Neoplasms

Nervous System Diseases

Immune System Diseases

All Conditions

Symptoms and General Pathology

Musculoskeletal Diseases

Rare Diseases

Myasthenia Gravis

Asthenia

Muscle Weakness

Paresis

Muscular Diseases

Neuromuscular Manifestations

Neurologic Manifestations

Syndrome

Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

Nervous System Neoplasms

Autoimmune Diseases

Autoimmune Diseases of the Nervous System

Neurodegenerative Diseases

Neuromuscular Junction Diseases

Neuromuscular Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

The placebo group will receive a vehicle control infusion

Intervention (rituximab): The treatment group will receive a total of two cycles of rituximab separated by 6 months. Each cycle is defined as one infusion (375mg/m2 IV) per week for four consecutive weeks

Placebo

Richard J Nowak, MD, MS

The specific primary objective of this study is to determine whether rituximab is a safe and beneficial therapeutic for Myasthenia Gravis (MG) that warrants further study in a phase III efficacy trial.

Investigators plan on conducting a multicenter randomized, double-blind, placebo controlled Phase II clinical trial utilizing a futility design. The study would include acetylcholine receptor (AChR) antibody positive generalized MG subjects. This study also presents a unique opportunity to study both drug and disease mechanisms because unlike many other autoimmune diseases in which rituximab has been used, MG affords the investigation of antigen-specific components that participate in the immunopathology of the disease, namely autoantibodies, autoantibody-producing B cells, and antigen-specific T cells. This work will further our understanding of MG immunopathology and it represents the first step toward gaining a more complete understanding of the immune mechanisms underlying treatment of MG with rituximab leading to new ways to treat the disease.

The specific aim of this study is to determine whether rituximab is a safe and effective treatment for subjects with MG.

The SNOMED code for MG is 31839002.

BeatMG: Phase II Trial of Rituximab In Myasthenia Gravis

B Cell Targeted Treatment In Myasthenia Gravis (BeatMG): A Phase II Trial of Rituximab In Myasthenia Gravis

Percent of subjects that achieve a ≥ 75% reduction in mean daily prednisone dose in the 4 weeks prior to week 52 and have clinical improvement or no significant worsening of symptoms (≤ 2 point increase in MGC score) as compared to 4-week period prior to randomization and initiation of treatment.

Evaluate treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)

Evaluate whether there is a trend towards clinical benefit at end of 52 week treatment period, as measured by mean change in the MGC score, an MG-specific clinical outcomes scale used as endpoint in prior MG clinical trials. The Myasthenia Gravis Composite (MGC) scale consists of test items from the MG-ADL (Myasthenia Gravis Activities of Daily Living) scale and the QMG (Quantitative Myasthenia Gravis Scale) that measure symptoms and signs of MG, with weighted response options. The minimum score is 0, and the maximum score is 50. Higher scores correlate with clinical worsening of the disease.

Evaluate whether there is a trend towards clinical benefit at end of 52 week treatment period, as measured by the mean change in the QMG score - a specific clinical outcome scale used as endpoint in prior MG clinical trials. The Quantitative Myasthenia Gravis Score (QMG) is a commonly used objective outcome measure in myasthenia gravis (MG) comprising 13 items, each with a possible score from 0 to 3, and a maximum possible of 39 points, where a higher score indicates more severe disease.

National Institute of Neurological Disorders and Stroke (NINDS)

Yale University

- Treatment group received two cycles of rituximab (375mg/m2 iv), separated by 6 months. Each cycle defined as one infusion per week for four consecutive weeks. For the main study, participants were followed for 52 weeks. Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter.

- Placebo group received infusion containing only vehicle components of rituximab solution. Infusion was done in 2 cycles, separated by 6 months. Each cycle defined as one infusion per week for four consecutive weeks. For the main study, participants were followed for 52 weeks. Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter.

Placebo Group

Total

Age, Continuous

Sex: Female, Male

Race and ethnicity

Race/Ethnicity, Customized

Baseline Prednisone Dose

The Myasthenia Gravis Composite (MGC) scale consists of test items from the MG-ADL (Myasthenia Gravis Activities of Daily Living) scale and the QMG (Quantitative Myasthenia Gravis Scale) that measure symptoms and signs of MG, with weighted response options. The minimum score is 0, and the maximum score is 50. Higher scores correlate with clinical worsening of the disease.

Baseline Myasthenia Gravis Composite (MGC)

The Quantitative Myasthenia Gravis Score (QMG) is a commonly used objective outcome measure in myasthenia gravis (MG) comprising 13 items measuring ocular, bulbar, extremity fatigue/strength, and respiratory function (forced vital capacity), each with a possible score from 0 to 3, and a maximum possible of 39 points, where a higher score indicates more severe disease.

Baseline Quantitative Myasthenia Gravis (QMG)

This 8 point scale with a maximum score of 24 and a minimum of 0 assesses the subject's ability to perform daily activities and can be performed in approximately 5 minutes. A higher score indicates more severe disease.

Baseline MG-Activities of Daily Living Score

The subject completes the 15-question MG-QOL questionnaire and reports the effect of MG on their quality of life. The MG-QOL should be administered prior to other outcomes evaluations at each visit.The maximum score is 60 and the minimum is 0. A higher score indicates more severe disease.

Baseline MG-Quality of Life (MG-QOL) score

Class I- Any ocular muscle weakness, may have weakness of eye closure, all other muscle strength is normal. Class II - Mild weakness affecting other than ocular muscles, may also have ocular muscle weakness of any severity. Class III - Moderate weakness affecting other than ocular muscles, may also have ocular muscle weakness of any severity. Class IV - Severe weakness affecting other than ocular muscles, may also have ocular muscle weakness of any severity. A higher grade is indicative of a worse outcome.

Baseline MGFA Clinical Classification Grade

Thymectomy

Dr. Richard Nowak, MD,MS

This futility design tests the following hypothesis:

H0: Rituximab improves outcome by at least 30% compared to placebo (pR - pP ≥ 0.30 - not futile) versus HA: Rituximab does not improve outcome by at least 30% compared to placebo (pR - pP \< 0.30 - futile)

Steroid Sparing Effect

% of study participants with treatment related AEs

% study participants with treatment related SAEs

% of participants with treatment related AEs

% participants with treatment related SAEs

- Treatment group received two cycles of rituximab (375mg/m2 iv), separated by 6 months.Each cycle defined as one infusion per week for four consecutive weeks.For the main study, participants were followed for 52 weeks.Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter.

- Placebo group received infusion containing only vehicle components of rituximab solution. Infusion was done in 2 cycles

, separated by 6 months. Each cycle defined as one infusion per week for four consecutive weeks. For the main study, participants were followed for 52 weeks. Study participants had clinical evaluations performed by a blinded evaluator at baseline and every 4 weeks thereafter.

Safety:Percentage of Study Participants With Treatment-related Adverse Experiences

This objective was assessed longitudinally by comparing the final score at the end of the study to the score obtained at baseline. The outcome was defined as the change from baseline to week 52 in the MGC. This hypothesis was assessed using a linear regression model, adjusted for differences in baseline MGC scores.

Change in Myasthenia Gravis Composite (MGC) Scores From Baseline to Week 52

This objective was assessed longitudinally by comparing the final score at the end of the study to the score obtained at baseline. The outcome was defined as the change from baseline to week 52 in the QMG. This hypothesis was assessed using a linear regression model, adjusted for differences in baseline QMG scores.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
BeatMG: Phase II Trial of Rituximab In Myasthenia Gravis	NCT02110706	Myasthenia Grav...	Rituximab Placebo	21 Years - 90 Years	Yale University
BeatMG: Phase II Trial of Rituximab In Myasthenia Gravis	NCT02110706	Myasthenia Grav...	Rituximab Placebo	21 Years - 90 Years	Yale University

Spots Global Cancer Trial Database for snomed code 31839002