Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Immune System Diseases

Musculoskeletal Diseases

Rare Diseases

Asthenia

Myasthenia Gravis

Autoimmune Diseases

Muscle Weakness

Autoimmune Diseases of the Nervous System

Paresis

Muscular Diseases

Neuromuscular Manifestations

Neurologic Manifestations

Syndrome

Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

Nervous System Neoplasms

Neurodegenerative Diseases

Neuromuscular Junction Diseases

Neuromuscular Diseases

Participants in this group will be recruited from the outpatient clinical population at MGNet participating sites. Treating physicians will make the initial determination of patients' potential eligibility to participate in the study.

Each blood draw will involve removing approximately 75 mL (5 tablespoons) of blood

Blood sample

Alex Hammett

Helen Girma

Ali Habib, MD

Richard Lewis, MD

Bailey Sheldon

Richard Nowak, MD, MS

Henry Kaminski, MD

Betty Soliven, MD

Amanda Guidon, MD, MPH

Vern Juel, MD

Rachana Mehta, MD

Katherine Ruzhansky, MD

Richard Nowak, MD

The goal of this prospective observational study is to create a network repository of clinical data and biological samples to help researchers learn more about myasthenia gravis.

The EXPLORE-MG2 (EXPLoring Outcomes and chaRactEristics of Myasthenia Gravis 2) study is a multi-center natural history study of myasthenia gravis (MG), a rare autoimmune disease characterized by weakness of the voluntary muscles. MG has a prevalence of approximately 14-40 per 100,000 people in the United States. There is no cure for MG, however, understanding the disease is crucial to pave the way for development of new therapies and a deeper mechanistic understanding to improve patient outcomes. Thus, EXPLORE-MG2 aims to accomplish comprehensive clinical phenotyping linked to bio-specimen collection in an effort to better understand disease characteristics and identify treatment predictive and responsive biomarkers. The primary purpose of this project is to create a network repository of data and biological samples to help researchers learn more about myasthenia gravis.

Exploring Outcomes and Characteristics of Myasthenia Gravis 2

National Center for Advancing Translational Sciences (NCATS)

National Institute of Neurological Disorders and Stroke (NINDS)

Yale University

Principal Investigator

Eye Diseases

Infections

Recurrence

Neuromyelitis Optica

Myelitis

Myelitis, Transverse

Demyelinating Autoimmune Diseases, CNS

Neuritis

Optic Neuritis

Optic Nerve Diseases

Cranial Nerve Diseases

Demyelinating Diseases

Communicable Diseases

Central Nervous System Infections

Central Nervous System Diseases

Spinal Cord Diseases

Neuroinflammatory Diseases

Leukoencephalopathies

Brain Diseases

Neuromyelitis Optica Spectrum Disorder

Antineoplastic Agents

Analgesics

All Drugs and Chemicals

Mitoxantrone

Enzyme Inhibitors

Bianca Weinstock-Guttman, M.D.

Neuromyelitis optica (NMO) is a severe demyelinating disease that selectively involves the optic nerves and the spinal cord but usually spares the brain. NMO is considered to have a B cell induced pathogenesis. Mitoxantrone (MITO, Novantrone®), a synthetic anthracenedione approved for worsening relapsing-remitting multiple sclerosis (MS) and secondary progressive MS, has been shown to primarily suppress the humoral response. We conducted a prospective 2-year study to evaluate the benefit of MITO in five relapsing NMO patients.

The treatment protocol consisted of monthly 12 mg/m2 MITO intravenous infusions for 6 months followed by 3 additional treatments every 3 months. Neurological assessment including the determination of the Expanded Disability Status Scale (EDSS) score was performed every 3 months and during relapses. Orbital, brain and spinal cord MRI was performed at baseline, 3, 6, 12, 18, and 24 months. Visual evoked potentials and ophthalmologic evaluations were performed at baseline and annually.

A Pilot Study of Mitoxantrone for the Treatment of Recurrent Neuromyelitis Optica (Devic's Disease)

EMD Serono

State University of New York at Buffalo

Blood and Lymph Conditions

Diseases and Abnormalities at or Before Birth

Sclerosis

Multiple Sclerosis

Encephalitis

Myositis

Polyradiculoneuropathy

Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

POEMS Syndrome

Polyneuropathies

Peripheral Nervous System Diseases

Chronic Disease

Disease Attributes

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Congenital Abnormalities

Abnormalities, Multiple

Immunoproliferative Disorders

Chronic Graft Versus Host Disease

Autoimmune Encephalitis

Hashimoto Encephalopathy

Inclusion Body Myositis

Idiopathic Inflammatory Myopathy

Chronic Inflammatory Demyelinating Polyneuropathy

Antirheumatic Agents

Antibodies

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunoglobulins

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

The tolerability and safety of CT103A cells will be assessed in an initial dose of 0.5×10\^6 CAR-T cells/Kg and three subjects will be enrolled firstly. If no dose-limiting toxicity (DLT) occurs and at least one subject benefits from the treatment, there will be two options for the investigator based on the available data: 1) three more subjects will be enrolled in the 0.5 × 10\^6 CAR-T cells/Kg group and DLT will be evaluated in a total of six subjects; 2) another three subjects will be treated with 1 × 10\^6 CAR-T cells/Kg instead of 0.5 × 10\^6 CAR-T cells/Kg.

If DLT occurs in one of the first three subjects, three more subjects will be enrolled in this cohort to reach the total subjects of six.

If neither DLT nor efficacy is shown in the first three subjects, the dose of CAR-T cells will be increased to 1 × 10\^6 CAR-T cells/kg to assess DLT.

If DLT occurs in two subjects, whether to test the safety and efficacy in 0.25 × 10\^6 CAR-T cells/kg group will be determined by the investigator based on the initial data of efficacy, PK and PD.

Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) to manufacture CT103A cells, during which cyclophosphamide will be administered for the purpose of lymphocytes depletion. After lymphodepletion, subjects will receive one dose treatment with CT103A cells by intravenous (IV) infusion. The initial dose of 0.5×10\^6 CAR+ T cells/kg will be infused on day 0.

CT103A cells

Subjects will receive one 3-day cycle of lymphodepletion starting 4 days prior to CT103A infusion on Day 0.

Subjects will be given IV infusion of cyclophosphamide 500 mg/m2/day on day -4, -3 and -2, and fludarabine 30 mg/m2 over 30 minutes administered immediately after cyclophosphamide.

Cyclophosphamide and fludarabine

Chuan Qin, MD

Chuan Qin, PhD

Wei Wang, MD

Bitao Bu, MD

Min Zhang, MD

Daishi Tian, MD

Jianfeng Zhou, MD

Chunrui Li, MD

Di Wang, MD

Antibody-mediated inflammatory diseases of the nervous system (also known as autoimmune diseases of the nervous system) are autoimmune diseases in which autoimmune cells and immune molecules attack the nervous system as the main pathogenic mechanism. In the immune response, pathogenic antibodies acting on autoantigens of the nervous system are collectively referred to as autoantibodies of the nervous system, and antibody-mediated inflammatory diseases of the nervous system can occur in the central nervous system, peripheral nervous system, and neuromuscular junctions, and muscles. In this study, we 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 myopathyand (IIM), multiple sclerosis (MS), autoimmune encephalitis (AE), Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) and POEMS Syndrome. B-cell maturation antigen (BCMA) is expressed on the surface of plasma cells, thus making it an ideal target for targeted therapies. Chimeric antigen receptor (CAR) T cells against BCMA offers another potential therapeutic option to eliminate plasma cells in patients with neurological autoimmune diseases driven by abnormal antibody who still suffer recurrent attacks from conventional treatments. In the current study, the safety and efficacy of a novel CAR-T cell therapy using CT103A cells, are evaluated in patients with relapsed/refractory antibody-mediated idiopathic inflammatory diseases.

Safety and Efficacy of CT103A Cells for Relapsed/Refractory Antibody-associated Inflammatory Diseases of the Nervous System

An Open Label Clinical Trial to Evaluate the Safety and Efficacy of CT103A Cells for the Treatment of Relapsed/Refractory Antibody-associated Inflammatory Diseases of the Nervous System

the number of attacks divided by observed year after CT103A cells infusion

the number of accumulate total active MRI lesions after CT103A infusion

EDSS and its associated functional system (FS) score provide a system for quantifying disability and monitoring changes in the level of disability over time. EDSS is a scale for assessing neurologic impairment in multiple sclerosis (MS). It consists of 7 FS (visual FS, brainstem FS, pyramidal FS, cerebellar FS, sensory FS, bowel and bladder FS, and cerebral FS) which are used to derive EDSS score ranging from 0 (normal neurological exam) to 10 (death from MS). A negative change from baseline indicates improvement. A participant was considered to have a worsening in overall EDSS score of at least 2 if baseline EDSS score was 0, or at least 1 point if baseline EDSS score is 1 to 5, or at least 0.5 point if baseline EDSS score is 5.5 or more.

Modified Rankin Scale (mRS) is a profoundly valid and reliable measure of disability and is broadly utilized for assessing stroke outcomes and degree of disability. We characterized a favorable outcome as mRS ranging from zero up to two, while unfavorable outcome ranging for 3 up to 6.

Corrected visual acuity is determine by Snellen E chart held at a distance of 5 meters. Higher score indicates better vision.

The QMG score is a 13-item scale used to quantify disease severity in myasthenia gravis. The scale measures ocular, bulbar, respiratory, and limb function, grading each finding, and ranges from 0 (no myasthenic findings) to 39 (maximal myasthenic deficits).

The MG-ADL is an eight-question survey of symptom severity, with each response graded from 0 (normal) to 3 (most severe). Two questions concern ocular, three oropharyngeal, one respiratory, and two extremity functions. Cumulative MG-ADL scores range from 0 to 24

The INCAT score comprises two parts, the arm score and the leg score. Based on a patient's level of impairment in their arms and legs, each part is scored between 0 and 5 points, resulting in an INCAT total score between 0 and 10.

The MRC score system for testing and grading of muscle function aims to provide a standardized and objective way to assess muscle function. It ranges from 0 to 5.

Including motor nerve distal latency, proximal latency, compound muscle motor potential (CMAP), motor nerve conduction velocity, sensory nerve conduction velocity, sural nerve potential

For MMT score, 16 muscle groups/ motions will be tested (not individual muscles). 14 of these are tested bilaterally.

If the creatine kinase level drops to twice the upper limit of normal or below, it is defined as effective, and the effective rate is calculated

Calculating the hyperintensity of muscle MRI T2/STIR sequence in patients with IMNM

SF-36 will used to understand the health related quality-of -life of the subjects after CT103A infusion. The eight health concepts: limitations in physical activities because of health problems; limitations in social activities because of physical or emotional problems; limitations in usual role activities because of physical health problems; bodily pain; general mental health (psychological distress and well-being); limitations in usual role activities because of emotional problems; vitality (energy and fatigue); and general health perceptions will be searched. These outcomes will be grouped as physical component summary and mental component summary. The norm data is 0-100, the health related quality of life is increases as the scores are increased. The average score is 50.

Health status is measured with the EuroQuality of Life Five Dimensions (EQ-5D) after CT103A infusion, which includes five dimensions and is used to evaluate the quality of life of sepsis survivors. They are mobility, self-care, usual activities, discomfort or pain and depression or anxiety. Levels are coded 1-5 and a total score is then generated. Results for the demographic measured will be displayed as a percentage value.

usual visual analog scale (VAS) of pain is used to evaluate pain after CT103A infusion (line from 0: no pain to 10:worst pain)

The number of In-patient hospitalization is defined as a stay in hospital that goes beyond midnight of the first day of admission.

Changes of concentration( pg/mL) of cytokines ( such as ferritin, CRP, IL-6 and procalcitonin) will be analyzed after CT103A cells infusion.

Anti-drug antibodies (ADA) against CAR on CT103A cells will be analyzed after CT103A cells infusion.

Levels of replication competent lentivirus (RCL) will be monitored after CT103A cells infusion.

Changes in cells in infused CAR T products, blood and CSF (including proportion of CD3+ T cells, CD3+CD4+ T cells and CD3+CD8+ T cells, ratio of CD4+ T/CD8+T, and single-cell sequencing) will be analyzed after CT103A cells infusion.

Annualized relapse rate (ARR): Number of MS relapses divided by observed year after CT103A cells infusion

Time from CT103A infusion to the first relapse of MS

The changes of enhancing Lesions as detected by brain Magnetic Resonance Imaging (MRI)

Annualized rate of T2 lesions： Number of New, and/or Enlarging T2 Hyperintense Lesions as detected by MRI divided by observed year after CT103A cells infusion

The percent change of T2 lesions volume as detected by MRI from the baseline

EDSS and its associated functional system (FS) score provide a system for quantifying disability and monitoring changes in the level of disability over time. EDSS is a scale for assessing neurologic impairment in multiple sclerosis (MS).

The no evidence of disease activity-3 (NEDA-3), defined as no relapse, no disability worsening, and no MRI activity

Time to onset of 3-month CDP as assessed by EDSS score

Time to onset of 6-month CDP as assessed by EDSS score

Including Fatigue Symptoms and Impacts Questionnaire -Relapsing Multiple Sclerosis (FSIQ-RMS), General Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire (PHQ-9), Health Utilities Index (HUI-III), Multiple Sclerosis Impact Scale (MSIS-29).

Definition of Response:

1. There is a one-point improvement in ECOG performance score; and/or
2. ≥ 50% reduction in ONLS score.

Hematological response rate: Percentage of subjects who achieved partial response (PR) or better according to 2021 IMWG Uniform Response Criteria.

Definition of Neural Response: a) There is a one-point improvement in ONLS score; and/or b) ≥ 15% reduction in mNIS+7 score.

The changes of VEGF levels after CT103A cells infusion.

PET response rate: Percentage of subjects who achieved response according to 2021 IMWG Uniform Response Criteria.

Percentage of subjects who achieved response of other organs.

Time to ≥1point improvement in modified Rankin score (mRS) from baseline without rescue therapy.

Time to first relapse: Time from CT103A infusion to the first relapse of AE (days).

The time to seizure-free (Patients with autoimmune encephalitis have sympotmatic seizures in the acute phase) or the time from seizure-free (without rescue therapy) to rescue therapy.

The changes of Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score from baseline.

The changes of Montreal Cognitive Assessment Scale (MoCA) total scores from baseline.

The changes of Total Clinical Global Impressions (CGI) score from baseline.

The changes of Total Glasgow Coma Score (GCS) from baseline.

The changes of Total Minimum Mental State Examination Score (MMSE) from baseline.

The number of faciobrachial dystonic seizure (FBDS) in patients with LGI1 antibody-positive encephalitis.

Annualized recurrence rate: The number of MOGAD relapses divided by observed year after CT103A cells infusion

Time to first relapse: Time from CT103A infusion to the first relapse of MOGAD.

The changes of enhancing Lesions as detected by MRI.

To evaluate the DLT occurred within 3 months after CT103A infusion

To evaluate the AEs occurred within 2 years after CT103A infusion

The changes of concentration of soluble BCMA in the peripheral blood after CT103A infusion.

The changes of pathogenic antibody titers in peripheral blood or cerebrospinal fluid.

The changes of peripheral blood Neurofilament Light chain (NfL) concentration in patients with MS.

The number of BCMA CAR gene copies (VCN，copies/μg DNA) in peripheral blood and cerebrospinal fluid after administration.

The concentration of BCMA CAR T cells (cells/mL) in peripheral blood after administration was detected by flow cytometry.

Nanjing IASO Biotechnology Co., Ltd.

Tongji Hospital

Professor of Neurology, President of Tongji Hospital

Participants in this group will be recruited from the outpatient clinical population at participating MGNet sites. Treating physicians will make the initial determination of patients' potential eligibility to participate in the study.

Two video telehealth visits will be conducted and recorded within 3 days of one another (+/- 1 day)

Telehealth

The goal of this pilot study is to determine the reliability of myasthenia gravis (MG) specific outcome measures obtained during virtual encounters with patients with myasthenia gravis. The main question it aims to answer is: Are MG-specific outcome measures obtained during virtual encounters reliable?

Participants will complete two virtual study visits in which they will be administered common MG-specific outcome measures and a newly developed outcome measure developed specifically for telemedicine assessments of MG patients.

The purpose of this study is to better understand the use of modified clinical assessments during telehealth visits for patients with Myasthenia Gravis (MG). The study will consist of 2 virtual telemedicine visits. A screening visit will be conducted to optimize the telemedicine environment, provide training on the telemedicine platform being used in the study, and collect demographic, medical history, and medication information. Participants who meet eligibility requirements will have a telemedicine visit (Visit 1) with a study doctor where assessments adapted for the telemedicine environment will be performed. Participants will also be asked to fill out questionnaires related to MG or their experience with telemedicine either online or with the study investigators. A second visit (Visit 2), conducted within 3 days (+/- 1 day), will replicate the assessments performed in V1. Visit 1 and Visit 2 will be recorded for later review by study team members. The investigators hope to establish the effectiveness of these clinical tools in order to better manage MG in the future in clinical care and research study visits.

The Adapting Disease Specific Outcome Measures Pilot Trial for Telehealth in Myasthenia Gravis

The Adapting Disease Specific Outcome Measures Pilot Trial for Telehealth in Myasthenia Gravis (ADAPT-teleMG)

Interrater reliability of the virtual Myasthenia Gravis Composite (MGC-v) score will be estimated between two independent rater assessments performed on Visit 1 (V1) and Visit 2 (V2). The MGC score is a validated, patient-reported 10-item assessment tool for evaluating the symptoms and signs of MG. Patient assessment includes self-report of impact (normal, mild, moderate, or severe) and is additionally weighted for clinical significance. Total score ranges from 0 to 50, with higher scores indicating a greater impact of MG on functional activities. A three point change is considered clinical meaningful. This brief assessment takes approximately 10 minutes to complete.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Exploring Outcomes and Characteristics of Myasthenia Gravis 2	NCT06002945	Myasthenia Grav...	Blood sample	18 Years -	Yale University
A Pilot Study of Mitoxantrone for the Treatment of Recurrent Neuromyelitis Optica (Devic's Disease)	NCT00304291	Neuromyelitis O... Myelitis, Trans... Demyelinating A... Autoimmune Dise...	Mitoxantrone	18 Years - 55 Years	State University of New York at Buffalo
Safety and Efficacy of CT103A Cells for Relapsed/Refractory Antibody-associated Inflammatory Diseases of the Nervous System	NCT04561557	Autoimmune Dise... Autoimmune Dise... Neuromyelitis O... Myasthenia Grav... Chronic Inflamm... Idiopathic Infl... Multiple Sclero... Autoimmune Ence... Myelin Oligoden... POEMS Syndrome	CT103A cells Cyclophosphamid...	18 Years - 75 Years	Tongji Hospital
The Adapting Disease Specific Outcome Measures Pilot Trial for Telehealth in Myasthenia Gravis	NCT05917184	Myasthenia Grav...	Telehealth	18 Years -	Yale University
Study of Tcelna (Imilecleucel-T) in Secondary Progressive Multiple Sclerosis	NCT01684761	Autoimmune Dise... Multiple Sclero... Secondary Progr... Disease Progres... Brain Atrophy	Tcelna Placebo	18 Years - 60 Years	Opexa Therapeutics, Inc.
The Impact of Myasthenia Gravis in the Real World	NCT04176211	Myasthenia Grav...		18 Years -	Vitaccess Ltd
The Impact of Myasthenia Gravis in the Real World	NCT04176211	Myasthenia Grav...		18 Years -	Vitaccess Ltd
Predictors and Prognostic Factors of Myasthenia Gravis Outcome	NCT05214612	Myasthenia Grav... Autoimmune Dise... Neuromuscular J... Thymoma Thymus Hyperpla... Nervous System ... Myasthenia Grav... Myasthenia Grav... Myasthenia Grav... Myasthenia Grav... Myasthenia Grav... Myasthenia Grav...	Drug treatment ...	16 Years -	Assiut University
Safety and Efficacy of CT103A Cells for Relapsed/Refractory Antibody-associated Inflammatory Diseases of the Nervous System	NCT04561557	Autoimmune Dise... Autoimmune Dise... Neuromyelitis O... Myasthenia Grav... Chronic Inflamm... Idiopathic Infl... Multiple Sclero... Autoimmune Ence... Myelin Oligoden... POEMS Syndrome	CT103A cells Cyclophosphamid...	18 Years - 75 Years	Tongji Hospital

Spots Global Cancer Trial Database for autoimmune diseases of the nervous system