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

Phase 2

Terminated

Conditions: Generalized Myasthenia Gravis

Interventions: Drug: M281

Registration Number: NCT03896295

Lead Sponsor: Momenta Pharmaceuticals, Inc.

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

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 37

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
M281	M281	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Up to 257 days post-baseline (Baseline is Day 1)	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.
Number of Participants With Serious Adverse Events (SAEs)	Up to 257 days post-baseline	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.
Number of Participants With Treatment-emergent Abnormal Vital Signs	Up to 257 days post-baseline	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.
Number of Participants With Abnormalities in Physical Examinations	Week 12	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.
Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESIs)	Up to 257 days post-baseline	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.
Change From Baseline in Chemistry Laboratory Parameters: Albumin and Protein	Baseline up to Week 12	Change from baseline in chemistry laboratory parameters: albumin and protein were reported.
Change From Baseline in Chemistry Laboratory Parameters: Bicarbonate, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium, Sodium, Triglycerides, Urate and Urea Nitrogen	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 were reported.
Change From Baseline in Chemistry Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase	Baseline up to Week 12	Change from baseline in chemistry laboratory parameters alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), creatine kinase, gamma glutamyl transferase, lactate dehydrogenase were reported.
Change From Baseline in Chemistry Laboratory Parameters: Bilirubin, Creatinine and Direct Bilirubin	Baseline up to Week 12	Change from baseline in chemistry laboratory parameters: bilirubin, creatinine and direct bilirubin were reported.
Change From Baseline in Hematology Laboratory Parameter: Erythrocytes (Red Blood Cell)	Baseline up to Week 12	Change from baseline in erythrocytes (red blood cells) (hematology laboratory parameter) was reported.
Change From Baseline in Hematology Laboratory Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes	Baseline up to Week 12	Change from baseline in hematology laboratory parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes were reported.
Change From Baseline in Hematology Laboratory Parameter: Hematocrit	Baseline up to Week 12	Change from baseline in hematocrit (hematology laboratory parameter) was reported.
Change From Baseline in Urinalysis Laboratory Parameter: pH	Baseline up to Week 12	Change from baseline in pH (urinalysis laboratory parameter) was reported.
Change From Baseline in Urinalysis Laboratory Parameter: Specific Gravity	Baseline up to Week 12	Change from baseline in specific gravity (urinalysis laboratory parameter) was reported.
Number of Participants With Treatment-emergent Abnormal Electrocardiograms (ECG) Values	Up to 257 days post-baseline	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.
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration	Baseline up to Week 12	Change from baseline in erythrocytes mean corpuscular hemoglobin (HGB) concentration (hematology laboratory parameter) were reported.
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (HGB)	Baseline up to Week 12	Change from baseline in erythrocytes mean corpuscular HGB (hematology laboratory parameter) was reported.
Change From Baseline in Hematology Laboratory Parameter: Hemoglobin	Baseline up to Week 12	Change from baseline in hemoglobin (hematology laboratory parameter) was reported.
Change From Baseline in Hematology Laboratory Parameter: Erythrocytes Mean Corpuscular Volume	Baseline up to Week 12	Change from baseline in erythrocytes mean corpuscular volume (hematology laboratory parameter) was reported.
Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Scores	Up to 257 days post-baseline	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).
Number of Participants With Below/Above Normal Values of Coagulation Laboratory Parameter	Up to 257 days post-baseline	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Total Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score Over 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)	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.
Change From Baseline in Total Quantitative Myasthenia Gravis (QMG) Score Over 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)	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.
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	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 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.
Change From Baseline in Total Revised Myasthenia Gravis Quality of Life - 15 Scale (MG-QoL15r) Score Over 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)	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.
Number of Participants With Anti-drug Antibodies (ADA) to Nipocalimab	Up to 257 days post-baseline	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.
Number of Participants With Neutralizing Antibodies (NAbs) to Nipocalimab	Up to 257 days post-baseline	Number of participants with NAbs were reported. Neutralizing antibodies to nipocalimab were assessed using a non-cell based competitive ligand binding ECLIA assay.
Change From Baseline in Serum Immunoglobulin (Ig)G Concentration Over Time	Baseline to Weeks 2, 4, 8, 12, 24, up to 253 days post-baseline, up to 257 days post-baseline	Change from baseline in serum immunoglobulin (Ig)G concentration over time was reported.
Change From Baseline in Clinical Global Impression of Severity (CGI-S) Rating Score Over 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)	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.
Number of Participants With Change From Baseline in Myasthenia Gravis Foundation of America (MGFA) Classification Score Over Time	Weeks 8, 24 and End of Treatment (EoT) (up to 253 days post-baseline)	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).
Number of Participants With Improvement of Illness Over Time Based on Clinical Global Impression of Improvement (CGI-I) Scale Score	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 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.