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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03896295

Enrollment

Registered

2019-03-29

Start date

2019-08-06

Completion date

2020-12-09

Last updated

2023-06-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Generalized Myasthenia Gravis

Keywords

M281, Generalized Myasthenia Gravis

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)

Interventions

DRUGM281

M281 injection administered as intravenous infusion

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

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.

Design outcomes

Primary

Measure	Time frame	Description
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.
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 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 Laboratory Parameter: Hematocrit	Baseline up to Week 12	Change from baseline in hematocrit (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 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.
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).
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: 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 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 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.
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.
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.

Secondary

Measure	Time frame	Description
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 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.
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.
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 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.
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 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 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.

Countries

Belgium, Canada, Germany, Italy, Poland, Spain, United Kingdom, United States

Participant flow

Pre-assignment details

Participants from study MOM-M281-004 (NCT03772587) who completed the Day 113 visit of that study were eligible to enroll in this open-label extension study (MOM-M281-005). The Day 113 visit of MOM-M281-004 occurred approximately 8 weeks after the last dose in that study.

Participants by arm

Arm	Count
Placebo-Nipocalimab Participants who received placebo in MOM-M281-004 (NCT03772587) study rolled-over and received intravenous (IV) infusion of nipocalimab (M281) 30 milligrams per kilogram (mg/kg) every 4 weeks (Q4W) starting Day 1 up to 8 weeks. After 8 weeks of treatment on a stable dose of nipocalimab, the dose and/or dosing frequency could be individually adjusted, at the investigator's discretion to receive maximum dose of 60 mg/kg at a frequency of not exceeding every 2 weeks (Q2W).	7
Nipocalimab-Nipocalimab Participants who received nipocalimab in MOM-M281-004 study rolled-over and received IV infusion of nipocalimab 30 mg/kg Q4W starting Day 1 up to 8 weeks. After 8 weeks of treatment on a stable dose of nipocalimab, the dose and/or dosing frequency could be individually adjusted, at the investigator's discretion to receive maximum dose of 60 mg/kg at a frequency of not exceeding Q2W.	30
Total	37

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	1
Overall Study	COVID-19	7	29

Baseline characteristics

Characteristic	Placebo-Nipocalimab	Total	Nipocalimab-Nipocalimab
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	2 Participants	12 Participants	10 Participants
Age, Categorical Between 18 and 65 years	5 Participants	25 Participants	20 Participants
Age, Continuous	53.7 years STANDARD_DEVIATION 20.39	53.2 years STANDARD_DEVIATION 17.33	53 years STANDARD_DEVIATION 16.93
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	4 Participants	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants	33 Participants	28 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Black or African American	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized More than one race	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Other	2 Participants	2 Participants	0 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized White	5 Participants	34 Participants	29 Participants
Region of Enrollment GERMANY	1 Participants	2 Participants	1 Participants
Region of Enrollment ITALY	0 Participants	2 Participants	2 Participants
Region of Enrollment POLAND	0 Participants	7 Participants	7 Participants
Region of Enrollment SPAIN	4 Participants	11 Participants	7 Participants
Region of Enrollment UNITED STATES	2 Participants	15 Participants	13 Participants
Sex: Female, Male Female	4 Participants	22 Participants	18 Participants
Sex: Female, Male Male	3 Participants	15 Participants	12 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 7	1 / 30
other Total, other adverse events	4 / 7	17 / 30
serious Total, serious adverse events	1 / 7	4 / 30

Outcome results

Primary

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.