A Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of M281 Administered to Adults With Generalized Myasthenia Gravis

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of M281 Administered to Adults With Generalized Myasthenia Gravis

The purpose of this study is to evaluate the safety, tolerability, and efficacy of M281 administered to participants with generalized myasthenia gravis (gMG) who have an insufficient clinical response to ongoing standard of care therapy.

Study Overview

• Status: Completed
• Conditions: Generalized Myasthenia Gravis
• Intervention / Treatment: Other: Placebo; Drug: M281

• Study Type: Interventional
• Enrollment (Actual): 68
• 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
  • Düsseldorf, 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
    • Badalona, 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
  • Southampton, United Kingdom, SO16 6YD
    • Momenta Investigational Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Momenta Investigational Site
    • Tucson, Arizona, United States, 85724
      • 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
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Momenta Investigational Site
  • Illinois
    • Lake Barrington, Illinois, United States, 60010
      • 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
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Momenta Investigational Site
    • East Lansing, Michigan, United States, 48824
      • Momenta Investigational Site
  • Missouri
    • Columbia, Missouri, United States, 65212
      • 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: 18 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, and no history of any neurologic disorder other than MG that might interfere with the accuracy of study assessments.

Additional, more specific criteria are defined in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 2	Drug: M281; M281 administered as IV infusion
Experimental: Group 3	Drug: M281; M281 administered as IV infusion
Experimental: Group 4	Drug: M281; M281 administered as IV infusion
Experimental: Group 5	Drug: M281; M281 administered as IV infusion
Placebo Comparator: Group 1	Other: Placebo; Placebo administered as intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability	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. TEAE are defined as any AE occurring during or after the initiation of the first infusion of study drug.	Up to Day 113
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)	An 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. An 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 Day 113
Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESI)	An 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. For this study, any common terminology criteria for adverse events (CTCAE) Grade 3 or higher event of severe infection or hypoalbuminemia was considered as AESI.	Up to Day 113
Change From Baseline to Day 57 in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) Total Score	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 to Day 57

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total MG-ADL Score as a Function of Total Serum Immunoglobulin G (IgG) at Day 57	Estimate of additional change from baseline in MG-ADL total score for every 10 percent (%) additional reduction in IgG based on a linear regression of change from baseline in MG-ADL total score on percent reduction in IgG at Day 57. 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 and Day 57
Change From Baseline in Total MG-ADL Score as a Response to Percent Change in Total Serum IgG, for Participants Positive for Anti-acetylcholine Receptor (Anti-AChR) Antibodies, at Day 57	Estimate of additional change from baseline in MG-ADL total score for every 10% additional reduction in IgG based on a linear regression of change from baseline in MG-ADL total score on percent reduction in IgG at Day 57 in anti-AChR positive participants. The MG-ADL was used to assess 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). Total score is sum of eight function scores and ranges from 0 to 24. Higher scores indicated greater symptom severity/difficulty in performing daily living activities.	Baseline and Day 57
Change From Baseline in Total Quantitative Myasthenia Gravis (QMG) Score as a Function of Total Serum IgG at Day 57	Estimate of additional change from baseline in QMG total score for every 10% additional reduction in IgG based on a linear regression of change from baseline in QMG total score on percent reduction in IgG at Day 57. 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 and Day 57
Change From Baseline in Total QMG Score as a Response to Percent Change in Total Serum IgG, for Participants Positive for Anti-acetylcholine Receptor (Anti-AChR) Antibodies, at Day 57	Estimate of additional change from baseline in QMG total score for every 10% additional reduction in IgG based on a linear regression of change from baseline in QMG total score on percent reduction in IgG at Day 57 in anti-AChR positive participants. 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 and Day 57
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 at Day 57	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.	Day 57
Change From Baseline in Total QMG Score at Day 57	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 and Day 57
Number of Participants With a 3-, 4-, 5-, 6-, 7-, or >= 8-point Improvement in Total QMG Score at Day 57	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.	Day 57
Change From Baseline in Total Revised Myasthenia Gravis Quality of Life - 15 (MG-QoL-15r) Scale Score at Day 57	The MG-QoL15r was used to assess the participant's limitations related to living with MG. 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 and Day 57
Change From Baseline in Total Serum IgG at Day 57	Change from baseline in total serum IgG was reported. Blood samples were collected for analysis of total serum IgG.	Baseline and Day 57
Change From Baseline in Total MG-ADL Score at Day 85 and Day 113	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, Day 85 and Day 113
Change From Baseline in Total QMG Score at Day 85 and Day 113	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, Day 85 and Day 113
Change From Baseline in Total MG-QoL15r Score at Day 85 and Day 113	The MG-QoL15r was used to assess the participant's limitations related to living with MG. 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, Day 85 and Day 113
Number of Participants With Shift From Baseline in Myasthenia Gravis Foundation of America (MGFA) Classification at Day 57	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).	Baseline and Day 57
Number of Participants With Shift From Baseline in MGFA Classification to Day 113	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).	Baseline to Day 113
Change From Baseline in Total Serum IgG at Day 85 and Day 113	Change from baseline in total serum IgG at Day 85 and Day 113 was analyzed. Blood samples were collected for analysis of total serum IgG.	Baseline, Day 85 and Day 113
Serum Concentrations of Nipocalimab	Serum concentrations of nipocalimab were reported. Concentrations below the lowest quantifiable concentration (< LLOQ) that is <0.15 microgram/milliliter (mcg/mL) was treated as zero in calculating the summary statistics.	Baseline (Pre Infusion and Post Infusion), Day 15 (Pre Infusion), Day 29 (Pre Infusion), Day 43 (Pre Infusion), Day 57 (Pre Infusion and Post Infusion) and Day 85

Collaborators and Investigators

• Sponsor: Momenta Pharmaceuticals, Inc.
• Investigators: Study Director: Momenta General Queries, Momenta Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2019
• Primary Completion (Actual): June 25, 2020
• Study Completion (Actual): June 25, 2020

Study Registration Dates

• First Submitted: December 10, 2018
• First Submitted That Met QC Criteria: December 10, 2018
• First Posted (Actual): December 11, 2018

Study Record Updates

• Last Update Posted (Actual): June 27, 2023
• Last Update Submitted That Met QC Criteria: June 6, 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-M281-004; 2018-002247-28 (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