Clinical trial NCT03896295
Conditions: Generalized Myasthenia Gravis
Keywords: M281 Generalized Myasthenia Gravis
Sponsor: Momenta Pharmaceuticals, Inc.
Start date: 2019-08-06; Completion date: 2020-12-09
Enrollment: 37 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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:

Arms: arm 1: None
Interventions: intervention 1: M281
Intervention descriptions: intervention 1: M281 injection administered as intravenous infusion

Protocol documents:
Prot_000.pdf: 
Confidential
Page 1 of 53
Clinical Trial Protocol: MOM-M281-005
Study Title:
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  
Study Number:
MOM-M281-005
Study Phase:
2
Product Name:
M281
IND Number:
138975
EudraCT 
Number:
2018-003618-41
Indication:
Generalized myasthenia gravis
Investigators:
Multicenter
Sponsor:
Momenta Pharmaceuticals, Inc.
301 Binney Street
Cambridge, MA 02142 USA
Sponsor Contact:
Santiago Arroyo, MD
Chief Medical Officer
Date
Original Protocol:
01 Oct 2018
Amendment 1:
03 Dec 2018
Amendment 2:
01 August 2019
Confidentiality Statement
The confidential information in the following document is provided to you as an Investigator, 
potential Investigator, or consultant for review by you, your staff, and applicable Institutional 
Review Board/Independent Ethics Committee or Regulatory Health Authority. The 
information contained herein should not be disclosed to others, without written authorization 
from Momenta Pharmaceuticals, Inc.
PPD
PPD
NCT03896295


M281
Momenta Pharmaceuticals, Inc.
Clinical Trial Protocol: MOM-M281-005
01 August 2019
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SYNOPSIS
Sponsor:
Momenta Pharmaceuticals, Inc.
Name of Finished Product:
M281
Study Title:
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 
Study Number:
MOM-M281-005
Study Phase: 2
Objectives and Endpoints:
Objectives
Endpoints
Primary

To evaluate the long-term safety 
and tolerability of M281 in 
patients with generalized 
myasthenia gravis (gMG)

Incidence and severity of adverse events (AEs; 
including serious AEs [SAEs], and AEs of special 
interest [AESIs]), vital signs, physical examinations, 
clinical laboratory testing (including chemistry, 
hematology, coagulation, and urinalysis), 
electrocardiograms (ECGs), and the Columbia-Suicide 
Severity Rating Scale (C-SSRS)
Secondary

To evaluate the long-term 
efficacy of M281

Change from baseline in the total Myasthenia Gravis –
Activities of Daily Living (MG-ADL) score over time

Number of patients with a 2-, 3-, 4-, 5-, 6-, 7-, or 
≥8-point improvement in total MG-ADL score over 
time

Change from baseline in total Quantitative Myasthenia 
Gravis (QMG) score over time

Change from baseline in total Revised Myasthenia 
Gravis Quality of Life – 15 Scale (MG-QoL15r) score 
over time

Change from baseline in Clinical Global Impression 
of Severity (CGI-S) over time and Clinical Global 
Impression of Improvement (CGI-I) ratings

Change from baseline in Myasthenia Gravis 
Foundation of America (MGFA) classification over 
time

To evaluate the long-term 
immunogenicity of M281

To evaluate the long-term 
pharmacodynamic (PD) activity 
of M281

Incidence of anti-drug antibody (ADA) and 
neutralizing ADA (nADA) seroconversion over time

Total serum immunoglobulin (Ig)G concentrations 
over time and change from baseline


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Clinical Trial Protocol: MOM-M281-005
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Objectives
Endpoints
Exploratory

To evaluate the effect of M281 on 
fatigue and level of physical 
activity 

Change from baseline in Neuro-QOL Fatigue scores 
over time 

Quantitative level of physical activity over time and 
changes from baseline

To evaluate the long-term PD 
activity of M281 on serum 
concentrations of IgA, IgM, and 
IgE

To evaluate the long-term PD 
activity of M281 on serum titers 
of pathogenic autoantibodies 
associated with gMG (anti-
acetylcholine receptor [anti-
AChR] and/or anti-muscle-
specific kinase [anti-MuSK])

Serum concentrations of IgA, IgM, and IgE over time 
and changes from baseline

Titers of serum anti-AChR or anti-MuSK antibodies 
over time and change from baseline

To evaluate the long-term 
response to treatment with M281 
in relation to other treatment(s) 
and/or clinical status

Changes in dose/regimen of standard-of-care 
concomitant medications for gMG over time

Number of patients who discontinued 
immunosuppressive medications over time

Need for rescue therapy over time

Number of patients with clinical deterioration

Number of episodes of myasthenic exacerbation 
requiring hospitalization/intensive care unit 
admission, and length of stay

Proportion of patients with minimal manifestations, 
and change in status per the Myasthenia Gravis 
Foundation of America Post-intervention Status 
(MGFA-PIS) over time, and proportion of patients 
with pharmacologic remission 

To evaluate the potential 
relationship between change in 
MG-ADL score and change in 
anti-AChR antibody levels

A model-based analysis of MG-ADL score change 
from Baseline in relationship to total serum IgG and 
anti-AChR titer (the latter is only for patients with 
anti-AChR antibodies)
Study Design:
This is a long-term, open-label extension (OLE) study of patients who completed the
proof-of-concept (POC) study (MOM-M281-004) without discontinuing study drug during 
the POC study for reasons other than the need for rescue therapy (eg, glucocorticosteroids, 
intravenous immunoglobulin [IVIG], plasmapheresis) as specified in the POC protocol, and 
who completed the protocol-specified 8 weeks of follow-up after the last dose of study drug 
in the POC study.  If the patient received rescue therapy during the POC, the Medical 
Monitor should be consulted before the patient is enrolled in the OLE study.
The Screening Period for the OLE study begins (at the earliest) at the Day 85 POC Visit


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Momenta Pharmaceuticals, Inc.
Clinical Trial Protocol: MOM-M281-005
01 August 2019
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(ie, 4 weeks after the last dose of study drug in the POC study) and ends upon enrollment in 
the OLE study.  The screening procedures consist of signing the informed consent form for 
the OLE study and initiation of continuous physical activity monitoring via a medical device
(Embrace device, Empatica, Inc., Cambridge, MA) worn on the wrist. Any screening 
procedure for the OLE study must not be done until after completion of all the assessments 
and procedures required by the POC protocol for the Day 85 POC Visit.
Eligibility for the OLE study will be assessed and enrollment into the OLE study will occur 
(at the earliest) at the patient’s last follow-up visit in the POC study (Day 113 POC Visit).  
After completion of all Day 113 POC Visit assessments, the patient will be assessed for 
eligibility for enrollment into the OLE study per the OLE inclusion and exclusion criteria.  
Any OLE assessment or procedure designated on the Day 113 POC Visit must not be
performed until after completion of all the assessments and procedures required by the POC 
protocol for the Day 113 POC Visit. Eligibility for the OLE study will be determined based 
on results of safety laboratory testing from the patient’s Day 85 POC Visit, the assessments 
from the patient’s Day 113 POC Visit, and additional procedures to be performed predose on 
OLE Day 1.  Patients meeting all eligibility criteria will be enrolled into the OLE study and 
may receive the first infusion of M281 under this protocol (day of first infusion is considered 
OLE Day 1).  Patients not meeting all OLE eligibility criteria will be considered screening 
failures for the OLE study and will not be enrolled or receive treatment under this protocol.
If it is not feasible to complete any/all designated OLE assessments/procedures on the same 
day as the Day 113 POC Visit, or if there is a valid reason to delay enrollment of the patient 
in the OLE study, the Investigator can confirm the patient’s eligibility and enroll the patient 
at a later date as agreed between the Investigator and Medical Monitor; however, depending 
on the length of the delay the patient may need to have an additional unscheduled blood draw 
for safety laboratory testing to confirm eligibility for the OLE study.  
Patients who are enrolled in the OLE study will initially receive M281 30 mg/kg every 
4 weeks (Q4W) by intravenous (IV) infusion.  This dose (M281 30 mg/kg Q4W) is one of 
the doses evaluated in the POC study.  This starting dose and dosing frequency may be
revised if available results from the POC study reveal a different optimal dose for 
development.  However, the revised dose and dosing frequency in the OLE study will not 
exceed 60 mg/kg every 2 weeks (Q2W), which is the highest dose and most frequent dosing 
interval evaluated in the POC study.  
Patients should be maintained on a stable M281 dose and dosing frequency for at least the 
first 8 weeks of the OLE study.  If the starting dose and dosing frequency for the study is 
revised after the patient started receiving the dose of 30 mg/kg Q4W, it is recommended that 
the patient receives the revised dose for at least 8 weeks regardless of the length of time the 
patient received the 30 mg/kg Q4W treatment. 
After at least 8 weeks of treatment on a stable dose of M281, the dose and/or dosing 
frequency of M281 may be individually adjusted for a given patient at the discretion of the 
Investigator and previous consultation with the Medical Monitor, based on the patient’s
tolerability to M281 and the patient’s MG status.  The individually adjusted dose will not 
exceed 60 mg/kg and the dosing frequency will not exceed Q2W.
Each patient will be observed for safety after their first 2 infusions in the study; if no 
clinically relevant AEs or abnormal vital signs related to the infusion are observed in these 


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Clinical Trial Protocol: MOM-M281-005
01 August 2019
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first 2 infusions, the post-infusion observation period is no longer needed unless the M281 
dose level is later increased. A post-infusion observation period is also required for the 
patient’s first infusion at the higher M281 dose level.  All patients must attend clinic visits at 
2, 4, and 8 weeks after the first infusion (on OLE Day 1) to undergo safety, tolerability, 
efficacy, PD, and immunogenicity assessments.  Serum biomarkers will also be explored. 
After Week 8, patients will receive an infusion of M281 on a Q2W or Q4W basis, depending 
on the dosing frequency established for the patient. All infusions may be administered at the 
site, or every other infusion (except those that fall every 12 weeks [Q12W]) may be
administered in the home or at another location per the Infusion Manual, at the discretion of 
the Investigator and if this option is made available to the site. As an example, for patients 
continuing on a Q4W regimen at Week 8, the schedule for optional home infusions would be
as follows: Weeks 16, 28, and 40 (assuming no M281 dose increase and assuming end of 
treatment at Week 52).  As an example, for patients switching to a Q2W regimen at Week 8, 
the schedule for optional home infusions would be as follows:  Weeks 14, 18, 22, 26, 30, 34, 
38, 42, 46, and 50 (assuming no M281 dose increase and assuming end of treatment at 
Week 52).
Each infusion will be administered per the Infusion Manual. On each infusion day predose 
vital signs will be measured. For infusions administered in the clinic, ECGs will also be 
measured, and AEs and concomitant medication/therapy since the previous clinical visit will 
be recorded.  If the M281 dose and/or dosing frequency is adjusted, the first infusion at the 
new dose/frequency must occur at a clinic visit; for increases in the M281 dose level (but not
for change in dosing frequency), the patient will undergo a post-infusion observation period 
following the first infusion at the higher dose level per the Infusion Manual. In the event of 
either a dose increase and/or dosing frequency increase, the patient’s next scheduled infusion 
must be conducted in the clinic because a blood sample for safety laboratory testing must be 
obtained and a physical examination must be performed within 2 to 4 weeks after the first 
infusion at the new dose/dosing frequency.  Regardless of the patient’s dosing frequency, the 
full schedule of safety, tolerability, efficacy, PD, and immunogenicity assessments will be 
done at Week 12 and Q12W thereafter.  The duration of each patient’s participation in the 
study is planned to be approximately 1 year or until the study is terminated by the Sponsor.  
Patients will return to the clinic approximately 8 weeks after their last infusion for follow-up 
assessments.
Patients should continue their stable therapeutic regimen (standard of care) for gMG and 
should maintain the same dose and regimen for at least the first 8 weeks of the OLE study 
(unless toxicity or safety/tolerability issues mandate a change).  In the event the starting dose 
of M281 (30 mg/kg Q4W) is revised to a different dose and/or dosing frequency, it is 
recommended that the dose and regimen of concomitant treatment not be changed until the 
patient’s M281 dose has been stable for at least 8 weeks.  A consultation with the Medical 
Monitor regarding changes to the patient’s standard-of-care therapy is recommended.
An independent Drug Safety Monitoring Board (DSMB) will be responsible for oversight of 
patient safety during the study.  The DSMB will meet on a regular basis and review all 
available data (AEs, SAEs, AESIs, and laboratory results); ad hoc meetings will be scheduled 
as needed. The specific responsibilities of the DSMB will be outlined in a DSMB charter.


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Clinical Trial Protocol: MOM-M281-005
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Study Population:
The sample size for the OLE study will depend on the enrollment in the POC study, which 
plans for approximately 60 patients with possible expansion up to 90 patients.  
Test Product, Dose, and Mode of Administration:
M281 for IV infusion, initially at a dose of 30 mg/kg (Q4W); the starting dose and/or dosing 
frequency may be revised depending on available results from the POC study.  After at least 
8 weeks of treatment on a stable dose of M281, the dose/regimen may be individually 
adjusted for a given patient upon agreement between the Investigator and Medical Monitor.  
The revised dose and dosing frequency or any individually adjusted dose or dosing frequency 
will not exceed 60 mg/kg Q2W, which is the highest dose and most frequent dosing interval 
evaluated in the POC study.
Duration of Treatment:
Patients will receive IV administration of M281 for approximately 1 year or until the study is 
terminated by the Sponsor.
Efficacy Assessments:
Efficacy will be assessed at designated site visits prior to start of M281 infusion (ie, predose), 
using these measures in the following preferred order: MG-ADL, QMG, MG-QoL15r, 
applicable elements of the MGFA-PIS, physician-rated CGI scales, patient-reported 
Neuro-QOL Fatigue, and MGFA classification. If possible, these efficacy assessments
throughout the study should be done at approximately the same time of day as performed on 
Day 1. 
In addition, the level of physical activity will be monitored via the Embrace device worn 
continuously on the wrist during the Screening Period (to establish a baseline) and for the 
first 6 months of the treatment period during of the study.  
Safety Assessments:
Safety assessments include collection of AEs (including serious AEs, AESIs, and device-
related AEs), vital signs, physical examinations, clinical laboratory testing (including 
chemistry, hematology, coagulation, and urinalysis), ECGs, and the C-SSRS. Severe 
infections and events of hypoalbuminemia (Grade 3 or higher according to the Common 
Terminology Criteria for Adverse Events [CTCAE] v5.0) will be considered AESIs.
Reporting of device-related AEs in the OLE study will start following the patient signing the 
OLE informed consent form.  AEs from the POC study that are ongoing at the Day 113 POC 
Visit will be recorded as medical history for the OLE study.  Recording of new AEs (ie, any 
new clinically relevant finding or worsening of a pre-existing condition, such as an ongoing 
AE from the POC study) will start at the time of enrollment into the OLE study.


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Clinical Trial Protocol: MOM-M281-005
01 August 2019
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Assessments of Pharmacodynamics and Biomarkers:
Blood samples will be drawn for analysis of the following PD parameters: concentrations of 
total serum IgG; serum concentrations of IgA, IgM, and IgE; and titers of anti-AChR and
anti-MuSK autoantibodies. 
Immunogenicity Assessments:
Total and neutralizing anti-M281 antibodies will be assessed, as applicable.
Statistical Methods:
Baseline is defined as the assessment obtained at the time of enrollment into the OLE study 
(Day 1) for all assessments except physical activity; baseline for physical activity will be 
established during the Screening Period.
Adverse events will be coded using a standardized medical dictionary (Medical Dictionary 
for Regulatory Activities [MedDRA]). Analysis of AEs in terms of incidence by severity 
and by relatedness to study drug/device will also be provided. Concomitant medications will 
be coded by the World Health Organization Drug Dictionary Enhanced and will be 
summarized. Medical history (to include AEs from the POC study that are ongoing at OLE 
Day 1) will be listed by patient and coded using MedDRA and will be summarized. 
Descriptive statistics and a summary of abnormalities using shift tables will be presented for 
safety laboratory tests, vital signs, ECGs, and C-SSRS. For vital signs and ECGs, descriptive 
statistics at each visit and change from baseline to each subsequent visit will be provided.
Physical examinations will be summarized as shift tables.
All efficacy data will be analyzed using descriptive summary statistics.
PD parameters, and immunogenicity results will be summarized using descriptive statistics.  
Selected serum biomarkers will be assayed and their potential relationship to clinical status 
may be explored.
Date of Protocol Amendment 2: 01 August 2019


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Clinical Trial Protocol: MOM-M281-005
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TABLE OF CONTENTS
SYNOPSIS............................................................................................................................2
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS........................................11
1
INTRODUCTION.......................................................................................................13
2
STUDY OBJECTIVES................................................................................................15
2.1
Primary Objective ..............................................................................................15
2.2
Secondary Objectives.........................................................................................15
2.3
Exploratory Objectives.......................................................................................15
3
INVESTIGATIONAL PLAN ......................................................................................16
3.1
Overall Study Design and Plan...........................................................................16
3.2
Rationale for Study Design ................................................................................17
3.3
Study Duration...................................................................................................18
4
STUDY POPULATION SELECTION ........................................................................18
4.1
Study Population................................................................................................18
4.2
Screening Period................................................................................................18
4.3
Enrollment .........................................................................................................19
4.4
Inclusion Criteria ...............................................................................................19
4.5
Exclusion Criteria ..............................................................................................20
5
STUDY TREATMENT...............................................................................................21
5.1
Description of Treatment....................................................................................21
5.2
Treatment Administered.....................................................................................22
5.3
Selection and Timing of Dose for Each Patient...................................................22
5.4
Method of Assigning Patients to Treatment Groups............................................22
5.5
Blinding.............................................................................................................22
5.6
Concomitant Therapy.........................................................................................22
5.7
Restrictions........................................................................................................23
5.7.1
Prior Therapy ...........................................................................................23
5.7.2
Fluid and Food Intake...............................................................................23
5.7.3
Patient Activity Restrictions .....................................................................23
5.8
Treatment Compliance .......................................................................................23
5.9
Packaging and Labeling .....................................................................................23
5.10
Storage and Accountability ................................................................................23
6
STUDY ASSESSMENTS AND PROCEDURES ........................................................24
6.1
Safety Assessments............................................................................................29
6.1.1
Adverse Events.........................................................................................29
6.1.1.1
Performing Adverse Events Assessments........................................29
6.1.1.2
Timing............................................................................................29
6.1.1.3
Severity ..........................................................................................29


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6.1.1.4
Relationship....................................................................................30
6.1.1.5
Expectedness ..................................................................................31
6.1.1.6
Adverse Events of Special Interest..................................................31
6.1.1.7
Clinical Laboratory Adverse Events................................................31
6.1.1.8
Serious Adverse Events ..................................................................31
6.1.1.9
Treatment-Emergent Adverse Events..............................................32
6.1.1.10
Pregnancy.......................................................................................32
6.1.2
Concomitant Medication Assessments......................................................33
6.1.3
Physical Examination ...............................................................................33
6.1.4
Vital Signs................................................................................................33
6.1.5
Clinical Laboratory Tests .........................................................................34
6.1.6
Electrocardiograms...................................................................................35
6.1.7
Columbia-Suicide Severity Rating Scale...................................................35
6.2
Efficacy Assessments.........................................................................................35
6.2.1
Myasthenia Gravis – Activities of Daily Living........................................36
6.2.2
Quantitative Myasthenia Gravis................................................................36
6.2.3
Revised Myasthenia Gravis Quality of Life – 15.......................................36
6.2.4
Myasthenia Gravis Foundation of America Post-Intervention Status.........37
6.2.5
Clinical Global Impression Scales ............................................................37
6.2.6
Patient-Reported Assessment of Fatigue...................................................38
6.2.7
Measurement of Physical Activity............................................................38
6.2.8
Myasthenia Gravis Foundation of America Clinical Classification............38
6.3
Assessments of Pharmacodynamics and Biomarkers..........................................38
6.4
Immunogenicity Assessments ............................................................................39
6.5
Removal of Patients from the Trial or Study Drug..............................................39
6.6
Stopping Criteria................................................................................................39
6.6.1
Study Drug Stopping/Interruption Rules for Individual Patients................39
6.6.2
Study Stopping Rules ...............................................................................40
6.7
Other Study Procedures......................................................................................41
6.8
Appropriateness of Measurements......................................................................41
7
QUALITY CONTROL AND ASSURANCE...............................................................42
8
PLANNED STATISTICAL METHODS .....................................................................42
8.1
General Considerations ......................................................................................42
8.2
Determination of Sample Size............................................................................42
8.3
Analysis Populations..........................................................................................42
8.4
Demographics and Baseline Characteristics .......................................................42
8.5
Patient Disposition.............................................................................................43
8.6
Primary Endpoints .............................................................................................43
8.7
Secondary Endpoints..........................................................................................43


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8.7.1
Efficacy Endpoints ...................................................................................43
8.7.2
Immunogenicity Endpoint ........................................................................43
8.7.3
Pharmacodynamic Endpoint .....................................................................44
8.8
Exploratory Endpoints .......................................................................................44
8.9
Interim Analysis.................................................................................................44
9
ADMINISTRATIVE CONSIDERATIONS.................................................................44
9.1
Investigators and Study Administrative Structure...............................................44
9.2
Institutional Review Board or Independent Ethics Committee Approval.............45
9.3
Ethical Conduct of the Study..............................................................................45
9.4
Patient Information and Consent ........................................................................45
9.5
Patient Confidentiality .......................................................................................46
9.6
Study Monitoring...............................................................................................46
9.7
Case Report Forms and Study Records...............................................................47
9.8
Data Monitoring Committee...............................................................................47
9.9
Protocol Violations/Deviations...........................................................................47
9.10
Access to Source Documentation .......................................................................47
9.11
Data Generation and Analysis ............................................................................48
9.12
Retention of Data...............................................................................................48
9.13
Publication and Disclosure Policy ......................................................................48
10
REFERENCE LIST.....................................................................................................50
LIST OF IN-TEXT TABLES
Table 1.
Schedule of Study Assessments ........................................................25
Table 2.
List of Clinical Laboratory Tests.......................................................34
Table 3.
Assessments Based on the Myasthenia Gravis Foundation of 
America Post-intervention Status......................................................37
LIST OF APPENDICES
Appendix 1
Sponsor Signature.............................................................................52
Appendix 2
Investigator’s Signature ....................................................................53


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
AChR
acetylcholine receptor
ADA
anti-drug antibody
AE
adverse event
AESI
adverse event of special interest
ALT
alanine aminotransferase
AST
aspartate aminotransferase
CFR
Code of Federal Regulations
CGI
Clinical Global Impression
CGI-I
Clinical Global Impression of Improvement
CGI-S
Clinical Global Impression of Severity
CK
creatine kinase
CK-MB
creatine kinase MB isoenzyme
CK-MM
creatine kinase MM isoenzyme
CRA
clinical research associate
CS
clinically significant
C-SSRS
Columbia-Suicide Severity Rating Scale
CTCAE
Common Terminology Criteria for Adverse Events
CV
coefficient of variation
D5W
dextrose 5% in water
DSMB
Drug Safety Monitoring Board
ECG
electrocardiogram
eCRF
electronic case report form
FcRn
neonatal Fc receptor
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
gMG
generalized myasthenia gravis
ICF
informed consent form
ICH
International Council for Harmonisation 
IEC
Independent Ethics Committee
Ig
immunoglobulin
IRB
Institutional Review Board
IV
intravenous
IVIG
intravenous immunoglobulin
MedDRA
Medical Dictionary for Regulatory Activities
MG
myasthenia gravis
MG-ADL
Myasthenia Gravis – Activities of Daily Living


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MGFA
Myasthenia Gravis Foundation of America
MGFA-PIS
Myasthenia Gravis Foundation of America Post-intervention Status
MG-QoL15r
Revised Myasthenia Gravis Quality of Life – 15 Scale
MuSK
muscle-specific kinase
nADA
neutralizing anti-drug antibody
NCS
not clinically significant
OLE
open-label extension
PD
pharmacodynamics
POC
proof of concept
Q2W
every 2 weeks
Q4W
every 4 weeks
Q12W
every 12 weeks
QMG
Quantitative Myasthenia Gravis
QTc
QT interval corrected for heart rate
SAE
serious adverse event
SAP
statistical analysis plan
TEAE
treatment-emergent adverse event
ULN
upper limit of normal
US
United States
US FDA
United States Food and Drug Administration


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1
INTRODUCTION
Myasthenia gravis (MG) is a rare, heterogeneous, neuromuscular disease characterized by 
fluctuating, fatigable muscle weakness. Generalized myasthenia gravis (gMG) is 
characterized by the fluctuating and variable combination of weakness in ocular, bulbar, 
limb, neck, and respiratory muscles. Myasthenia gravis is caused by pathogenic 
autoantibodies directed against proteins in the postsynaptic membrane of the neuromuscular 
junction. In most patients (approximately 85% of cases), circulating antibodies target the
acetylcholine receptor (AChR); to a lesser extent (<10% of cases), antibodies to the 
muscle-specific kinase (MuSK), or lipoprotein-related protein 4 are present (Meriggioli and 
Sanders 2012; Zhang et al 2012). 
Preferred symptomatic treatment is with the acetylcholinesterase inhibitor, pyridostigmine. 
However, to meet the treatment goals of restoring or maintaining full or nearly full physical 
function and high quality of life, most patients with MG also require treatment with 
immunosuppressive medication(s) (Gilhus 2016; Gilhus et al 2016; Mantegazza and Antozzi 
2018). This includes treatment aimed at reducing the production of autoantibodies, such as 
immunosuppression with corticosteroids and second-line agents (azathioprine, 
cyclophosphamide, mycophenolate mofetil/mycophenolic acid, and B cell 
modification/ablation), as well as those aimed at increasing autoantibody removal such as 
plasma exchange, immunoadsorption, or immunomodulatory doses of intravenous 
immunoglobulin (IVIG) (Sanders et al 2016; Gilhus 2016; Gilhus et al 2016).
While many patients with gMG can be managed with current therapies, 10%-15% of patients 
fail to respond adequately to or cannot tolerate multiple therapies for MG and continue to 
suffer profound muscle weakness and severe disease symptoms that limit function and can be 
life-threatening (Silvestri and Wolfe 2014; Howard et al 2013; Howard et al 2017; Sanders 
et al 2016; Sathasivam 2014; Mantegazza and Antozzi 2018), and up to 80% fail to achieve 
complete and stable remission (Mantegazza and Antozzi 2018). Despite medical advances in 
patient care, a recent analysis of data from patient registries indicates that gMG is still 
associated with increased mortality compared to the general population, with an estimated 
mortality rate ratio of 1.4 (range 1.24–1.60) (Hansen et al 2016). Thus, there is a clear unmet 
medical need for new safe and effective treatments for gMG.
Momenta Pharmaceuticals, Inc. (Momenta) is developing M281 for the treatment of patients 
with gMG.  M281 is a fully human, aglycosylated immunoglobulin (Ig)G1 antibody that 
targets the neonatal Fc receptor (FcRn) IgG binding site with high affinity, thereby 
interfering with the binding of native IgG.  In cells of the reticuloendothelial system, FcRn 
binding of IgG protects it from degradation and contributes to its long half-life.  In patients 
with gMG, M281 is expected to reduce circulating levels of IgG antibodies by blocking IgG 
recycling, including the pathogenic autoantibodies that cause MG, potentially leading to 
improvement of the disease manifestations. Administration of M281 is not expected to 
reduce levels of other immunoglobulins, including IgA, IgM, or IgE, or impact other aspects 
of immune system response to infection, considering FcRn blockage only affects IgG 
half-life.


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A completed Phase 1 study of M281 in healthy volunteers (MOM-M281-001) showed that 
M281 was well tolerated in single infusions of doses up to 60 mg/kg (the highest single dose 
tested) and in up to 4 weekly infusions of doses up to 30 mg/kg (the highest repeat dose 
tested).  Self-limited, recoverable decreases in total serum IgG concentrations to a mean of 
approximately 15% to 20% of baseline values (an 80% to 85% decrease from baseline) were 
observed, confirming the drug’s mechanism of action.  Further details are provided in the 
Investigator Brochure.
The Phase 2, placebo-controlled, proof-of-concept (POC) study (MOM-M281-004, hereafter 
referred to as the POC study) in patients with gMG is evaluating the therapeutic potential of 
single (60 mg/kg) and repeat doses of M281 (5 mg/kg every 4 weeks [Q4W], 30 mg/kg 
Q4W, and 60 mg/kg every 2 weeks [Q2W]) for the treatment of patients with gMG who have 
an insufficient clinical response to ongoing, stable standard-of-care therapy.  Safety, 
tolerability, efficacy, pharmacodynamics (PD), and immunogenicity of M281 compared with 
placebo are being evaluated in the Phase 2 study over an 8-week Treatment Period and an 
8-week Follow-up Period after the last infusion of study drug.  Upon completion of the 
placebo-controlled POC study, patients have the option to enroll in this open-label extension 
(OLE) study to receive treatment with M281.  
The purpose of this OLE study is to collect long-term safety, tolerability, efficacy, PD, and 
immunogenicity data for M281 in patients who completed the POC study 
(MOM-M281-004). 
Potential Risks and Plans for Mitigation
Reduction of Serum Albumin Levels:
Asymptomatic decreases in serum albumin concentrations to a mean of 20% to 25% decrease 
from baseline were observed in the Phase 1 clinical study (MOM-M281-001).  This mild 
hypoalbuminemia was self-limited over the duration of dosing of M281 and recovered 
rapidly following dose cessation.  Serum albumin levels and clinical symptoms related to 
hypoalbuminemia will be monitored throughout the study, and hypoalbuminemia-related 
adverse event (AE) stopping rules are included in Section 6.6.1 of this protocol.
Reduction of Circulating IgG Levels:
In the Phase 1 clinical study (MOM-M281-001), subjects administered with M281 showed 
dose-dependent reduction of circulating IgG levels, which is an anticipated PD effect of 
M281 and contributes to its potential benefit in MG.  It is important to note that the normal 
immune response to produce IgM and IgG in response to a foreign antigen proceeds during 
treatment with FcRn blockers (Nixon et al 2015).  To date, M281 has not been associated 
with an increase in infection-related events in nonclinical or clinical studies.  Published 
clinical studies of other investigational agents that interfere with FcRn have not revealed an 
increase in incidence or severity of infections (Kiessling et al 2017; Argenx 2017; Blumberg 
et al 2017; Robak et al 2017).  These observations are suggestive, but not definitive, that the 
risk for infections associated with M281 administration may prove to be low.  Given the 
theoretical potential for increased infection risk with reduced circulating IgG levels, 


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procedures have been included in this protocol to mitigate the theoretical risk, including 
related criteria for study eligibility and infection-related AE stopping rules.
Elevation of Serum Creatine Kinase (CK):
Transient and asymptomatic elevations in serum CK levels were observed in 3 subjects in the 
15 mg/kg multiple-ascending-dose cohort in the Phase 1 study.  No CK elevations were 
observed in any of the preclinical studies of M281.  To mitigate any potential risk in the 
present study, patients who have serum CK level ≥2 × upper limit of normal (ULN) are 
excluded from entering the study, except in the case of stable CK ≥2×ULN, but <5×ULN in a 
patient with no CK related disease and CK level is believed to be the result of non-pathologic 
factors.  Serum CK levels will be monitored during the study and CK-related AE stopping 
rules are included in Section 6.6.1 of this protocol.
2
STUDY OBJECTIVES
2.1
Primary Objective
The primary objective of this study is to evaluate:
•
The long-term safety and tolerability of M281 in patients with gMG.
2.2
Secondary Objectives
The secondary objectives of this study are to evaluate:
•
The long-term efficacy of M281, 
•
The long-term immunogenicity of M281, and
•
The long-term PD activity of M281.
2.3
Exploratory Objectives
The exploratory objectives are to evaluate:
•
The effect of M281 on fatigue and level of physical activity,
•
The long-term PD activity of M281 on serum concentrations of IgA, IgM, and IgE,
•
The long-term PD activity of M281 on serum titers of pathogenic autoantibodies 
associated with gMG (anti-AChR and/or anti-MuSK),
•
The long-term response to treatment with M281 in in relation to other treatment(s) and/or 
clinical status, and
•
The potential relationship between change in Myasthenia Gravis – Activities of Daily 
Living (MG-ADL) score and change in anti-AChR antibody levels.


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3
INVESTIGATIONAL PLAN
3.1
Overall Study Design and Plan
This is a long-term, OLE study of patients who completed the POC study (MOM-M281-004) 
without discontinuing study drug during the POC study for reasons other than the need for 
rescue therapy (eg, glucocorticosteroids, IVIG, plasmapheresis) as specified in the POC 
protocol, and who completed the protocol-specified 8 weeks of follow-up after the last dose 
of study drug in the POC study.  
The Screening Period for the OLE study begins (at the earliest) at the Day 85 POC Visit 
(ie, 4 weeks after the last dose of study drug in the POC study) and ends upon enrollment in 
the OLE study.  The screening procedures consist of signing the informed consent form for 
the OLE study and initiation of continuous physical activity monitoring via a medical device 
(Embrace device, Empatica, Inc., Cambridge, MA) worn on the wrist.  
Eligibility for the OLE study will be assessed and enrollment into the OLE study will occur 
(at the earliest) after completion of assessments at the patient’s last follow-up visit in the 
POC study (Day 113 POC Visit).  Thus, the Day 113 POC Visit can be Day 1 for the OLE; 
patients who meet the eligibility criteria for the OLE study can receive their first open-label 
infusion of M281 on the same day.  
Patients who are enrolled in the OLE study will initially receive M281 30 mg/kg Q4W by 
intravenous (IV) infusion.  This dose (M281 30 mg/kg Q4W) is one of the doses evaluated in 
the POC study.  This starting dose and dosing frequency may be revised if available results 
from the POC study reveal a different optimal dose for development.  However, the revised 
dose and dosing frequency in the OLE study will not exceed 60 mg/kg Q2W, which is the 
highest dose and most frequent dosing interval evaluated in the POC study.  
After at least 8 weeks of treatment on a stable dose of M281, the dose and/or dosing 
frequency of M281 may be individually adjusted for a given patient at the discretion of the 
Investigator and previous consultation with the Medical Monitor, based on the patient’s 
tolerability to M281 and the patient’s MG status.  The individually adjusted dose will not 
exceed 60 mg/kg and the dosing frequency will not exceed Q2W.
Each patient will be observed for safety after their first 2 infusions in the study; if no 
clinically relevant AEs or abnormal vital signs related to the infusion are observed in these 
first 2 infusions, the post-infusion observation period is no longer needed unless the M281 
dose level is later increased. A post-infusion observation period is also required for the 
patient’s first infusion at the higher M281 dose level.  All patients must attend clinic visits at 
2, 4, and 8 weeks after the first infusion (on OLE Day 1) to undergo safety, tolerability, 
efficacy, PD, and immunogenicity assessments.  Serum biomarkers will also be explored.  
After Week 8, patients will receive an infusion of M281 on a Q2W or Q4W basis depending 
on the dosing frequency established for the patient. All infusions may be administered at the 
site, or every other infusion (except those that fall every 12 weeks [Q12W]) may be 
administered in the home or at another location per the Infusion Manual, at the discretion of 


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the Investigator and if this option is made available to the site.  As an example, for patients 
continuing on a Q4W regimen at Week 8, the schedule for optional home infusions would be
as follows:  Weeks 16, 28, and 40 (assuming no M281 dose increase and assuming end of 
treatment at Week 52).  As an example, for patients switching to a Q2W regimen at Week 8, 
the schedule for the optional home infusions would be as follows:  Weeks 14, 18, 22, 26, 30, 
34, 38, 42, 46, and 50 (assuming no M281 dose increase and assuming end of treatment at 
Week 52).
Each infusion will be administered per the Infusion Manual.  On each infusion day predose 
vital signs will be measured. For infusions administered in the clinic, electrocardiograms 
(ECGs) will also be measured, and AEs and concomitant medication/therapy since the 
previous clinical visit will be recorded. If the M281 dose and/or dosing frequency is 
adjusted, the first infusion at the new dose/frequency must occur at a clinic visit; for 
increases in the M281 dose level (but not for change in dosing frequency), the patient will 
undergo a post-infusion observation period following the first infusion at the higher dose 
level per the Infusion Manual. In the event of either a dose increase and/or dosing frequency 
increase, the patient’s next scheduled infusion must be conducted in the clinic because a 
blood sample for safety laboratory testing must be obtained and a physical examination must 
be performed within 2 to 4 weeks after the first infusion at the new dose/dosing frequency.  
Regardless of the patient’s dosing frequency, the full schedule of safety, tolerability, efficacy, 
PD, and immunogenicity assessments will be done at Week 12 and Q12W thereafter.  The 
duration of each patient’s participation in the study is planned to be approximately 1 year or 
until the study is terminated by the Sponsor.  Patients will return to the clinic approximately 
8 weeks after their last infusion for follow-up assessments.
Patients should continue their stable therapeutic regimen (standard of care) for gMG and 
should maintain the same dose and regimen for at least the first 8 weeks of the OLE study 
(unless toxicity or safety/tolerability issues mandate a change).  In the event the starting dose 
of M281 (30 mg/kg Q4W) is revised to a different dose and/or dosing frequency, it is 
recommended that the dose and regimen of concomitant treatment not be changed until the 
patient’s M281 dose has been stable for at least 8 weeks.  A consultation with the Medical 
Monitor regarding changes to the patient’s standard-of-care therapy is recommended.
The Schedule of Study Assessments is provided in Section 6.
3.2
Rationale for Study Design
The study will enroll patients with gMG who completed the POC study (MOM-M281-004) 
without discontinuing study drug during the POC study for reasons other than the need for 
rescue therapy as specified in the POC protocol, and who completed the protocol-specified 
8 weeks of follow-up after the last dose of study drug in the POC study.  Such patients may 
have been exposed to one or more doses of M281 or may have received placebo in the POC 
study.  Therefore, the safety, tolerability, efficacy, PD, and immunogenicity assessments for 
first 8 weeks of this OLE study are similar to those for the POC study.  PK sampling is not 
being done for this study because PK is being characterized in the POC study.


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Using data derived from nonclinical studies in nonhuman primates and data from the 
completed Phase 1 study of M281 in healthy volunteers (MOM-M281-001), the M281 dose 
that will initially be used at the start of the OLE study is 30 mg/kg given Q4W.  This dose 
(M281 30 mg/kg Q4W) is one of the doses evaluated in the POC study.  The dose regimen of 
30 mg/kg Q4W was selected to achieve significant IgG lowering while not fully saturating 
the FcRn receptor for the dosing interval.  The top dose allowed for adjustment (60 mg/kg 
Q2W) is expected to achieve maximum IgG reduction over the treatment period.  The 
starting dose and dosing frequency may be revised based on available results from the POC 
study.  Unlike the POC study, dose adjustment of M281 and of gMG standard-of-care 
therapy is allowed for individual patients after at least 8 weeks on a stable M281 dose to 
reflect real-world practice of tailoring the medication regimen based on tolerability and/or
gMG status.  The dose and dosing frequency in the OLE study will not exceed 60 mg/kg 
Q2W, which is the highest dose and most frequent dosing interval evaluated in the POC 
study.
The approximate 1-year duration of the study will be sufficient to characterize the long-term 
safety and tolerability, and to further evaluate efficacy, PD, and immunogenicity of M281.
3.3
Study Duration 
Following a Screening Period, the duration of each patient’s participation in the study is 
planned to be approximately 1 year or until the study is terminated by the Sponsor.
4
STUDY POPULATION SELECTION
4.1
Study Population
The sample size for the OLE study will depend on the enrollment in the POC study, which 
plans for approximately 60 patients with possible expansion up to 90 patients. 
4.2
Screening Period
The Screening Period for the OLE study begins (at the earliest) at the Day 85 POC Visit and 
ends upon enrollment in the OLE study.  The screening procedures consist of signing the 
informed consent form for the OLE study and initiation of continuous physical activity 
monitoring via the Embrace device.  Any screening procedure for the OLE study must not be 
done until after completion of all the assessments and procedures required by the POC 
protocol for the Day 85 POC Visit.  
If the patient received rescue therapy during the POC study, the Medical Monitor should be 
consulted before the patient is enrolled in the OLE study.
As specified in the POC protocol, patients who receive rescue therapy in the POC study are
discontinued from study drug infusions but are to continue assessments in the POC study.  
The follow-up visits in the POC study are the Day 85 POC Visit and the Day 113 POC Visit.  
Thus, for patients who receive rescue therapy during the Treatment Period of the POC study, 
the Day 85 POC Visit translates to 4 weeks after their last dose of study drug in the POC 


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study regardless of the study day of their last dose in the POC study.  Likewise, the Day 113 
POC Visit translates to 8 weeks after their last dose of study drug in the POC study 
regardless of the study day of their last dose in the POC study.
4.3
Enrollment
Eligibility for the OLE study will be assessed and enrollment into the OLE study will occur 
(at the earliest) on the same day as the patient’s last follow-up visit in the POC study 
(Day 113 POC Visit).  Any OLE assessment or procedure designated on the Day 113 POC 
Visit must not be performed until after completion of all the assessments and procedures 
required by the POC protocol for the Day 113 POC Visit.  After completion of all Day 113 
POC Visit assessments, the patient will be assessed for eligibility for enrollment into the 
OLE study per the OLE inclusion and exclusion criteria. Eligibility for the OLE study will 
be determined based on results of safety laboratory testing from the patient’s Day 85 POC 
Visit, the assessments from the patient’s Day 113 POC Visit, and additional procedures to be 
performed predose on OLE Day 1.  Patients meeting all eligibility criteria will be enrolled 
into the OLE study and may receive the first infusion of M281 under this protocol (day of 
first infusion is considered OLE Day 1).  Patients not meeting all OLE eligibility criteria will 
be considered screening failures for the OLE study and will not be enrolled or receive 
treatment under this protocol.
If it is not feasible to complete any/all designated OLE assessments/procedures on the same 
day as the Day 113 POC Visit, or if there is a valid reason to delay enrollment of the patient 
in the OLE study, the Investigator can confirm the patient’s eligibility and enroll the patient 
at a later date as agreed between the Investigator and Medical Monitor; however, depending 
on the length of the delay the patient may need to have an additional unscheduled blood draw 
for safety laboratory testing to confirm eligibility for the OLE study.  
4.4
Inclusion Criteria
1. Has completed the M281 POC study (ie, participated in the POC study without 
discontinuing study drug for reasons other than the need for rescue therapy as specified in 
the POC protocol, and completed the protocol-specified 8 weeks of follow-up after the 
last dose of study drug) and had no major eligibility deviations or other major protocol 
deviations in the POC study.  If the patient received rescue therapy during the POC, the 
Medical Monitor should be consulted before the patient is enrolled in the OLE study.
2. Has sufficient venous access to allow drug administration by infusion and blood sampling 
as per this OLE protocol.
3. Is up to date on all age-appropriate vaccinations as per routine local medical guidelines.
4. Women of childbearing potential, defined as women physiologically capable of 
becoming pregnant, must have a negative urine pregnancy test predose on OLE study 
Day 1.  Menopausal women who did not have elevated follicle-stimulating hormone 
(FSH) at the time of enrollment in the POC study must also have a negative urine 
pregnancy test predose on OLE study Day 1.
5. Women of childbearing potential (including menopausal women who did not have 
elevated FSH at the time of enrollment in the POC study) must agree to remain totally


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abstinent (ie, refrain from sexual intercourse during the study) or to consistently use a 
reliable and highly effective method of contraception (eg, condom plus diaphragm, 
condom plus spermicide, diaphragm plus spermicide, or intrauterine device or 
oral/injectable/implanted hormonal contraceptive used in combination with an additional 
barrier method) during the OLE study and for 30 days after the last M281 infusion.
Note:  Periodic abstinence (calendar, symptothermal, post-ovulation methods), 
withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method 
are not acceptable methods of contraception. Female condom and male condom should 
not be used together.
6. Male patients must agree to remain totally abstinent (ie, refrain from sexual intercourse 
during the study) or to consistently use a reliable and highly effective method of 
contraception (eg, condom plus diaphragm, condom plus spermicide, diaphragm plus 
spermicide, or intrauterine device or oral/injectable/implanted hormonal contraceptive 
used in combination with an additional barrier method) to avoid pregnancy of the 
patient’s partner(s) during the OLE study and for 100 days following the last M281 
infusion, unless the patient provides documentation of a vasectomy at least 6 months 
prior to OLE study enrollment.  Male patients must also abstain from sperm donation 
during the OLE study and for 100 days following the last M281 infusion.
Note:  Periodic abstinence (calendar, symptothermal, post-ovulation methods), 
withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method 
are not acceptable methods of contraception. Female condom and male condom should 
not be used together.
7. A patient using herbal, naturopathic, and traditional Chinese remedies and ayurvedic and 
nutritional supplements is eligible if the use of these medications is acceptable to the 
Investigator.  These remedies should be at a stable dose and regimen using the same 
preparation since enrollment in the POC study.
8. Is able to understand and voluntarily provide written informed consent to participate in 
the long-term OLE study and comply with all study procedures for duration of the OLE 
study.
4.5
Exclusion Criteria
1. Has Myasthenia Gravis Foundation of America (MGFA) Class IVb or V disease.
2. Met any of the study drug stopping criteria in the POC study or discontinued study drug 
in the POC study for any reason (eg, adverse event [AE]) other than the need for rescue 
therapy as specified in the POC protocol. (If the patient received rescue therapy during 
the POC, the Medical Monitor should be consulted before the patient is enrolled in the 
OLE study.)
3. Has current suicidal ideation evidenced by a “yes” response to Questions 4 or 5 in the 
Suicidal Ideation section of the Columbia-Suicide Severity Rating Scale (C-SSRS) 
administered predose on OLE study Day 1.
4. Currently has a serious or clinically significant infection (eg, pneumonia, biliary tract
infection, diverticulitis, Clostridium difficile infection) requiring parenteral anti-infectives 
and/or hospitalization, or currently has any infection requiring oral anti-infectives. 
Note:  An uncomplicated, presumably viral, upper respiratory tract infection (eg, ‘the 
common cold’) is not an exclusion.


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5. Has current alcohol/substance abuse/dependence, or in the Investigator’s opinion, shows 
evidence of ongoing alcohol/substance abuse/dependence.
6. Has donated or had significant loss of whole blood (480 mL or more) within 30 days, or 
plasma within 14 days prior to OLE study Day 1.
7. Has a hypersensitivity to M281 or any constituent of the study drug solution.
8. Has had a prior severe drug reaction that included shock or severe hypersensitivity.
9. Has liver impairment with Child-Pugh Class B or C.
10. Has any other medical condition(s) likely to require treatment with oral or parenteral 
glucocorticosteroids (eg, severe asthma), or has required oral or parenteral 
glucocorticosteroids in the past 3 months before OLE study Day 1 for conditions other 
than MG (inhalational, intra-articular, topical or ocular glucocorticosteroids are not 
exclusionary), or taking any immunosuppressive agents not being used to treat MG.
11. Is receiving a systemic biologic antibody for any concurrent disease.
12. Has a QT interval corrected for heart rate (QTc) at OLE study Day 1 of >450 msec for 
males or >470 msec for females; or QTc >480 msec in patients with Bundle Branch 
Block, by the Fridericia formula.
13. Had any of the following abnormal laboratory values based on the safety laboratory tests 
done at the Day 85 POC Visit: aspartate aminotransferase (AST), alanine 
aminotransferase (ALT), or alkaline phosphatase ≥2× upper limit of normal (ULN); or 
bilirubin ≥1.5×ULN (isolated bilirubin greater than 1.5×ULN is acceptable if bilirubin is 
fractionated and direct bilirubin is <35%, or if there is a prior diagnosis of Gilbert disease
without any condition that causes elevation of bilirubin).
14. Had elevated CK ≥2×ULN based on the safety laboratory tests done at the Day 85 POC 
Visit.
Note:  If the CK value is ≥2×ULN at the Day 85 POC visit, the value from the Day 113 
POC Visit can be used to assess eligibility.  If the value from the Day 113 POC Visit is 
also ≥2×ULN, but <5×ULN, and in the opinion of the investigator the patient has no 
CK-related disease and CK level is believed to be the result of non-pathologic factors, the 
CK may be repeated once within 28 days and if stable/improved the patient can be 
enrolled.
5
STUDY TREATMENT
5.1
Description of Treatment
M281 is a sterile solution intended for IV infusion following dilution with dextrose 5% in 
water (D5W). It will be supplied in an open-label fashion to the study centers in 20-mL glass 
vials nominally containing 30 mg/mL (600 mg) of M281 protein in solution. The glass vial 
has a 20 mm chlorobutyl stopper and an aluminum overseal.
M281 is formulated to a target concentration of 30 mg/mL in 25 mM sodium phosphate, 
25 mM sodium chloride, 8.7% weight/weight trehalose, 0.01% weight/volume 
polysorbate 80, pH 6.5.


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5.2
Treatment Administered
M281 will be diluted with D5W and administered by IV infusion.  The starting dose of M281 
will be 30 mg/kg Q4W based on body weight at the time of enrollment into the OLE study.
Details for preparation of the infusion will be provided in the Drug Handling Manual.
Infusion is to be administered as specified in the Infusion Manual.
5.3
Selection and Timing of Dose for Each Patient
Patients who are enrolled in the OLE study will initially receive M281 30 mg/kg Q4W.  
After at least 8 weeks of treatment on a stable dose of M281, the dose and/or dosing 
frequency of M281 may be individually adjusted for a given patient at the discretion of the 
Investigator and previous consultation with the Medical Monitor, based on the patient’s 
tolerability to M281 and the patient’s MG status.  If the M281 dose and/or dosing frequency 
is adjusted, the first infusion at the new dose/frequency must occur at a clinic visit (not at a 
home infusion).  The individually adjusted dose will not exceed 60 mg/kg and the dosing 
frequency will not exceed Q2W.
The M281 infusions will be administered without regard to mealtimes or time of day.  
Guidelines for management of infusion site reactions are provided in the study manual. Each 
patient will be observed for safety after their first 2 infusions in the study; if no clinically 
relevant AEs or abnormal vital signs related to the infusion are observed in these first 
2 infusions, the post-infusion observation period is no longer needed unless the M281 dose 
level is later increased. A post-infusion observation period is also required for the patient’s 
first infusion at the higher M281 dose level.
The date of infusion, start and end times, the volume administered, and the time of the 
infusion rate change (if applicable) for all doses are to be recorded.  The infusion time is 
noted in the Infusion Manual.
5.4
Method of Assigning Patients to Treatment Groups
No comparator arm is included in the OLE study.  All patients will receive M281.
5.5
Blinding
Not applicable.
5.6
Concomitant Therapy
Patients should continue their stable therapeutic regimen (standard of care) for gMG and 
must maintain the same dose and regimen for at least the first 8 weeks of the OLE study 
(unless toxicity or safety issues mandate a change), after which the dose/regimen can be 
changed at the Investigator’s discretion, as appropriate based on the patient’s gMG status.  It 
is recommended that the dose and regimen of concomitant treatment is not changed until the 


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patient’s M281 dose has been stable for at least 8 weeks.  A consultation with the Medical 
Monitor regarding changes to the patient’s standard-of-care therapy is recommended.
Use of herbal, naturopathic, and traditional Chinese remedies, and ayurvedic and nutritional 
supplements may also continue during the study, if the patient is on a stable dose and 
regimen at study enrollment and the use of these medications is acceptable to the 
Investigator.  The patient should maintain the same dose and regimen using the same 
preparation (and new preparations should not be initiated) for at least the first 8 weeks of the 
OLE study (unless toxicity or safety issues mandate a change).
5.7
Restrictions
5.7.1
Prior Therapy
Patients should continue their stable standard-of-care MG therapy (eg, glucocorticosteroids, 
acetylcholinesterase inhibitor, statins, immunosuppressants) as described in Section 5.6. 
5.7.2
Fluid and Food Intake
Patients are not required to be fasting at any time during the study and the study does not 
include any requirements with respect to food intake. Patients may only have room 
temperature food/fluids within 1 hour before the efficacy assessments are conducted for the 
study visit and until efficacy assessments are completed.
5.7.3
Patient Activity Restrictions
Patients may continue their usual activities during the study, including exercise, but should 
notify their Investigator about starting any new exercise program during the study. Patients 
should avoid excessive exertion on the day of or day before a study visit.
5.8
Treatment Compliance
Scheduled IV infusions of study drug will occur at the study center under observation by 
study staff, or by a qualified healthcare provider for optional home infusions (at the 
discretion of the Investigator and if this option is made available to the site), thus ensuring 
treatment compliance.   
5.9
Packaging and Labeling
Open-label M281 will be supplied as one container per carton.  Supplies of M281 will be 
labeled with the local language.
5.10
Storage and Accountability
Vials of M281 must be stored at 2°C to 8°C in a secure, controlled-access location. M281 
must only be used for patients who have consented to participate in this OLE study.


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At the end of the study, a final reconciliation must be made between the amount of study 
drug supplied, dispensed, and subsequently destroyed or returned to the Sponsor. A written 
explanation must be provided for any discrepancies.
6
STUDY ASSESSMENTS AND PROCEDURES
The Schedule of Study Assessments is presented in Table 1.


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Table 1.
Schedule of Study Assessments
Study Week
Start of 
Screening 
for OLE 
Studya
OLE Study Enrollment 
(Day 1)b
Week 2
Week 4 
and 
Week 8
Week 10 
(only for 
Q2W 
regimen) 
Week 12 
and Q12W
thereafter
(both 
regimens)
Q2W or Q4W,
depending on 
regimenc
Last 
Treatment/ 
Early 
Termination
Follow-up 
Visit
Visit/Window
After 
completion 
of Day 85 
POC Visit
Day 113 POC 
Visit (ie, 
8 weeks after 
last infusion in 
POC)
Additional 
OLE 
proceduresb ±3 days
±3 days
±7 days 
±7 days 
±7 days
NA
8 weeks 
(±7 days) 
after last 
infusion 
Vital Signsd
X
Xd
X
Xd
X
X
X
X
X
Weight 
X
X
X
X
Physical Examinatione
Xe
X
X
X
X 
Xf
Xe
X
12-Lead ECGd
X
Xd
X
X
X
X
X
Xd
X
Efficacy Assessmentsg
MG-ADL
X
X
X
X
X
QMG
X
X
X
X
X
MG-QoL15r
X
X
X
X
X
MGFA-PIS – applicable
elements
X
X
X
X
Blood sample for anti-AChR 
and anti-MuSK autoantibody 
levels (as applicable for the 
patient)h
X
X
X
X
X
Safety Laboratory Testingh
X
X
X
X
X
Xf
X
X
Blood sample for total and 
neutralizing anti-M281 
antibodiesh
X
X
X
X
X
Blood sample for levels of 
total IgGh
X
X
X
X
X
X
Blood sample for IgA, IgM, 
and IgE levelsh
X
X
X


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Clinical Trial Protocol: MOM-M281-005
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Table 1.
Schedule of Study Assessments
Study Week
Start of 
Screening 
for OLE 
Studya
OLE Study Enrollment 
(Day 1)b
Week 2
Week 4 
and 
Week 8
Week 10 
(only for 
Q2W 
regimen) 
Week 12 
and Q12W
thereafter
(both 
regimens)
Q2W or Q4W,
depending on 
regimenc
Last 
Treatment/ 
Early 
Termination
Follow-up 
Visit
Visit/Window
After 
completion 
of Day 85 
POC Visit
Day 113 POC 
Visit (ie, 
8 weeks after 
last infusion in 
POC)
Additional 
OLE 
proceduresb ±3 days
±3 days
±7 days 
±7 days 
±7 days
NA
8 weeks 
(±7 days) 
after last 
infusion 
Informed Consent for OLE
X
Review Incl/Excl criteria for 
OLE and confirm patient 
eligibility
Xi
Medical History, 
Demographics, and Height
X
Urine pregnancy testj
X
C-SSRS
X
X
X
X
X
AEs / Concomitant 
Medications/Rescue Therapyk
X
X
Monitored throughout the study
CGI-S
X
X
X
X
X
CGI-I
X
X
X
X
Neuro-QOL Fatigue 
assessment
X
X
X
X
X
MGFA clinical classification
X
Week 8 
only
Every 
24 Weeks
X
Monitor physical activity 
(Embrace device)
Continuous from screening through 6 months after first OLE M281 dose
Study Drug Infusionl
X
X
X
X
X
Xm
Abbreviations:  AE = adverse event; anti-AChR= anti-acetylcholine receptor autoantibody; anti-MuSK = anti-muscle-specific kinase autoantibody; 
CGI-I = clinical global impression of improvement; CGI-S = clinical global impression of severity; C-SSRS = Columbia-Suicide Severity Rating Scale; 
ECG = electrocardiogram; Ig = immunoglobulin; MG = myasthenia gravis; MG-ADL= Myasthenia Gravis – Activities of Daily Living; MGFA = Myasthenia 
Gravis Foundation of America; MGFA-PIS = Myasthenia Gravis Foundation of America Post-intervention Status; MG-QoL15r = revised Myasthenia Gravis 


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Clinical Trial Protocol: MOM-M281-005
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Quality of Life – 15 Scale; NA = not applicable; OLE = open-label extension; PD = pharmacodynamic; Q2W = every 2 weeks; Q4W = every 4 weeks; 
QMG = Quantitative Myasthenia Gravis.
a
The Screening Period for the OLE study begins (at the earliest) at the Day 85 POC Visit (which translates to 4 weeks after the last dose of study drug in the 
POC study).  Any screening procedure for the OLE study must not be done until after completion of all the assessments and procedures required by the POC 
protocol for the Day 85 POC Visit.  
b
OLE enrollment will occur (at the earliest) on the same day as the patient’s last follow-up visit (Day 113 POC Visit) in the POC study.  Any OLE 
assessment or procedure designated on the Day 113 POC Visit must not be performed until after completion of all the assessments and procedures required 
by the POC protocol for the Day 113 POC Visit.  If it is not feasible to complete any/all designated OLE assessments/procedures on the same day as the 
Day 113 POC Visit, or if there is a valid reason to delay enrollment of the patient in the OLE study, the Investigator can confirm the patient’s eligibility and 
enroll the patient at a later date as agreed between the Investigator and Medical Monitor; however, depending on the length of the delay the patient may need 
to have an additional unscheduled blood draw for safety laboratory testing to confirm eligibility for the OLE study.
c
Only predose vital signs (but not physical examination, ECG, or safety laboratory testing) are required if the infusion is administered in the home.  Every 
other infusion (except those that fall every 12 weeks [Q12W]) may be administered in the home or at another location per the Infusion Manual, at the 
discretion of the Investigator and if this option is made available to the site.  As an example, for patients continuing on a Q4W regimen at Week 8, the 
schedule for optional home infusions would be as follows:  Weeks 16, 28, and 40 (assuming no M281 dose increase and assuming end of treatment at 
Week 52).  As an example, for patients switching to a Q2W regimen at Week 8, the schedule for optional home infusions would as follows:  Weeks 14, 18, 
22, 26, 30, 34, 38, 42, 46, and 50 (assuming no M281 dose increase and assuming end of treatment at Week 52)
d
Vital signs (temperature, recumbent systolic blood pressure and diastolic blood pressure, and pulse rate) will be measured immediately prior to the start of 
each infusion. For the first 2 infusions in the OLE study, vital signs will also be measured after completion of the infusion as specified in the Infusion 
Manual. Twelve-lead ECGs will be recorded before the start of the M281 infusion. For the first infusion in the OLE study, a single 12-lead ECG will also be 
conducted within 10 minutes after the infusion has been completed. Predose ECGs will not be required on days when the infusion is administered in the 
home.
e
Full physical examinations to be performed at study enrollment and end of treatment/early termination, and a focused physical examination at all other site 
visits.  Focused physical examinations should determine if there has been any change in neurologic function, upper respiratory tract (ears, nose, throat, and 
sinuses), eyes and lungs, abdomen, or skin.
f
If the M281 dose and/or dosing frequency is increased (which must occur at a clinic visit, not at a home infusion), the patient’s next infusion must be 
conducted in the clinic because a blood sample for safety laboratory testing must be obtained and a physical examination must be done within 2 to 4 weeks 
after the first infusion at the new dose/dosing frequency.
g
All MG assessments must be done starting at approximately the same time of day, and prior to study drug administration on infusion days.  It is preferable to 
perform the applicable MG assessments in the order shown in this Schedule of Study Assessments.
h
Blood samples must be collected before the start of the M281 infusion.  Safety laboratory testing includes chemistry, hematology, coagulation function 
(including prothrombin time), and urinalysis.
i
The assessment of patient eligibility for the OLE study includes review of the safety laboratory testing results from the patient’s Day 85 POC Visit.
j
Women of childbearing potential must have a negative urine pregnancy test at study enrollment prior to the first M281 infusion in the OLE study.  
Menopausal women who did not have elevated FSH at the time of enrollment in the POC study must also have a negative urine pregnancy test prior to the 
first M281 infusion in the OLE study. 


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Clinical Trial Protocol: MOM-M281-005
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k
All medications/therapies are to be recorded from the time of enrollment into OLE study (ie, Day 1) throughout the patient’s participation in the study, 
including administration of rescue therapy during the study for worsening of MG-related symptoms.  Reporting of device-related AEs in the OLE study will 
start following the patient signing the OLE informed consent form.  AEs from the POC study that are ongoing at the Day 113 POC Visit will be recorded as 
medical history for the OLE study.  Recording of new AEs (ie, any new clinically relevant finding or worsening of a pre-existing condition, such as an 
ongoing AE from the POC study) will start at the time of enrollment into the OLE study. 
l
Infusion to be administered as specified in the Infusion Manual.  Each patient will be observed for safety after their first 2 infusions in the OLE study; if no 
clinically relevant AEs or abnormal vital signs related to the infusion are observed in these first 2 infusions, the post-infusion observation period is no longer 
needed unless the M281 dose level is later increased. A post-infusion observation period is also required for the patient’s first infusion at the higher M281 
dose level.
m
Study drug will not be administered at an Early Termination Visit.


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Clinical Trial Protocol: MOM-M281-005
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6.1
Safety Assessments
Safety assessments include collection of AEs, vital signs, physical examinations, clinical 
laboratory testing (including chemistry, hematology, coagulation, and urinalysis), ECGs, and 
the C-SSRS. Severe infections and hypoalbuminemia (Grade 3 or higher according to the 
Common Terminology Criteria for Adverse Events [CTCAE] v5.0) will be considered AEs
of special interest (AESIs).
6.1.1
Adverse Events
An AE can be any unfavorable and unintended sign (eg, an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a drug, without any judgment 
about causality. An AE can therefore be any unfavorable and unintended sign, symptom, 
disease, concurrent illness, or clinically significant abnormal laboratory finding that emerges 
or worsens (ie, aggravated in severity or frequency from the baseline condition) during the 
study. Clinically significant abnormal results of laboratory tests or diagnostic procedures are 
to be reported as AEs.
The manufacturer of the Embrace device advises that it should only be worn on the surface of 
healthy skin, and to suspend or discontinue use if the skin becomes red, itchy, or if any pain 
is felt.  Adverse events associated with wearing the Embrace device are to be recorded as 
device-related AEs and the use of the Embrace device should be discontinued.
6.1.1.1
Performing Adverse Events Assessments
At each contact with the patient, the Investigator or designee will capture AEs by specific 
questioning and, as appropriate, by examination. Patients will be asked non-leading 
questions to capture medically related changes to their well-being. Participants will also be 
asked if they have been hospitalized, had any accidents, sought care from a health 
professional, used any new medications/therapies, or changed concomitant medication 
regimens (both prescription and over-the-counter) due to an AE.
6.1.1.2
Timing
Reporting of device-related AEs in the OLE study will start following the patient signing the 
OLE informed consent form.  Adverse events from the POC study that are ongoing at the 
Day 113 POC Visit will be recorded as medical history for the OLE study.  Recording of new 
AEs (ie, any new clinically relevant finding or worsening of a pre-existing condition, such as 
an ongoing AE from the POC study) will start at the time of enrollment into the OLE study
(Day 1). 
6.1.1.3
Severity
The Investigator will grade the severity/intensity of each AE using the National Cancer 
Institute, CTCAE v5.0 classifications
(https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quic
k_Reference_8.5x11.pdf).


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The CTCAE provides specific criteria for grading AEs as well as laboratory tests; in general,
the grades are as follows:
Grade 1, Mild:  asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated 
Grade 2, Moderate:  minimal, local or noninvasive intervention indicated; limiting age 
appropriate instrumental activities of daily living 
Grade 3, Severe or medically significant but not immediately life-threatening: 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care
activities of daily living 
Grade 4, Life-threatening consequences: urgent intervention indicated 
Grade 5, Death related to AE
6.1.1.4
Relationship
The Investigator must assess all AEs for relationship to study drug/device by examining and 
evaluating the patient based on temporal relationship and his/her clinical judgment. The 
degree of certainty about causality will be graded using the categories below:
Definitely Related – There is clear evidence to suggest a causal relationship to study 
drug/device; other possible contributing factors can be ruled out. The clinical event, 
including an abnormal laboratory test result, occurs in a plausible time relationship to study 
drug administration and cannot be explained by concurrent disease or other drugs or 
chemicals. The response to withdrawal of the study drug (dechallenge) should be clinically 
plausible. The event must be pharmacologically or phenomenologically definitive, with use 
of a satisfactory rechallenge procedure if necessary.
Probably Related – There is evidence to suggest a causal relationship to study drug/device, 
and the influence of other factors is unlikely. The clinical event, including an abnormal 
laboratory test result, occurs within a reasonable time after administration of the study 
intervention, is unlikely to be attributed to concurrent disease or other drugs or chemicals, 
and follows a clinically reasonable response on withdrawal (dechallenge). Rechallenge 
information is not required to fulfill this definition.
Possibly Related – There is some evidence to suggest a causal relationship to study 
drug/device (eg, the event occurred within a reasonable time after administration of the study 
drug). However, other factors may have contributed to the event (eg, the patient’s clinical 
condition, other concomitant events). Although an AE may rate only as “possibly related” 
soon after discovery, it can be flagged as requiring more information and later be upgraded to 
“probably related” or “definitely related”, as appropriate.
Unlikely to be related – A clinical event, including an abnormal laboratory test result, 
whose temporal relationship to study intervention administration makes a causal relationship 


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Clinical Trial Protocol: MOM-M281-005
01 August 2019
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improbable (eg, the event did not occur within a reasonable time after administration of the 
study drug) and in which other drugs or chemicals or underlying disease provides plausible 
explanations (eg, the patient’s clinical condition, other concomitant treatments).
Not Related – The AE is completely independent of study drug administration, and/or 
evidence exists that the event is definitely related to another etiology. There must be an 
alternative, definitive etiology documented by the clinician.
6.1.1.5
Expectedness
The Sponsor will be responsible for determining whether an AE is expected or unexpected. 
An AE will be considered unexpected if the nature, severity, or frequency of the event is not 
consistent with the Reference Safety Information (the Investigator’s Brochure for M281 and 
the manufacturers information for the Embrace device).
6.1.1.6
Adverse Events of Special Interest
For this study, any CTCAE Grade 3 or higher severe infection or event of hypoalbuminemia 
will be considered an AESI. These cases will be handled similarly to a serious adverse event
(SAE) for reporting purposes (see Section 6.1.1.8) and reviewed by the Drug Safety 
Monitoring Board (DSMB) as they occur.
6.1.1.7
Clinical Laboratory Adverse Events
Investigators will indicate on the laboratory report whether abnormal values are clinically 
significant (CS) or not clinically significant (NCS). All CS abnormal laboratory results will 
be considered as AEs and are to be reported in the electronic case report form (eCRF).
6.1.1.8
Serious Adverse Events
DEFINITION
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.
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, 
they may jeopardize the patient and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse.


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Clinical Trial Protocol: MOM-M281-005
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REPORTING SERIOUS ADVERSE EVENTS
The Investigator will report to the Sponsor via MMS Holdings, the safety group that will be 
processing the information, any SAE or AESI within 24 hours of becoming aware of the 
event, whether or not the event is considered related to study drug. The report must include 
an assessment of whether there is a reasonable possibility that the study drug caused the 
event.
Send SAE and AESI reports to:
MMS Holdings
6880 Commerce Blvd
Canton, MI 48187
USA
E-mail:
MomentaPharmaDrugSafety@mmsholdings.com
The Sponsor will be responsible for notifying the regulatory authorities per local 
requirements of any unexpected fatal or life-threatening suspected adverse reaction as soon 
as possible, but in no case later than 7 calendar days after the Sponsor’s initial receipt of the 
information. In addition, the Sponsor must notify the regulatory authorities and all 
participating investigators of any safety reports of potential serious risks, from clinical trials 
or any other source, as soon as possible, but in no case later than 15 calendar days after the 
Sponsor determines that the information qualifies for reporting.
It is the responsibility of the Sponsor to determine the reportability of SAEs. 
All SAEs will be followed until satisfactory resolution or until the Investigator deems the 
event to be chronic or the patient is stable. Other supporting documentation of the event may 
be requested by the DSMB or Sponsor and should be provided as soon as possible.
6.1.1.9
Treatment-Emergent Adverse Events
A treatment-emergent AE (TEAE) is defined as any AE occurring during or after the 
initiation of the first infusion of study drug.
6.1.1.10
Pregnancy
Any pregnancy (including the pregnancy of the partner of a male study patient) occurring 
during OLE study participation and at any time during the 30 days for female patients or 
100 days for the female partner of a male patient after the last dose of study drug must be 
reported to the Sponsor using a clinical trial pregnancy form. To ensure patient safety, each 
pregnancy must be reported to the Sponsor, via MMS Holdings, the safety group that will be 
processing the information (see Section 6.1.1.8), within 24 hours of the Investigator learning 
of its occurrence.  The pregnancy should be followed up to determine outcome (including 
premature termination) and status of mother and child. The patient and/or patient’s partner 
will be requested to provide written informed consent to enable collection of information 
pertaining to the outcome of the pregnancy. 


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Clinical Trial Protocol: MOM-M281-005
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While pregnancy itself is not an AE/SAE, any pregnancy complication or elective 
termination of a pregnancy for medical reasons will be reported as an AE or SAE as 
appropriate and must be communicated by the Investigator to MMS Holdings within 
24 hours of receipt of notification of an event. An abortion, whether accidental, therapeutic, 
or spontaneous, should always be reported as an SAE. Similarly, any congenital anomaly 
birth defect in a child born to a patient exposed to the study treatment should be recorded and 
reported as an SAE.  
Any SAE occurring in association with a pregnancy brought to the Investigator’s attention 
after the patient has completed the study and considered by the Investigator as possibly 
related to the study drug must be promptly reported to MMS Holdings.
6.1.2
Concomitant Medication Assessments
From the time of enrollment into the OLE study (ie, Day 1) all medications/therapies, and 
procedures administered to patients at any time during the study, including MG rescue 
medication/therapy, are to be recorded in the eCRF. Medications to be reported in the eCRF 
are concomitant prescription medications, over-the-counter medications and supplements. 
Other therapies and procedures (eg, immunizations) are also to be recorded.
6.1.3
Physical Examination
Height will be measured at Day 1 only. Weight will be measured at Day 1 and every 
12 weeks thereafter. A full physical examination will be performed at Day 1 and at the end 
of the study; at all other visits, a focused physical examination will be performed to 
determine if there has been any change in neurologic function, upper respiratory tract (ears, 
nose, throat, and sinuses), eyes and lungs, abdomen, or skin.
6.1.4
Vital Signs
Vital signs measurements will include recumbent blood pressure and pulse rate, and body 
temperature. The patient will be resting in the recumbent position for 3 to 5 minutes before 
all vital signs are recorded, according to the practices of the investigative site. 
The Investigator will determine if any of the vital sign measurements are CS or NCS. 
Clinical significance is defined as any variation in assessment results that has medical 
relevance and may result in an alteration in medical care (eg, active observation, diagnostic 
measures, or therapeutic measures). If a CS change from baseline values is noted, the CS
value and reason for clinical significance will be documented on the AE page of the patient’s 
eCRF. The Investigator will continue to monitor the patient with additional assessments until
the values have reached reference range and/or the values at baseline, or until the Investigator 
determines that follow-up is no longer medically necessary.


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Clinical Trial Protocol: MOM-M281-005
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6.1.5
Clinical Laboratory Tests
Patients will be in a seated or supine position during blood collection. Patients are not 
required to be fasting. Instructions for blood sample collection, processing, storage, and 
shipping are described in the Laboratory Manual.  
Clinical laboratory tests will include the parameters listed in Table 2.
Table 2.
List of Clinical Laboratory Tests
Hematology:
Hematocrit
Hemoglobin
Mean corpuscular hemoglobin 
Mean corpuscular hemoglobin concentration 
Mean corpuscular volume
Platelet count
Red blood cell count 
White blood cell count with differential 
Urinalysis: 
Appearance
Bilirubin
Color
Glucose
Ketones
Microscopic examination of sediment 
Nitrite 
Occult blood
pH
Protein
Myglobin (if serum creatine kinase is 
elevated)
Specific gravity
Urobilinogen
Urine pregnancy test (for females of childbearing 
potential and menopausal females if follicle-
stimulating hormone was not elevated at time of 
enrollment in the POC study)
Serum Chemistry:
Albumin
Alkaline phosphatase
Alanine aminotransferase
Aspartate aminotransferase 
Blood urea nitrogen
Calcium
Carbon dioxide
Chloride
Creatinine
Creatine kinase (MB and MM isoenzyme 
fractionation if creatine kinase is elevated)
Troponin if creatine kinase is elevated
Gamma-glutamyl transferase 
Glucose
Lactate dehydrogenase 
Phosphorus
Potassium
Sodium
Total bilirubin
Direct bilirubin
Total cholesterol
Total protein
Triglycerides
Uric acid
Coagulation: 
Prothrombin time
Activated partial thromboplastin time
Clinically significant changes from baseline in laboratory results must be considered an AE 
and recorded in the eCRF. Clinical significance is defined as any variation in a laboratory 
result that has medical relevance and that results in a change in medical care. The 
Investigator will continue to monitor the patient until the finding is resolved, or in the 
judgment of the Investigator follow-up is no longer medically necessary.


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6.1.6
Electrocardiograms
A single 12-lead ECG will be obtained after the patient has been in the supine position for at 
least 5 minutes. A central ECG service will measure and interpret all ECG recordings except 
those obtained at the follow-up visit, which will be evaluated by the Investigator. 
Electrocardiogram reports will include comments on whether the tracings are normal or 
abnormal, rhythm, presence of arrhythmia or conduction defects, morphology, any evidence 
of myocardial infarction, or ST segment, T Wave, and U Wave abnormalities. In addition, 
the following intervals will be measured and reported: RR, PR, QRS, QT, and QTc.
The Investigator will determine if the ECG results are CS or NCS. Clinical significance is 
defined as any variation in assessment results that has medical relevance and may result in an 
alteration in medical care (eg, active observation, diagnostic measures, or therapeutic 
measures). If an ECG finding is identified as CS, the patient should be assessed by the 
Investigator for symptoms (for example, palpitations, near syncope, syncope). Any CS
finding should be documented as an AE on the AE eCRF, and the Investigator must to 
continue to monitor the patient until the finding is resolved, or in the judgment of the 
Investigator, follow-up is no longer medically necessary.
6.1.7
Columbia-Suicide Severity Rating Scale
The C-SSRS is administered by trained study personnel (ie, personnel who are C-SSRS 
certified). The C-SSRS Since Last Visit version will be used. When the C-SSRS is 
administered on an infusion day in the clinic as specified in Table 1, the C-SSRS must be 
administered before the infusion. 
Any patient who answers “yes” to Questions 4 or 5 in the Suicidal Ideation section of the 
C-SSRS on Day 1 should not be enrolled and should be referred to a mental health specialist 
by the Investigator. During the course of the study after initiation of study treatment, any 
patient who answers “yes” to Questions 4 or 5 in the Suicidal Ideation section or answers 
“yes” to any question in the Suicidal Behavior section of the C-SSRS will be referred by 
Investigators to a mental health specialist. After initiation of study treatment, affirmative 
answers to Questions 4 or 5 for suicidal ideation or to any question for suicidal behavior will 
be reported in the eCRF as an AE.
6.2
Efficacy Assessments
Efficacy will be assessed at designated site visits prior to M281 infusion (ie, predose), using 
these measures in the following preferred order: MG-ADL, Quantitative Myasthenia Gravis 
(QMG), revised Myasthenia Gravis Quality of Life – 15 Scale (MG-QoL15r), applicable 
elements of the Myasthenia Gravis Foundation of America Post-Intervention Status
(MGFA-PIS), physician-rated Clinical Global Impression (CGI) scales, patient-reported 
Neuro-QOL Fatigue, and MGFA classification.  If possible, these efficacy assessments 
throughout the study should be done at approximately the same time of day as performed on 
Day 1.


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Clinical Trial Protocol: MOM-M281-005
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In addition, the level of physical activity will be monitored via the Embrace device worn 
continuously on the wrist during the Screening Period (to establish a baseline) and for the 
first 6 months of the study.
6.2.1
Myasthenia Gravis – Activities of Daily Living
The MG-ADL is administered by a trained qualified healthcare professional (eg, physician, 
physician assistant, nurse practitioner, nurse) and provides a rapid assessment of the patient’s 
MG symptom severity. The MG-ADL should be administered by the same healthcare 
professional for a given patient throughout the study, if possible. 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, eyelid droop) are rated on a 4-point 
scale. The total score can range from 0 to 24. A higher score indicates greater symptom 
severity.
6.2.2
Quantitative Myasthenia Gravis
The QMG test is a standardized quantitative strength assessment comprising 13 components
and is administered by a trained qualified healthcare professional (eg, physician, physician 
assistant, nurse practitioner, nurse). The QMG should be administered by the same 
healthcare professional for a given patient throughout the study, if possible. The quantitative 
results of each strength component are mapped to the following 4-point scale:
•
0 = None
•
1 = Mild
•
2 = Moderate
•
3 = Severe
The total score can range from 0 to 39. A higher score indicates greater weakness.
6.2.3
Revised Myasthenia Gravis Quality of Life – 15
The MG-QoL15r is a 15-item, health-related quality of life measure designed to assess 
limitations related to living with MG (Burns et al, 2016). Responses to each item are rated 
by the patient, using a reflection period of “over the past few weeks” on the following 
3-point scale:
•
0 = Not at all
•
1 = Somewhat
•
2 = Very much
The total score can range from 0 to 30. A higher score indicates more limitation.


M281
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6.2.4
Myasthenia Gravis Foundation of America Post-Intervention Status
The MGFA-PIS is a measure of the patient’s MG status after treatment/intervention. For the 
purpose of this study, the selected elements of the MGFA-PIS as shown in Table 3 will be 
assessed.
Table 3.
Assessments Based on the Myasthenia Gravis Foundation of 
America Post-intervention Status
Assessment
Definition
Investigator assessment of 
Minimal Manifestations
The patient has no symptoms of functional limitations from MG, 
but has some weakness on examination of some muscles (Yes/No)
Change in Status derived from
QMG score

Improved = A decrease of ≥3 in the QMG score from baseline.

Unchanged = No change in the QMG score over baseline.

Worse = Any increase in the QMG score over baseline.

Died of MG = The patient died of MG or of complications of 
MG therapy
Investigator Assessment of 
Pharmacologic Remission (not
applicable if the treatment 
duration is <1 year)
The patient has had no symptoms or signs of MG for at least 
1 year and has received no therapy for MG, other than M281, 
during that time.  There is no weakness of any muscle on careful 
examination by someone skilled in the evaluation of 
neuromuscular disease.  Isolated weakness of eyelid closure is 
accepted.  
Note:  Baseline referred to the as the assessment obtained at the time of enrollment into the OLE study (Day 1).
6.2.5
Clinical Global Impression Scales
The CGI scales should be administered by the same clinician/physician for a given patient 
throughout the study, if possible.  
The CGI Severity (CGI-S) scale is the clinician/physician’s global assessment of the patient’s 
illness severity, and is rated by answering the following question on an 8-point scale:
CGI-S:  Considering your total clinical experience, how do you rate the current 
severity of the patient’s gMG?
•
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 the most extremely ill patients


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The CGI of Improvement (CGI-I) scale is the clinician/physician’s global assessment of the 
change in severity of the patient’s gMG since starting the OLE study, and is rated by 
answering the following question on an 8-point scale:
CGI-I:  Compared to the beginning of the MOM-M281-005 study, how would you 
rate the current severity of the patient’s gMG?
•
0 = Not performed
•
1 = Very much improved
•
2 = Much improved
•
3 = Minimally improved
•
4 = No change
•
5 = Minimally worse
•
6 = Much worse
•
7 = Very much worse
6.2.6
Patient-Reported Assessment of Fatigue 
Fatigue will be assessed by the patient using Neuro-QOL Fatigue.
6.2.7
Measurement of Physical Activity
The patient’s physical activity will be measured during the study via the Embrace device, 
which is a removable digital health device worn on the wrist.  The Embrace device is United 
States (US)-licensed for use in neurology.  It provides sleep, rest, and physical activity 
analysis.  Before using the Embrace device, patients will be trained on its use and procedures 
for electronic data transmission.
6.2.8
Myasthenia Gravis Foundation of America Clinical Classification
This clinical classification system was established by the MGFA for clinician/physician 
assessment of a patient’s MG severity (Jaretzki et al 2000).  The system comprises 5 classes 
of disease severity ranging from Class I (ocular muscle weakness only) to Class V (the 
patient is intubated).  Classes II through IV are each further divided into 2 subclasses based 
on which muscle groups are primarily affected. The MGFA classification should be assessed 
by the same clinician/physician for a given patient throughout the study, if possible.
6.3
Assessments of Pharmacodynamics and Biomarkers
Blood samples will be drawn for analysis of the following PD parameters: concentrations of 
total serum IgG; serum concentrations of IgA, IgM, and IgE; and titers of anti-AChR or
anti-MuSK autoantibodies, as applicable for each patient.  Blood samples will be collected at 
the visits specified in Table 1.


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Instructions for blood sample collection, processing, storage, and shipping are described in 
the Laboratory Manual.
6.4
Immunogenicity Assessments
Blood samples will be drawn to determine the presence/absence and titers of total and 
neutralizing anti-M281 antibodies, as applicable.
6.5
Removal of Patients from the Trial or Study Drug
The Investigator may withdraw a patient for any of the following reasons:
•
A protocol violation occurs,
•
A serious or intolerable AE occurs,
•
A clinically significant change in a laboratory parameter occurs, 
•
The sponsor or Investigator terminates the study, or
•
The patient requests to be discontinued from the study.
6.6
Stopping Criteria
Unless patient safety precludes doing so, the Medical Monitor should be consulted prior to 
stopping or interrupting the dosing schedule of M281.  The DSMB will be informed about 
any such changes, with the reason they were initiated, and any laboratory data that were a 
part of the discussions.  Any patient who meets the study drug stopping criteria will be 
withdrawn from the OLE study and followed for safety for 8 weeks after the last infusion of 
M281 or until the AE resolves/stabilizes, whichever is the longest.
6.6.1
Study Drug Stopping/Interruption Rules for Individual Patients
Treatment with M281 must be stopped, and the Medical Monitor notified, if any of the 
following events occur:
•
A patient becomes pregnant.
•
A patient develops a CTCAE Grade 4 infection.
•
A patient develops a CTCAE Grade 3 infection that is unresponsive or worsens while on 
anti-infective therapy. 
•
The patient requires initiation of a new MG therapy that was not already part of their 
standard of care.
•
Any circumstance or finding that, in the clinical judgment of the Investigator, would 
represent undue risk to the patient.


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Treatment with M281 may be interrupted after consultation with the Medical Monitor for the 
following events:
•
If a patient develops a CTCAE Grade 3 infection, the Investigator may elect to withhold 
M281 until the clinical scenario clarifies whether the infection is improving or getting 
worse.
•
If a patient develops 3+ pedal edema, ascites, or pleural or pericardial effusions, the 
Investigator will monitor the patient’s condition.  The decision to continue treatment or 
withhold additional doses of M281 will be made by the Investigator, in consultation with 
the Medical Monitor.
•
If a patient develops elevated CK levels, CK fractionation (CK-MB isoenzyme, CK-MM
isoenzyme) and troponin will be automatically tested by the laboratory. If the CK-MB or 
troponin level is elevated, the patient will be asked to go immediately to the emergency 
room for further evaluation. 
For any patient with elevated CK levels, additional assessments will be as follows:
-
CK elevations <5× ULN – further assessment can be made at the discretion of the 
Investigator.
-
CK elevations ≥5× ULN – the Investigator will call the patient to inquire about 
excessive exercise, trauma, and any muscle or cardiac-related symptoms. The CK 
will be repeated and if there is a decrease, no action will be taken. However, if the 
CK is of similar or higher level, the patient will be asked to return to the clinic, where 
further investigation will be done (in-depth clinical assessment, ECG, myoglobin in 
urine, repeat CK with fractionation and troponin level, ALT, and AST). The decision 
to continue treatment or withhold additional doses of study drug for the patient will 
be made by the Investigator, in consultation with the Medical Monitor.
6.6.2
Study Stopping Rules
•
In the event of the death of a study patient, treatment will be held in all patients pending 
evaluation by the Sponsor and DSMB recommendation, and until approval is received by 
the applicable regulatory authority(ies) to resume.
•
If a CTCAE Grade 4 event considered potentially related to treatment occurs, treatment 
will not be initiated in new patients (ie, enrollment in the extension study will be held), 
pending evaluation by the Sponsor and DSMB recommendation, and until approval is 
received by the applicable regulatory authority(ies) to resume.
•
If a CTCAE Grade 3 or higher infection considered potentially related to treatment 
occurs in three separate patients, treatment will be temporarily held in all patients, 
pending evaluation by the Sponsor and DSMB recommendation, and until approval is 
received by the applicable regulatory authority(ies) to resume.
NOTE: Deaths that are definitely not related to M281 (eg, accidents or other external causes) 
will not trigger study stopping rules.


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6.7
Other Study Procedures
Clinical Deterioration and Use of Rescue Therapy 
Study sites are required to evaluate a patient's report of clinical deterioration within 48 hours 
of the patient notifying the Investigator of the onset or worsening of symptoms of gMG.
Clinical deterioration is defined as any of the following: 
•
An MG crisis, defined as MG-related weakness sufficiently severe to necessitate 
intubation, or requires noninvasive ventilation to avoid intubation, or would be severe 
enough to delay extubation following surgery (Sanders et al, 2016), with the respiratory 
failure being due to weakness of respiratory muscles. Severe bulbar (oropharyngeal) 
muscle weakness may accompany the respiratory muscle weakness or may be the 
predominant feature in some patients. 
•
Significant symptomatic worsening on any MG-ADL item of 3 or more points, excluding 
double vision or eyelid droop (ie, talking, chewing, swallowing, breathing, upper and 
lower extremity weakness).
•
Any patient whom the Investigator believes will jeopardize his/her health if MG rescue 
therapy is not given (eg, emergent situations).
Depending on the severity of worsening of MG-related symptoms, rescue therapy 
(eg, glucocorticosteroids, IVIG, plasmapheresis) will be permitted, as per the clinical 
judgment of the Investigator. If a patient receives rescue therapy, the Investigator and 
Medical Monitor will jointly determine whether to continue treatment with M281 or 
withdraw the patient from the study.
6.8
Appropriateness of Measurements
The efficacy scales in this study have been shown to be reliable and valid for measuring
clinical status of patients with MG. The use of the wearable Embrace device for quantifying 
physical activity is being explored for potential use in later studies.  The routine safety 
assessments included in this study are standard for Phase 2 clinical studies in patients. The 
PD biomarkers being studied are relevant for patients with MG based on scientific literature 
and clinical practice.
Although preclinical studies and the first-in-human study with M281 did not indicate any 
central nervous system effects, the C-SSRS will be used in this study as an additional safety 
assessment based on the recommendation by the United States Food and Drug 
Administration (US FDA) for all clinical trials involving the development of drugs or 
biologics for neurologic indications to assess suicide risk. The US FDA has provided 
guidance to prospectively assess suicidal ideation and behavior in clinical trials to ensure that 
patients in clinical trials who are experiencing suicidal ideation and behavior are properly 
recognized and adequately treated and to ensure the collection of more timely and more 
complete data on suicidal ideation and behavior than have been collected in the past (US 
FDA, 2012).


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7
QUALITY CONTROL AND ASSURANCE
To assure quality and consistency of study data, procedures will only be carried out by the 
Principal Investigator or trained staff under the direction of the Principal Investigator. Study 
related procedures will be carried out in accordance with written materials (eg, study manual, 
Drug Handling Manual, eCRF completion guidelines, etc).
To ensure compliance with Good Clinical Practice (GCP) and all applicable regulatory 
requirements, the Sponsor or a Sponsor’s designee may conduct a quality assurance audit of
one or more study centers.
8
PLANNED STATISTICAL METHODS
8.1
General Considerations
Baseline is defined as the assessment obtained at the time of enrollment into the OLE study 
(Day 1) for all assessments except physical activity; baseline for physical activity will be 
established during OLE screening.
Continuous data will be summarized using descriptive statistics (number of patients, mean, 
standard deviation, median, minimum, and maximum) and, where appropriate, coefficient of 
variation (CV%) and graphic representation. Categorical data will be summarized by sample 
size and proportions. Graphs of actual values and changes over time may also be created as 
appropriate.
Further details on endpoints and analyses will be provided in the Statistical Analysis Plan 
(SAP).
8.2
Determination of Sample Size
The sample size for the OLE study will depend on the enrollment in the POC study, which 
plans for enrollment of approximately 60 patients with possible expansion up to 90 patients.
8.3
Analysis Populations
The Safety Population will include all patients who received any amount of M281 in the 
OLE study. 
The PD Population will include all patients in the Safety Population with at least one 
evaluable PD value in the OLE study.
8.4
Demographics and Baseline Characteristics
Descriptive summary statistics will be provided for demographic data and other baseline 
characteristics for the Safety Population. 


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8.5
Patient Disposition
Descriptive summary statistics will be provided for disposition data.  The number and 
percentage of patients who discontinued from the study, along with reasons for 
discontinuations, will be tabulated and described in listings.
8.6
Primary Endpoints
Safety and tolerability of M281 will be evaluated in terms of the incidence and severity of 
AEs (including SAEs, and AESIs), vital signs, physical examinations, clinical laboratory 
testing (including chemistry, hematology, coagulation, and urinalysis), ECGs, and the 
C-SSRS.
Analysis of all safety data will be performed using the Safety Population. Adverse events 
will be coded using a standardized medical dictionary (Medical Dictionary for Regulatory
Activities [MedDRA]). Analysis of AEs in terms of incidence by severity and by relatedness 
to study drug/device will also be provided. Concomitant medications will be coded by the 
World Health Organization Drug Dictionary Enhanced and will be summarized. Medical 
history (to include AEs from the POC study that are ongoing at OLE Day 1) will be listed by 
patient and coded using MedDRA and will be summarized. Descriptive statistics and a 
summary of abnormalities using shift tables will be presented for safety laboratory tests, vital 
signs, ECGs, and C-SSRS. For vital signs and ECGs, descriptive statistics at each visit and 
change from baseline to each subsequent visit will be provided. Physical examinations will 
be summarized as shift tables. Listings will also be provided for each type of safety data.
8.7
Secondary Endpoints
Descriptive summary statistics will be provided for each endpoint.
8.7.1
Efficacy Endpoints
•
Change from baseline in the total MG-ADL score over time
•
Number of patients with a 2-, 3-, 4-, 5-, 6-, 7-, or ≥8-point improvement in total 
MG-ADL score over time
•
Change from baseline in total QMG score over time
•
Change from baseline in total MG-QoL15r score over time
•
Change from baseline in CGI-S over time and CGI-I ratings
•
Change from baseline in MGFA classification over time
8.7.2
Immunogenicity Endpoint
•
The incidence of anti-drug antibody (ADA) and neutralizing ADA (nADA) 
seroconversion over time


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8.7.3
Pharmacodynamic Endpoint
•
Total serum IgG concentrations over time and change from baseline
8.8
Exploratory Endpoints
•
Change from baseline in Neuro-QOL Fatigue scores over time 
•
Quantitative level of physical activity over time and changes from baseline
•
Serum concentrations of IgA, IgM, and IgE over time and changes from baseline
•
Titers of serum anti-AChR or anti-MuSK antibodies over time and change from baseline
•
Changes in dose/regimen of standard-of-care concomitant medications for gMG over 
time
•
Number of patients who discontinued immunosuppressive medications over time
•
Need for rescue therapy over time
•
Number of patients with clinical deterioration
•
Number of episodes of myasthenic exacerbation requiring hospitalization/intensive care 
unit admission, and length of stay
•
Proportion of patients with minimal manifestations, and change in status per the 
MGFA-PIS over time, and proportion of patients with pharmacologic remission 
•
A model-based analysis of MG-ADL score change from Baseline in relationship to total 
serum IgG and anti-AChR titer (the latter is only for patients with anti-AChR antibodies)
Descriptive summary statistics will be provided for each endpoint, as applicable. 
8.9
Interim Analysis
No interim analysis is planned.
9
ADMINISTRATIVE CONSIDERATIONS
9.1
Investigators and Study Administrative Structure
A Coordinating Investigator for the study will be identified by the Sponsor or designee. 
Contact information for the Medical Monitor is as follows:  
, MD
Pharmaceutical Product 
Development, Inc.
Phone (US):
Fax (US):
Phone (EU):
PPD
PPD
PPD
PPD


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9.2
Institutional Review Board or Independent Ethics Committee 
Approval
The final study protocol, including the final version of the informed consent form (ICF), 
must be approved or given a favorable opinion in writing by the Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC). The Investigator must submit written approval 
from the IRB/IEC to the Sponsor before he or she can enroll any patient into the study. In 
addition, the IRB/IEC must approve any written materials used to recruit patients for the 
study.
The Investigator is responsible for informing the IRB/IEC of any amendment to the protocol 
in accordance with local requirements. Protocol amendments will be prepared and approved 
by the Sponsor or Sponsor’s designee and sent to the appropriate IRB/IEC for review and 
approval. Documentation of IRB/IEC approval must be forwarded to the Sponsor or 
designee before the procedures associated with the amendment commence.
The Investigator is also responsible for providing the IRB/IEC with reports of any reportable 
serious adverse drug reactions from any other study conducted with the study drug. The 
Sponsor will provide this information to the Investigator.
Progress reports and notifications of serious adverse drug reactions will be provided to the 
IRB/IEC according to local regulations and guidelines.
9.3
Ethical Conduct of the Study
The procedures set out in this protocol, pertaining to the conduct, evaluation, and 
documentation of this study, are designed to ensure that the Sponsor, its authorized 
representative and Investigators abide by GCP as described in International Council for 
Harmonisation (ICH) guideline E6(R2), and in 21 Code of Federal Regulations (CFR) 
parts 11, 50, 54, 56, and 312. Compliance with these regulations also constitutes compliance 
with the ethical principles described in the most recent revision of the Declaration of Helsinki 
(October 2013) that is recognized by the US FDA, the European Medicines Agency, and 
other regulatory agencies.
Investigators from countries who are not permitted to sign the US FDA Form 1572 must sign 
a statement of compliance with internationally recognized rules (ICH E6) governing conduct 
of clinical trials, that satisfies the US FDA regulation in 21 CFR 312 regarding foreign 
clinical studies not conducted under an Investigational New Drug application.
9.4
Patient Information and Consent
A template ICF will be provided by the Sponsor or designee. The ICF must be reviewed and 
approved by the IRB/IEC and must contain all elements required, as applicable, by national 
or local laws/regulations or requirements, US FDA regulations or regulations of the authority 
having jurisdiction over the location in which the study is being conducted, and institutional 
policies. If, during the approval process, the IRB/IEC makes any substantive changes to the 


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ICF, then this altered ICF must be provided to the Sponsor or designee for review before it is 
implemented.
All patients will be provided with the approved written ICF for this study, which will provide 
sufficient information for the patient to make an informed decision about participation in this 
study and to facilitate comprehension of the information. Each patient will be provided
adequate opportunity to ask questions and to consider whether to participate. The 
Investigator is responsible for obtaining the potential participant’s voluntary agreement to 
participate, and to continue providing information as the clinical trial progresses or as the 
patient or situation requires. 
Voluntary informed consent must be obtained from each eligible patient before any protocol-
defined procedures are performed. The patient’s signature on the ICF indicates his/her 
willingness to participate in this study. Other study personnel (eg, Principal Investigator, 
Study Nurse) will sign the ICF in accordance with local procedures.
9.5
Patient Confidentiality
The Investigator must assure that the privacy of the patients, including their identity and all 
personal medical information, will be maintained at all times. In the eCRFs and other 
documents (eg, laboratory reports) submitted to the Sponsor, patients will not be identified 
by name, but by a randomly assigned, patient identification number.
Personal medical information may be reviewed for the purpose of verifying data recorded in 
the eCRF by the study monitor, Sponsor or designee, IRB/IEC, and regulatory authorities. 
Personal medical information will always be treated as confidential and in compliance with 
applicable laws and regulations.
9.6
Study Monitoring
Clinical research associates (CRAs) representing the Sponsor will routinely visit the study 
site throughout the study. The Investigator will also ensure that the monitor, or other 
compliance or quality assurance reviewer, is given access to all study-related documents and 
study related facilities (eg, pharmacy, diagnostic laboratory, medical records, etc), and has 
adequate space to conduct the monitoring visit. In addition to the monitoring visits, frequent 
communications (email, letter, telephone, and/or fax) by the CRA will ensure that the 
investigation is conducted according to protocol design and regulatory requirements. The 
Investigator, or appropriate designee, will allocate adequate time for monitoring activities 
and follow-up correspondences. 
The CRA will review ICFs, eCRFs, and laboratory and other diagnostic reports, comparing 
them with source documents to verify adherence to the protocol, and to ensure complete, 
accurate, consistent, and timely collection of data. The CRA will record and report any 
protocol deviations not previously sent to the Sponsor. The CRA will also confirm that AEs 
and SAEs have been properly documented on eCRFs and confirm that any SAEs have been 
forwarded to the Sponsor and those SAEs that met criteria for reporting have been forwarded 
to the IRB/IEC. The Investigator will be asked to provide any missing information or to 


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clarify any discrepancies found by the CRA/monitor. It is expected that the Investigator will 
be present for a concluding review at the end of each monitoring visit.
9.7
Case Report Forms and Study Records
Wherever possible, all data will be entered directly into the eCRFs. In some cases, source 
documents will be used. The eCRF Completion Guideline will identify any data to be 
recorded directly in the eCRF (ie, no prior written or electronic record of data), and which 
data should be considered source data. 
Source documents are all original documents, data, and records that pertain to a study patient
and can be either electronic or physical in origin. Examples of source documents are: 
hospital records, clinical and office charts, laboratory notes, memoranda, patient diaries or 
evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies or transcriptions certified after verification as being accurate and 
complete, microfiches, photographic negatives, microfilm or magnetic media, X-rays, patient
files and records kept at the pharmacy, at the laboratories and at technical departments 
involved in the study. When source document data are shared with originating files 
(eg, hospital records or other clinic charts), photocopies of specific components of these data 
can be included as source document provided that these copies are signed and dated by 
appropriate research site personnel.
Source data must be legible and written concurrently with the patient visit, and no data may 
be obliterated. If the source document contains a patient’s address and phone number, it 
must be obliterated before it is included as a study document and the patient’s name will be 
obliterated except for the first letters of the first, middle (if present), and last names. The 
completed eCRF must be reviewed and approved by an authorized Investigator before it can 
be considered final.
9.8
Data Monitoring Committee
An independent DSMB will be responsible for safety oversight of the patients in the study. 
The DSMB will meet on a regular basis and review all available data (AEs, SAEs, AESIs, 
and laboratory results); ad hoc meetings will be scheduled as needed. The specific 
responsibilities of the DSMB will be outlined in a DSMB charter.
9.9
Protocol Violations/Deviations
Except for a change intended to eliminate an immediate hazard to a participant, the protocol 
shall be conducted as described without any changes or deviations. Any change must be 
reported immediately to the Sponsor and to the IRB/IEC, as required by their regulations.
9.10
Access to Source Documentation
The Investigator will permit study related monitoring, audits, and inspections by the 
IRB/IEC, the Sponsor, government regulatory bodies, and compliance and quality assurance 
groups of all study related documents (eg, source documents, regulatory documents, data 


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collection instruments, study data, etc). All authorized personnel, including health authority 
inspector(s), Sponsor and designees, CRAs, Medical Monitor(s), and auditor(s) will be given 
direct access to source data and documentation (eg, medical records, laboratory results, etc) 
for source data verification, provided that patient confidentiality is maintained in accordance 
with local requirements.
9.11
Data Generation and Analysis
Data management and control processes specific to the study will be described in the data 
management plan. Details on the study’s analysis methods will be provided in the SAP, 
which will be developed prior to study completion and database lock.
9.12
Retention of Data
The Principal Investigator shall retain all study-related documentation, including source data, 
source documents, eCRFs, laboratory and diagnostic results, protocol and amendments, study 
drug accountability records, regulatory documentation and correspondence, ICFs, patient 
identification lists, and correspondence. These records should be retained in the format they 
were originally obtained (eg, electronic or paper) unless a quality controlled and authorized 
complete electronic version is created for long-term storage at the end of the study. The 
Sponsor will provide an electronic copy of the final eCRF for each study patient after study 
closeout.
The Investigator must retain an organized file with all study-related documentation that is 
suitable for inspection by the Sponsor and representatives of Regulatory Authorities.
The Investigator must retain essential documents until notified by the Sponsor, and at least 
for 15 years after study completion. 
Documents should be stored in such a way that they can be accessed for data retrieval at a 
later date. Consideration should be given to security and environmental risks.
Documentation retention will generally comply with Section 8 of the ICH consolidated 
guideline on GCP, Essential Documents for the Conduct of a Clinical Trial.
No study document will be destroyed without prior written agreement between the Sponsor 
and the Investigator or the Research Site should the Investigator leave the institution. Should 
the Investigator wish to assign the study records to another party or move them to another 
location, written agreement must be obtained from the Sponsor prior to any actions being 
taken.
9.13
Publication and Disclosure Policy
This trial will be registered at ClinicalTrials.gov and after study completion, results 
information from this trial will be posted to ClinicalTrials.gov. In addition, every attempt 
will be made to publish results in peer-reviewed journals. Publication of the results by the 


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Investigator will be subject to mutual written agreement between the Investigator and the 
Sponsor or determined by the publication/steering committee.


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myasthenia gravis. Management call; December 11, 2017. Available from:
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24 June 2019.
Blumberg L, Humphries JE, Lasseter KC, Blumberg RS. A humanized IgG4 monoclonal 
antibody that disrupts the interaction of FcRn and IgG for the treatment of IgG mediated 
autoimmune diseases. Poster presented at American Society of Hematology (ASH) 
59th Annual Meeting and Exposition; 2017 December 9-12; Atlanta, Georgia.
Burns TM, Sadjadi R, Utsugisawa K, Gwathmey KG, Joshi A, Jones S, et al. International 
clinimetric evaluation of the MG-QOL15, resulting in slight revision and subsequent 
validation of the MG-QOL15r. Muscle Nerve. 2016;54:1015-22.
Gilhus NE. Myasthenia gravis. N Engl J Med. 2016;375(26):2570-81.
Gilhus NE, Skeie GO, Romi F, Lazaridis K, Zisimopoulou P, Tzartos S. Myasthenia gravis –
autoantibody characteristics and their implications for therapy. Nat Rev Neurol. 
2016;12(5):259-68.
Hansen JS, Danielsen DH, Somnier FE, Frøslev T, Jakobsen J, Johnsen SP, et al. Mortality in 
myasthenia gravis: A nationwide population-based follow-up study in Denmark. Muscle 
Nerve. 2016;53(1):73-7.
Howard JF Jr, Barohn RJ, Cutter GR, Freimer M, Juel VC, Mozaffar T, et al. A randomized, 
double blind, placebo controlled phase II study of eculizumab in patients with refractory 
generalized myasthenia gravis. Muscle Nerve. 2013;48(1):76-84.
Howard JF Jr, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I, et al. Safety and 
efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised 
myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, 
multicentre study. Lancet Neurol. 2017;16(12):976-86.
Jaretzki A, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, Sanders DB. 
Myasthenia gravis: recommendations for clinical research standards. Task Force of the 
Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. 
Neurology. 2000;55:16-23.
Kiessling P, Lledo-Garcia R, Watanabe S, Langdon G, Tran D, Bari M, et al. The FcRn 
inhibitor rozanolixizumab reduces human serum IgG concentration: A randomized phase 1 
study. Sci Transl Med. 2017;9(419). Erratum in: Sci Transl Med. 2017;9(419).
Mantegazza R, Antozzi C. When myasthenia gravis is deemed refractory: clinical signposts 
and treatment strategies. Ther Adv Neurol Disord. 2018;11:1756285617749134. Erratum in: 
Ther Adv Neurol Disord 2018;11:1756286418765591.


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Clinical Trial Protocol: MOM-M281-005
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Meriggioli MN, Sanders DB. Muscle autoantibodies in myasthenia gravis: beyond diagnosis? 
Expert Rev Clin Immunol. 2012;8(5):427-38.
Nixon AE, Chen J, Sexton DJ, Muruganandam A, Bitonti AJ, et al. Fully human monoclonal 
antibody inhibitors of the neonatal fc receptor reduce circulating IgG in non-human primates. 
Front Immunol. 2015;6:176. doi: 10.3389/fimmu.2015.00176. eCollection 2015.
Robak T, Jarque I, Musteata V, Kiessling P, Massow U, Higginson J, et al. Phase II, 
multiple-dose study of anti-FcRn antibody, rozanolixizumab (UCB7665), in patients with 
primary immune thrombocytopenia: Interim analysis. Blood. 2017;Dec;130(Suppl 1):15.
Sanders DB, Wolfe GI, Benatar M, Evoli A, Gilhus NE, Illa I, et al. International consensus 
guidance for management of myasthenia gravis: executive summary. Neurology. 
2016;87:419-25.
Sathasivam S. Diagnosis and management of myasthenia gravis. Progress in Neurology and 
Psychiatry. 2014. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/pnp.315.  
Accessed 21 May 2018.
Silvestri N, Wolfe G. Treatment-refractory myasthenia gravis. J Clin Neuromuscul Dis. 
2014;15(4):167-78.
US FDA. Guidance for Industry. Suicidal ideation and behavior: Prospective assessment of 
occurrence in clinical trials, Draft Guidance. August 2012. Revision 1. Available from: 
https://www.fda.gov/downloads/Drugs/Guidances/UCM225130.pdf. Accessed on 
11 June 2018.
Zhang B, Tzartos JS, Belimezi M, Ragheb S, Bealmear B, Lewis RA, et al. Autoantibodies to 
lipoprotein-related protein 4 in patients with double-seronegative myasthenia gravis. Arch 
Neurol. 2012;69(4):445-51.


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Appendix 2
Investigator’s Signature
Study Title:
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 
Study Number:
MOM-M281-005
Amendment 2 Date:
01 August 2019
I have read the protocol described above. I agree to conduct the study as described in the 
protocol. I also agree to conduct this study in compliance with Good Clinical Practice (GCP) 
and all applicable national and local laws and regulations, as well as with the requirements of 
the appropriate Institutional Review Board or Independent Ethics Committee (IRB/IEC) and 
any other institutional requirements. These are stated in “Guidance for Good Clinical 
Practice,” International Council for Harmonisation (ICH) guideline E6(R2) of Technical 
Requirements for Registration of Pharmaceuticals for Human Use, the Declaration of 
Helsinki, and any other applicable regulatory requirements. No changes will be made to the 
study protocol without prior written approval of the Sponsor and the IRB/IEC.
Signed:
Date:
Printed name: ____________________________________
Title:
____________________________________
Affiliation:
____________________________________

SAP_001.pdf: 
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved, Date: 7 July 2021
Janssen Research & Development
Statistical Analysis Plan
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
Protocol MOM-M281-005; Phase 2
JNJ-80202135; M281  (nipocalimab)
Status:
Approved
Date:
7 July 2021
Prepared by:
Janssen Research & Development, LLC
Document No.: EDMS-RIM-395154
Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise.
NCT03896295


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TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
VERSION HISTORY..................................................................................................................................... 4
1.
INTRODUCTION.................................................................................................................................. 5
1.1.
Objectives and Endpoints ................................................................................................................ 5
1.2.
Study Design.................................................................................................................................... 5
2.
STATISTICAL HYPOTHESES............................................................................................................ 6
3.
SAMPLE SIZE DETERMINATION...................................................................................................... 6
4.
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS....................................................................... 6
5.
STATISTICAL ANALYSES................................................................................................................. 6
5.1.
General Considerations ................................................................................................................... 6
5.2.
Participant Dispositions.................................................................................................................... 7
5.3.
Primary Endpoint(s) Analysis........................................................................................................... 7
5.4.
Secondary Endpoint(s) Analysis ...................................................................................................... 7
5.4.1.
Definition of Endpoint(s) ............................................................................................................... 7
5.4.1.1.
Myasthenia Gravis – Activities of Daily Living (MG-ADL) ......................................................... 7
5.4.1.2.
Quantitative Myasthenia Gravis (QMG) Test ............................................................................ 8
5.4.1.3.
Revised Myasthenia Gravis Quality of Life 15 (MG-QoL-15r)................................................... 8
5.4.1.4.
Clinical Global Impression of Severity (CGI-S) ......................................................................... 8
5.4.1.5.
Clinical Global Impression of Improvement (CGI-I)................................................................... 9
5.4.1.6.
Myasthenia Gravis Foundation of American (MGFA) Classification ......................................... 9
5.4.2.
Analysis Methods.......................................................................................................................... 9
5.5.
Tertiary/Exploratory Endpoint(s) Analysis........................................................................................ 9
5.5.1.
Definition of Endpoint(s) ............................................................................................................... 9
5.5.1.1.
Neuro-QoL Fatigue.................................................................................................................... 9
5.5.1.2.
Myasthenia Gravis Foundation of America Post-intervention Status (MGFA-PIS)................. 10
5.5.1.3.
Measurement of Physical Activity............................................................................................ 10
5.5.2.
Analysis Methods........................................................................................................................ 10
5.6.
Safety Analyses ............................................................................................................................. 10
5.6.1.
Extent of Exposure ..................................................................................................................... 10
5.6.2.
Adverse Events........................................................................................................................... 11
5.6.3.
Additional Safety Assessments .................................................................................................. 12
5.6.3.1.
Clinical Laboratory Tests......................................................................................................... 12
5.6.3.2.
Vital Signs and Physical Examination Findings....................................................................... 13
5.6.3.3.
Electrocardiogram ................................................................................................................... 13
5.6.3.4.
Columbia Suicide Severity Rating Scale (C-SSRS)................................................................ 15
5.7.
Other Analyses............................................................................................................................... 16
5.7.1.
Immunogenicity........................................................................................................................... 16
5.7.2.
Pharmacodynamics .................................................................................................................... 17
5.7.2.1.
Immunoglobulin G ................................................................................................................... 17
5.7.2.2.
Immunoglobulin A, M, and E ................................................................................................... 17
5.7.2.3.
Anti-AChR and Anti-MuSK Autoantibodies ............................................................................. 17
5.7.3.
Myasthenia Gravis Medication Usage........................................................................................ 17
5.7.4.
Definition of Subgroups .............................................................................................................. 18
5.8.
Interim Analyses............................................................................................................................. 18
5.8.1.
Data Monitoring Committee (DMC) or Other Review Board ...................................................... 18
6.
SUPPORTING DOCUMENTATION .................................................................................................. 19
6.1.
Appendix 1 List of Abbreviations.................................................................................................... 19
6.2.
Appendix 2 Changes to Protocol-Planned Analyses ..................................................................... 20


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6.3.
Appendix 3 Demographics and Baseline Characteristics.............................................................. 21
6.4.
Appendix 4 Protocol Deviations ..................................................................................................... 22
6.5.
Appendix 5 Prior and Concomitant Medications............................................................................ 23
6.6.
Appendix 6 Medical History ........................................................................................................... 24
6.7.
Appendix 7 Intervention Compliance ............................................................................................. 25
6.8.
Appendix 8 Adverse Events of Special Interest............................................................................. 26
6.9.
Appendix 9 Medications of Special Interest................................................................................... 27
6.10.
Appendix 10 Laboratory Toxicity Grading...................................................................................... 28
6.11.
Appendix 11 Myasthenia Gravis – Activities of Daily Living .......................................................... 29
6.12.
Appendix 12 Quantitative Myasthenia Gravis................................................................................ 30
6.13.
Appendix 13 Revised Myasthenia Gravis Quality of Life............................................................... 31
6.14.
Appendix 14 Myasthenia Gravis Foundation of America Classification ........................................ 32
7.
REFERENCES................................................................................................................................... 33


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VERSION HISTORY
Table 1 – SAP Version History Summary
SAP Version
Approval Date
Change
Rationale
1
7 July 2021
Not Applicable
Initial release


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1.
INTRODUCTION
This document summarizes the planned analyses for study MOM-M281-005 which was an open-
label extension study of the randomized, double-blind study MOM-M281-004.
Because of the coronavirus disease 2019 (COVID-19) pandemic, all study drug administrations in 
both the 004 and 005 studies were stopped as of 17 April 2020 and the 005 study was subsequently 
terminated. Because of the termination, only 37 of a possible 65 patients who completed the 004 
study entered the 005 study. The planned treatment duration for a patient was to be approximately 
1 year, but because of the termination of dosing, no patient had more than 9 months of study drug 
exposure and approximately 50% of patients had <3 months of study drug exposure. Given the 
reduced number of patients enrolled and reduced duration of exposure, limited summaries of 
efficacy results are planned for this study.
1.1.
Objectives and Endpoints
Primary objective

To evaluate the long-term safety and tolerability of nipocalimab in generalized myasthenia 
gravis (gMG).
Secondary objectives

To evaluate the long-term efficacy of nipocalimab

To evaluate the long-term immunogenicity of nipocalimab

To evaluate the long-term pharmacodynamic (PD) activity of nipocalimab
Exploratory objectives

To evaluate the effect of nipocalimab on fatigue and physical activity

To evaluate the long-term PD activity of nipocalimab on serum concentrations of 
immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin E (IgE)

To evaluate the long-term PD activity of nipocalimab on serum titers of pathogenic 
autoantibodies associated with gMG (anti-AChR and/or anti-MuSK)

To evaluate the long-term response to treatment with nipocalimab in relation to other 
treatment(s) and/or clinical studies

To evaluate the potential relationship between change in the Myasthenia Gravis – Activities 
of Daily Living (MG-ADL) total score and change in anti-AChR antibody levels 
1.2.
Study Design
MOM-M281-005 is a long-term, open-label extension study of patients who completed the MOM-
M281-004 study without discontinuing study drug during the 004 study for reasons other than the 
need for rescue therapy as specified in the 004 protocol, and who completed the protocol-specified
8 weeks of follow-up after the last dose of study drug in the 004 study.


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Eligibility for the 005 study was assessed and enrollment into the 005 study occurred (at the 
earliest) after completion of assessments at the patient’s last follow-up visit in the 004 study (the 
Day 113 visit of the 004 study). Thus, the Day 113 visit of the 004 study can be Day 1 for the 005
study; patients who meet the eligibility criteria for the 005 study could receive their first open-
label infusion of nipocalimab on the same day.
Patients enrolled in the 005 study initially received nipocalimab 30 mg/kg every 4 weeks (q4w) 
by intravenous (IV) infusion. This dose was one of the doses evaluated in the 004 study. After at 
least 8 weeks of treatment on a stable dose of nipocalimab, the dose and/or dosing frequency of 
nipocalimab could have been individually adjusted for a given patient at the discretion of the 
investigator and previous consultation with the medical monitor, based on the patient’s tolerability 
to nipocalimab and the patient’s MG status. The individually adjusted dose could not exceed 60 
mg/kg and the dosing frequency could not exceed every 2 weeks (q2w).
2.
STATISTICAL HYPOTHESES
No statistical hypothesis is specified for this study. The objective of the study is to estimate the 
frequency of adverse events, laboratory abnormalities, and vital signs abnormalities with long term 
exposure to nipocalimab.
3.
SAMPLE SIZE DETERMINATION
The sample size of the 005 study depended on the enrollment in the 004 study. In the 004 study, 
68 patients were randomized and given at least one administration of study drug and 65 patients 
completed the Day 113 visit.
4.
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS
Analysis Sets
Description
Enrolled
All patients who sign the ICF
Full Analysis Set (FAS)
The full analysis set (FAS) includes all patients who 
received at least 1 dose of study drug.
Safety
The safety analysis set includes all patients who 
received at least 1 dose of study drug.
Immunogenicity Analysis Set
The immunogenicity analysis set is defined as all 
patients who received at least 1 dose of study drug and 
had 1 or more samples obtained after their first study 
drug administration for the assessment of antibodies to 
nipocalimab.
5.
STATISTICAL ANALYSES
5.1.
General Considerations
The reference start date for the calculation of study day is defined as the date of the first infusion 
in the 005 study. Study day of a visit or start/end date of an event is defined as the visit/start/end 
date – reference start date + 1.


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The Day 113 visit of the 004 study is the baseline visit of the 005 study. For assessments not 
collected at the Day 113 visit of the 004 study or collected at both the Day 113 visit of the 004 
study and the Day 1 visit of the 005 study, the Day 1 visit of the 005 study will serve as baseline.
Analysis visit windows are not defined. Results collected per visit will be summarized by nominal 
visit.
Results will be summarized by 2 subject groups, 1 for patients who were randomized to the placebo 
group in the 004 study and 1 for patients who were randomized to a nipocalimab group in the 004 
study:

Placebo-Nipocalimab

Nipocalimab-Nipocalimab
All tables will also include an “All Nipocalimab” column, which combines the “Placebo-
Nipocalimab” and “Nipocalimab-Nipocalimab” subject groups.
5.2.
Participant Dispositions
Screened patients and reason for screen failures will be summarized overall.
The number of patients in the following disposition categories will be summarized throughout the 
study by subject group and overall:

Patients who received study drug

Patients who completed the study

Patients who discontinued study drug

Reasons for discontinuation of study drug

Patients who terminated study prematurely

Reasons for termination of study
5.3.
Primary Endpoint(s) Analysis
The primary endpoints for this open-label extension study are safety- and tolerability-related. See 
Section 5.6 for definitions.
5.4.
Secondary Endpoint(s) Analysis
Secondary endpoints will be summarized using the full analysis set.
5.4.1.
Definition of Endpoint(s)
5.4.1.1.
Myasthenia Gravis – Activities of Daily Living (MG-ADL)
The MG-ADL is an 8-item questionnaire administered by a qualified healthcare professional that 
assesses the severity of the impairment of 8 activities (talking, chewing, swallowing, breathing, 
impairment of ability to brush teeth or comb hair, impairment of ability to arise from a chair, 


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double vision, and eyelid droop) on a 4-point scale (0 = normal, 1, 2, or 3 = severe) (Wolfe 1999). 
See Appendix 11 for definitions of each score for each function. The MG-ADL is assessed at 
Weeks 4, 8, and 12, then every 12 weeks, at the end of treatment visit, and at the end of study visit.
The MG-ADL total score is defined as the sum of the 8 individual items (range: 0 to 24). The total 
score is missing if any item is missing. Higher scores indicate greater impairment.
Change from baseline in MG-ADL total score will be calculated for each post-baseline visit.
5.4.1.2.
Quantitative Myasthenia Gravis (QMG) Test
The QMG test is a standardized quantitative strength assessment with 13 components (Barohn 
1998). It is administered by a trained qualified healthcare professional. For each item a raw score 
is measured, for example, the number of seconds before double vision occurs on lateral gaze or 
the right-hand grip strength in kilograms. The raw score is converted to a 4-point scale score (0 = 
none, 1 = mild, 2 = moderate, and 3 = severe). See Appendix 12 for the definition of each item and 
how the raw score is converted to a scale score. The QMG is assessed at Weeks 4, 8, and 12, and
then every 12 weeks, at the end of treatment visit, and at the end of study visit.
The QMG total score is defined as the sum of the 13 individual item scale scores (range: 0 to 39). 
The total score is missing if any item is missing. Higher scores indicate greater impairment.
Change from baseline in QMG total score will be calculated for each post-baseline visit.
5.4.1.3.
Revised Myasthenia Gravis Quality of Life 15 (MG-QoL-15r)
The MG-QoL-15r is a 15-item, health-related quality of life measure designed to assess limitations 
related to living with MG. Responses to each item are rated by the patient, using a reflection period 
of “over the past few weeks” on a 3-point scale (0 = not at all, 1 = somewhat, and 2 = very much). 
See Appendix 13 for a list of the 15 items. The MG-QoL-15r is assessed at Weeks 4, 8, and 12, 
then every 12 weeks, at the end of treatment visit, and at the end of study visit.
The MG-QoL-15r total score is defined as the sum of the 15 individual items (range: 0 – 30). The 
total score is missing if any item is missing. Higher scores indicate more limitation.
Change from baseline in MG-QoL-15r total score will be calculated for each post-baseline visit.
5.4.1.4.
Clinical Global Impression of Severity (CGI-S)
The CGI-S scale is the clinician/physician’s global assessment of a patient’s illness severity in 
response to the question “Considering your total clinical experience, how do you rate the current 
severity of the patient’s MG?”. The rating is given on a 7-point scale with higher scores indicating 
greater severity (1 = Normal, not at all ill; 2 = Borderline illness; 3 = Mildly ill; 4 = Moderately 
ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill patients). If the assessment 
was not performed, a score of 0 is assigned; 0 scores will be treated as missing. The CGI-S is 
assessed at Day 1; Weeks 4, 8, and 12; then every 12 weeks, at the end of treatment visit, and at 
the end of study visit.


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Change from baseline in CGI-S will be calculated for each post-baseline visit.
5.4.1.5.
Clinical Global Impression of Improvement (CGI-I)
The CGI-I scale is the clinician/physician’s global assessment of the change in severity of the 
patient’s gMG since starting the OLE study in response to the question “Compared to the 
beginning of the MOM-M281-005 study, how would you rate the current severity of the patient’s 
MG?”. 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). If the assessment was not performed, 
a score of 0 is assigned; 0 scores will be treated as missing. The CGI-I is assessed at Weeks 4, 8, 
and 12, then every 12 weeks, at the end of treatment visit, and at the end of study visit.
5.4.1.6.
Myasthenia Gravis Foundation of American (MGFA) Classification
The MGFA system classifies a patient’s MG severity into one of 5 classifications of increasing 
severity from Class I (ocular muscle weakness only) to Class V (the patient is intubated) (Jaretzki 
2000). Classes II through IV are each further divided into 2 subclasses (‘a’ or ‘b’) based on which 
muscle groups are primarily affected (see Appendix 14). The MGFA classification is assessed at 
Weeks 8 and 12, then every 24 weeks, and at the end of treatment visit.
5.4.2.
Analysis Methods
Descriptive statistics (mean, standard deviation, median, minimum, maximum) of values and 
changes from baseline at each visit will be provided for the MG-ADL total score, QMG total score, 
MG-QoL-15r total score, and CGI-S by subject group and overall. Plots of mean (±SE) values and 
changes over time for each endpoint will also be provided.
The distribution of the CGI-S ratings, CGI-I ratings, and MGFA classification will be summarized 
with the number and percentage of patients with each value at each visit. The shift from baseline 
MGFA classification to the classification at each post-baseline visit will also be summarized.
The number and percentage of patients with a 2-, 3-, 4-, 5-, 6-, 7-, or ≥8-point improvement in 
MG-ADL total score will be summarized at each post-baseline visit. In addition, the number and 
percentage of patients with an MG-ADL total score of 0 or 1 will be summarized at each post-
baseline visit.
5.5.
Tertiary/Exploratory Endpoint(s) Analysis
Tertiary/exploratory endpoints will be summarized using the full analysis set.
5.5.1.
Definition of Endpoint(s)
5.5.1.1.
Neuro-QoL Fatigue
The Neuro-QoL fatigue version 1.0 is a 19-item questionnaire developed and validated for use in 
common neurological conditions which assess patient-reported fatigue and associated impact on 
physical, mental, and social activities during the past 7 days. Each item is graded on a 5-point scale 
(1 = never, 2 = rarely, 3 = sometimes, 4 = often, 5 = always). The Neuro-QoL fatigue is assessed 


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at Day 1; Weeks 4, 8, and 12; then every 12 weeks, at the end of treatment visit, and at the end of 
study visit.
The Neuro-QoL fatigue total score is defined as the sum of the 19 individual items (range: 19 –
95). The total score is missing if any item is missing. Higher scores indicate more fatigue.
Change from baseline in Neuro-QoL fatigue total score will be calculated for each post-baseline 
visit.
5.5.1.2.
Myasthenia Gravis Foundation of America Post-intervention Status 
(MGFA-PIS)
The MGFA-PIS is a measure of the patient’s MG status after treatment/intervention. In this study, 
the investigator assessment of minimal manifestations is collected in which the investigator 
indicates (yes or no) if “[t]he patient has no symptoms of functional limitations from MG but has 
some weakness on examination of some muscles.” The assessment is collected every 12 weeks, at 
the end of treatment visit, and at the end of study visit.
5.5.1.3.
Measurement of Physical Activity
The patient’s physical activity was measured during the study via a removable digital health device 
(Embrace) worn on the wrist. The Embrace device is licensed in the US for use in neurology. It 
provides sleep, rest, and physical activity analysis.
5.5.2.
Analysis Methods
Descriptive statistics (mean, standard deviation, median, minimum, maximum) of values and 
changes from baseline at each visit will be provided for the Neuro-QoL fatigue total score by 
subject group and overall. Plots of mean (±SE) values and changes over time will also be provided.
MGFA-PIS result will be provided in a listing.
Results from the Embrace device were deemed to be of little utility given the study termination 
and will not be summarized or listed.
5.6.
Safety Analyses
All safety analyses will be based on the safety analysis set.
For all continuous safety variables, descriptive statistics by subject group will include the N, mean, 
standard deviation, median, minimum, and maximum. Categorical variables will be summarized 
by subject group using frequency counts and percentages.
5.6.1.
Extent of Exposure
The number and percentage of patients who receive study drug will be summarized. The number 
and percentage of patients at each dose level and dose frequency will also be summarized by visit.


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Descriptive statistics for duration of study drug (N, mean, SD, median, and range (minimum, 
maximum)) will be provided. Patient-years of intervention are calculated as days of 
intervention/365.25. Patient-years will be presented by subject group.
Duration of intervention will be summarized in the following duration categories:

<3 months (<90 days)

≥3 to <6 months (≥90 to <180 days)

≥6 to <9 months (≥180 to <270 days)
Duration of intervention is defined as (date of last infusion – date of first infusion) + 1.
Descriptive statistics will be presented for the following parameters:

Number of infusions

Cumulative total dose. Cumulative total dose is the total dose in mg a patient received over 
all infusions in the study. The dose in mg for a given infusion is the dose level administered 
in mg/kg multiplied by the patient’s weight.
A listing of patients with an infusion interruption or change in infusion flow rate will be provided.
5.6.2.
Adverse Events
The verbatim terms used in the CRF by investigators to identify adverse events will be coded using 
the Medical Dictionary for Regulatory Activities (MedDRA). Any AE occurring at or after the 
initial infusion of study drug through the day of last infusion plus 56 days is considered to be 
treatment emergent. If the event occurs on the day of the initial infusion of study drug, and either 
event time or time of administration are missing, then the event will be assumed to be treatment 
emergent. If the event date is recorded as partial or completely missing, then the event will be 
considered to be treatment emergent unless it is known to be prior to the first administration of 
study intervention based on partial onset date or resolution date. All reported treatment-emergent
adverse events will be included in the analysis.  For each adverse event, the number and percentage 
of patients who experience at least 1 occurrence of the given event will be summarized by subject
group.
Summary tables will be provided for treatment-emergent adverse events:

AEs

AEs by NCI-CTCAE toxicity grade

AEs with CTCAE toxicity grade ≥3

AEs by relationship to study drug
Five patients had 5 SAEs in the study and no patient discontinued study drug because of an adverse 
event. One patient had an adverse event with onset after the sponsor discontinued all treatment 
because of the Covid-19 pandemic and that adverse event ultimately had a fatal outcome. Summary 
tables will not be provided for these events. Listings will be provided for patients who:


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
Had SAEs

Had AEs with a fatal outcome

Had onset or worsening of symptoms of gMG (clinical deterioration). These include patients 
with AEs coded to the preferred term “myasthenia gravis”.
Incidence of other treatment-emergent adverse events of clinical or special interest will be 
summarized. See Appendix 8 for the list of adverse events in each category. Listings of patients 
with adverse events of clinical or special interest will be provided.
5.6.3.
Additional Safety Assessments
5.6.3.1.
Clinical Laboratory Tests
Clinical laboratory tests will be displayed for the patients included in the safety analysis set.
Descriptive statistics will be presented for all chemistry, hematology, and urinalysis (pH and 
specific gravity) laboratory tests at scheduled time points.
Change from baseline to each scheduled time point will be summarized for chemistry, hematology, 
and urinalysis (pH and specific gravity) tests and displayed by subject group. Percent change from 
baseline to each scheduled time point will also be summarized for albumin and total cholesterol
and displayed by subject group. Boxplots and plots of mean (±SE) value, change, and percent 
change from baseline to each scheduled time point will be provided for albumin and total 
cholesterol. Plots of mean (±SE) value and change to each scheduled time point will be provided 
for ALT (alanine aminotransferase), AST (aspartate aminotransferase), and total bilirubin.
Abnormality criteria based on normal ranges will be applied to baseline and postbaseline values.
The number and percentage of patients with a maximum post-baseline value greater than the upper 
limit of normal (ULN) and the number and percentage of patients with a minimum post-baseline 
value less than the lower limit of normal (LLN) will be summarized. Shift tables will be provided 
summarizing the shift in laboratory values from baseline to the maximum post-baseline value and 
to the minimum post-baseline value with respect to the abnormality criteria (low, normal, high).
The number and percentage of patients with a markedly abnormal laboratory post-baseline value
will be presented by subject group. A listing of markedly abnormal laboratory values will be 
provided.
The markedly abnormal laboratory findings to be reported for albumin and liver function-related 
tests are described below:

Albumin <20 g/L

ALT ≥3xULN, ≥5xULN, ≥10xULN, and ≥20xULN

AST ≥3xULN, ≥5xULN, ≥10xULN, and ≥20xULN

ALP (alkaline phosphatase) ≥3xULN, ≥5xULN, ≥10xULN, and ≥20xULN

Total bilirubin ≥2xULN


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Markedly abnormal criteria for additional selected tests are provided in Appendix 10.
A listing of patients meeting the biochemical Hy’s Law criteria will be provided:

ALT or AST ≥3xULN, and

Either total bilirubin ≥2xULN or INR>1.5
5.6.3.2.
Vital Signs and Physical Examination Findings
Continuous vital sign parameters including temperature, weight, pulse, blood pressure (systolic 
and diastolic), and Body Mass Index (BMI) will be summarized at each assessment time point. 
BMI will be calculated as weight (kg)/(height (m))2 at each time point that body weight is 
measured. The height measurement collected at screening will be used in the calculation. Change 
from baseline will be summarized at each assessment time point. Descriptive statistics (mean, 
standard deviation, median, minimum, and maximum) will be presented.
Incidence of treatment-emergent markedly abnormal vital signs during intervention, as defined in 
Table 2, will be summarized for patients who had a baseline assessment and at least 1 postbaseline 
assessment for that vital sign. A listing of patients with treatment-emergent markedly abnormal
vital signs will be presented.
Pulse, blood pressure, and temperature were measured in the recumbent position prior to every 
infusion and at selected time points after the first 2 infusions (15 minutes, 30 minutes, 1 hour, 2 
hours or at end of infusion, 4 hours or at least 2 hours after end of infusion). Descriptive statistics 
of values and change from baseline will be summarized for pre-infusion time points only. 
Identification of clinically important vital signs will consider both pre- and post-infusion time 
points.
Table 2: Markedly Abnormal Vital Signs
Vital Sign
Criteria
Pulse
≥120 bpm and with ≥15 bpm increase from baseline
≤50 bpm and with ≥15 bpm decrease from baseline
Systolic blood pressure
≥160 mmHg and with ≥20 mmHg increase from baseline
≤90 mmHg and with ≥20 mmHg decrease from baseline
Diastolic blood pressure
≥100 mmHg and with ≥15 mmHg increase from baseline
≤50 mmHg and with ≥15 mmHg decrease from baseline
5.6.3.3.
Electrocardiogram
A single 12-lead ECG was obtained prior to each infusion, after the patient was in the supine 
position for at least 5 minutes. A central ECG service measured and interpreted all ECG recordings 
except those obtained at the follow-up visit, which were evaluated by the investigator. At the Day 
1 visit, a post-infusion ECG was also obtained. The Day 1 ECG prior to the infusion will be used 
as Baseline for the calculation of change.


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The ECG parameters that will be analyzed are heart rate, PR interval, RR interval, QRS interval, 
QT interval, and corrected QT (QTc) interval using the following correction methods: Bazett’s 
formula (QTcB) and Fridericia’s formula (QTcF).

Bazett’s formula: QTcB (msec) = QT (msec) / (RR (msec)/1000)1/2; if RR is missing, use QT 
(msec) * (HR(bpm)/60)1/2

Fridericia’s formula: QTcF (msec) = QT (msec) / (RR (msec)/1000)1/3; if RR is missing, use 
QT (msec) * (HR(bpm)/60)1/3
The number and percentage of patients with abnormal QTc interval will be summarized at each 
scheduled time point. The number and percentage of patients with QTc interval increases from 
baseline to the maximum postbaseline value will be summarized. Refer to the following table for 
summary categories.
Criteria for Abnormal QTc Values and Changes From Baseline
QTc value
≤450
>450 – 480
>480 – 500
>500
QTc change from baseline
≤30
>30 – ≤60
> 60
A shift table will be provided summarizing the shift from baseline to maximum post-baseline QTc 
interval classification.
Descriptive statistics of ECG parameters and change from baseline will be summarized at each 
scheduled time point.
Abnormality criteria (based on criteria defined below) will be applied to baseline and postbaseline 
values.
Postbaseline abnormalities will be compared with their corresponding baseline result:

Treatment-emergent will be concluded if the postbaseline value is above the upper limit and 
the baseline value is below the upper limit (e.g., Normal or Low). The same applies to the 
postbaseline value being below the lower limit with the baseline value being above the lower 
limit (e.g., Normal or High).

If the baseline value is missing, a postbaseline abnormality will always be considered as TE.
The number and percentage of patients with treatment-emergent ECG values outside predefined 
limits (relative to baseline) will be presented by subject group:

Heart rate (bpm): ≤50 and ≥120

PR interval (msec): <120 and >200

RR interval (msec): <600 and >1200


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
QRS interval (msec): >120
The interpretation of the ECGs as determined by the central ECG service will be displayed by the 
number and percentage of patients meeting the abnormality criteria. The interpretation will be 
summarized over time. Findings from the ECGs as determined by the central ECG service will be 
displayed by the number and percentage of patients with at least one occurrence of each finding.
A listing of patients with QTc >450 msec or QTc change from baseline >30 msec will also be 
provided.
5.6.3.4.
Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS was administered by trained study personnel at Day 1; Weeks 2, 4, 8, and 12; then 
every 12 weeks. On visits when an infusion was given, the C-SSRS was administered prior to the 
infusion. The C-SSRS is a semi-structured clinician-administered questionnaire designed to solicit 
the occurrence, severity, and frequency of suicide-related ideation and behaviors during the
assessment period.
The following are C-SSRS categories and have binary responses (yes/no). Each category is based 
on a direct question in the C-SSRS. The categories are ordered by increasing seriousness.
Suicidal Ideation (1-5)

Category 1: Wish to be dead

Category 2: Non-specific active suicidal thoughts

Category 3: Active suicidal ideation with any methods (not plan) without intent to act

Category 4: Active suicidal ideation with some intent to act, without specific plan

Category 5: Active suicidal ideation with specific plan and intent
Suicidal Behavior (6-10)

Category 6: Preparatory acts or behavior

Category 7: Aborted attempt

Category 8: Interrupted attempt

Category 9: Non-fatal suicide attempt

Category 10: Completed suicide
Self-injurious behavior without suicidal intent is also a C-SSRS outcome (although not suicide-
related) and has a binary response (yes/no).
The shift from baseline category to worst post-baseline category will be summarized with 
categories defined as ‘no suicidal ideation or behavior’, ‘suicidal ideation’, and ‘suicidal behavior’. 


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5.7.
Other Analyses
5.7.1.
Immunogenicity
Blood samples for antibodies to nipocalimab were to be collected at Weeks 4, 8, and 12, then every 
12 weeks, at the end of treatment visit and at the end of study visit.
Patients evaluable for immunogenicity are defined as patients who received at least 1 dose of study 
drug and had 1 or more post-treatment serum samples evaluable for antibodies to nipocalimab.
Results from the analysis of anti-drug antibodies (ADA) to nipocalimab will be classified as 
positive or negative. 
Patients who were positive for antibodies to nipocalimab will include patients who were positive 
for treatment-boosted or treatment-induced antibodies to nipocalimab at any time after their first 
nipocalimab administration in study 005.
1.
Patients with treatment-induced antibodies to nipocalimab had a negative ADA sample prior 
to nipocalimab administration and at least one post-treatment sample positive for ADA.
2.
Patients with treatment-boosted antibodies to nipocalimab had a positive ADA sample prior 
to nipocalimab administration and at least one post-treatment sample positive for ADA with 
titer at least 2-fold higher (i.e., ≥2-fold) than the titer of the baseline sample.
Patients who were negative for antibodies to nipocalimab will include patients with no post-
treatment samples positive for ADA, patients with post-treatment samples positive for ADA with 
titers remaining the same as the baseline titers, or patients with post-treatment samples positive for 
ADA with reduced or disappeared titers. Patients who had no appropriate samples available for 
immunogenicity assessment following intervention will be classified as “patients with baseline 
ADA samples only”.
The summary and analysis of antibodies to nipocalimab will be based on the observed data; no 
imputation of missing data will be performed.
Incidence of antibodies to nipocalimab (evaluable, treatment-emergent ADA positive, ADA 
negative) and peak titers of ADA will be summarized. In addition, listings of patients with baseline 
positive ADA samples and patients who are classified as positive for treatment-emergent
antibodies to nipocalimab will be provided.
In addition, a list of patients who were positive for antibodies to nipocalimab (treatment-emergent 
or treatment-boosted) will be provided with individual IgG, MG-ADL, and infusion-site reactions
(if any).
The efficacy and infusion-site reactions will be summarized by patient ADA status (positive and 
negative).


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5.7.2.
Pharmacodynamics
5.7.2.1.
Immunoglobulin G
Blood samples for levels of total immunoglobulin G (IgG) were collected at Weeks 2, 4, 8, and 
12, then every 12 weeks, at the end of treatment visit, and at the end of study visit.
Descriptive statistics of the value, change from baseline, percent change from baseline, and percent 
of baseline value will be presented at each scheduled time point. Plots of mean (±SE) percent of 
baseline value and percent change from baseline at each scheduled sampling time point will be 
provided.
The number and percentage of patients with IgG ≤1 g/L will be summarized and a listing of 
patients meeting that criteria will be provided. A listing of IgG levels will be provided for patients 
who had an infection adverse event of special interest (see Appendix 8).
5.7.2.2.
Immunoglobulin A, M, and E
Blood samples for levels of immunoglobulin A, M, and E were collected every 12 weeks and at 
the end of treatment visit.
Descriptive statistics of value, change from baseline, percent change from baseline, and percent of 
baseline value will be presented at each scheduled time point.
5.7.2.3.
Anti-AChR and Anti-MuSK Autoantibodies
Blood samples for levels of anti-AChR and anti-MuSK autoantibodies were collected at Weeks 4, 
8, and 12, then every 12 weeks, at the end of treatment visit, and at the end of study visit.
For anti-AChR autoantibodies, descriptive statistics of value, change from baseline, percent 
change from baseline, and percent of baseline value will be presented at each scheduled time point. 
Plots of mean (±SE) percent of baseline value and percent change from baseline at each scheduled 
time point will be provided.
No anti-MuSK positive patient entered the 005 study. Therefore, no summaries or listings of anti-
MuSK antibodies will be presented.
5.7.3.
Myasthenia Gravis Medication Usage
A listing of myasthenia gravis medications taken to treat the onset or worsening of symptoms of 
gMG (rescue therapy for clinical deterioration) will be provided.
Usage of myasthenia gravis medications will be displayed graphically over time for each patient, 
with lines for each medication extending from the start day to the end day relative to the date of
the first infusion of nipocalimab in the study.


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5.7.4.
Definition of Subgroups
The frequency of treatment-emergent adverse events will be summarized by the following 
subgroups: 
Subgroup
Definition
Age Group
<45
45-64
≥65
Sex
Female
Male
5.8.
Interim Analyses
No interim analysis was performed
5.8.1.
Data Monitoring Committee (DMC) or Other Review Board
A Data Safety Monitoring Board performed periodic review of safety data from the 005 study.


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6.
SUPPORTING DOCUMENTATION
6.1.
Appendix 1 List of Abbreviations
AChR
acetylcholine receptor
ADA
anti-drug antibody
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
ATC
anatomic and therapeutic class
BMI
body mass index
CGI-I
Clinical global impression – improvement
CGI-S
Clinical global impression – severity
CRF
case report form
C-SSRS
Columbia – Suicide Severity Rating Scale
CTCAE
Common Terminology Criteria for Adverse Events
ECG
electrocardiogram
FAS
full analysis set
gMG
generalized myasthenia gravis
ICF
informed consent form
IgG
Immunoglobulin G
LLN
lower limit of normal
MedDRA
Medical Dictionary for Regulatory Activities
MG-ADL
Myasthenia Gravis – Activities of Daily Living
MGFA
Myasthenia Gravis Foundation of America
MG-QoL-15r
Revised Myasthenia Gravis Quality of Life
MuSK
muscle-specific kinase
NAb
neutralizing antibodies
NCI
National Cancer Institute
PD
pharmacodynamic(s)
QMG
Quantitative Myasthenia Gravis
SAE
serious adverse event
SD
standard deviation
SE
standard error
SMQs
standardised MedDRA queries
TEAE
treatment-emergent adverse event
ULN
upper limit of normal
WHO-DD
World Health Organization Drug Dictionary


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6.2.
Appendix 2 Changes to Protocol-Planned Analyses
The secondary endpoint of the incidence of neutralizing anti-drug antibody seroconversion over time will 
not be summarized because neutralizing anti-drug antibody data was not available.
The exploratory endpoint of quantitative level of physical activity over time (based on data from the 
Embrace device) and changes over time will not be summarized because the data from the device was not 
deemed useful given the study termination due to the Covid-19 pandemic.
The exploratory model-based analysis of MG-ADL score change from baseline in relationship to total 
serum IgG and anti-AChR titer will not be performed because of the limited number of subjects and 
limited duration of exposure as a result of the study termination due to the Covid-19 pandemic.


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6.3.
Appendix 3 Demographics and Baseline Characteristics
The number of patients in each analysis set will be summarized and listed by subject group and 
overall. In addition, the distribution of patients by country and site ID will be presented.
Table 3 presents a list of the demographic variables that will be summarized by subject group and 
overall for the safety analysis set.
Table 3: Demographic Variables
Continuous Variables:
Summary Type
Age (years)
Descriptive statistics (N, mean, 
standard deviation [SD], median 
and range [minimum and 
maximum]).
Weight (kg)
Height (cm)
Body Mass Index (BMI) (kg/m2)
Categorical Variables
Age (18-25 years, 26-50 years, 51-64 years, and >=65 years)
Frequency distribution with the 
number and percentage of patients
in each category.
Sex (male, female, undifferentiated)
Racea (American Indian or Alaska Native, Asian, Black or African 
American, Native Hawaiian or other Pacific Islander, White, Multiple)
Ethnicity (Hispanic or Latino, not Hispanic or Latino)
BMI (underweight <18.5 kg/m2, normal 18.5-<25 kg/m2, overweight 25-
<30 kg/m2, obese >=30 kg/m2)
aIf multiple race categories are indicated, the Race is recorded as 'Multiple'
Table 4 presents a list of the baseline characteristic variables that will be summarized by subject
group and overall for the full analysis set.
Table 4: Baseline Characteristic Variables
Continuous Variables:
Summary Type
Baseline MG-ADL total score
Descriptive statistics (N, mean, 
standard deviation [SD], median 
and range [minimum and 
maximum]).
Baseline QMG total score
Categorical Variables
Baseline MGFA Clinical Classification
Frequency distribution with the 
number and percentage of patients
in each category.


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6.4.
Appendix 4 Protocol Deviations
In general, the following list of major protocol deviations may have the potential to impact 
participants’ rights, safety or well-being, or the integrity and/or result of the clinical study. 
Participants with major protocol deviations will be identified prior to database lock and the 
participants with major protocol deviations will be summarized by category.

Inclusion criteria (enrolled despite failing an inclusion criteria)

Exclusion criteria (enrolled despite meeting an exclusion criteria)

Study drug (e.g., incorrect drug assignment, preparation, or administration, etc.)

Assessment – Safety (e.g., missing or incorrectly performed safety assessment)

Lab/Endpoint data (e.g, lab sample or efficacy assessment not performed per protocol)

Visit window (visit out of protocol-specified window)

Informed consent (ICF) (patient not consented properly)

Missed visit (when an entire visit is missed)

Prohibited co-medication

Overdose/mis-use

Withdrawal criteria (patient met withdrawal criteria; or, study drug stopping rule was met; or,
study drug interruption rule was met and patient was not withdrawn or study drug was not 
stopped/paused)

Other
Visits or assessments not conducted or conducted remotely because of the Covid-19 pandemic will 
be identified as such in the protocol deviation description with the prefix “COVID-19:”.


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6.5.
Appendix 5 Prior and Concomitant Medications
Prior and Concomitant medications will be coded using the World Health Organization Drug 
Dictionary (WHO-DD). Prior medications are defined as any therapy used before the day of first 
dose (partial or complete) of study intervention. Concomitant medications are defined as any 
therapy used on or after the same day as the first dose of study intervention, including those that 
started before and continue after the first dose of study drug.
Summaries of concomitant medications will be presented by ATC term and subject group. The 
proportion of patients who receive each concomitant medication will be summarized as well as the 
proportion of patients who receive at least 1 concomitant medication.
A separate summary of concomitant medications that comprise background therapy for myasthenia 
gravis will also be provided.
Prior medications will be summarized by subject group and ATC term. A summary of prior 
medications for myasthenia gravis (medications started and stopped before entry into the 005 
study) will also be provided.


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6.6.
Appendix 6 Medical History
The verbatim terms used in the CRF by investigators to identify medical history events and 
diseases will be coded using MedDRA. For each medical history preferred term, the number and 
percentage of patients with at least 1 ongoing occurrence of the given event/disease will be 
summarized by subject group and overall.


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6.7.
Appendix 7 Intervention Compliance
Not applicable


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6.8.
Appendix 8 Adverse Events of Special Interest
Adverse events of special interest are defined as follows:
AE Special Interest Category
SOC
Additional condition
Infections
Infection and Infestations
≥Grade 3 and/or serious
AE Special Interest Category
Preferred term
Additional condition
Hypoalbuminaema
Hypoalbuminaemia
≥Grade 3
Other adverse events of clinical interest are defined as follows:
AE of Clinical Interest Category
Preferred term
Additional condition
Infusion site reaction
Any preferred term containing 
“infusion site” or “vessel puncture 
site”
Serum sickness reaction
Serum sickness
Serum sickness-like reaction
AE of Clinical Interest Category
SMQ
Additional condition
Opportunistic infections
Opportunistic infections
Narrow scope
Anaphylactic reaction
Anaphylactic reaction
Narrow and broad scope
Suicidal ideation/behavior
Suicide/self-injury
Narrow and broad scope
Drug related hepatic disorders
Drug related hepatic disorders –
comprehensive search
Narrow scope


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6.9.
Appendix 9 Medications of Special Interest
Not applicable.


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6.10.
Appendix 10 Laboratory Toxicity Grading
Markedly abnormal criteria for selected laboratory tests are provided in the table below. Change 
and percent change are in reference to the baseline value.
Markedly Abnormal Criteria
Laboratory test
Units
1 – High
2 - Low
Albumin
g/L
High: Change >10 and value >60
Low: Change < -10 and value <25
Alkaline Phosphatase
U/L
High: Change >100 and value >250
Alanine Aminotransferase
U/L
Value ≥3xULN
Aspartate Aminotransferase
U/L
Value ≥3xULN
Bicarbonate
mmol/L
High: Percent change >20 and value 
>34.9
Low: Percent change < -20 and value 
<15.1
Bilirubin
mcmol/L
High: Percent change >20 and value 
>45
Blood Urea Nitrogen
mmol/L
High: Percent change >20 and value 
>17.9
Calcium
mmol/L
High: Percent change >20 and value 
>3
Low: Percent change < -20 and value 
<1.5
Chloride
mmol/L
High: Change >5 and value >120
Low: Change < -5 and value <85
Creatinine
mcmol/l
High: Percent change >20 and value 
>250
Gamma Glutamyl Transferase
U/L
High: Change >100 and value >300
Glucose
mmol/L
High: Percent change >30 and value 
>16.7
Low: Percent change < -20 and value 
<2.2
Phosphate
mmol/L
High: Percent change >10 and value 
>2.6
Low: Percent change < -10 and value 
<0.6
Potassium
mmol/L
High: Percent change >20 and value 
>6
Low: Percent change < -10 and value 
<3
Protein
g/L
Low: Percent change < -20 and value 
<50
Sodium
mmol/L
High: Percent change >10 and value 
>155
Low: Percent change < -10 and value 
<125
Creatine Kinase
U/L
High: Percent change >20 and value 
>960
Hematocrit
L/L
High: Percent change >15 and value 
>0.5(female) or >0.55 (male)
Low: Percent change < -15 and value 
<0.28
Hemoglobin
g/L
High: Percent change >10 and value 
>190
Low: Percent change < -10 and value 
<80
Neutrophils/Leukocytes
%
High: Percent change >30 and value
>90
Low: Percent change < -30 and value 
<30
Monocytes/Leukocytes
%
High: Percent change >20 and value 
>20
Eosinophils/Leukocytes
%
High: Percent change >20 and value 
>10
Basophils/Leukocytes
%
High: Percent change >20 and value 
>6
Lymphocytes/Leukocytes
%
High: Percent change >20 and value 
>60
Low: Percent change < -20 and value 
<8
Platelets
10^9/L
High: Percent change >20 and value 
>600
Low: Percent change < -20 and value 
<100
Erythrocytes
10^12/L
High: Percent change >20 and value 
>6.1(female) or >6.4(male)
Low: Percent change < -20 and value 
<3
Leukocytes
10^9/L
High: Percent change >20 and value 
>15
Low: Percent change < -10 and value 
<2.5
pH
pH
High: >7


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6.11.
Appendix 11 Myasthenia Gravis – Activities of Daily Living
Item
None = 0
Mild = 1
Moderate = 2
Severe = 3
Talking
Normal
Intermittent slurring 
or nasal speech
Constant slurring or 
nasal speech, but 
can be understood
Difficult-to-
understand speech
Chewing
Normal
Fatigue with solid 
food
Fatigue with soft 
food
Gastric tube
Swallowing
Normal
Rare episode of 
choking
Frequent choking 
necessitating 
changes in diet
Gastric tube
Breathing
Normal
Shortness of breath 
with exertion
Shortness of breath 
at rest
Ventilator 
dependence
Impairment of ability to 
brush teeth or comb hair
None
Extra effort, but no 
rest periods needed
Rest periods needed
Cannot do these 
functions
Impairment of ability to 
rise from a chair
None
Mild, sometimes 
uses arms
Moderate, always 
uses arms
Severe, requires 
assistance
Double vision
None
Occurs, but not 
daily
Daily, but not 
constant
Constant
Eyelid droop
None
Occurs, but not 
daily
Daily, but not 
constant
Constant


JNJ-80202135; M281  (nipocalimab)
Statistical Analysis Plan MOM-M281-005
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
30
Status: Approved, Date: 7 July 2021
6.12.
Appendix 12 Quantitative Myasthenia Gravis
Item
None = 0
Mild = 1
Moderate = 2
Severe = 3
Double vision on lateral 
gaze right or left, 
seconds
61
11-60
1-10
Spontaneous
Ptosis (upward gaze), 
seconds
61
11-60
1-10
Spontaneous
Facial muscles
Normal lid 
closure
Complete, weak, 
some resistance
Complete, without 
resistance
Incomplete
Swallowing 4 oz. of 
water (1/2 cup)
Normal
Minimal coughing 
or throat clearing
Severe 
coughing/choking 
or nasal 
regurgitation
Cannot swallow 
(test not attempted)
Speech after counting 
aloud from 1 to 50 
(onset of dysarthria)
None at 50
Dysarthria at 30-
49
Dysarthria at 10-29
Dysarthria at 9
Right arm outstretched 
(90-degree sitting), 
seconds
240
9—230
10-89
0-9
Left arm outstretched 
(90-degree sitting), 
seconds
240
9—230
10-89
0-9
Vital capacity, % 
predicted
≥80
65-79
50-64
<50
Right-hand grip (men), 
kgW
≥45
15-44
5-14
0-4
Right-hand grip 
(women), kgW
≥30
10-29
5-9
0-4
Left-hand grip (men), 
kgW
≥35
15-34
5-14
0-4
Left-hand grip 
(women), kgW
≥25
10-24
5-9
0-4
Head lifted (45-degree 
supine), seconds
120
30-119
1-29
0
Right leg outstretched 
(45-degree supine), 
seconds
100
31-99
1-30
0
Left leg outstretched 
(45-degree supine), 
seconds
100
31-99
1-30
0


JNJ-80202135; M281  (nipocalimab)
Statistical Analysis Plan MOM-M281-005
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
31
Status: Approved, Date: 7 July 2021
6.13.
Appendix 13 Revised Myasthenia Gravis Quality of Life
Responses to each item below are rated by the patient, using a reflection period of “over the past 
few weeks” on a 3-point scale (0 = not at all, 1 = somewhat, and 2 = very much).

I am frustrated by my MG

I have trouble with my eyes because of my MG (eg, double vision)

I have trouble eating because of my MG

I have limited my social activity because of my MG

My MG limits my ability to enjoy hobbies and fun activities

I have trouble meeting the needs of my family because of my MG

I have to make plans around my MG

I am bothered by limitations in performing my work (including work at home) because of my MG

I have difficulty speaking due to my MG

I have lost some personal independence because of my MG (eg. Driving, shopping, running errans)

I am depressed about my MG

I have trouble walking due to my MG

I have trouble getting around public places because of my MG

I feel overwhelmed by my MG

I have trouble performing my personal grooming needs due to my MG


JNJ-80202135; M281  (nipocalimab)
Statistical Analysis Plan MOM-M281-005
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
32
Status: Approved, Date: 7 July 2021
6.14.
Appendix 14 Myasthenia Gravis Foundation of America Classification
Class I: Any ocular muscle weakness; may have weakness of eye closure. All other muscle 
strength is normal.
Class II: Mild weakness affecting muscles other than ocular muscles; may also have ocular 
muscle weakness of any severity.
A. IIa. Predominantly affecting limb, axial muscles, or both. May also have lesser 
involvement of oropharyngeal muscles.
B. IIb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have 
lesser or equal involvement of limb, axial muscles, or both.
Class III: Moderate weakness affecting muscles other than ocular muscles; may also have ocular 
muscle weakness of any severity.
A. IIIa. Predominantly affecting limb, axial muscles, or both. May also have lesser 
involvement of oropharyngeal muscles.
B. IIIb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have 
lesser or equal involvement of limb, axial muscles, or both.
Class IV: Severe weakness affecting muscles other than ocular muscles; may also have ocular 
muscle weakness of any severity.
A. IVa. Predominantly affecting limb, axial muscles, or both. May also have lesser 
involvement of oropharyngeal muscles.
B. IVb. Predominantly affecting oropharyngeal, respiratory muscles, or both. May also have 
lesser or equal involvement of limb, axial muscles, or both.
Class V: Defined as intubation, with or without mechanical ventilation, except when employed 
during routine postoperative management. The use of a feeding tube without intubation places 
the patient in class IVb.


JNJ-80202135; M281  (nipocalimab)
Statistical Analysis Plan MOM-M281-005
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
33
Status: Approved, Date: 7 July 2021
7.
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