a contracted home infusion company once a week to ensure convenience, safety and validity. Patients will be randomized by the Jefferson Pharmacy to receiving Hytrulo or identical hyaluronidase-containing placebo for 3 months; then they will be crossed-over to placebo/Hytrulo for another 3 months. Efficacy will be based on one primary endpoint, the stiffness index, previously validated by the PI, and on two also validated secondary endpoints of time to walk and excitability index. This design provides the statistical power to objectively assess a 25-50% or greater change and objectively determine if Hytrulo offers meaningful benefits in reducing stiffness and spasms, improving gait and increasing quality of life in SPS patients poorly responding to current therapies.

The purpose of this study is to evaluate the efficacy and safety of QIVIGY (Intravenous Human Normal Immune Globulin 10%) compared with placebo in adult participants with stiff person syndrome (SPS).

This is a single-arm, open-label, multicenter, ascending dose Phase 1/2 trial evaluating the safety and preliminary efficacy of CTX112 in adult participants with neurological autoimmune diseases (AIDs), including Progressive Multiple Sclerosis, relapsing Neuromyelitis Optica Spectrum Disorder, relapsing Myelin Oligodendrocyte Glycoprotein Antiody-Associated Disease, refractory AutoImmune Encephalitis, and refractory Stiff Person Syndrome

Neurological autoimmune diseases are a group of disorders characterized by the abnormal immune response attacking the nervous system, including the brain, spinal cord and peripheral nerves. These diseases exhibit high heterogeneity, diverse clinical presentations, and are challenging to diagnose and manage due to a lack of effective treatments. In this study, the investigators will recruit eight kinds of autoimmune diseases of nervous system including Neuromyelitis Optica Spectrum Disorder (NMOSD), Myasthenia Gravis (MG), Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), idiopathic inflammatory myopathy (IIM), and multiple sclerosis (MS), autoimmune encephalitis (AE), Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD). Through this study, the investigators aim to discover biomarkers with high sensitivity, specificity, and stability, which can support early diagnosis, disease monitoring, and personalized treatment for neurological autoimmune diseases, thereby improving the quality of life and prognosis for patients.

The purpose of this long-term follow-up (LTFU) study is to collect delayed adverse events (AEs) and understand the persistence of KYV-101 (autologous CAR T cell product; gene-modified product), in participants who have been administered KYV-101 (gene-modified product; autologous CAR T cell product). This LTFU protocol will be open to any participant who received at least one infusion of KYV-101 in a previous Kyverna sponsored clinical trial or Investigator Initiated Trial (IIT).

This is an investigator-initiated, single-center, open-label study of C-CAR168, an autologous bi-specific CAR-T therapy targeting CD20 and BCMA, for the treatment of adult patients with central nervous system autoimmune diseases refractory to standard therapy

The goal of this clinical trial is to examine the proportion of patients with stiff person syndrome with no worsening in stiffness and/or spasms while on efgartigimod-hyaluronidase (EFD) when compared to their current treatment. The main questions it aims to answer are: * proportion of patients with stiff person syndrome with no worsening in DSI and HSS scores * whether there are changes in laboratory values, vital signs, electrocardiogram, or depression, and suicide risk during the trial, as well as the incidence of any adverse events. Participants will come to the clinic up to 18 times and have up to 5 phone call visits during the course of the trial. During these visits a variety of measures will be collected, including blood samples, neurological and physical exams, patient reported outcomes on stiffness, spasms, depression, and suicide risk.