Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03772587
Recruitment Status : Completed
First Posted : December 11, 2018
Results First Posted : October 27, 2021
Last Update Posted : October 27, 2021
Sponsor:
Information provided by (Responsible Party):
Momenta Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE December 10, 2018
First Posted Date  ICMJE December 11, 2018
Results First Submitted Date  ICMJE June 22, 2021
Results First Posted Date  ICMJE October 27, 2021
Last Update Posted Date October 27, 2021
Actual Study Start Date  ICMJE April 10, 2019
Actual Primary Completion Date June 25, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 22, 2021)
  • Number of Participants With Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability [ Time Frame: Up to Day 113 ]
    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.
  • Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) [ Time Frame: Up to Day 113 ]
    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.
  • Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESI) [ Time Frame: Up to Day 113 ]
    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.
  • Change From Baseline to Day 57 in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) Total Score [ Time Frame: Baseline to 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 10, 2018)
  • Number of Participants With Adverse Events [ Time Frame: Up to Day 113 ]
  • Change From Baseline in the Total Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score at Day 57 [ Time Frame: Baseline; Day 57 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 28, 2021)
  • Change From Baseline in Total MG-ADL Score as a Function of Total Serum Immunoglobulin G (IgG) at Day 57 [ Time Frame: Baseline and 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.
  • 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 [ Time Frame: Baseline and 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.
  • Change From Baseline in Total Quantitative Myasthenia Gravis (QMG) Score as a Function of Total Serum IgG at Day 57 [ Time Frame: Baseline and 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.
  • 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 [ Time Frame: Baseline and 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.
  • 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 [ Time Frame: 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.
  • Change From Baseline in Total QMG Score at Day 57 [ Time Frame: Baseline and 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.
  • Number of Participants With a 3-, 4-, 5-, 6-, 7-, or >= 8-point Improvement in Total QMG Score at Day 57 [ Time Frame: 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.
  • Change From Baseline in Total Revised Myasthenia Gravis Quality of Life - 15 (MG-QoL-15r) Scale Score at Day 57 [ Time Frame: Baseline and 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.
  • Change From Baseline in Total Serum IgG at Day 57 [ Time Frame: Baseline and Day 57 ]
    Change from baseline in total serum IgG was reported. Blood samples were collected for analysis of total serum IgG.
  • Change From Baseline in Total MG-ADL Score at Day 85 and Day 113 [ Time Frame: Baseline, 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.
  • Change From Baseline in Total QMG Score at Day 85 and Day 113 [ Time Frame: Baseline, 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.
  • Change From Baseline in Total MG-QoL15r Score at Day 85 and Day 113 [ Time Frame: Baseline, 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.
  • Number of Participants With Shift From Baseline in Myasthenia Gravis Foundation of America (MGFA) Classification at Day 57 [ Time Frame: Baseline and 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).
  • Number of Participants With Shift From Baseline in MGFA Classification to Day 113 [ Time Frame: Baseline 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).
  • Change From Baseline in Total Serum IgG at Day 85 and Day 113 [ Time Frame: Baseline, 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.
  • Serum Concentrations of Nipocalimab [ Time Frame: 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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2018)
  • Change From Baseline in Total MG-ADL Score as a Function of Total Serum Immunoglobulin G (IgG) at Day 57 [ Time Frame: Baseline; 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 [ Time Frame: Baseline; Day 57 ]
  • Number of Participants With a 2-, 3-, 4-, 5-, 6-, 7-, or ≥8-point Improvement in Total MG-ADL Score [ Time Frame: Baseline to Day 57 ]
  • Change From Baseline in Total Quantitative Myasthenia Gravis (QMG) Score at Day 57 [ Time Frame: Baseline; Day 57 ]
  • Change From Baseline in Total Revised Myasthenia Gravis Quality of Life - 15 Scale (MG-QoL15r) Score at Day 57 [ Time Frame: Baseline; Day 57 ]
  • Shift From Baseline in Myasthenia Gravis Foundation of America (MGFA) Classification at Day 57 [ Time Frame: Baseline; Day 57 ]
  • Change From Baseline in Total Serum IgG at Day 57 [ Time Frame: Baseline; Day 57 ]
  • Change in Total MG-ADL Score Over Time After the Last Dose [ Time Frame: Last dose (Day 57) to Day 113 ]
  • Change in Total QMG Score Over Time After the Last Dose [ Time Frame: Last dose (Day 57) to Day 113 ]
  • Change in Total MG-QoL15r Score Over time After the last Dose [ Time Frame: Last dose (Day 57) to Day 113 ]
  • Number of Participants With a 2-, 3-, 4-, 5-, 6-, 7-, or ≥8-point Improvement in Total QMG Score Over Time After the Last Dose [ Time Frame: Last dose (Day 57) to Day 113 ]
  • Shift in MGFA Classification Over Time After the Last Dose [ Time Frame: Last dose (Day 57) to Day 113 ]
  • Change in Total Serum IgG Over Time After the Last Dose [ Time Frame: Last dose (Day 57) to Day 113 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of M281 Administered to Adults With Generalized Myasthenia Gravis
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Generalized Myasthenia Gravis
Intervention  ICMJE
  • Drug: M281
    M281 administered as IV infusion
  • Other: Placebo
    Placebo administered as intravenous (IV) infusion
Study Arms  ICMJE
  • Placebo Comparator: Group 1
    Intervention: Other: Placebo
  • Experimental: Group 2
    Intervention: Drug: M281
  • Experimental: Group 3
    Intervention: Drug: M281
  • Experimental: Group 4
    Intervention: Drug: M281
  • Experimental: Group 5
    Intervention: Drug: M281
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 4, 2021)
68
Original Estimated Enrollment  ICMJE
 (submitted: December 10, 2018)
60
Actual Study Completion Date  ICMJE June 25, 2020
Actual Primary Completion Date June 25, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   Germany,   Italy,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03772587
Other Study ID Numbers  ICMJE MOM-M281-004
2018-002247-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Momenta Pharmaceuticals, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Momenta Pharmaceuticals, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Momenta General Queries Momenta Pharmaceuticals, Inc.
PRS Account Momenta Pharmaceuticals, Inc.
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP