An Extension Study of MOM-M281-004 to Evaluate the Safety, Tolerability, and Efficacy of M281 Administered to Patients With Generalized Myasthenia Gravis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the long-term safety and tolerability of M281 in participants with generalized myasthenia gravis (gMG)

Official Title
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An Open-label Extension Study of MOM-M281-004 to Evaluate the Safety, Tolerability, and Efficacy of M281 Administered to Patients With Generalized Myasthenia Gravis

Conditions
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Generalized Myasthenia Gravis

Intervention / Treatment
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* Drug: M281


Participation Criteria
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Eligibility Criteria
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Participants must be ≥18 years of age with a documented history of Generalized Myasthenia Gravis (gMG) and clinical signs/symptoms of gMG, not pregnant or breastfeeding, previously participated in the MOM-281-004 study, had no major eligibility deviations or other major protocol deviations or not met any of the stopping criteria or discontinued study drug in the MOM-M281-004 study for any reason other than the need for rescue therapy as specified in the MOM-M281-004 study. Additional, more specific criteria are defined in the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M281<br> | Drug: M281<br>* M281 injection administered as intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Number of participants with TEAEs were reported. An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are defined as any AE occurring during or after the initiation of the first infusion of study drug in this study. | Up to 257 days post-baseline (Baseline is Day 1) | 
| Number of Participants With Serious Adverse Events (SAEs) | An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. SAE is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. | Up to 257 days post-baseline | 
| Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESIs) | Number of participants with treatment-emergent AESIs were reported. Severe infections and hypoalbuminemia (Grade 3 or higher according to the Common Terminology Criteria for Adverse Events [CTCAE] v5.0) were considered as AESIs. | Up to 257 days post-baseline | 
| Number of Participants With Treatment-emergent Abnormal Vital Signs | Number of participants with treatment-emergent abnormal vital signs including pulse rate (less than or equal to [<=] 50 beats per minutes [bpm] with greater than or equal to [>=] 15 bpm decrease from baseline, >= 120 bpm with >=15 bpm increase from baseline), systolic blood pressure (SBP) (<= 90 millimeters of mercury [mmHg] with >= 20 mmHg decrease from baseline, >= 160 mmHg with >= 20 mmHg increase from baseline) and diastolic blood pressure (DBP) (<= 50 mmHg with >=15 mmHg decrease from baseline, >=100 mmHg with >=15 mmHg decrease from baseline) were reported. | Up to 257 days post-baseline | 
| Number of Participants With Abnormalities in Physical Examinations | Number of participants with abnormalities in physical examinations (abdomen, head, ears, eyes, nose, throat, and sinuses, lungs, neurological, skin, blood and lymphatic system, cardiovascular, chest, gastrointestinal, general appearance and musculoskeletal) were reported. | Week 12 | 
| Change From Baseline in Chemistry Laboratory Parameters: Albumin and Protein | Change from baseline in chemistry laboratory parameters: albumin and protein were reported. | Baseline up to Week 12 | 
| Change From Baseline in Chemistry Laboratory Parameters: Bicarbonate, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium, Sodium, Triglycerides, Urate and Urea Nitrogen | Change from baseline in chemistry laboratory parameters: bicarbonate, calcium, chloride, cholesterol, glucose, phosphate, potassium, sodium, triglycerides, urate and urea nitrogen were reported. | Baseline up to Week 12 | 
| Change From Baseline in Chemistry Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase | Change from baseline in chemistry laboratory parameters alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), creatine kinase, gamma glutamyl transferase, lactate dehydrogenase were reported. | Baseline up to Week 12 | 
| Change From Baseline in Chemistry Laboratory Parameters: Bilirubin, Creatinine and Direct Bilirubin | Change from baseline in chemistry laboratory parameters: bilirubin, creatinine and direct bilirubin were reported. | Baseline up to Week 12 | 
| Change From Baseline in Hematology Laboratory Parameter: Erythrocytes (Red Blood Cell) | Change from baseline in erythrocytes (red blood cells) (hematology laboratory parameter) was reported. | Baseline up to Week 12 | 
| Change From Baseline in Hematology Laboratory Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes | Change from baseline in hematology laboratory parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes were reported. | Baseline up to Week 12 | 
| Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration | Change from baseline in erythrocytes mean corpuscular hemoglobin (HGB) concentration (hematology laboratory parameter) were reported. | Baseline up to Week 12 | 
| Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (HGB) | Change from baseline in erythrocytes mean corpuscular HGB (hematology laboratory parameter) was reported. | Baseline up to Week 12 | 
| Change From Baseline in Hematology Laboratory Parameter: Erythrocytes Mean Corpuscular Volume | Change from baseline in erythrocytes mean corpuscular volume (hematology laboratory parameter) was reported. | Baseline up to Week 12 | 
| Change From Baseline in Hematology Laboratory Parameter: Hematocrit | Change from baseline in hematocrit (hematology laboratory parameter) was reported. | Baseline up to Week 12 | 
| Change From Baseline in Hematology Laboratory Parameter: Hemoglobin | Change from baseline in hemoglobin (hematology laboratory parameter) was reported. | Baseline up to Week 12 | 
| Change From Baseline in Urinalysis Laboratory Parameter: pH | Change from baseline in pH (urinalysis laboratory parameter) was reported. | Baseline up to Week 12 | 
| Change From Baseline in Urinalysis Laboratory Parameter: Specific Gravity | Change from baseline in specific gravity (urinalysis laboratory parameter) was reported. | Baseline up to Week 12 | 
| Number of Participants With Treatment-emergent Abnormal Electrocardiograms (ECG) Values | Number of participants with treatment-emergent abnormal ECG values for variables including mean heart rate (abnormally low refers to less than or equal to [<=] 50 beats per minute [bpm], abnormally high refers greater than or equal to [>=] 120 bpm), PR interval (abnormally low refers to < 120 and abnormally high refers to >200 milliseconds [msec]), RR interval (abnormally low refers to <600 msec and abnormally high refers to >1200 msec) and QRS duration (abnormally > 120) were reported. | Up to 257 days post-baseline | 
| Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Scores | Number of participants with C-SSRS scores were reported. C-SSRS is a clinician-administered questionnaire designed to solicit occurrence, severity, and frequency of suicide-related ideation and behaviors. Total score ranges from 1 to 10, score of 0 was assigned (0=no event that can be assessed based on C-SSRS). Higher total scores indicate greater severity. Maximum score assigned for each participant was summarized into one of 3 categories: no suicidal ideation or behavior (0), suicidal ideation (1 to 5): higher score indicates more suicidal ideation, suicidal behavior (6 to 10): higher score indicates more suicidal behavior. Suicidal ideation includes participants who did not have suicidal ideation or behavior at baseline and had suicidal ideation without behavior at some time point post-baseline. Suicidal behavior includes participants who did not have suicidal ideation or behavior at baseline and had suicidal behavior at some time point post-baseline (baseline=Day 1). | Up to 257 days post-baseline | 
| Number of Participants With Below/Above Normal Values of Coagulation Laboratory Parameter | Number of participants with at least one value above upper limit of normal (>ULN) or below the lower limit of normal (< LLN) value of coagulation parameters (activated partial thromboplastin time [APTT] and prothrombin time [PT]) were reported. The lab reference range for APTT is 25.1 to 36.5 seconds. The lab reference range for PT is 9.4 to 12.5 seconds. | Up to 257 days post-baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score Over Time | The MG-ADL was used to assess the participant's MG symptom severity. It assesses eight functions (talking, chewing, swallowing, breathing, impairment of ability to brush teeth or comb hair, impairment of ability to arise from a chair, double vision, and eyelid droop) which were rated on a 4-point scale: 0 (no impairment) to 3 (severe impairment). The total score is the sum of the eight function scores and ranges from 0 to 24. Higher scores indicated greater symptom severity/difficulty in performing daily living activities. | Baseline up to Weeks 4, 8, 12, 24, End of treatment (EoT) (up to 253 days post-baseline), Follow-up (up to 257 days post-baseline) | 
| Number of Participants With a 2-, 3-, 4-, 5-, 6-, 7-, or Greater Than or Equal to (>=) 8-point Improvement in Total MG-ADL Score Over Time | Number of Participants With a 2-, 3-, 4-, 5-, 6-, 7-, or greater than or equal to (>=) 8-point improvement in total MG-ADL score over time were reported. MG-ADL was used to assess the participant's MG symptom severity. It assesses eight functions (talking, chewing, swallowing, breathing, impairment of ability to brush teeth or comb hair, impairment of ability to arise from a chair, double vision, and eyelid droop) which were rated on a 4-point scale: 0 (no impairment) to 3 (severe impairment). The total score is the sum of the eight function scores and ranges from 0 to 24. Higher scores indicated greater symptom severity/difficulty in performing daily living activities. | Weeks 4, 8, 12, 24, End of treatment (EoT) (up to 253 days post-baseline), Follow-up (up to 257 days post-baseline) | 
| Change From Baseline in Total Quantitative Myasthenia Gravis (QMG) Score Over Time | The QMG test was used to assess the participant's strength. The quantitative results of each of the 13 strength components were mapped to a 4-point scale where 0 equals to (=) none, 1= mild, 2= moderate and 3= severe. The total score is the sum of the 13 scale scores and ranges from 0 to 39. Higher scores indicated more severe impairment. | Baseline up to Weeks 4, 8, 12, 24, End of Treatment (EoT) (up to 253 days post-baseline), Follow-up (up to 257 days post-baseline) | 
| Change From Baseline in Total Revised Myasthenia Gravis Quality of Life - 15 Scale (MG-QoL15r) Score Over Time | The MG-QoL15r was used to assess the participant's limitations related to living with MG. It consists of 15 questions and each of the 15 questions were rated by the participant on a 3-point scale (0= Not at all, 1= somewhat, 2=very much) based on a recall period of over the past few weeks. The total score is the sum of the 15 question scores and ranges from 0 to 30. Higher scores indicated more limitation. | Baseline up to Weeks 4, 8, 12, 24, End of Treatment (EoT) (up to 253 days post-baseline), Follow-up (up to 257 days post-baseline) | 
| Change From Baseline in Clinical Global Impression of Severity (CGI-S) Rating Score Over Time | The CGI-S scale is the clinician/physician's global assessment of participants illness severity of MG and is rated by answering on 8-point scale. Considering total clinical experience, participant is assessed on severity of illness according to: 0=not performed; 1=normal, not at all ill; 2=borderline illness; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among most extremely ill patients. Higher scores indicated more severity of illness. Values of 0 (not assessed) were excluded from analysis. CGI-S permits global evaluation of participant's condition at given time. | Baseline up to Weeks 4, 8, 12, 24, End of Treatment (EoT) (up to 253 days post-baseline), Follow-up (up to 257 days post-baseline) | 
| Number of Participants With Improvement of Illness Over Time Based on Clinical Global Impression of Improvement (CGI-I) Scale Score | Number of participants with improvement of illness based on CGI-I scale score over time were reported. The CGI-I scale is the clinician/physician's global assessment of the change in severity of the patient's generalized myasthenia gravis (gMG) since starting this study. The rating is given on a 7-point scale with lower scores indicating greater improvement (1= Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 =Minimally worse; 6 = Much worse; 7 = Very much worse. Values of 0 (not assessed) were excluded from analysis. Higher score indicates more severity. | Weeks 4, 8, 12, 24, End of Treatment (EoT) (up to 253 days post-baseline), Follow-up (up to 257 days post-baseline) | 
| Number of Participants With Change From Baseline in Myasthenia Gravis Foundation of America (MGFA) Classification Score Over Time | Number of participants with change from baseline in MGFA classification score over time were reported. The MGFA was used to assess the participant's MG severity. MGFA classification identifies the subgroup participants with MG who share distinct clinical features or severity of disease: Class I (ocular MG), classes II, III and IV generalized MG with mild, moderate and severe disease, respectively; Class V MG crisis. Separate subclasses under classes II, III and IV are designed: a if the predominant weakness is affecting limb/axial weakness or both; subclass b if the predominant weakness is affecting oropharyngeal or respiratory muscles or both. In the MGFA classification, lower roman numerals mean less severity. Changes in MGFA classification (regardless of subclass) are categorized as Improved (example, III to II), Same (example, II to II), or Worsened (example, II to III). | Weeks 8, 24 and End of Treatment (EoT) (up to 253 days post-baseline) | 
| Number of Participants With Anti-drug Antibodies (ADA) to Nipocalimab | Number of participants with ADA to nipocalimab were reported. The presence of ADA to nipocalimab in serum was determined by a sensitive and drug-tolerant electrochemiluminescence immunoassay (ECLIA) method. | Up to 257 days post-baseline | 
| Number of Participants With Neutralizing Antibodies (NAbs) to Nipocalimab | Number of participants with NAbs were reported. Neutralizing antibodies to nipocalimab were assessed using a non-cell based competitive ligand binding ECLIA assay. | Up to 257 days post-baseline | 
| Change From Baseline in Serum Immunoglobulin (Ig)G Concentration Over Time | Change from baseline in serum immunoglobulin (Ig)G concentration over time was reported. | Baseline to Weeks 2, 4, 8, 12, 24, up to 253 days post-baseline, up to 257 days post-baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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M281, Generalized Myasthenia Gravis