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

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.

Diseases and Abnormalities at or Before Birth

Eye Diseases

Lambert-Eaton Myasthenic Syndrome

Myasthenic Syndromes, Congenital

Nystagmus, Pathologic

Genetic Diseases, Inborn

Lambert Eaton Myasthenic Syndrome

Congenital Myasthenic Syndromes

Channel Blockers

All Drugs and Chemicals

Amifampridine

Potassium Channel Blockers

Dosage form: tablets containing the equivalent of 10 mg amifampridine per tablet.

Amifampridine Phosphate given based on Investigator assessment of optimal neuromuscular benefit. In adult patients \> 16 years of age, Doses ranged from 30 mg to 80 mg, divided into doses taken 3 to 4 times per day and in pediatric patients age \< 16 years the maximum daily dose was 60 mg/day. No single dose to exceed 20 mg.

Amifampridine Phosphate

Perry Shieh, MD, PhD

Primary:

The primary objective of this study under the original protocol was to provide neuromuscular specialists and neurologists access to amifampridine phosphate therapy for their patients with LEMS, CMS or downbeat nystagmus until the product became commercially available.

Secondary:

The secondary objective of this study under the original protocol was to provide additional long-term safety data on amifampridine phosphate in patients.

Primary The primary objective of this study after its fifth amendment was to provide access to amifampridine phosphate therapy to pediatric patients with LEMS, and pediatric and adult patients with CMS until the product became commercially available for these indications or development of the product for the indication was terminated.

Secondary:

The secondary objective of this study after its fifth amendment was to assess the long-term safety of amifampridine phosphate in pediatric patients with LEMS, and pediatric and adult patients with CMS.

This multicenter, expanded access study was designed to allow EAP-001 Investigators, neuromuscular specialists, and neurologists access to amifampridine phosphate therapy for their patients with LEMS, CMS, or downbeat nystagmus until such time the product became commercially available for these specific indications or development of the product for the indication was terminated. Given that these are chronic conditions, this study obtained some long-term safety data by evaluating Adverse Events, physical exams, vital signs, standard safety laboratory tests (chemistry, hematology, and urinalysis), pregnancy testing (if applicable) and abnormal ECG findings, where each of these data/measures were performed as part of a routine standard of care treatment provided by the Principal Investigator or the patient's personal physician(s) (i.e., could be performed by a different physician not involved in the treatment of neuromuscular disease).

Planned -100 sites in US and up to 200 patients. Actual- 50 sites activated and 200 patients enrolled.

Patients were seen at screening/baseline, Day 1 and at least once per year at the PIs discretion. With the COVID-19 Pandemic, telehealth visits were allowed and assessments that could be completed via remote telehealth visits were performed via phone or videoconference. Follow-up visits included Physical exams, vital signs, standard safety laboratory tests (chemistry, hematology, and urinalysis), pregnancy testing (if applicable) and ECGs.

Patients were titrated to an optimal individualized dose of amifampridine phosphate based on Principal Investigator assessment of optimal neuromuscular benefit. In patients already taking amifampridine base, amifampridine phosphate was started at an equivalent or lower dose of amifampridine phosphate, at the Principal Investigator's discretion. Therapeutic doses were to range from 10 to 80 mg, divided into doses taken two (2) to four (4) times per day, with a maximum single dose of 20 mg. For upward titration, amifampridine phosphate could be increased by 10 mg increments every four (4) to five (5) days to a maximum of 80 mg per day (ages \>16 years), and to a maximum of 60 mg (ages 2 to 16 years) based on optimal neuromuscular benefit and at the discretion of the Principal Investigator. If needed, titration could occur in 5 mg/dose and per day increments. Drug was shipped to the clinic for the first dose ( Day 1) and subsequent shipments were sent to the patients home by a specialty pharmacy.

In addition to amifampridine phosphate, patients received best supportive care (BSC) treatment as determined by the Principal Investigator using concomitant medications permitted by protocol, including selected oral immunosuppressant's (i.e., prednisone or other corticosteroids, azathioprine, mycophenolate) and peripherally acting cholinesterase inhibitors (e.g., pyridostigmine). Changes to BSC could be made at the Principal Investigator's discretion, as long as prohibited concomitant medications were not used.

Firdapse® was approved for adult patients with LEMS in November 2018 and approved for pediatric patients with LEMS ages 6 years and older in September 2022. The indications for CMS and DBN were not pursued.

Expanded Access Study Amifampridine Phosphate in Lambert-Eaton Myasthenic Syndrome (LEMS),Congenital Myasthenic Syndrome

An Open-Label, Expanded Access Protocol for Firdapse® (Amifampridine Phosphate; 3,4-Diaminopyridine Phosphate) Treatment in Pediatric Patients With Lambert-Eaton Myasthenic Syndrome (LEMS), and in Pediatric and Adult Patients With Congenital Myasthenic Syndromes (CMSs)

Catalyst Pharmaceuticals, Inc.

Antineoplastic Agents

Antirheumatic Agents

Antibodies

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunoglobulins

AChR Antibody-Positive Cohort AChR Antibody-Negative Cohort

Single intravenous infusion of CABA-201 at a single dose level following preconditioning with fludarabine and cyclophosphamide

CABA-201

Cabaletta Bio

Medical Director

RESET-MG: A Phase 1/2 Open-Label Study to Evaluate the Safety and Efficacy of CABA-201 in Participants with Generalized Myasthenia Gravis

Myasthenia gravis (MG) is a rare autoimmune disorder characterized by autoantibody responses that cause defective transmission of signals at the neuromuscular junction, resulting in a distinctive pattern of weakness. Patients with generalized MG (gMG) typically experience symptoms associated with ocular disease in addition to weakness of many other voluntary muscle groups, including extremity, bulbar, and respiratory muscles. MG is considered a classic example of a B-cell mediated autoimmune disease. Currently, there are no curative treatments for MG. This study is being conducted to evaluate the safety and efficacy of an investigational cell therapy, CABA-201, that can be given to patients with gMG. A single dose of CABA-201 in combination with cyclophosphamide (CY) and fludarabine (FLU) will be evaluated.

RESET-MG: A Study to Evaluate the Safety and Efficacy of CABA-201 in Participants With Generalized Myasthenia Gravis

RESET-MG: A Phase 1/2, Open-Label Study to Evaluate the Safety and Efficacy of Autologous CD19-specific Chimeric Antigen Receptor T Cells (CABA-201) in Participants With Generalized Myasthenia Gravis

An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal result of an investigation), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. The term AE is used to include both serious and non-serious AEs.

Levels of CABA-201-positive T cells in the blood

Levels of MG-specific autoantibodies in the serum

The MG-ADL scale is a validated instrument administered by a qualified assessor with 8 areas of activities of daily living as reported by patients: talking, chewing, swallowing, breathing, ability to brush teeth or comb hair, ability to rise from a chair, double vision, and eyelid droop. In each area, the score ranges from 0 (normal) to 3 (most severe). The total score is the sum of all subscores.

The QMG score is a 13-item scale conducted by a qualified assessor to evaluate disease severity in patients with MG. The total score ranges from a minimum of 0 (no myasthenic findings) to 39 (maximum myasthenic deficits).

The MGC scale is a physician-reported instrument for the assessment of MG patients' symptoms and impairments. It includes 10 domains, and the total score ranges from 0 (normal) to 50 (most severe).

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
The Adapting Disease Specific Outcome Measures Pilot Trial for Telehealth in Myasthenia Gravis	NCT05917184	Myasthenia Grav...	Telehealth	18 Years -	Yale University
Expanded Access Study Amifampridine Phosphate in Lambert-Eaton Myasthenic Syndrome (LEMS),Congenital Myasthenic Syndrome	NCT02189720	Congenital Myas... Lambert-Eaton M... Nystagmus, Acqu...	Amifampridine P...	2 Years -	Catalyst Pharmaceuticals, Inc.
Expanded Access Study Amifampridine Phosphate in Lambert-Eaton Myasthenic Syndrome (LEMS),Congenital Myasthenic Syndrome	NCT02189720	Congenital Myas... Lambert-Eaton M... Nystagmus, Acqu...	Amifampridine P...	2 Years -	Catalyst Pharmaceuticals, Inc.
RESET-MG: A Study to Evaluate the Safety and Efficacy of CABA-201 in Participants With Generalized Myasthenia Gravis	NCT06359041	Generalized Mya...	CABA-201	18 Years - 70 Years	Cabaletta Bio

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