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

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

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

Study Overview

• Status: Terminated
• Conditions: Generalized Myasthenia Gravis
• Intervention / Treatment: Drug: M281

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, 2650
    • Momenta Investigational Site
  • Bruxelles, Belgium, 1070
    • Momenta Investigational Site
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • Momenta Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2G3
      • Momenta Investigational Site
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Momenta Investigational Site
    • Toronto, Ontario, Canada, M5G 2C4
      • Momenta Investigational Site
  • Quebec
    • Quebec City, Quebec, Canada, G1J 1Z4
      • Momenta Investigational Site
• Germany
  • Dusseldorf, Germany, 40225
    • Momenta Investigational Site
  • Gummersbach, Germany, 51643
    • Momenta Investigational Site
  • Munster, Germany, 48149
    • Momenta Investigational Site
  • Niedersachsen
    • Gottingen, Niedersachsen, Germany, 37075
      • Momenta Investigational Site
• Italy
  • Cefalu, Italy, 90015
    • Momenta Investigational Site
  • Messina, Italy, 98125
    • Momenta Investigational Site
  • Milano, Italy, 20133
    • Momenta Investigational Site
• Poland
  • Krakow, Poland, 31-505
    • Momenta Investigational Site
  • Lodz, Poland, 90-324
    • Momenta Investigational Site
  • Warsaw, Poland, 01-684
    • Momenta Investigational Site
  • Warsaw, Poland, 01-868
    • Momenta Investigational Site
• Spain
  • Madrid, Spain, 28007
    • Momenta Investigational Site
  • Madrid, Spain, 28040
    • Momenta Investigational Site
  • Sevilla, Spain, 41013
    • Momenta Investigational Site
  • Valencia, Spain, 46026
    • Momenta Investigational Site
  • Catalan
    • Barcelona, Catalan, Spain, 08035
      • Momenta Investigational Site
    • Barcelona, Catalan, Spain, 08041
      • Momenta Investigational Site
  • Cataluna
    • Barcelona, Cataluna, Spain, 08036
      • Momenta Investigational Site
    • L'hospitalet De Llobregat, Cataluna, Spain, 08907
      • Momenta Investigational Site
  • Gipuzkoa
    • San Sebastian, Gipuzkoa, Spain, 20014
      • Momenta Investigational Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Momenta Investigational Site
  • Sheffield, United Kingdom, S11 9NE
    • Momenta Investigational Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Momenta Investigational Site
  • California
    • Los Angeles, California, United States, 90048
      • Momenta Investigational Site
    • Orange, California, United States, 92868
      • Momenta Investigational Site
    • Stanford, California, United States, 94305
      • Momenta Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Momenta Investigational Site
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Momenta Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33487
      • Momenta Investigational Site
    • Maitland, Florida, United States, 32751
      • Momenta Investigational Site
    • Port Charlotte, Florida, United States, 33952
      • Momenta Investigational Site
    • Saint Petersburg, Florida, United States, 33713
      • Momenta Investigational Site
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Momenta Investigational Site
  • Kansas
    • Fairway, Kansas, United States, 66205
      • Momenta Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Momenta Investigational Site
    • Boston, Massachusetts, United States, 02115
      • Momenta Investigational Site
    • Boston, Massachusetts, United States, 02215
      • Momenta Investigational Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08550
      • Momenta Investigational Site
  • New York
    • New York, New York, United States, 10021
      • Momenta Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Momenta Investigational Site
    • Durham, North Carolina, United States, 27710
      • Momenta Investigational Site
    • Raleigh, North Carolina, United States, 27607
      • Momenta Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Momenta Investigational Site
    • Columbus, Ohio, United States, 43210
      • Momenta Investigational Site
  • Tennessee
    • Cordova, Tennessee, United States, 38106
      • Momenta Investigational Site
  • Texas
    • Austin, Texas, United States, 78756
      • Momenta Investigational Site
    • Round Rock, Texas, United States, 78681
      • Momenta Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: M281	Drug: M281; M281 injection administered as intravenous infusion

What is the study measuring?

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)
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
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

Collaborators and Investigators

• Sponsor: Momenta Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2019
• Primary Completion (Actual): December 9, 2020
• Study Completion (Actual): December 9, 2020

Study Registration Dates

• First Submitted: March 28, 2019
• First Submitted That Met QC Criteria: March 28, 2019
• First Posted (Actual): March 29, 2019

Study Record Updates

• Last Update Posted (Actual): June 27, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Generalized Myasthenia Gravis; M281
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis
• Other Study ID Numbers: MOM-M281-005; 2018-003618-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No