A Phase 2, Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerability, and Efficacy of TAK-079 in Patients With Generalized Myasthenia Gravis
Phase: PHASE2
Conditions: Myasthenia Gravis
Sponsor: Takeda

CLINICAL STUDY PROTOCOL 
NCT Number: 
Study Title: 
Study Number: 
NCT04159805 
A Phase 2, Randomized, Placebo-Controlled Study to Evaluate Safety, 
Tolerability, and Efficacy of TAK-079 in Patients With Generalized 
Myasthenia Gravis 
TAK-079-1005
Protocol Version and Date: 
Version 4.0: 03-Feb-2021 
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

PROTOCOL
A Phase 2, Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerability, and 
Efficacy of TAK-079 in Patients With Generalized Myasthenia Gravis
Safety, Tolerability, and Efficacy of TAK-079 in Patients With Generalized Myasthenia Gravis
Sponsor:
Millennium Pharmaceuticals, Inc.*
40 Landsdowne Street
Cambridge, MA 02139
USA
Please note: Millennium Pharmaceuticals, Inc, a wholly owned 
subsidiary of Takeda Pharmaceutical Company Limited, may be 
referred to in this protocol as “Millennium,” “sponsor,” or “Takeda”.
Study Number:
TAK-079-1005
EudraCT Number:
2019-003383-47
Compound:
TAK-079
Date:
02 February 2021
Version/Amendment 
Number:
4
Amendment History: 
Date
Amendment Number
Type
Region
02 February 2021
Amendment 4
Substantial
Global
28 September 2020
Amendment 3
Substantial
Global
05 March 2020
Amendment 2
Substantial
Global
18 October 2019
Amendment 1
Nonsubstantial
Global
05 September 2019
Initial Protocol
Not applicable
Global
CONFIDENTIAL PROPERTY OF TAKEDA
This document is a confidential communication of Takeda. Acceptance of this document constitutes the agreement by 
the recipient that no information contained herein will be published or disclosed without written authorization from 
Takeda except to the extent necessary to obtain informed consent from those persons to whom the drug may be 
administered. Furthermore, the information is only meant for review and compliance by the recipient, his or her staff, 
and applicable institutional review committee and regulatory agencies to enable conduct of the study.
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CONFIDENTIAL
1.0
ADMINISTRATIVE INFORMATION
1.1
Contacts 
A separate contact information list will be provided to each site.
Serious adverse event and pregnancy reporting information is presented in Section 10.0, as is 
information on reporting product complaints. 
Takeda Development Center–sponsored investigators per individual country requirements will be 
provided with emergency medical contact information cards to be carried by each patient.
General advice on protocol procedures should be obtained through the monitor assigned to the 
study site. Information on service providers is given in Section 3.1 and relevant guidelines 
provided to the site.
The names and contact information for the medical monitor and responsible medical officer are in 
the study contact list.
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CONFIDENTIAL
1.2
Approval 
REPRESENTATIVES OF TAKEDA 
This study will be conducted with the highest respect for the individual participants in accordance 
with the requirements of this clinical study protocol and in accordance with the following:
!
The ethical principles that have their origin in the Declaration of Helsinki.
!
International Council for Harmonisation E6 Good Clinical Practice: Consolidated Guideline.
!
All applicable laws and regulations, including, without limitation, data privacy laws, clinical 
study disclosure laws, and regulations.
SIGNATURES
The signature of the responsible Takeda medical officer (and other signatories, as applicable) can 
be found on the signature page.
Electronic Signatures may be found on the last page of this document.
, MD, PhD
 Autoimmune Diseases
Date
, PhD
, Biostatistics
Statistical and Quantitative Sciences
Date
, PhD (or designee)
Quantitative Clinical Pharmacology
Date
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CONFIDENTIAL
1.3
Protocol Amendment 4 Summary of Changes
Rationale for Amendment 4
This section describes the changes in reference to the protocol incorporating Amendment 4. The 
primary reason for this amendment is to clarify the intent of Exclusion Criterion No 1. Other minor 
changes and clarifications to the protocol are summarized in the table below.
Protocol Amendment 4
Summary of Changes Since the Last Version of the Approved Protocol
Sections Affected by Change
Description of Each Change and Rationale
Location
Description 
Rationale
Section 1.2 Approval
Change name of Biostatics approver 
from 
 to 
.
To update study personnel.
Section 2.0 STUDY SUMMARY
Section 6.1 Overview of Study
Section 9.5 Study Procedures
Section 9.5.4 Medical/Surgical 
History
Section 9.5.5 Concomitant 
Medications and Procedures
Section 9.5.7 Height and Weight
Appendix A Schedule of Events
Increase the length of the screening 
period from 21 days 28 days.
To lengthen the screening period by 
1 week due to COVID-19-related 
shipping delays.
Section 2.0 STUDY SUMMARY
Section 6.3 Number of Patients 
Increase number of study centers 
from 40 to 50.
To mitigate the delayed enrollment 
caused by COVID-19.
Section 2.0 STUDY SUMMARY
Section 7.2 Exclusion Criteria 
Exclusion Criterion No 1: Changed 
from: “history of thymoma or other 
thymic neoplasms” to read: 
“Presence of a thymoma (previous 
history of a fully encapsulated 
thymoma removed ≥12 months 
before screening is allowed) or 
history of invasive thymic 
malignancy unless deemed cured by 
adequate treatment with no evidence 
of recurrence for ≥5 years before 
screening.”
To clarify that the intent is to exclude 
subjects with a current thymoma and 
not a previous history of a fully 
encapsulated thymoma (removed 
≥12 months before screening) and to 
provide further detail regarding other 
malignancies of the thymus.
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Protocol Amendment 4
Summary of Changes Since the Last Version of the Approved Protocol
Sections Affected by Change
Description of Each Change and Rationale
Location
Description 
Rationale
Section 2.0 STUDY SUMMARY
Section 5.2.2 Secondary Endpoints
Section 5.2.3 Exploratory Endpoints 
Section 13.1.3 Efficacy Analysis 
Secondary Endpoint: The 
MG-QoL15r scale has been removed 
as one of the MG clinical impairment 
scales to assess the percentage of 
patients meeting minimal clinically 
important difference criteria.
Exploratory Endpoint: The 
MG-QoL15r scale has been removed 
as one of the MG clinical impairment 
scales to assess the duration of a 
clinically meaningful effect on MG 
disease severity.
To remove the MG-QoL15r scale 
from this analysis as it does not have 
an established cutoff of clinically 
meaningful change.
Section 8.1 Study Drug 
Administration
Changed “...the Week 1 dose will be 
administered by giving each SC 
injection 30 minutes apart” to read: 
“the Week 1 dose will be 
administered by giving each SC 
injection 30 minutes apart 
(±10minutes)...”
To provide a 10 minute window to 
the 30-minute intervals between 
injections.
Section 8.1.2 Postdose Medication
Appendix A Schedule of Events, 
footnote v
Modify timing of medication
following the first dose of study drug 
from: “Considering the timing of the 
greatest pharmacologic effect of 
TAK-079, postdose medication 
should be given after the first dose 
and 1 day after the first dose of study 
drug.” to read: Considering the 
timing of the greatest pharmacologic 
effect of TAK-079, postdose 
medication should be given 2 hours 
(±15 minutes) after the first injection 
of the first dose and 1 day after the 
first dose of study drug in the 
morning.”
To provide more detailed guidance 
on the administration of postdose 
medication.
Section 9.5.6 Physical Examination
Appendix A, footnote g
The following sentence has been 
added: “Women of childbearing 
potential should be asked about their 
menstrual history at each visit. A 
serum pregnancy test should be 
conducted for delayed menses (see 
Section 9.5.10).”
To ensure a woman is not pregnant 
before study drug administration.
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Protocol Amendment 4
Summary of Changes Since the Last Version of the Approved Protocol
Sections Affected by Change
Description of Each Change and Rationale
Location
Description 
Rationale
Section 9.5.8 Vital Signs
Appendix A Schedule of Events, 
footnote i.
A window of ±10 minutes has been 
added to 2 hour timeframe for 
assessing vital signs postdose after 
the first and second administration of 
study drug. 
To provide a 10-minute window for 
obtaining vital signs after 
administration of study drug
In addition, footnote “i” in 
Appendix A was revised to remove 
unclear wording about which vital 
signs are to be taken during the 
visits.
Section 9.5.10 Pregnancy Test
Appendix A Schedule of Events, 
footnote j
Text has been revised to indicate that 
if the subject reports delayed 
menses, a serum pregnancy test 
should be completed and a negative 
result obtained before dosing with 
the study drug.
To ensure a woman is not pregnant 
before study drug administration.
Section 9.5.10.1 Definition of Women 
of Childbearing Potential
Removed: “Has not been naturally 
postmenopausal (amenorrhea after 
cancer therapy does not rule out 
childbearing potential) for at least 
24 consecutive months, ie, has had 
menses at any time in the preceding 
24 consecutive months.”
Clarified the definition of 
postmenopausal.
To remove confusing wording from 
template language that does not 
apply to this protocol.
Section 9.5.13.5 MG-QoL 15r 
Revised total score range from “0 to 
60” to read: “0 to 30.”
Removed last sentence that read: A 
reduction by 7 to 8 points in the total 
MG-QoL15r score is considered a 
clinically meaningful improvement.
To correct the total score of the 
MG-QoL15r scale. 
Removed criteria for clinically 
meaningful improvement as this 
pertained to the MG-QoL15 scale, 
not the revised MG-QoL15r scale.
Section 9.12 Coronavirus Disease 
2019-Related Procedural Changes
Appendix A Schedule of Events, 
footnote s
Added text: “The assessment of 
forced vital capacity for the QMG 
test may be omitted for 
COVID-19-related reasons.”
To allow added flexibility for sites 
with varying policies and procedures 
due to COVID-19.
Date of FDA guidance on 
COVID-19 changed from 02 
July 2020 to 04 December 2020. 
To update date of most recent FDA 
guidance on COVID-19.
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CONFIDENTIAL
INVESTIGATOR AGREEMENT 
I confirm that I have read and that I understand this protocol, the investigator’s brochure (IB), 
prescribing information, and any other product information provided by the sponsor. I agree to 
conduct this study in accordance with the requirements of this protocol and to protect the rights, 
safety, privacy, and well-being of study patients in accordance with the following:

The ethical principles that have their origin in the Declaration of Helsinki.

ICH, E6 Good Clinical Practice: Consolidated Guideline.

All applicable laws and regulations, including, without limitation, data privacy laws and 
regulations.

Regulatory requirements for reporting serious adverse events defined in Section 10.0 of this 
protocol.

Terms outlined in the clinical study site agreement.

Responsibilities of the investigator (Appendix B).
I further authorize that my personal information may be processed and transferred in accordance 
with the uses contemplated in Appendix E of this protocol.
Signature of Investigator
Date
Investigator Name (print or type)
Investigator’s Title
Location of Facility (City, State/Province)
Location of Facility (Country)
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TABLE OF CONTENTS
1.0
ADMINISTRATIVE INFORMATION ...........................................................................2
1.1
Contacts.....................................................................................................................2
1.2
Approval....................................................................................................................3
1.3
Protocol Amendment 4 Summary of Changes............................................................4
2.0
STUDY SUMMARY ....................................................................................................14
3.0
STUDY REFERENCE INFORMATION ......................................................................19
3.1
Study-Related Responsibilities.................................................................................19
3.2
Coordinating Investigator.........................................................................................19
3.3
List of Abbreviations ...............................................................................................20
3.4
Corporate Identification...........................................................................................21
4.0
INTRODUCTION.........................................................................................................22
4.1
Disease Background ................................................................................................22
4.2
Rationale for the Proposed Study.............................................................................23
4.3
Dose Rationale.........................................................................................................24
4.4
Benefits and Risks Assessment ................................................................................30
5.0
STUDY OBJECTIVES AND ENDPOINTS..................................................................31
5.1
Objectives................................................................................................................31
5.1.1
Primary Objective............................................................................................31
5.1.2
Secondary Objectives ......................................................................................31
5.1.3
Exploratory Objectives ....................................................................................31
5.2
Endpoints.................................................................................................................31
5.2.1
Primary Endpoint.............................................................................................31
5.2.2
Secondary Endpoints .......................................................................................31
5.2.3
Exploratory Endpoints .....................................................................................32
6.0
STUDY DESIGN..........................................................................................................32
6.1
Overview of Study Design.......................................................................................32
6.2
Safety and Disease Assessments ..............................................................................34
6.2.1
PK and Pharmacodynamic Assessments ..........................................................35
6.3
Number of Patients ..................................................................................................35
6.4
Duration of Study ....................................................................................................35
6.4.1
Duration of an Individual Patient’s Study Participation....................................35
6.4.2
End of Study/Study Completion Definition and Planned Reporting..................35
6.4.3
Time Frames for Primary and Secondary Endpoints to Support Disclosures.....35
6.4.4
Total Study Duration .......................................................................................35
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7.0
STUDY POPULATION................................................................................................36
7.1
Inclusion Criteria .....................................................................................................36
7.2
Exclusion Criteria ....................................................................................................37
8.0
STUDY DRUG .............................................................................................................38
8.1
Study Drug Administration......................................................................................38
8.1.1
Premedication..................................................................................................40
8.1.2
Postdose Medication........................................................................................40
8.1.3
Rescue Therapy ...............................................................................................41
8.2
Excluded Concomitant Medications and Procedures ................................................41
8.3
Permitted Concomitant Medications and Procedures................................................41
8.4
Study Stopping Rules...............................................................................................42
8.4.1
Assessment and Criteria for Terminating Patient Dosing..................................42
8.5
Precautions and Restrictions ....................................................................................45
8.5.1
Pregnancy, Lactation, and Contraception .........................................................45
8.5.2
Drug Interactions.............................................................................................46
8.5.3
Interference with Serological Testing...............................................................47
8.6
Management of Clinical Events ...............................................................................47
8.6.1
Hypersensitivity Reactions: Infusion Reactions................................................47
8.6.1.1
Management Recommendations for Hypersensitivity Reactions ..............48
8.6.2
Cytokine Release Syndrome ............................................................................49
8.6.2.1
Management Recommendations for CRS.................................................50
8.6.3
Hematologic Effects ........................................................................................51
8.6.4
Infections.........................................................................................................51
8.6.5
Injection Site Reactions ...................................................................................52
8.6.6
Antidrug Antibody Interactions........................................................................52
8.6.7
Overdose .........................................................................................................52
8.7
Description of Investigational Agents ......................................................................53
8.7.1
Study Drug: TAK-079 .....................................................................................53
8.7.1.1
Preparation, Reconstitution, and Dispensation .........................................53
8.7.1.2
Packaging and Labeling...........................................................................53
8.7.1.3
Storage, Handling, and Accountability.....................................................53
8.7.2
Clinical Study Drug Blinding...........................................................................54
8.7.3
Randomization Code Creation and Storage......................................................54
8.7.4
Clinical Study Blind Maintenance/Unblinding Procedure.................................54
8.7.5
Destruction of Sponsor-Supplied Drugs ...........................................................55
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9.0
STUDY CONDUCT......................................................................................................56
9.1
Study Personnel and Organizations..........................................................................56
9.2
Arrangements for Recruitment of Patients................................................................56
9.3
Assignment of Randomization Numbers ..................................................................56
9.4
Treatment Group Assignments.................................................................................56
9.5
Study Procedures.....................................................................................................57
9.5.1
Informed Consent ............................................................................................57
9.5.2
Inclusion and Exclusion...................................................................................57
9.5.3
Patient Demographics......................................................................................57
9.5.4
Medical/Surgical History.................................................................................57
9.5.5
Concomitant Medications and Procedures........................................................57
9.5.5.1
Background MG Therapy ........................................................................58
9.5.6
Physical Examination ......................................................................................58
9.5.7
Height and Weight...........................................................................................58
9.5.8
Vital Signs.......................................................................................................58
9.5.9
12-Lead ECG...................................................................................................58
9.5.10
Pregnancy Test ................................................................................................59
9.5.10.1
Definition of Women of Childbearing Potential.......................................59
9.5.10.2
Timing of Pregnancy Testing...................................................................59
9.5.11
AEs .................................................................................................................60
9.5.12
Clinical Laboratory Evaluations.......................................................................60
9.5.12.1
Clinical Chemistry and Hematology ........................................................60
9.5.13
Disease Assessment.........................................................................................60
9.5.13.1
MG-ADL Score.......................................................................................60
9.5.13.2
MGII Score..............................................................................................61
9.5.13.3
MGC Score..............................................................................................61
9.5.13.4
QMG Score for Disease Severity .............................................................61
9.5.13.5
MG-QoL15r ............................................................................................61
9.5.13.6
Patient Global Impression of Change.......................................................62
9.5.13.7
Patient Global Impression of Severity......................................................62
9.5.13.8
Quantification of Ig .................................................................................62
9.5.14
Biomarker, Pharmacodynamic, and PK Samples..............................................62
9.5.14.1
Primary Specimen Collection...................................................................63
9.5.15
PK Measurements............................................................................................63
9.5.16
Pharmacodynamic/Biomarker Measurements...................................................63
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9.5.16.1
Autoantibodies.........................................................................................64
9.5.16.2
Pharmacodynamics..................................................................................64
9.5.16.3
Circulating Biomarkers............................................................................64
9.5.16.4
Immunoprofiling......................................................................................64
9.5.16.5
Vaccine-Induced Protective Antibodies ...................................................64
9.5.17
Immunogenicity Sample Collection .................................................................64
9.6
End of Safety Follow-up Assessments .....................................................................65
9.7
Completion of Study Treatment (for Individual Patients) .........................................65
9.8
Completion of Study (for Individual Patients)..........................................................65
9.9
Discontinuation of Treatment With Study Drug .......................................................65
9.10
Withdrawal of Patients From Study .........................................................................66
9.11
Study Compliance....................................................................................................66
9.12
Coronavirus Disease 2019–Related Procedural Changes..........................................67
10.0
ADVERSE EVENTS ....................................................................................................68
10.1
Definitions...............................................................................................................68
10.1.1
Pretreatment Event Definition..........................................................................68
10.1.2
AE Definition ..................................................................................................69
10.1.3
SAE Definition................................................................................................71
10.2
Procedures for Recording and Reporting AEs and SAEs..........................................72
10.3
Monitoring of AEs and Period of Observation .........................................................73
10.4
Procedures for Reporting Drug Exposure During Pregnancy and Birth Events.........74
10.5
Procedures for Reporting Including Overdose..........................................................74
10.6
Safety Reporting to Investigators, IRBs or IECs, and Regulatory Authorities...........74
11.0
STUDY-SPECIFIC COMMITTEES .............................................................................75
12.0
DATA HANDLING AND RECORDKEEPING............................................................75
12.1
eCRFs......................................................................................................................75
12.2
Record Retention .....................................................................................................76
13.0
STATISTICAL METHODS..........................................................................................76
13.1
Statistical and Analytical Plans ................................................................................76
13.1.1
Analysis Sets ...................................................................................................76
13.1.2
Analysis of Demographics and Other Baseline Characteristics.........................77
13.1.3
Efficacy Analysis.............................................................................................77
13.1.4
PK Analysis.....................................................................................................78
13.1.5
Immunogenicity Analyses................................................................................78
13.1.6
Safety Analysis................................................................................................78
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13.2
Interim Analysis and Criteria for Early Termination ................................................79
13.3
Determination of Sample Size..................................................................................79
14.0
QUALITY CONTROL AND QUALITY ASSURANCE...............................................79
14.1
Study-Site Monitoring Visits ...................................................................................79
14.2
Protocol Deviations..................................................................................................79
14.3
Quality Assurance Audits and Regulatory Agency Inspections ................................80
15.0
ETHICAL ASPECTS OF THE STUDY........................................................................80
15.1
IRB and/or IEC Approval ........................................................................................80
15.2
Patient Information, Informed Consent, and Patient Authorization...........................81
15.3
Patient Confidentiality .............................................................................................82
15.4
Publication, Disclosure, and Clinical Study Registration Policy ...............................83
15.4.1
Publication.......................................................................................................83
15.4.2
Clinical Study Registration ..............................................................................83
15.4.3
Clinical Study Results Disclosure ....................................................................84
15.4.4
Data Sharing....................................................................................................84
15.5
Insurance and Compensation for Injury....................................................................84
16.0
REFERENCES..............................................................................................................84
LIST OF IN-TEXT TABLES
Table 8.a
Summary of TAK-079/Placebo Dose Administration.........................................39
Table 8.b
Excluded Concomitant Medications ...................................................................41
Table 8.c
Permitted Concomitant Medications...................................................................42
Table 8.d
Summary of Subsequent Dosing Criteria............................................................44
Table 8.e
Highly Effective and Other Effective Methods of Contraception for Female 
Patients ..............................................................................................................46
Table 8.f
Highly Effective and Other Effective Methods of Contraception for Male 
Patients ..............................................................................................................46
Table 9.a
Clinical Chemistry and Hematology Tests..........................................................60
Table 9.b
Primary Specimen Collection.............................................................................63
Table 9.c
End of Safety Follow-Up Period Clinical Parameters .........................................65
Table 10.a
Takeda Medically Significant Adverse Event List..............................................71
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LIST OF IN-TEXT FIGURES
Figure 4.a
Change in Serum Baseline Levels of Total IgA, IgG, and IgM in Healthy 
Subjects .............................................................................................................28
Figure 4.b
Serum Levels of Total IgA, IgG, and IgM in Patients With RRMM ...................29
Figure 4.c
Pharmacodynamic Effects of TAK-079 on Plasma Cells in Bone Marrow 
Aspirate Samples From Patients With RRMM ...................................................30
Figure 6.a
Study Schematic ................................................................................................34
LIST OF APPENDICES
Appendix A
Schedule of Events.............................................................................................88
Appendix B
Clinical Signs and Symptoms of Cytokine Release Syndrome............................93
Appendix C
Grading System for Cytokine Release Syndrome ...............................................94
Appendix D
Responsibilities of the Investigator.....................................................................95
Appendix E
Investigator Consent to Use of Personal Information..........................................97
Appendix F
MG-ADL Score .................................................................................................98
Appendix G
MGII Score........................................................................................................99
Appendix H
MGC Score......................................................................................................100
Appendix I
QMG Score......................................................................................................101
Appendix J
MG-QoL15r.....................................................................................................102
Appendix K
PGIC................................................................................................................103
Appendix L
PGIS................................................................................................................104
Appendix M
Protocol History...............................................................................................105
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CONFIDENTIAL
2.0
STUDY SUMMARY
Name of Sponsor: Millennium Pharmaceuticals, Inc
Compound: TAK-079
Title of Protocol: A Phase 2, Randomized, 
Placebo-Controlled Study to Evaluate Safety, Tolerability, 
and Efficacy of TAK-079 in Patients With Generalized 
Myasthenia Gravis
EudraCT No.: 2019-003383-47
Study Number: TAK-079-1005
Phase: 2
Study Design:
This is a phase 2, randomized, double-blind, placebo-controlled study designed to assess the safety, tolerability, and 
efficacy of TAK-079 in patients with generalized myasthenia gravis (MG) in combination with standard background 
therapy. 
It is expected that approximately 36 patients will be randomized into the study. After a screening period of up to 28 
days, eligible patients will be randomized in a 1:1:1 ratio to one of the following treatment groups:

TAK-079 300 mg added to stable standard background therapy.

TAK-079 600 mg added to stable standard background therapy.

Matching placebo added to stable standard background therapy.
The study will be divided into 3 sequential periods: a dosing period (8 weeks), a safety follow-up period (SFP; 8 
weeks), and a long-term follow-up period (LFP; 16 weeks). 
During the 8-week dosing period, TAK-079/matching placebo will be administered via subcutaneous (SC) injection 
once weekly for 8 weeks. Patients will be premedicated with an antipyretic (such as acetaminophen) and an 
antihistamine (such as diphenhydramine) 1 to 3 hours before TAK-079 administration.
Safety assessment, including safety laboratory tests, will be performed each week before subsequent dosing. Patients 
may have study drug (TAK-079/placebo) doses modified (eg, withheld or delayed) for safety reasons. 
After completing the 8-week dosing period, patients will enter an 8-week blinded SFP, completing safety and efficacy 
assessments every 2 weeks. After completion of the Week 16 visit in the SFP, patients will be unblinded before 
entering the LFP visit at Week 20. 
Patients randomized to TAK-079 will be followed every 4 weeks from Week 20 through to Week 32 of the LFP for 
MG clinical activity scores and autoantibody levels; the end-of-study visit will take place at Week 32 of the LFP. For 
patients randomized to placebo, the end-of-study visit will take place at Week 20 of the LFP. 
Adverse events (AEs) ongoing at the Week 16 visit of the SFP (including unresolved clinical/laboratory parameters) 
should be monitored through the LFP until they are resolved, return to baseline, or are clearly determined to be due to 
a patient’s stable or chronic condition or intercurrent illness(es). Study drug–related AEs/serious adverse events 
(SAEs) with onset after the SFP will be collected through the LFP. Overall, the maximum follow-up period is 
approximately 24 weeks after the last dose of study drug. 
Patients will be permitted to receive rescue medication, as determined by the investigator, eg, intravenous 
immunoglobulin (IVIg), high dose corticosteroids, or plasmapheresis/plasma exchange. If the patient receives rescue 
therapy during the dosing period, they will automatically enter the SFP.
Primary Objective:
To evaluate the safety and tolerability of TAK-079 in patients with generalized MG who are receiving stable 
background therapy for MG.
Secondary Objective:
To assess the effects of TAK-079 on MG disease activity using clinical rating scales and autoantibody levels.
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Patient Population: Generalized MG positive anti–acetylcholine receptor (AChR) or anti–muscle-specific tyrosine 
kinase (MuSK) antibodies, class II to IV disease according to the Myasthenia Gravis Foundation of America (MGFA), 
and a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or higher.
Number of Patients: 36 patients
Number of Sites: Approximately 50 sites
Dose Level: TAK-079 300 mg, 600 mg, or matching 
placebo administered once weekly for 8 weeks.
Route of Administration: TAK-079/matching 
placebo: SC injection
Duration of Treatment: 
Dosing period: maximum of 8 weeks.
Period of Evaluation: From first dose of TAK-079 
until last LFP visit.
Main Criteria for Inclusion:
Each patient must meet all the following inclusion criteria to be randomized to treatment:
1.
Aged 18 years or older.
2.
Diagnosis of MG supported by a positive serologic test for anti-AChR or anti-MuSK antibodies at screening.
3.
MGFA clinical classification class II to IV at screening.
4.
MG-ADL total score of 6 or greater at screening, with at least 4 points of this score attributed to nonocular items.
5.
If receiving immunosuppressive drugs (ie, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, 
cyclophosphamide), therapy must be ongoing for at least 6 months, with a stable dosing ongoing for at least 3 
months before screening. Patients receiving azathioprine must be on a stable dose for at least 6 months before 
screening.
6.
If receiving oral corticosteroids, therapy must be ongoing for at least 3 months, with a stable dose at least 1 month 
before screening. Corticosteroids, including dexamethasone, must be given as oral, daily or every-other-day 
therapy, as opposed to pulse therapy.
7.
If receiving cholinesterase inhibitors, therapy with a stable dose is required at least 2 weeks before screening.
8.
The doses of concomitant standard background therapy must be expected to remain stable throughout the study 
unless dose reduction is required due to toxicities. Allowed background therapy is defined as no more than a 
cholinesterase inhibitor ± corticosteroid ± 1 steroid-sparing immunosuppressive drug (limited to azathioprine, 
mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, or cyclophosphamide). Patients must be on at 
least 1 allowed background medication.
9.
Female patients of childbearing potential are required to have a negative pregnancy test. Both male and female 
patients must practice an effective, reliable and approved contraceptive regimen during the study and for up to 90 
days or 5 half-lives, whichever is longer, after discontinuation of treatment.
10. Patients must be able and willing to comply with study procedures.
Main Criteria for Exclusion:
Patients meeting any of the following exclusion criteria are not to be randomized to treatment:
1.
Presence of a thymoma (previous history of a fully encapsulated thymoma removed ≥12 months before screening 
is allowed) or history of invasive thymic malignancy unless deemed cured by adequate treatment with no 
evidence of recurrence for ≥5 years before screening. 
2.
History of thymectomy within 12 months before screening.
3.
MGFA class I or V.
4.
Received IVIg, SCIg (subcutaneous immunoglobulin), or plasmapheresis/plasma exchange within 4 weeks 
before screening, or an expectation that any therapy besides the patient’s standard background therapies may be 
used for treatment of MG (eg, a rescue therapy) between screening and dosing.
5.
Chronic obstructive pulmonary disease (COPD) or asthma with a pre-bronchodilatory forced expiratory volume 
in 1 second (FEV1) <50% of predicted normal.
Note: FEV1 testing is required for patients suspected of having COPD or asthma.
6.
Received rituximab, belimumab, eculizumab, or any monoclonal antibody for immunomodulation within 6 
months before first dosing. Patients with prior exposure to rituximab must have CD19 counts within the normal 
range at screening. 
7.
Known autoimmune disease other than MG that would interfere with the course and conduct of the study.
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8.
Received a live vaccine within 4 weeks before screening or has any live vaccination planned during the study.
9.
Any medical condition that, in the opinion of the investigator, might interfere with the patient’s participation in 
the study (such as significant cardiovascular, pulmonary, hematologic, gastrointestinal, endocrinologic, hepatic, 
renal, neurologic, malignancy, or infectious disease), poses added risk for the patient, or could confound the 
assessment of the patient.
10. Pregnancy or lactation during the screening period or on Day 1 before first dose of study drug.
11. Participation in any other investigational drug study or exposure to other investigational agent within 4 weeks or 5 
half-lives, whichever is longer, before Day 1.
12. An opportunistic infection ≤12 weeks before initial study dosing or is currently receiving treatment for a chronic 
opportunistic infection, such as tuberculosis (TB), pneumocystis pneumonia, cytomegalovirus, herpes simplex 
virus, herpes zoster, or atypical mycobacteria. A mild, localized herpes simplex infection within 12 weeks of 
study dosing is allowed, as long as the lesion has resolved without systemic therapy before Day 1.
13. Inadequate organ and bone marrow function:
a)
Alanine aminotransferase or aspartate aminotransferase >3 times the upper limit of normal (ULN).
b)
Total bilirubin >1.5 times ULN (Note: Patients with a confirmed and documented diagnosis of Gilbert 
syndrome are not excluded based on this criterion).
c)
Platelets <75,000/mm3.
d)
Absolute neutrophil count <1500/mm3.
e)
Hemoglobin <8 g/dL.
f)
IgG <5 g/L (500 mg/dL).
g)
Lymphocyte count <500/mm3.
14. A positive T-cell interferon-γ release assay (TIGRA) (result through QuantiFERON-TB Gold test or 
T-Spot/Elispot) at the screening visit, noting the following: 
a)
A purified protein derivative (PPD) skin test may be used if TIGRA testing is not available.
b)
Patients with an indeterminate TIGRA result must meet the following criteria:
i.
Negative PPD skin test (defined as <5 mm induration).
ii.
At low risk of acquiring TB (eg, avoids close contact with TB-positive individual[s]) and/or chest x-ray 
≤6 months before the screening visit that is consistent with no evidence of latent or active TB.
15. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the 
completion of treatment according to this protocol.
16. A positive test result for hepatitis B surface antigen, or hepatitis B core antibody, hepatitis C antibody, or HIV 
antibody/antigen, at screening. However, an individual who has a known history of chronic hepatitis C and has 
been treated and fully cured of the disease, confirmed with a negative hepatitis C virus RNA polymerase chain 
reaction test at screening, is not excluded on the basis of positive hepatitis C antibody alone.
17. A history of severe allergic or anaphylactic reactions to recombinant proteins or excipients used in the 
TAK079/placebo formulation.
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Main Criteria for Evaluation and Analyses:
Primary: Percentage of patients with treatment-emergent adverse events, including Grade 3 or higher events, SAEs, 
and AEs leading to TAK-079 discontinuation.
Secondary: 
1.
Score change from baseline in the following:
a)
MG Activities of Daily Living (MG-ADL) score.
b)
Quantitative Myasthenia Gravis (QMG) score.
c)
Myasthenia Gravis Composite (MGC) score.
d)
Revised 15-item Myasthenia Gravis Quality of Life scale (MG-QoL15r).
2.
Change from baseline in anti-AChR antibody or anti-MuSK antibody levels
3.
Percentage of patients meeting minimal clinically important difference criteria in the respective MG clinical 
impairment scales (MG-ADL, QMG, MGC).
Exploratory:
1.
Serum concentration-time profile of TAK-079 PK parameters will include, but are not limited to, observed 
concentration at the end of a dosing interval (Ctrough) over time.
2.
Change in serum immunoglobulin levels.
3.
Pharmacodynamic analysis of the presence and changes of immune cells in peripheral blood before and during 
therapy.
4.
Score change from baseline in the Myasthenia Gravis Impairment Index (MGII) score.
5.
Duration of a clinically meaningful effect on MG disease severity (in all clinical disease impairment scales: 
MG-ADL, QMG, MGC, MGII).
6.
Percentage of patients meeting minimal clinically important difference criteria in the MGII scale.
7.
Frequency and proportion of patients requiring rescue therapy.
8.
Immunogenicity assessment of TAK-079 in peripheral blood, including antidrug antibody (ADA).
9.
Biomarkers of disease activity such as complement levels (C3, C4, complement split products); specific markers 
of CD38 pathway modulation may also be evaluated.
10. Change in levels of the following vaccine-protective antibodies: measles, mumps, rubella, diphtheria, and tetanus.
Statistical Considerations:
Safety Analysis
The safety analysis set will include all patients who have received at least 1 dose of study drug. 
Safety will be evaluated by the frequency of AEs, severity and types of AEs, and by changes from baseline in patients’ 
vital signs, weight, and clinical laboratory results using the safety analysis set. Exposure to study drug and reasons for 
discontinuation will be tabulated. 
TEAEs that occur after administration of the first dose of study drug and through to the end of the SFP period will be 
tabulated. 
AEs will be tabulated according to the Medical Dictionary for Regulatory Activities, and data will be summarized 
using Preferred Term and primary System Organ Class. All safety analyses will be performed using the safety analysis 
population 
Efficacy Endpoint Analyses: The analysis of the efficacy endpoints will be performed on the full analysis set, defined 
as all randomized patients who had baseline and at least 1 postbaseline efficacy assessment. Efficacy endpoints will be 
summarized by descriptive statistics and presented by treatment groups. Where appropriate, efficacy endpoints may be 
analyzed with the following methods:

Binary endpoints will be analyzed using a Fisher’s exact test. 

Changes from baseline endpoints measured repeatedly over time will be analyzed using a mixed-model 
repeated-measures analysis, which includes treatment, visit, and (treatment × visit) interaction terms as the 
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factors, with baseline values as covariates.
All tests of treatment effects will be conducted at a 2-sided α level of 0.05, and 95% CIs for the differences in 
proportions and least square means will be provided. No inferential hypothesis was tested in these endpoints, so CIs 
and p-values are not adjusted for multiplicity. 
Sample Size Justification: 
Approximately 36 patients are planned to be randomized to treatment in a ratio of 1:1:1 (TAK-079 300 mg, TAK-079 
600 mg, or placebo). This study is exploratory and not powered to address any predefined hypothesis. 
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3.0
STUDY REFERENCE INFORMATION
3.1
Study-Related Responsibilities
The sponsor will perform all study-related activities except for those identified in the clinical 
supplier list in the study manual/binder. The identified vendors will perform specific study-related 
activities either in full or in partnership with the sponsor.
3.2
Coordinating Investigator
Takeda will select a signatory coordinating investigator from the investigators who participate in 
the study. Selection criteria for this investigator will include significant knowledge of the study 
protocol, the study medication, their expertise in the therapeutic area and the conduct of clinical 
research, and study participation. The signatory coordinating investigator will be required to 
review and sign the clinical study report and by doing so agrees that it accurately describes the 
results of the study.
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3.3
List of Abbreviations
AChR
acetylcholine receptor
ADA
antidrug antibody
AE
adverse event
AUC
area under the plasma concentration-time curve
Cmax
maximum observed plasma concentration
COPD
chronic obstructive pulmonary disease
COVID-19
coronavirus disease 2019
CRO
contract research organization
CRS
cytokine release syndrome
Ctrough
observed concentration at the end of a dosing interval
DSMB
data safety monitoring board
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
FcRn
neonatal Fc receptor
FDA
Food and Drug Administration (US)
FEV1
forced expiratory volume in 1 second
GCP
Good Clinical Practice
GLP
Good Laboratory Practice
hCG
human chorionic gonadotropin
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
IEC
independent ethics committee
Ig
immunoglobulin
IRB
institutional review board
IRR
infusion-related reaction
ISR
injection site reaction
IV
intravenous(ly)
IVIg
intravenous immunoglobulin
IXRS
interactive voice/web response system
LFP
long-term follow-up period
MedDRA
Medical Dictionary for Regulatory Activities
MG
myasthenia gravis
MG-ADL
Myasthenia Gravis Activities of Daily Living
MGC
Myasthenia Gravis Composite
MGFA
Myasthenia Gravis Foundation of America
MGII
Myasthenia Gravis Impairment Index
MG-QoL15r
revised 15-item Myasthenia Gravis Quality of Life scale
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MHRA
Medicines and Healthcare products Regulatory Agency
MuSK
muscle-specific tyrosine kinase
NCI CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events
NK
natural killer
NMJ
neuromuscular junction
NOAEL
no-observed-adverse-effect level
PGIC
Patient Global Impression of Change
PGIS
Patient Global Impression of Severity
PK
pharmacokinetic(s)
PMDA
Pharmaceuticals and Medical Devices Agency
PPD
purified protein derivative
PTE
pretreatment event
QMG
Quantitative Myasthenia Gravis
RBC
red blood cell
RRMM
relapsed and/or refractory multiple myeloma
SAE
serious adverse event
SC
subcutaneous(ly)
SFP
safety follow-up period
SLE
systemic lupus erythematosus
SOE
schedule of events
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
TEAE
treatment-emergent adverse event
TIGRA
T-cell interferon-γ release assay
TNF-α 
tumor necrosis factor alpha
UK
United Kingdom
ULN
upper limit of the normal range
US
United States
WHO
World Health Organization
3.4
Corporate Identification 
Millennium
Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical 
Company Limited
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4.0
INTRODUCTION
4.1
Disease Background
Myasthenia gravis (MG) is a rare autoimmune disorder in which autoantibodies target the 
neuromuscular junction (NMJ) and postsynaptic membrane and interfere with neuromuscular 
transmission, which leads to progressive weakness of skeletal muscles. The estimated annual 
incidence of MG in the United States (US) is 5.3 per million, with a prevalence of approximately 
77.7 per million [1-4]. 
Characteristically for MG, the skeletal muscle weakness and fatigability worsens with physical 
activity and improves with rest [5]. In some cases, muscle weakness can lead to respiratory and 
cardiac dysfunction [6]. The disease remains life-threatening; in a myasthenic crisis, the muscles 
that control breathing become too weak, which can result in death due to paralysis of the 
respiratory muscles. 
MG is caused by pathogenic autoantibodies that are produced by plasma cells. Most patients 
(80%-90%) with MG produce immunoglobulin (Ig)G1 and IgG3 autoantibodies against the 
acetylcholine receptor (AChR), while the remaining patients either produce IgG4 autoantibodies
against muscle specific tyrosine kinase (MuSK; ~5% of patients), IgG1-3 antibodies against the 
low-density lipoprotein receptor-related protein 4 (~1% of patients), or produce no detectable 
autoantibodies [7]. The binding of autoantibodies to proteins in the NMJ ultimately leads to 
damage of the postsynaptic membrane [5].
Reducing the levels of pathogenic autoantibodies is challenging. The autoantibody-producing 
plasma cells are resistant to many conventional pharmacologic strategies because they are not 
actively cycling and express relatively few surface antigens. 
The current standard of care for MG consists of a combination of symptomatic therapy 
(acetylcholinesterase inhibitors, to increase the levels on acetylcholine in the synapse) and 
immunosuppression. Immunosuppressive or immunomodulatory therapies (such as 
corticosteroids, azathioprine, methotrexate, cyclosporine, tacrolimus, cyclophosphamide, 
plasmapheresis/plasma exchange, and intravenous immunoglobulin [IVIg]) are given to patients 
who do not have satisfactory results with symptomatic therapy alone. Nevertheless, approximately 
10% of patients have treatment-refractory disease, and up to 80% of patients fail to reach a 
complete stable remission [8]. Immunosuppressive medications have several drawbacks, 
including limited efficacy and severe dose-limiting toxicities. Furthermore, these drugs do not 
directly affect autoantibody production. 
Autoantibody levels can be lowered by targeting the B-cell progenitors of plasma cells. Rituximab 
(an anti-CD20 antibody) targets these plasma cell progenitors, thereby indirectly decreasing 
autoantibody production by preventing the replenishment of autoreactive plasma cells. However, 
rituximab’s efficacy in MG has been limited, likely because the long-lived plasma cells that are 
thought to be primarily responsible for anti-AChR antibody production do not express CD20 and 
are therefore not targeted by rituximab [5]. 
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There are some therapeutic options available to lower the antibody levels by increasing the 
clearance of pathogenic autoantibodies, eg, plasmapheresis/plasma exchange, administration of 
IVIg, or neonatal Fc receptor (FcRn) antagonists. Plasmapheresis and IVIg are mostly used until 
other medications take effect, before surgery, or for myasthenic crisis because of their fast but 
short-lived impact. An alternative approach to increase the clearance of autoantibodies may be 
achieved by blocking the FcRn, and several FcRn antagonists are currently in clinical development. 
These drugs decrease pathogenic IgG by accelerating their clearance via inhibiting FcRn-mediated 
IgG recycling. None of these 3 therapeutic strategies inhibit IgG production, and the duration of 
the effect is relatively short; consequently, most likely chronic administration would be required to 
maintain low levels of pathogenic autoantibodies [9]. 
Another therapeutic strategy in MG that does not eliminate the root cause of the disease is to 
reduce the complement-mediated damage of the postsynaptic membrane at the NMJ. This can be 
achieved with eculizumab, a monoclonal antibody against complement protein C5. While showing 
moderate efficacy, eculizumab therapy is related to increased risks of meningococcal infections 
and thereby is restricted by risk evaluation and mitigation strategies [10]. 
In conclusion, there is a need for novel therapies in MG that can provide deeper and sustained 
responses with a favorable safety profile, to help decrease use of corticosteroids and to improve 
patients’ quality of life. Targeting CD38, a cell surface molecule whose expression is restricted to 
subsets of hematopoietic cells and that is highly expressed on plasmablasts, short-lived plasma 
cells, and long-lived plasma cells, is an attractive therapeutic strategy in MG. TAK-079 could 
eliminate the production of autoantibodies by depleting plasma cells, thus providing effective and 
more durable disease control, with a favorable safety and tolerability profile. 
4.2
Rationale for the Proposed Study
TAK-079 is a fully human recombinant monoclonal antibody directed against CD38, an antigen 
that is highly expressed on plasma cells, plasmablasts, and natural killer (NK) cells and is induced 
on activated T cells and B cells. TAK-079 administration results in depletion of cells expressing 
high levels of CD38 through a mechanism that involves apoptosis, antibody-dependent 
cell-mediated cytotoxicity, and complement-dependent cytotoxicity [11]. TAK-079 depletes the 
cells that produce the pathogenic autoantibodies (plasmablasts, plasma cells, and especially 
long-lived plasma cells). A reduction in plasmablasts and long-lived plasma cells by TAK-079 is 
expected to result in a reduction in the levels of pathogenic autoantibodies, thereby improving the 
autoantibody-mediated pathology in MG, eg, reducing damage at the NMJ and improving the 
reversible neuromuscular deficits in these patients.
TAK-079 is therefore being proposed as a potential treatment for generalized MG in adult patients.
The pharmacodynamic effects of TAK-079 have been confirmed experimentally in vitro and in 
vivo and have also been shown in human clinical studies. In an in vitro study, TAK-079 reduced 
both short- and long-lived plasma cells isolated from bone marrow aspirates or blood from healthy 
control subjects and patients with systemic lupus erythematosus (SLE) (TKD-BCS-00416-R1). 
TAK-079 also reduced the number of cells producing autoantibodies, including VH4-34 (9G4) 
(reduced in 71% of samples) and anti-Ro (reduced in 58% of samples) in SLE patient samples. 
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These effects on autoantibodies corresponded to comparable reductions in total IgG-producing 
cells, indicating that total IgG could be used as a surrogate biomarker for autoantibodies, in the 
absence of autoantibody data.
An in vivo study in a monkey collagen-induced arthritis model of autoimmune disease 
demonstrated the therapeutic efficacy of TAK-079 (TAK-079-10032). Treatment of arthritic 
monkeys with TAK-079 (3 mg/kg intravenously [IV] weekly) was well tolerated and reduced 
disease progression. Arthritis scores and joint swelling were significantly lower than with the 
vehicle control and were accompanied by decreases in blood levels of C-reactive protein, alkaline 
phosphatase, and NK, B, and T cells. Histopathology, morphometry, and radiology revealed 
significantly less joint damage in animals treated with TAK-079 or dexamethasone (0.1 mg/kg 
oral gavage daily) compared with vehicle control animals, illustrating potential disease-modifying 
activity of TAK-079. These data indicate that depletion of CD38-expressing cells could be a 
therapeutic mechanism for treating autoimmune diseases.
In a study in healthy subjects (TAK-079_101), a single subcutaneous (SC) injection of 0.6 mg/kg 
TAK-079 led to >90% reduction in peripheral blood plasmablasts. The cells reverted to 
pretreatment levels within 50 days. The levels of immunoglobulins (IgM, IgA and IgG) were 
reduced by 15% to 60% and did not fully return to prestudy baseline by the end of the study 
(78 days). These data indicate that TAK-079 may reduce autoantibody levels for a comparable 
duration, which is unique among therapeutics in clinical development for MG. 
Preliminary data from the ongoing clinical study in patients with relapsed and/or refractory 
multiple myeloma (RRMM; TAK-079-1501) confirm the expected pharmacodynamic profile of 
TAK-079. Peripheral blood samples and bone marrow biopsies from patients dosed at 45, 135, 300, 
and 600 mg demonstrated target occupancy and reduction of target cells (ie, plasmablasts, short-
and long-lived plasma cells) in the target organ, ie, bone marrow. Reductions in IgA, IgG, and IgM 
levels were also observed. Maximal pharmacodynamic effects were observed in the bone marrow 
of patients dosed at ≥300 mg. 
In conclusion, TAK-079 reduced levels of autoantibodies in SLE patient samples, an effect that 
was mirrored by corresponding reductions in total IgG production. Similar reductions in total IgG 
were observed in healthy subjects after a single SC dose of TAK-079 and in patients with multiple 
myeloma receiving multiple SC doses. It is therefore hypothesized that similar SC dosing in MG 
patients with TAK-079 will reduce levels of AChR and MuSK antibodies because they are 
components of the total IgG profile. TAK-079 has a unique mechanism of action that inhibits 
production of autoantibodies and total IgG, one that could include sustained efficacy in patients 
with MG, and suggests that TAK-079 may have the potential to address the unmet needs of 
patients suffering from autoantibody-mediated diseases such as MG.
4.3
Dose Rationale
The criteria for selecting doses and a regimen of TAK-079 for treating patients with MG was based 
upon identifying safe and well-tolerated doses that demonstrate pertinent pharmacodynamic 
activity.
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The clinical experience to date has demonstrated that TAK-079 is safe and well-tolerated in 
3 different populations (ie, healthy subjects, patients with RRMM, and patients with SLE) and 
across a broad range of doses (≤600 mg), vascular concentrations, and exposures. 
In healthy subjects, single doses of TAK-079 up to 0.06 mg/kg IV and 0.6 mg/kg SC were well 
tolerated: adverse events (AEs) were mild to moderate in intensity, with most of the AEs being 
mild. There were no serious adverse events (SAEs) or deaths reported in the study, and no AEs led 
to either study or visit discontinuation. No remarkable findings for laboratory tests, 
electrocardiograms (ECGs), vital signs, or physical examinations were reported that were related 
to TAK-079 treatment (see TAK-079 Investigator’s Brochure [IB]). 
As of June 2019, 31 patients have been enrolled in the ongoing RRMM study across 4 dose 
escalation cohorts (4 patients in 45 mg; 3 patients in 135 mg; 12 patients in 300 mg; and 
12 patients in 600 mg). The maximum duration of exposure is 9 and 11 months for a patient 
continuing to receive 300 mg and 135 mg, respectively. The maximum tolerated dose has not been 
identified. At the IB data cutoff date (20 March 2019), the safety profile was comparable for all 
tested doses (45 mg [n = 4], 135 mg [n = 3], 300 mg [n = 6], and 600 mg [n = 6]). No patients have 
experienced dose-limiting toxicity, injection site reactions, or systemic infusion reactions. 
Drug-related SAEs, AEs that led to study discontinuation, or on-study deaths have not been 
reported. The most commonly reported (≥20% of all patients) treatment-emergent adverse events 
(TEAEs) by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term regardless 
of causality at doses up to 600 mg include anaemia, decreased appetite, fatigue, headache, 
hypertension, and insomnia. All AEs have been Grade 1 or 2 other than 2 events reported as 
drug-related Grade 3 events (decreased neutrophil count and anaemia [in 1 patient each]), both of 
which were transient (see current TAK-079 IB for further details). 
As of June 2019, 4 patients have been enrolled and treated with 45 mg TAK-079 or placebo (in a 
blinded manner) in the ongoing study in SLE. Data are still blinded, but 1 patient has reported 
2 TEAEs: nausea and headache (both events Grade 1). No infusion reactions, cytokine release 
syndrome (CRS), or injection site reactions have been reported (see current TAK-079 IB [cutoff 
20 March 2019] for further details).
There were 3 adverse effects observed in nonclinical 3-month, Good Laboratory Practice 
(GLP)-compliant toxicology studies in pharmacologically responsive monkeys. These adverse 
effects were dose-dependent thrombocytopenia, anemia, and/or leukopenia (associated with 
infection only at nontolerated doses). Thrombocytopenia set the nonclinical 
no-observed-adverse-effect level (NOAEL) at a dose of 0.3 mg/kg, which corresponded to a 
maximum observed concentration (Cmax) of 8.1 µg/mL and an area under the concentration-time 
curve (AUC) of 28,875 day*ng/mL.
To further investigate the potential for anemia and thrombocytopenia in humans, a series of in 
vitro studies was performed. TAK-079 bound to CD38 on 11% to 17% of human platelets in 
platelet-rich plasma (1:8 platelet-rich plasma dilution, n = 2 healthy donors) with intensity 57% to 
70% that of isotype control antibody at concentrations of 20 µg/mL (TKD-BCS-00327-R1 
Amendment 1) (monkey platelets were not assessed because of technical limitations). Also, 
TAK-079 bound to CD38 on healthy human red blood cells (RBCs) (~10%-51%, n = 5) and 
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monkey RBCs (up to 19%, n = 1) with low intensity at concentrations 0.1 to 100 µg/mL in vitro 
(TKD-BCS-00064-R1-Report and TKD-BCS-00327-R1 Amendment 1) and did not induce 
hemolysis at ≤20 µg/mL, or hemagglutination at ≤1000 µg/mL, the highest concentrations tested 
(TKD-BCS-00327-R1 Amendment 1). TAK-079 also bound to human and monkey 
megakaryocyte and erythroid progenitors but did not induce direct cytotoxicity in these cells 
(TKD-BCS-00315-R1 and TKD-BCS-00407-R1). Lastly, TAK-079 bound to subsets of human 
and monkey leukocytes and depleted cells that express high densities of CD38, eg, plasma cells, 
plasmablasts, and NK cells (TAK-079-10010, TAK-079-10166, and TAK-079-1501). Importantly, 
despite binding activity observed in vitro, drug-related anemia or thrombocytopenia has not been 
observed in clinical studies to date, despite the current dosing regimens exceeding the associated 
nonclinical doses, concentrations, and exposures up to a maximum clinical dose of 600 mg 
(maximum individual concentration of 235 µg/mL and exposure of 698,070 day*ng/mL).
Two pharmacodynamic effects of TAK-079 are considered most pertinent to treating patients with 
MG. Changes in the level of serum Ig are used as a surrogate biomarker of anti-AChR and 
anti-MuSK antibodies because these autoantibodies are of the same IgG antibody class and are not 
present in healthy subjects, patients with RRMM, or patients with SLE. A single SC dose of 
TAK-079 at 0.1, 0.3, or 0.6 mg/kg to healthy subjects reduced serum mean IgA levels by 20% to 
30%; IgG levels by 40% to 60%; and IgM by 10% to 25% (Figure 4.a). Similarly, weekly dosing 
of patients with RRMM with 45, 135, 300, or 600 mg generally reduced serum IgA to 30% to 95%, 
IgG to 5% to 60%, and IgM to 0% to 50% of baseline levels (Figure 4.b). 
The second pharmacodynamic effect is a reduction in the level of plasma cells in bone marrow 
aspirates. The elimination of nonmalignant plasma cells in the bone marrow aspirates of patients in 
the RRMM study was examined as a surrogate for the elimination of pathogenic 
autoantibody-secreting plasma cells, as the bone marrow is a known site for autoantibody 
production in MG [12]. The desired 80% reduction in nonmalignant bone marrow plasma cells 
required dosing at 300 and 600 mg of TAK-079 (Figure 4.c). Reductions in nonmalignant bone 
marrow plasma cells generally appeared similar with exposure to 300 and 600 mg of TAK-079. 
Considering the small sample size, variability in pharmacokinetics (PK), and comparable safety 
profiles, selecting both doses for assessing potential efficacy is warranted.
The dosing schedule was estimated based on the desired effect of achieving autoantibody 
reductions that are correlated with clinical improvement in MG. While there is no accepted 
consensus for such an autoantibody reduction threshold, group-level clinical improvements in MG 
patients have been reported with reductions in the >50% range with rituximab [13] and 
efgartigimod [14]. In the absence of data characterizing TAK-079 activity on autoantibody levels 
in MG patients, changes in serum IgG were used as a surrogate. In patients with RRMM, a ~50% 
reduction in IgG was observed only after 8 weekly doses of TAK-079 (in the 300 mg and 600 mg 
cohorts, Figure 4.b). Based on these data, a schedule of 8 weekly doses was selected for the present 
study, with weekly monitoring of clinical laboratory values (CBC, immunoglobulin levels, see 
Section 8.4.1) to ensure the safety of this approach. Following the 8-week dosing period, a 
6-month follow-up is planned for the continued monitoring of safety laboratory parameters and for 
evaluating the durability of any clinical benefit. Additionally, information will be obtained on the 
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PK of TAK-079 and the reconstitution kinetics of IgG and autoantibody levels in MG patients to 
facilitate modeling for revised dosing regimens in subsequent studies.
The dose finding performed in patients with RRMM is relevant for dose selection in patients with 
MG because of similarities in target cell levels between these 2 populations. The mean levels of 
target cells in the target organ (bone marrow) are similar between patients with MG and the 
patients with RRMM studied in the 300 mg and 600 mg dose cohorts. In patients with MG, the 
mean level of plasma cells was reported to be 2.6% ± 1.9% of total mononuclear cells [15], while 
the mean levels of myeloma cells in the 300 and 600 mg cohorts were 2.3 ± 1.8% and 2.1% ± 2.6%, 
respectively. As we have selected the 300 and 600 mg doses based on safety, tolerability, and 
pharmacodynamic analyses (discussions above), the similarity in target cell levels between these 
patient groups provides reassurance that these analyses are translatable across the MG and RRMM 
indications. 
Case reports exist of successfully treating antibody-driven diseases with anti-CD38 therapy using 
the same dose and schedule as in patients with multiple myeloma (daratumumab 16 mg/mL for ≥6 
weekly doses), despite the absence of overall elevations in target plasma cells. For example, 
daratumumab was used to treat a patient with pure red cell aplasia (and otherwise normal bone 
marrow) from persistent anti–red blood cell antibodies after an ABO-mismatched allogenic bone 
marrow transplant for myelodysplastic syndrome [16]. Similarly, daratumumab was used 
successfully in a pediatric patient with anti–red blood cell antibodies after bone marrow 
transplantation [17]. Lastly, a case of antibody-mediated rejection after renal transplantation for 
postinfectious membranoproliferative glomerulonephritis was treated successfully with 
daratumumab after failure of bortezomib and rituximab therapy in a patient with normal bone 
marrow (less than 1% plasma cells) and concurrently treated with tacrolimus and prednisone [18]. 
No specific safety concerns of daratumumab therapy were reported. Together, these case reports 
indicate that the myeloma dose of anti-CD38 therapy was safe and effective in nonmyeloma 
patients who did not have any plasma cell tumor burden, had normal if not hypocellular bone 
marrow, and who had a critical need for removal of plasma cells secreting pathogenic antibodies. 
In conclusion, the collective safety, tolerability and pharmacodynamic profiles of TAK-079 in 
dose-escalation studies in healthy subjects, patients with RRMM, and patients with SLE indicate 
that the optimal doses and schedule of TAK-079 for patients with MG consist of 8 weekly doses of 
300 or 600 mg.
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Figure 4.a
Change in Serum Baseline Levels of Total IgA, IgG, and IgM in Healthy 
Subjects
Ig: immunoglobulin; IV: intravenous; SC: subcutaneous; SEM: standard error mean.
Serum samples obtained after a single administration of TAK-079 or placebo, administered either as IV dosed 0.003 to 
0.06 mg/kg or SC injection dosed 0.03 to 0.6 mg/kg. 
Symbols represent the mean change for the cohort, and error bars represent the SEM.
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Figure 4.b
Serum Levels of Total IgA, IgG, and IgM in Patients With RRMM 
Ig: immunoglobulin; LLD: lower limit of detection; RRMM: relapsed and/or refractory multiple myeloma. 
Serum Ig levels (represented as percentage of baseline value for IgA, IgG, or IgM) for each subject obtained after 
TAK-079 subcutaneous dosing (45, 135, 300, or 600 mg) 1 week after the indicated number of doses. The 
myeloma-associated Ig is not shown. Ig profiles whose baseline values were already low (within 10% of the LLD of 
the assay) and subsequently dropped below the LLD are not shown.
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Figure 4.c
Pharmacodynamic Effects of TAK-079 on Plasma Cells in Bone Marrow 
Aspirate Samples From Patients With RRMM 
RO: receptor occupancy (target occupancy); RRMM: relapsed and/or refractory multiple myeloma. 
Target occupancy (blue lines, percentage of CD38 bound by TAK-079) and levels of plasma cells (red line, percent 
change from baseline level) in bone marrow aspirates from patients before treatment (screen) and then after 4 doses 
(Cycle 2), 12 doses (Cycle 4), and 14 doses (Cycle 6) of TAK-079 at 45, 135, 300, or 600 mg (dosed weekly for 8 
weeks, followed by biweekly for 8 weeks, then every 4 weeks until disease progression). Target occupancy and 
plasma cell levels were quantified by flow cytometry, and the data represent individual patients.
4.4
Benefits and Risks Assessment
Because TAK-079 has not yet been tested in patients with MG, the overall clinical benefits and 
risks of TAK-079 in treating patients with MG have not been fully determined.
Potential benefits of TAK-079 in patients with MG are based on nonclinical and clinical data 
presented in Section 4.2. TAK-079 has been shown to reduce autoantibodies in an in vitro study of 
long-lived plasma cells from lupus patients, reduce inflammation in a monkey collagen-induced 
arthritis model, and reduce total immunoglobulin levels (a surrogate marker for autoantibodies) in 
a clinical study of healthy subjects and a clinical study of patients with RRMM. It is therefore 
hypothesized that TAK-079 can reduce the levels of pathogenic autoantibodies in patients with 
MG, thereby improving the muscle weakness caused by autoantibody-mediated inflammatory 
damage at the NMJ.
Risks of TAK-079 are based on clinical and nonclinical data presented in Section 4.3 and the 
intrinsic pharmacology of TAK-079 discussed in Section 8.6. Risks may include, but are not 
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limited to, injection site reactions (ISRs), CRS, hypersensitivity reactions, changes in hematologic 
parameters and infections. Patients will be monitored closely for these AEs in clinical studies with 
TAK-079.
5.0
STUDY OBJECTIVES AND ENDPOINTS
5.1
Objectives
5.1.1
Primary Objective
To evaluate the safety and tolerability of TAK-079 in patients with generalized MG who are 
receiving stable background therapy for MG. 
5.1.2
Secondary Objectives
To assess the effects of TAK-079 on MG disease activity using clinical rating scales and 
autoantibody levels. 
5.1.3
Exploratory Objectives
1. To determine the pharmacokinetics (PK) of TAK-079.
2. To determine the pharmacodynamic profile of TAK-079.
3. To explore the effects of repeated administration of TAK-079 on MG disease activity using a 
novel clinical disease assessment scale.
4. To explore the duration of a clinically meaningful effect on MG disease severity (using at least 
1 MG clinical rating scale).
5. To explore the frequency and proportion of patients requiring rescue therapy.
6. To explore vaccine-induced protective antibodies.
7. To explore the effects of repeated administration of TAK-079 on exploratory biomarkers of 
disease activity.
5.2
Endpoints
5.2.1
Primary Endpoint
Percentage of patients with TEAEs, including Grade 3 or higher events, SAEs, and AEs leading to 
TAK-079 discontinuation. 
5.2.2
Secondary Endpoints
1. Score change from baseline in the following:
a) MG Activities of Daily Living (MG-ADL) score. 
b) Quantitative Myasthenia Gravis (QMG) score.
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c) Myasthenia Gravis Composite (MGC) score. 
d) Revised 15-item Myasthenia Gravis Quality of Life scale (MG-QoL15r).
2. Change from baseline in anti-AChR antibody or anti-MuSK antibody levels.
3. The percentage of patients meeting minimal clinically important difference criteria in the 
respective MG clinical impairment scales (MG-ADL, QMG, MGC).
5.2.3
Exploratory Endpoints
1. Serum concentration-time profile of TAK-079 PK parameters will include, but are not limited 
to observed concentration at the end of a dosing interval (Ctrough) over time.
2. Change in serum immunoglobulin levels.
3. Pharmacodynamic analysis of the presence and changes of immune cells in peripheral blood 
before and during therapy.
4. Score change from baseline in Myasthenia Gravis Impairment Index (MGII) scores. 
5. Duration of a clinically meaningful effect on MG disease severity (in all of the clinical disease 
impairment scales: MG-ADL, QMG, MGC, MGII).
6. Percentage of patients meeting minimal clinically important difference criteria in the MGII 
scale.
7. Frequency and proportion of patients requiring rescue therapy.
8. Immunogenicity assessment of TAK-079 in peripheral blood, including antidrug antibody 
(ADA). 
9. Biomarkers of disease activity such as complement levels (C3, C4, complement split products); 
specific markers of CD38 pathway modulation may also be evaluated. 
10. Change in levels of the following vaccine-protective antibodies: measles, mumps, rubella, 
diphtheria, and tetanus.
6.0
STUDY DESIGN
6.1
Overview of Study Design
This is a phase 2, randomized, double-blind, placebo-controlled study designed to assess the safety, 
tolerability, and efficacy of TAK-079 in patients with generalized MG in combination with 
standard background therapy. 
It is expected that approximately 36 patients will be randomized into the study. After a screening 
period of up to 28 days, eligible patients will be randomized in a 1:1:1 ratio to one of the following 
treatment groups:

TAK-079 300 mg added to stable standard background therapy.

TAK-079 600 mg added to stable standard background therapy.
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
Matching placebo added to stable standard background therapy.
Evaluation of intermediate doses and expansion of an existing dose level are all permissible after 
discussions between the sponsor and the investigators, if such measures are needed for patient 
safety or for a better understanding of the dose-related toxicity, clinical activity, exposure, or 
pharmacodynamics of TAK-079.
The study will be divided into 3 sequential periods: a dosing period (8 weeks), a safety follow-up 
period (SFP; 8 weeks), and a long-term follow-up period (LFP; 16 weeks). 
During the 8-week dosing period, TAK-079/matching placebo will be administered via SC 
injection once weekly for 8 weeks (see Section 8.1 for details on study drug administration). 
Safety assessment, including safety laboratory tests (as listed in Appendix A), will be performed 
each week before subsequent dosing. Patients may have study drug (TAK-079/placebo) doses 
modified (eg, withheld or delayed) for safety reasons (see further details on dose modification/ 
stopping criteria in Table 8.d). 
After completing the 8-week dosing period, patients will enter an 8-week blinded SFP, completing 
safety and efficacy assessments every 2 weeks. After completion of the Week 16 visit in the SFP, 
patients will be unblinded before entering the LFP visit at Week 20. 
Patients randomized to TAK-079 will be followed every 4 weeks from Week 20 through Week 32 
of the LFP for MG clinical activity scores and autoantibody levels; the end-of-study visit will take 
place at Week 32 of the LFP. For patients randomized to placebo, the end-of-study visit will take 
place at Week 20 of the LFP. The study schematic diagram is outlined in Figure 6.a.
AEs ongoing at the Week 16 visit of the SFP (including unresolved clinical/laboratory parameters 
[see Section 9.6]) should be monitored through the LFP until they are resolved, return to baseline, 
or are clearly determined to be due to a patient’s stable or chronic condition or intercurrent 
illness(es). Study drug–related AEs/SAEs with onset after the SFP will be collected through the 
LFP. 
Overall, the maximum follow-up period is approximately 24 weeks after the last dose of study 
drug.
Patients will be permitted to receive rescue medication (eg, IVIg, high dose corticosteroids, or 
plasmapheresis/plasma exchange) as determined by the investigator and described in Section 8.1.3. 
If the patient receives rescue therapy, they will automatically enter the SFP. Rescue therapy is 
defined as additional dosing of concomitant medications in accordance with institutional practices 
or the physician’s best medical judgment to control and manage underlying MG conditions.
Study procedures and assessments, with associated time points, are presented in the schedule of 
events (SOE) table in Appendix A. 
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Figure 6.a
Study Schematic
AE: adverse event; LFP: SAE: serious adverse event; W: week.
* Unresolved AEs as of Week 16 and related AEs/SAEs with onset after SFP will be collected through the LFP.
6.2
Safety and Disease Assessments
Safety evaluations will include monitoring of TEAEs per National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. Changes in clinical 
laboratory parameters (standard hematology and chemistry), vital signs, and ECGs that are judged 
by the investigator as clinically significant will be recorded on both the source documentation and 
in the electronic case report form (eCRF) as an AE.
Safety stopping rules are presented in Section 8.4.
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Efficacy evaluations will include measurements of changes in MG disease activity using clinical 
rating scales and autoantibody levels. 
Autoantibody levels will be measured at every visit, and MG clinical activity scores will be 
assessed throughout the study as shown in the SOE in Appendix A. 
6.2.1
PK and Pharmacodynamic Assessments
Samples for PK, pharmacodynamic, and immunogenicity testing will be obtained at prespecified 
time points as described in the SOE in Appendix A.
6.3
Number of Patients
Approximately 36 patients with moderate to severe MG will be randomized from approximately 
50 study sites in the US, Canada, and Europe. 
6.4
Duration of Study
6.4.1
Duration of an Individual Patient’s Study Participation
Study treatment duration will be a maximum of 8 weeks, followed by an 8-week blinded SFP. 
Patients will be unblinded after Week 16 of the SFP and before Week 20 of the LFP. Patients 
randomized to TAK-079 will be followed every 4 weeks for 16 weeks in total in the LFP for 
continued monitoring of MG clinical activity scores and autoantibody levels. Patients randomized 
to placebo will attend an end-of-study visit at Week 20 of the LFP.
The total duration of an individual patient’s study participation will be approximately 9 months.
6.4.2
End of Study/Study Completion Definition and Planned Reporting
The analyses for the clinical study report will be conducted after all patients randomized in the 
study have completed the end-of-study visit (ie, Week 20 for placebo patients or Week 32 for 
TAK-079 patients), as shown in Appendix A.
6.4.3
Time Frames for Primary and Secondary Endpoints to Support Disclosures
Refer to Section 15.4 for disclosure information for all primary and secondary endpoints.
6.4.4
Total Study Duration
It is anticipated that this study will end after all randomized patients have attended the 
end-of-study visit in the LFP (ie, Week 20 for placebo patients or Week 32 for TAK-079 patients) 
as shown in Appendix A. It is expected that the study will last for approximately 18 months 
(including enrollment, dosing period, SFP, and LFP).
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7.0
STUDY POPULATION
7.1
Inclusion Criteria
Each patient must meet all the following inclusion criteria to be randomized to treatment:
1. The patient understands and agrees to study participation by providing a signed and dated 
written informed consent form (ICF) and any required privacy authorization before the 
initiation of any study procedures (as applicable, the patient’s legally acceptable representative 
may provide written informed consent in accordance with local and regional regulatory 
requirements) and, in the opinion of the investigator, is capable of complying with protocol 
requirements.
2. Aged 18 years or older.
3. Diagnosis of MG supported by a positive serologic test for anti-AChR or anti-MuSK 
antibodies at screening.
4. Myasthenia Gravis Foundation of America (MGFA) clinical classification II to IV at 
screening.
5. MG-ADL total score of 6 or greater at screening, with at least 4 points attributed to nonocular 
items.
6. If receiving immunosuppressive drugs (ie, mycophenolate mofetil, methotrexate, cyclosporine, 
tacrolimus, cyclophosphamide), therapy must be ongoing for at least 6 months, with stable 
dosing ongoing for at least 3 months before screening. Patients receiving azathioprine must be 
on a stable dose for at least 6 months before screening.
7. If receiving oral corticosteroids, therapy must be ongoing for at least 3 months, with a stable 
dose at least 1 month before screening. Corticosteroids, including dexamethasone, must be 
given as oral, daily or every-other-day therapy, as opposed to pulse therapy.
8. If receiving cholinesterase inhibitors, therapy with a stable dose is required at least 2 weeks 
before screening.
9. The doses of concomitant standard background therapy must be expected to remain stable 
throughout the study unless dose reduction is required due to toxicities. Allowed background 
therapy is defined as no more than a cholinesterase inhibitor ± corticosteroid 
± 1 steroid-sparing immunosuppressive drug (limited to azathioprine, mycophenolate mofetil, 
methotrexate, cyclosporine, tacrolimus, or cyclophosphamide). Patients must be on at least one 
allowed background medication.
10. Female patients of childbearing potential are required to have a negative pregnancy test. Both 
male and female patients must practice an effective, reliable, and approved contraceptive 
regimen during the study and for up to 90 days or 5 half-lives, whichever is longer, after 
discontinuation of treatment (see Section 8.5.1). 
11. Patients must be able and willing to comply with study procedures.
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7.2
Exclusion Criteria
Patients meeting any of the following exclusion criteria are not to be randomized to treatment:
1. Presence of a thymoma (previous history of a fully encapsulated thymoma removed 
≥12 months before screening is allowed) or history of invasive thymic malignancy unless 
deemed cured by adequate treatment with no evidence of recurrence for ≥5 years before 
screening.
2. History of thymectomy within 12 months before screening.
3. MGFA class I or V.
4. Received IVIg, SCIg (subcutaneous immunoglobulin), or plasmapheresis/plasma exchange 
within 4 weeks before screening, or an expectation that any therapy besides the patient’s 
standard background therapies may be used for treatment of MG (eg, a rescue therapy) 
between screening and dosing.
5. Chronic obstructive pulmonary disease (COPD) or asthma with a pre-bronchodilatory forced 
expiratory volume in 1 second (FEV1) <50% of predicted normal.
Note: FEV1 testing is required for patients suspected of having COPD or asthma.
6. Received rituximab, belimumab, eculizumab, or any monoclonal antibody for 
immunomodulation within 6 months before first dosing. Patients with prior exposure to 
rituximab must have CD19 counts within the normal range at screening. 
7. Known autoimmune disease other than MG that could interfere with the course and conduct of 
the study.
8. Received a live vaccine within 4 weeks before screening or has any live vaccination planned 
during the study.
9. Any medical condition that, in the opinion of the investigator, might interfere with the patient’s 
participation in the study (such as significant cardiovascular, pulmonary, hematologic, 
gastrointestinal, endocrinologic, hepatic, renal, neurologic, malignancy, or infectious disease), 
poses added risk for the patient, or could confound the assessment of the patient.
10. Pregnancy or lactation during the screening period or on Day 1 before first dose of study drug. 
11. Participation in any other investigational drug study or exposure to other investigational agent 
within 4 weeks or 5 half-lives, whichever is longer, before Day 1.
12. An opportunistic infection ≤12 weeks before initial study dosing or currently receiving 
treatment for a chronic opportunistic infection, such as tuberculosis (TB), pneumocystis 
pneumonia, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria. A 
mild, localized herpes simplex infection within 12 weeks of study dosing is allowed, as long as 
the lesion has resolved without systemic therapy prior to Day 1.
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13. Inadequate organ and bone marrow function:
a) Alanine aminotransferase or aspartate aminotransferase >3 times the upper limit of normal 
(ULN).
b) Total bilirubin >1.5 times ULN (Note: Patients with a confirmed and documented 
diagnosis of Gilbert syndrome are not excluded based on this criterion).
c) Platelets <75,000/mm3.
d) Absolute neutrophil count <1500/mm3.
e) Hemoglobin <8 g/dL.
f)
IgG < 5 g/L (500 mg/dL).
g) Lymphocyte count <500/mm3.
14. A positive T-cell interferon-γ release assay (TIGRA) (result through QuantiFERON-TB Gold 
test or T-Spot/Elispot) at the screening visit, noting the following: 
a) A purified protein derivative (PPD) skin test may be used if TIGRA testing is not available.
b) Patients with an indeterminate TIGRA result must meet the following criteria:
i.
Negative PPD skin test (defined as <5 mm induration).
ii.
At low risk of acquiring TB (eg, avoids close contact with TB-positive individual[s]) 
and/or chest x-ray ≤6 months before the screening visit that is consistent with no 
evidence of latent or active TB.
15. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially 
interfere with the completion of treatment according to this protocol.
16. A positive test result for hepatitis B surface antigen, or hepatitis B core antibody, or hepatitis C 
antibody, or HIV antibody/antigen, at screening. However, an individual who has a known 
history of chronic hepatitis C and has been treated and fully cured of the disease, confirmed 
with a negative hepatitis C virus RNA polymerase chain reaction test at screening, is not 
excluded on the basis of the positive hepatitis C antibody alone.
17. A history of severe allergic or anaphylactic reactions to recombinant proteins or excipients 
used in the TAK-079/placebo formulation.
8.0
STUDY DRUG
8.1
Study Drug Administration
All protocol-specific criteria for administration of study drug must be met and documented before 
drug administration. Study drug will be administered only to eligible patients under the 
supervision of the investigator or identified subinvestigator(s). 
After completion of all screening assessments and procedures and confirmation of eligibility, 
patients will report to the study site on Week 1 of the dosing period and be dosed with TAK-079 
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300 mg, TAK-079 600 mg, or matching placebo in accordance with their assigned treatment. Both 
the patient and physician will be blinded to treatment. Before TAK-079/placebo administration, 
patients will receive premedication as listed in Section 8.1.1 and will undergo safety assessments 
as outlined in Table 8.d and Appendix A. 
Patients will receive study drug via SC injection, once weekly as outlined in Table 8.a and the SOE 
in Appendix A. The dosing period will last for 8 weeks. As dose levels (300 and 600 mg) will 
require multiple SC injections to administer the full dose, the Week 1 dose will be administered by 
giving each SC injection 30 minutes apart (±10 minutes) until the full scheduled dose has been 
administered. On all other drug administration days if the patient did not have a clinically 
significant infusion reaction per the investigator, the SC injections can be given at the same time 
without a waiting period.
Investigators will evaluate patients before each dose for the parameters outlined in Table 8.d. For 
the first dose, laboratory assessments in Table 8.d may be evaluated using results obtained at 
screening. Otherwise, laboratory results should be obtained on the day before or the day of dosing. 
In instances where clinical parameters do not meet criteria for continued dosing, the study drug 
must be temporarily withheld until parameters meet dosing levels, or discontinued, as outlined in 
Table 8.d or in accordance with the principal investigator’s judgment. Dosing of 
TAK-079/placebo may not otherwise be reduced or escalated for any given patient.
Note: If study dosing is held for 2 consecutive doses because of safety concerns or conditions 
outlined in Table 8.d, the patient will be discontinued from study dosing and will advance to the 
SFP. If 2 or more patients discontinue study dosing based on the dose discontinuation criteria in 
Table 8.d, the Takeda clinician or designee will review available safety data to determine if 
adjustments to the treatment plan should be made.
Patients should remain on their stable dose of standard background therapy (as listed in Table 8.c),
throughout the study unless dose reduction is required due to toxicities. Allowed background 
therapy is defined as no more than a cholinesterase inhibitor ± corticosteroid ± 1 steroid-sparing 
immunosuppressive drug (limited to azathioprine, mycophenolate mofetil, methotrexate, 
cyclosporine, tacrolimus, or cyclophosphamide). Patients must be on at least one allowed 
background medication.
Excluded and permitted medications are summarized in Table 8.b and Table 8.c, respectively. 
Rescue therapy information is outlined in Section 8.1.3.
Table 8.a
Summary of TAK-079/Placebo Dose Administration
Treatment Arm
Treatment a
Dose
Number of Patients
Arm 1
TAK-079
300 mg
12
Arm 2
TAK-079
600 mg
12
Arm 3
Matching placebo
Not applicable
12
a Patients will receive TAK-079 or matching placebo via subcutaneous administration once weekly over the course of 
8 weeks, for 8 total doses.
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8.1.1
Premedication
On each dosing day, 1 to 3 hours before TAK-079/placebo administration, patients are to be 
premedicated with an antipyretic (such as acetaminophen) and an antihistamine (such as 
diphenhydramine). The premedication regimen should be consistent with, but not limited to, the 
following:

Antipyretic: oral acetaminophen (650-1000 mg).

Antihistamine: oral or IV diphenhydramine (25-50 mg, or equivalent).
8.1.2
Postdose Medication
Patients will be closely monitored in the clinic for at least 2 hours after the first and second 
TAK-079/placebo dose; before discharge from the clinic, the possible signs and symptoms of 
anaphylactic reactions and CRS should be reviewed with patients.
After the first dose of study drug, patients will receive low-dose methylprednisolone (≤20 mg), or 
an equivalent, for the prevention of delayed injection-related reaction. Considering the timing of 
the greatest pharmacologic effect of TAK-079, postdose medication should be given 2 hours (±15 
minutes) after the first injection of the first dose and 1 day after the first dose of study drug in the 
morning.
Postdose low-dose methylprednisolone (≤20 mg) is not mandated after subsequent doses of 
TAK-079/placebo (Weeks 2-8); however, it may be given if clinically indicated and under the 
discretion of the principal investigator.
NOTE: Patients with a higher risk of respiratory complications (eg, patients with a history of 
COPD and patients with asthma) may be administered the following, after each study dose (at the 
investigator’s discretion):
a) An antihistamine (diphenhydramine or equivalent) on the first and second days after study 
dosing.
b) A short-acting β2-adrenergic receptor agonist, such as salbutamol (albuterol) aerosol.
c) Control medications for lung disease, such as the following: 
–
Inhaled corticosteroids with or without long-acting β2 adrenergic receptor agonists for 
patients with asthma. 
–
Long-acting bronchodilators, such as tiotropium or salmeterol, with or without inhaled 
corticosteroids, for patients with COPD.
The clinical site is responsible for sourcing treatments administered pre- or post–
TAK-079/placebo administration.
On the basis of emerging data, the Takeda physician/designee may enhance treatments 
administered pre- or post–TAK-079/placebo injection to ensure patient safety.
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8.1.3
Rescue Therapy
Rescue therapy is defined as additional dosing of concomitant medications in accordance with 
institutional practices or the physician’s best medical judgment to control and manage underlying 
MG conditions. Rescue medications may include, but are not limited to, high-dose corticosteroids, 
IVIg, and plasmapheresis/plasma exchange. Protocol-restricted and permitted concomitant 
medications are outlined in Table 8.b and Table 8.c, respectively.
Patients should remain on their stable dose of immunosuppressive and corticosteroid therapies 
throughout the study (as aligned with protocol requirements in Table 8.b and Table 8.c). If the 
patient receives rescue therapy, they will automatically enter the SFP.

Increasing, adding, or changing background immunosuppressive therapies, or adding a 
medication not otherwise within protocol limits, as deemed necessary by the principal 
investigator to treat manifestations of MG, should result in discontinuation of the patient from 
study dosing and advancement to SFP.
8.2
Excluded Concomitant Medications and Procedures
Excluded concomitant medications are provided in Table 8.b. If patients receive excluded 
medication, they will be discontinued from the dosing period and automatically enter the SFP.
Table 8.b
Excluded Concomitant Medications
Category or Agent
Exclusion Criteria
(Exclusion Criteria Must Be Upheld Throughout Study Participation, 
in Addition to the Time Points Indicated Below) a
Intravenous immunoglobulin b
Restricted from ≤4 weeks before the screening visit.
Plasmapheresis/plasma exchange b
Restricted from ≤4 weeks before the screening visit.
Subcutaneous immunoglobulin b
Restricted from ≤4 weeks before the screening visit.
Rituximab, belimumab, eculizumab, 
or any monoclonal antibody for 
immunomodulation 
Restricted from ≤6 months before first dosing.
Live vaccinations
Restricted from ≤4 weeks before the screening visit. 
AE: adverse event; MG: myasthenia gravis.
a Exceptions to excluded medications may be allowed for treatment of AEs, after discussion and agreement between 
the sponsor and principal investigator.
b Patients for whom any therapy (besides the allowed standard background therapies for MG) is reasonably expected 
between screening and dosing are excluded from study participation.
8.3
Permitted Concomitant Medications and Procedures
Permitted concomitant medications are summarized in Table 8.c.
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Table 8.c
Permitted Concomitant Medications
Medications
Criteria
(Criteria Are to Be Maintained From Screening to Completion of Study 
Dosing Phase)
Immunosuppressants

Azathioprine a
Therapy must be ongoing for at least 6 months with a stable dose for at least 3 
months before the screening visit.

Mycophenolate mofetil

Methotrexate

Cyclosporine

Tacrolimus

Cyclophosphamide
Oral corticosteroids
Therapy must be ongoing for at least 3 months with a stable dose at least 1 month 
before the screening visit.
Cholinesterase inhibitors
Therapy with a stable dose is required at least 2 weeks before the screening visit. 
a Azathioprine dosing must be stable for at least 6 months before screening visit.
8.4
Study Stopping Rules
Takeda clinicians/designee will provide ongoing safety oversight and surveillance throughout the 
study dosing period, SFP, and LFP. As such, TAK-079 clinicians/designee are to receive and trend 
all reported SAEs and conduct a review of all safety data periodically throughout the study. On the 
basis of outcomes of the Takeda safety reviews and in accordance with predefined criteria, 
decisions about the dosing regimen are to be made and implemented.
8.4.1
Assessment and Criteria for Terminating Patient Dosing
Investigators will evaluate patients before each dose for the parameters outlined in Table 8.d. In 
instances where clinical parameters do not meet criteria for continued dosing, study drug dosing 
must be temporarily withheld until parameters meet dosing levels, or discontinued. 
Patients whose clinical parameters meet dose discontinuation criteria, as outlined in Table 8.d, are 
to be permanently discontinued from study dosing and will advance to the SFP, completing all 
associated assessments listed in the SOE table in Appendix A.
In addition, patients should be permanently discontinued from study dosing if any of the following 
is experienced:

An AE or other medical condition in which the principal investigator deems it is not in the best 
interest of the patient to continue study dosing.

The patient receives rescue medication as described in Section 8.1.3.

If study dosing is held for 2 consecutive doses because of safety concerns or conditions 
outlined in Table 8.d.
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
The patient chooses to withdraw from study dosing.

The patient has a confirmed pregnancy.
NOTE: Safety reviews of all AEs will be conducted in an ongoing manner (see details in 
Section 13.1.6). If the stopping bounds for general AEs or SAEs is met, an investigation of the 
safety profile will be conducted and a decision regarding accrual will be made. Further, if 2 or 
more patients discontinue study drug dosing on the basis of the dose discontinuation criteria in 
Table 8.d, the Takeda clinician/designee will review available safety data to determine if 
adjustments to the treatment plan should be made. 
Immunoglobulin levels may be reduced with TAK-079; therefore, quantitative Ig levels (IgG, IgA, 
and IgM) will be evaluated during the treatment period at a central laboratory. If any of these 
are >50% below the lower limit of normal, the investigator should manage as clinically appropriate 
on the basis of signs and symptoms the patient is experiencing. If IgG levels are below the lower 
limit of normal and the patient is experiencing a severe infection, IVIg may be administered, as per 
physician discretion according to standard practice. If IVIg is given as a rescue treatment, as 
described in Section 8.1.3, the patient will be discontinued from the dosing period of the study and 
enter the SFP.
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Table 8.d
Summary of Subsequent Dosing Criteria
Safety Parameter
Dosing Criteria
Continue Dosing
Dose Hold a
Dose Discontinuation b
Laboratory Investigations
Neutrophils
ANC ≥1500/mm3
Total neutrophils ≥Grade 2 c
ANC <1500/mm3
Platelets
Thrombocytopenia ≤Grade 2 c
Platelets ≥50,000/mm3
Thrombocytopenia ≥Grade 3 c
Platelets <50,000/mm3
Total lymphocyte count
≥500/mm3 or ≥90% of the baseline 
level
<500/mm3 and <90% of the baseline level
Hgb
≥8 g/dL
<8 g/dL
Events of Clinical Interest
Hypersensitivity (IRR, allergic reaction, or 
anaphylaxis) (See Section 8.6.1).
NOTE: IRR, allergic reaction or anaphylaxis are 
each classified according to CTCAE v4.03. 
Anaphylaxis is diagnosed according to Sampson 
et al [19].
≤Grade 2 c
≥Grade 3c
or any signs or symptoms of an 
anaphylactic reaction [19]
CRS (See Section 8.6.2)
NOTE: CRS d is classified according to Lee et al 
[20].
Grade 1 with symptomatic treatment 
allowed in accordance with Lee et al 
[20].
≥Grade 2
Systemic infection
Grade 2 c
Hold dosing until the infection is resolved. 
≥Grade 3 c or infections requiring 
hospitalization
ANC: absolute neutrophil count; CRS: cytokine release syndrome; CTCAE: Common Terminology Criteria for Adverse Events; Hgb: hemoglobin; IRR: infusion-related reaction; 
MG: myasthenia gravis; NCI: National Cancer Institute; SFP: safety follow-up period.
a Patients whose clinical parameters meet dose-hold criteria will not receive the scheduled dose of TAK-079; patients instead return for reassessment and evaluation at next planned 
visit.
b Patients whose clinical parameters meet dose discontinuation criteria are to be permanently discontinued from study dosing; patients will advance to the SFP, completing all 
associated assessments. Standard background therapy for MG will be managed according to the principal investigator’s discretion.
c Laboratory, IRR, allergic reactions, anaphylaxis and infection grading are based on CTCAE v4.03.
d Afull cytokine panel is to be obtained for any suspected events, at any grade, of CRS; further information and suggested management of CRS is provided in the protocol. 
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8.5
Precautions and Restrictions
Patients will be closely monitored before all TAK-079/placebo administrations and for at least 
2 hours after the administration of the first and second dose of TAK-079/placebo, with additional 
assessment and observations as necessary based on the principal investigator’s best medical 
judgment, and as warranted by exhibited clinical signs or symptoms at each study clinic visit. 
Postdose monitoring should include vital sign assessments as outlined in Section 9.5.8, and 
additional postdose medications for those with a history of asthma or COPD may be considered, as 
outlined in Section 8.1.2.
On each dosing day, patients should not drive, operate dangerous tools or machinery, or engage in 
any other potentially hazardous activity that requires full alertness and coordination if they 
experience sedation from any premedication listed in Section 8.1.1.
Patients are to be instructed to limit the use of alcohol while enrolled in this study.
8.5.1
Pregnancy, Lactation, and Contraception
TAK-079 has not been administered to women who are pregnant or lactating. No reproductive or 
developmental toxicity studies have been performed for TAK-079 to date; hence, the effects of 
TAK-079 on fertility and the developing fetus are not known at this time. There were no 
TAK-079–related findings (organ weight changes or microscopic findings) noted in the 
reproductive tract (cervix, epididymis, ovary, oviduct, testis, and vagina) of sexually immature 
male and female monkeys after administration for up to 13 weeks. Women of childbearing 
potential may be enrolled in clinical studies with appropriate precautions to prevent pregnancy.
The half-life of TAK-079 has not yet been determined. Based on conservative information in the 
literature regarding the half-life of IgG1 as well as other IgG1 human monoclonal antibodies 
[21,22], a conservative time frame to continue contraception would be 150 days.
TAK-079 should not be administered to women who are pregnant or breastfeeding.
Female patients must meet 1 of the following:

Postmenopausal for at least 1 year before the screening visit, OR

Surgically sterile, OR

If they are of childbearing potential, agree to practice 1 highly effective method and 
1 additional effective (barrier) method of contraception at the same time (Table 8.e), from the 
time of signing of the ICF through 90 days or 5 half-lives*, whichever is longer, after 
discontinuation of treatment, OR

Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of 
the patient (periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation 
methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable 
methods of contraception. Female and male condoms should not be used together).
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Table 8.e
Highly Effective and Other Effective Methods of Contraception for Female 
Patients
Highly Effective Methods
Other Effective Methods (Barrier Methods)
IUD
Latex or nonlatex condom with or without a spermicidal 
agent
Hormonal (oral contraceptives, injectable contraceptives, 
contraceptive patches, or contraceptive implants)
Diaphragm with spermicide; cervical cap with a 
spermicide; sponge with a spermicide
IUD: intrauterine device.
It is recommended to combine a highly effective method with a barrier method. If one of the highly effective methods 
cannot be used, using 2 barrier methods at the same time is recommended.
Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to 1 of the 
following:

Agree to practice effective barrier contraception (Table 8.f) during the entire study treatment 
period and through 90 days or 5 half-lives*, whichever is longer, after discontinuation of 
treatment, OR

Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of 
the patient. Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation 
methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable 
methods of contraception. Female and male condoms should not be used together.
Table 8.f
Highly Effective and Other Effective Methods of Contraception for Male 
Patients
Highly Effective Methods
Other Effective Methods (Barrier Methods)
Vasectomy
Latex or nonlatex condom with or without a spermicidal 
agent
Diaphragm with spermicide; cervical cap with 
spermicide; sponge with spermicide
It is recommended to combine the highly effective method with a barrier method. If the highly effective method cannot 
be used post-vasectomy, using 2 barrier methods at the same time is recommended.

* Note that the half-life of TAK-079 has not yet been determined. Based on conservative 
information in the literature regarding the half-life of IgG1 as well as other IgG1 human 
monoclonal antibodies [21,22], a conservative time frame to continue contraception would be 
150 days.
8.5.2
Drug Interactions
Nonclinical drug interaction studies have not been conducted with TAK-079. However, as a fully 
human IgG1 monoclonal antibody, the risk of drug-drug interactions is low.
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8.5.3
Interference with Serological Testing
Anti-CD38 monoclonal antibodies have been reported to bind to CD38 on RBCs and results in a 
positive indirect Coombs test, which may persist for up to 6 months. The determination of a 
patient’s ABO and Rh blood type are not impacted, but the RBC binding may mask detection of 
antibodies to minor antigens in the patient’s serum [23,24]. It is possible TAK 079 may affect the 
results of these blood tests, this is being evaluated. Should a patient require a blood transfusion, 
blood transfusion centers should be informed of this interference with serological testing [24].
8.6
Management of Clinical Events
8.6.1
Hypersensitivity Reactions: Infusion Reactions
Because infusion reactions and other antibody-mediated hypersensitivity reactions have been 
reported with other biologic agents, similar AEs may be seen with TAK-079. Infusion reactions 
are potentially dose-limiting AEs, not uncommonly associated with IV administration of biologic 
agents, but are less frequently associated with SC injection of these therapies [20,25,26].
Symptoms of hypersensitivity may range from mild skin rash to more severe reactions, wheezing, 
hypotension, poor perfusion, respiratory arrest, and rarely death. Nonanaphylactic clinical 
hypersensitivity typically occurs within the first hour after dosing; however, delayed responses 
have been reported in literature with other biologic agents [27]. Symptoms of anaphylaxis, a 
potentially life-threatening condition, range from swelling, angioedema, and bronchospasm to 
respiratory distress and shock [27]. Hypersensitivity reactions in the literature often occur within a 
few hours following drug intake [20,27]. Based on outcomes from studies with daratumumab, 
patients who experience CRS and have preexisting COPD or asthma may be at particular risk for 
such respiratory complications as bronchospasm should an infusion reaction event occur. 
Therefore, patients whose FEV1 is <50% of predicted normal will be excluded from study 
participation (see Section 7.2) [28]. Eligible patients with a history of COPD may require 
additional postdose medications to manage respiratory complications (see Section 8.1.2) [26].
To date, subjects administered TAK-079 have not exhibited anaphylactic symptoms. In the 
clinical study of healthy subjects (TAK-079_101), an infusion-related reaction (IRR) was defined 
as a TEAE occurring within 2 hours after the start of an infusion; there were no IRRs in this study, 
and no allergic or cytokine release reactions were observed within this time period (TAK-079 IB).
In this study:

Patients with a history of severe allergic or anaphylactic reactions to recombinant proteins or 
excipients used in the TAK-079 formulation are not eligible and therefore will not be exposed 
to TAK-079. 

Premedication before each study dose, to prevent IRRs, is mandatory for all patients (as 
described in Section 8.1.1); postdose medication can be administered at the investigator’s 
discretion.
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
Patients who are treated with TAK-079/placebo will be carefully monitored in the clinic for 2 
hours after the first 2 doses, and any AE will be managed in accordance with available 
guidelines or institutional standards of care [19,29]. 
NOTE: Additional blood pressure measurements should be assessed any time the patient 
complains of symptoms consistent with an IRR. If the patient experiences hypotension (with or 
without symptoms), intensive blood pressure monitoring according to local practice should be 
instituted. The patient should not be released from the site until blood pressure has returned to 
Grade 1 or baseline for at least 1 hour.
8.6.1.1
Management Recommendations for Hypersensitivity Reactions
Patients in clinical studies receiving TAK-079 are to be carefully monitored for signs and 
symptoms of systemic hypersensitivity reactions (including IRRs, allergic reactions, or 
anaphylaxis; management recommendations for CRS are discussed separately in Section 8.6.2.1). 
Signs and symptoms of systemic hypersensitivity reactions include rash, urticaria, fever, and/or 
bronchospasms. Depending on the severity of the reaction, management of hypersensitivity 
reactions may include discontinuation of SC administration of TAK-079 and/or the administration 
of appropriate medical therapy.
Recommendations for the management of hypersensitivity reactions [19] are as follows:
Grade 1
a) Study Management:

If the full dose of TAK-079 has not yet been administered, hold dosing until symptoms 
resolve, at which time the remainder of TAK-079 dose may be administered. 
b) Patient Support: 

Monitor closely until resolution of symptoms.
Grade 2
a) Study Management:

If the full dose of TAK-079 has not yet been administered, hold dosing until symptoms 
resolve, at which time the remainder of TAK-079 dose may be administered.
b) Patient Support: 

Administer appropriate symptomatic and prophylactic medical care; consider 
postinjection medications as outlined in Section 8.1.2.

For allergic reaction, provide symptomatic treatment (eg, antihistamines, nonsteroidal 
anti-inflammatory drugs, narcotics, epinephrine) as medically appropriate and consider 
postinjection medications.
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Grade 3 or Greater (including any diagnosis of anaphylaxis according to Sampson et al [19]). 
a) Study Management: 

Patients are to discontinue study dosing and advance to the safety follow-up period of 
the study.
b) Patient Support: 

Provide symptomatic treatment, including epinephrine, until symptoms resolve. 

Consider hospitalization as appropriate.
8.6.2
Cytokine Release Syndrome
CRS represents an important infusion reaction often associated with the use of natural and 
bispecific monoclonal antibodies used in anti-inflammatory and antitumor therapies [20,30,31]. 
Onset of CRS may occur early in therapy, often after the first infusion of the drug [20,31,32], 
because of a high level of activation of the immune system and engagement and proliferation of T 
cells that can result in increased cytokine release. 
An in vitro study with human lymphocytes demonstrated that TAK-079 has no agonist activity, 
suggesting that TAK-079 is unlikely to cause cytokine release due to cell activation. In 
repeated-dose toxicity studies in cynomolgus monkeys, there were no TAK-079–related increases 
in cytokines at 0.1 mg/kg. At ≥0.3 mg/kg, dose-related increases (up to 29.5-fold for any 
individual monkey) in tumor necrosis factor alpha (TNF-α) were observed 30 minutes after the 
first dose of TAK-079. These increases were considered small compared with elevations observed 
during a cytokine storm event, were not accompanied by changes in other cytokines, and did not 
translate into clinical manifestation of CRS. Increases in serum TNF-α may be related to 
TAK-079–mediated lyses of CD38+ lymphocytes.
In the first-in-human study, conducted in healthy subjects, rarely observed symptoms consistent 
with mild CRS were reported, particularly at higher doses; dose adjustment or interruption was not 
required. No CRS has been reported in the ongoing SLE and RRMM studies (TAK-079 IB).
The CRS hallmark is fever [20]. CRS also presents with rash, urticaria, headache, chills, fatigue, 
nausea, and/or vomiting [20,30]. Severe CRS is characterized by severe dyspnea, often 
accompanied by bronchospasm and hypoxia, in addition to fever, chills, rigors, urticaria, and 
angioedema. The acute respiratory failure may be accompanied by such events as pulmonary 
interstitial infiltration or edema visible on a chest x-ray. The syndrome frequently manifests within 
1 or 2 hours of initiating the first infusion [20,32,33]. Patients with a history of pulmonary 
insufficiency or those with pulmonary tumor infiltration may be at greater risk of poor outcome 
and should be treated with increased caution. On the basis of outcomes from studies of the 
anti-CD38 monoclonal antibody daratumumab, patients with preexisting COPD or asthma may be 
at particular risk for respiratory complications, such as bronchospasm, should an infusion reaction 
or CRS event occur [28]. Therefore, if the patient’s FEV1 is <50% of predicted normal, they will 
be excluded from study participation (see Section 7.2). Eligible patients with a history of COPD 
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may require additional postinjection medications to manage respiratory complications [26] (see 
Section 8.1.2).
8.6.2.1
Management Recommendations for CRS
Premedication before each study dose, to prevent infusion reaction, is mandatory for all patients as 
described in Section 8.1.1. Postdosing medication, to be administered at the investigator’s 
discretion, is described in Section 8.1.2. 
Immediate clinical assessment and management of symptoms is key to symptom management. 
Patients will be monitored in the clinic for at least 2 hours after the first 2 TAK-079 doses. Medical 
symptomatic treatment according to guidelines or institutional standard of care is recommended 
[20]. Before discharge from the clinic, the possible signs and symptoms of anaphylactic reactions 
and CRS should be reviewed with patients. Further, patients should receive information about 
what to do if emergency care is needed (see Appendix C for further details on clinical signs and 
symptoms associated with CRS and the CRS grading system [20]).
If a patient is exhibiting signs or symptoms possibly assessed as CRS by the investigator, a blood 
draw should be performed for central evaluation that could include, but need not be limited to, 
immune markers and cytokine markers. Additional guidance for study management and patient 
support for CRS by grade is as follows: 
Grade 1 (defined as fever, constitutional symptoms) 
a) Study Management: 

Hold study dosing until symptoms resolve; resume dose of TAK-079 at same dose 
level after symptom resolution.
b) Patient Support: 

Provide vigilant supportive symptomatic treatment, which may include antipyretics, 
analgesics, and antihistamines. 
Grade 2 (defined as hypotension, hypoxia, organ toxicity) 
a) Study Management:

Discontinue study dosing and advance to SFP.
b) Patient Support:

Provide vigilant supportive symptomatic treatment, which may include antipyretics, 
analgesics, and antihistamines, with or without tocilizumab. 
Grade 3 (defined as hypotension, hypoxia, and severe organ toxicity) 
a) Study Management:

Discontinue study dosing and advance to SFP.
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b) Patient Support:

Provide vigilant supportive care, including but not limited to tocilizumab, antipyretics, 
analgesics, and antihistamines, as medically indicated [20].
8.6.3
Hematologic Effects
Reductions in platelets, lymphocytes, and RBCs occurred in nonclinical studies in some animals 
administered repeated doses of TAK-079 at ≥1 mg/kg, higher than the NOAEL of 0.3 mg/kg. In 
the first-in-human study, no decreases were seen in RBCs or platelets. 
In the healthy subjects study (TAK-079-101), which is completed, and in the SLE study 
(TAK-079-2001), which is ongoing, hematologic parameters were monitored closely. There were 
no markedly abnormal hematologic values in any subject or any AEs related to thrombocytopenia 
or anemia in the healthy subjects study or, as of the TAK-079 IB clinical data cutoff (20 March 
2019), in the SLE study. In the study in RRMM (TAK-079-1501), hematologic parameters were 
monitored according to standard practice. At doses up to 600 mg, no decreases in platelet counts 
below the lower limit of normal related to TAK-079 were seen (note: 1 event of Grade 3 
thrombocytopenia was reported as related to progression of the underlying myeloma). Two events 
of Grade 3 anemia have been reported, with one reported as related to study drug and the other 
reported as not related to study drug but related to progression of the underlying myeloma. No 
events of lymphocytopenia (or decreased lymphocyte count) have been reported (TAK-079 IB).
Patients will be monitored closely, including testing of hematologic parameters throughout this 
clinical study as described in Section 9.5.12 and Appendix A. In instances where clinical 
parameters do not meet dosing criteria, study dosing must be temporarily or permanently withheld 
as outlined in Table 8.d. Medical interventions may be administered according to institutional 
guidelines.
8.6.4
Infections
In a GLP-compliant, 13-week toxicology study, bacterial and/or viral infection, secondary to 
immune suppression, was observed in cynomolgus monkeys at IV doses of 3, 30, and 80 mg/kg 
administered once every 2 weeks. The NOAEL dose of 0.3 mg/kg, administered IV once every 
week, was not associated with infections. 
Mild infection, specifically nasopharyngitis, was reported across all SC dose levels in the healthy 
subjects study (TAK-079_101). As of the TAK-079 IB data cutoff (20 March 2019) in the study in 
patients with RRMM (TAK-079-1501), 4 of 19 patients treated at doses up to 600 mg reported an 
event in the infections and infestations System Organ Class; the most common AE reported was 
upper respiratory tract infection (n = 2); all were Grade 2, and only 1 was reported as related to 
study drug. No infections have been reported in the patients in the SLE study (TAK-079-2001) 
(TAK-079 IB). 
Patients will be monitored for any signs and symptoms of infections throughout this clinical study 
(see Appendix A and Table 8.d). In instances where clinical parameters do not meet dosing criteria, 
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study dosing must be temporarily or permanently withheld as outlined in Table 8.d. Management 
of infections according to standard medical care is recommended.
8.6.5
Injection Site Reactions
Local injection site abnormalities have not been observed in monkey and rat nonclinical studies 
after SC and/or IV administration of TAK-079. In the clinical study of healthy subjects 
(TAK-079-101), mild injection site AEs were reported; most were Grade 1 and included primarily 
erythema or tenderness. All injection reactions resolved within a few days.
In the literature, ISRs with anti-CD38 monoclonal antibodies have been reported [34]. ISRs 
consisted of induration, erythema, injection site discoloration, and hematomas (all grade 16.7%) 
[34].
Mild injection site AEs, reported as erythema or tenderness with palpation, were mostly observed 
at the 2 lowest SC doses in the healthy subjects study. All reactions resolved within a few days. No 
oral medications, such as paracetamol (acetaminophen) or antihistamines, were needed to treat 
these mild ISRs. In the study in patients with RRMM at doses up to 600 mg (given with 3 SC 
injections), no ISRs have been reported (TAK-079 IB). Patients receiving TAK-079 SC will be 
closely monitored for any ISR and will be managed with standard medical care.
8.6.6
Antidrug Antibody Interactions
Antidrug antibody (ADA) responses were detected in most monkeys in the single-dose PK studies 
and the 4-week (non-GLP) and 13-week (GLP) toxicology studies. Stronger positive ADA 
responses were generally associated with lower serum concentrations of TAK-079, and this was 
especially notable in the 13-week repeated-dose toxicity studies and at lower doses. In the 
single-dose healthy subjects study (TAK-079-101), 5 of 54 TAK-079–treated subjects were 
positive for ADA (3 subjects with transient ADA and 2 subjects with persistent ADA). Of these, 1 
subject was treated in the 0.06 mg IV cohort, and the remaining 4 subjects were treated with 0.03 
mg/kg (2 subjects), 0.1 mg/kg (1 subject), or 0.6 mg/kg (1 subject) SC TAK-079. Immunogenicity 
was not associated with clinically significant AEs, even in the 2 subjects with persistent 
immunogenicity (TAK-079 IB).
8.6.7
Overdose
As outlined in Section 10.1.2, an overdose is defined as a known deliberate or accidental 
administration of investigational drug, to or by the study subject, at a dose above that which was 
assigned to that individual subject (ie, patient) according to the study protocol. 
To date, there is no experience with overdose of TAK-079. If an overdose does occur, as defined in 
Section 10.1.2, close monitoring and supportive treatment, as medically required, are 
recommended. Events of overdose, with or without an associated AE, should be promptly reported 
to the study medical monitor and will be entered into the eCRFs as an AE.
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8.7
Description of Investigational Agents
8.7.1
Study Drug: TAK-079
TAK-079 is a full-length, human IgG1 monoclonal antibody directed against human CD38. The 
antibody is composed of 2 light chains of the lambda subclass and 2 heavy chains linked together 
by 2 disulfide bridges.
The strength of the TAK-079 drug product for SC use in this study is 100 mg TAK-079 in 1 mL 
(100 mg/mL). TAK-079 drug product and matching placebo are supplied in aseptically filled, 
single-use, clear, type I, borosilicate glass vials with fluoropolymer-coated butyl rubber stoppers 
and aluminum crimp seals with flip-off caps.
8.7.1.1
Preparation, Reconstitution, and Dispensation
Refer to the pharmacy manual for detailed instructions regarding the preparation of TAK-079 
study supply.
TAK-079 is a monoclonal antibody and caution should be exercised when handling TAK-079 as 
with other biologics.
8.7.1.2
Packaging and Labeling
Supplies of TAK-079 are labeled according to the current International Council for Harmonisation 
(ICH) guidelines on Good Clinical Practice (GCP) and Good Manufacturing Practices and include 
any locally required statements.
8.7.1.3
Storage, Handling, and Accountability
During shipping, vials are to be protected from light and maintained within temperatures provided 
in the pharmacy manual. Each TAK-079 shipment includes a packing slip listing the contents of 
the shipment, and any applicable forms. The investigator or designee must confirm that 
appropriate temperature conditions have been maintained for all TAK-079 received and that any 
discrepancies are reported and resolved before use.
Upon receipt of study medication, the investigator or designee must verify the contents of the 
shipments against the packing list. The verifier should ensure that the quantity is correct, the 
medication is received within the labeled storage conditions, and is in good condition. If quantity 
and conditions are acceptable, the investigator or designee should acknowledge the receipt of the 
shipment by signing the bottom half of the packing list and faxing per instructions provided on the 
form. If there are any discrepancies between the packing list and the actual product received, 
Takeda must be contacted to resolve the issue. The packing list should be filed in the investigator’s 
essential document file. The sponsor must be notified immediately of any temperature excursions 
and shipping and handling or storage discrepancies.
All clinical study material must be kept in an appropriate, limited access, secure location until used, 
destroyed, or returned to the sponsor or designee. TAK-079 must be stored according to the 
manufacturer’s stipulation, as specified on the label (see the pharmacy manual for additional 
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information). Detailed dosage preparation instructions are provided in the Directions for Use 
section of the pharmacy manual. Complete receipt, inventory, accountability, reconciliation, and 
destruction records must be maintained for all used and unused study drug vials. Detailed 
instructions and the associated forms for these activities are in the pharmacy manual. Drug 
supplies will be counted and reconciled at the site before being returned to Takeda or designee or 
being destroyed. 
The investigator or designee must ensure that the study medication is used in accordance with the 
approved protocol and is dispensed only to patients enrolled in the study. To document appropriate 
use of study medication (TAK-079), the investigator must maintain records of all study medication 
delivery to the site, site inventory, use by each patient, and return to the sponsor or designee.
The investigator will be notified of any expiry date or retest date extension of clinical study 
material during the study conduct. On expiry date notification from the sponsor or designee, the 
site must complete all instructions outlined in the notification, including segregation of expired 
clinical study material for return to the sponsor or its designee. 
Further guidance and information are provided in the pharmacy manual.
8.7.2
Clinical Study Drug Blinding
The assignment of study patients to 1 of 3 study arms is maintained through a blinded 
randomization schedule, available in instances of medical emergencies to the principal 
investigator. Otherwise, site staff will remain blinded through Week 16 of the study, as described 
in Section 6.1. Details on maintaining the study blind, and unblinding procedures, are outlined in 
Section 8.7.4.
8.7.3
Randomization Code Creation and Storage
The randomization and medication schedule will be generated and maintained by an interactive 
voice/web response system (IXRS). All randomization information will be stored in a secured area, 
accessible only by authorized personnel.
8.7.4
Clinical Study Blind Maintenance/Unblinding Procedure
To maintain the integrity of the study, all study personnel, including the investigators, site 
personnel, the contract research organization (CRO) medical monitor, study clinicians, and the 
sponsor, will be blinded to the treatment assignments during the treatment period. Treatment 
assignments will be obtained through the IXRS according to the procedures outlined in the study 
manual or relevant training materials. Information regarding the treatment assignments will be 
kept securely at Takeda or designee, per its standard operating procedures. 

Records of the patient number, the date the study drug was dispensed, and the treatment 
assignment will be maintained by the study site.
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
Emergency unblinding, if necessary, will be conducted via the IXRS. The following are key 
factors to be considered regarding breaking the study blind: 
–
If the treatment assignment must be revealed for the safety of the patient, to treat an AE, or 
to inform decisions for subsequent therapy, the investigator will contact the Takeda 
clinician or designee (in accordance to contact information and procedures outlined in the 
study manual or relevant training materials). 
–
A decision to break the blind must be reached by the Takeda clinician and the investigator. 
The investigator, or designee, may break the blind through the IXRS independent of the 
Takeda clinician only if the investigator considers the situation to be an emergency and 
requires specific knowledge of the blinded study treatment to properly treat the AE/safety 
issue. 
–
If the treatment of the AE/safety issue is anticipated to be the same regardless of study drug 
assignment, the blind should not be broken. 
–
The event requiring breaking the blind must be documented in the eCRF, including the date 
the blind was broken. 
After breaking the blind, the patient will be discontinued from further study drug administration in 
this study.
8.7.5
Destruction of Sponsor-Supplied Drugs
The investigator, institution, or head of the medical institution (where applicable) is responsible 
for TAK-079 accountability, reconciliation, and record maintenance, ie, receipt, reconciliation, 
and final disposition records.
The investigator must maintain 100% accountability for all study medication (TAK-079) received 
and dispensed during his or her entire participation in the study. Proper drug accountability 
includes, but is not limited to:

Continuously monitoring expiration dates if expiry date/retest date is provided to the 
investigator.

Frequently verifying that actual inventory matches documented inventory.

Verifying that the log is completed for the drug lot used to prepare each dose.

Verifying that all containers used are documented accurately on the log.

Verifying that required fields are completed accurately and legibly.
Per standard clinical practice, a site representative, otherwise uninvolved with study conduct, will 
review the patient dosing log before Day 1 dosing and after dosing to ensure that all patients 
received the correct dose of study medication. This review will be documented at the site.
If any dispensing errors or discrepancies are discovered, the sponsor must be notified immediately. 
Empty, partially used, and unused TAK-079 will be disposed of, retained, or returned to the 
sponsor or designee, as directed by the sponsor or designee. The investigator must maintain a 
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current inventory (drug accountability log) of all sponsor-supplied study medication delivered to 
the site, inventory at the site, and patients’ use records. This log must accurately reflect the drug 
accountability of the study medication at all times. The following information will be recorded at a 
minimum: protocol number and title, name of investigator, site identifier and number, description 
of sponsor-supplied medication, expiry/retest date, and amount dispensed including the initials of 
the person dispensing and the person receiving the study medication. The log should include all 
required information as a separate entry for each patient to whom study medication is dispensed.
Before site closure or at appropriate intervals, a representative from the sponsor or its designee will 
perform clinical study material accountability and reconciliation before clinical study materials are 
returned to the sponsor or its designee or destroyed at the site, as applicable. The investigator will 
retain the original documentation regarding clinical study material accountability, return, and/or 
destruction, and copies will be sent to the sponsor or designee.
Further guidance and information are provided in the pharmacy manual.
9.0
STUDY CONDUCT
This study will be conducted in compliance with the protocol, GCP, applicable regulatory 
requirements, and ICH guidelines.
9.1
Study Personnel and Organizations
Contact information for the project clinician, the central laboratory conducting the analysis of PK 
samples, coordinating investigator, interactive response technology provider, and CRO team may 
be found in the study manual/binder. The list of investigators is available in the sponsor’s
investigator database.
9.2
Arrangements for Recruitment of Patients
Recruitment and enrollment strategies for this study may include recruitment from the 
investigator’s local practice or referrals from other physicians. If advertisements become part of 
the recruitment strategy, they will be reviewed by the institutional review board (IRB)/ 
independent ethics committee (IEC). 
9.3
Assignment of Randomization Numbers
At the time of randomization, after completion of all screening assessments and procedures and 
confirmation of eligibility, patients are assigned a 4-digit randomization sequence number. 
Randomization numbers are generated by the IXRS.
9.4
Treatment Group Assignments
Patients will be randomly assigned in a 1:1:1 ratio to 1 of the 3 treatment arms as outlined in 
Table 8.a at the completion of study screening and before dosing on study Day 1, in accordance 
with the randomization schedule as generated by the IXRS. Randomization information is stored 
in a secured area, accessible only by authorized personnel, and necessary site staff in instances of 
emergency unblinding. 
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9.5
Study Procedures
Refer to the SOE (Appendix A) for timing of assessments. Additional details are provided as 
necessary in the sections that follow.
The screening period for this study is 28 days (Day -28 to Day -1). Assessments and procedures 
should be performed on schedule, within the time frame and window allowance in Appendix A. 
Further time allowance for most study procedures and assessments is acceptable in extenuating 
circumstances (ie, holidays, vacations, and other administrative reasons) on approval by the 
medical monitor or delegate; however, these time extensions should not deviate more than 
7 days from the scheduled procedural time.
9.5.1
Informed Consent
Each patient will be asked to provide written informed consent before any study-related 
procedures are conducted, unless those procedures are performed as part of the patient’s standard 
care.
9.5.2
Inclusion and Exclusion
Eligibility criteria and associated screening study assessments must be confirmed during the 
screening period, after a patient has signed the ICF, and before receiving study drug.
Principal investigators must provide the Takeda clinician/study medical monitor a summary of key 
eligibility criteria for review so eligibility can be verified before randomizing each patient. 
9.5.3
Patient Demographics
Patient demographics characteristics will be collected at screening and will include age, sex, race, 
and ethnicity (optional depending on country).
9.5.4
Medical/Surgical History
A complete medical history is compiled for each patient during the screening period (ie, ≤28 days 
before study Day 1) and includes assessment and documentation of prior medical history, 
comorbidities, and concomitant treatments. This includes assessments of current MG signs, 
symptoms, morbidities, as evaluated and scored by disease activity tools, and previous and current 
MG therapies.
9.5.5
Concomitant Medications and Procedures
Concomitant medications, blood products, and procedures from within 28 days before the first 
dose of TAK-079 through the end of the patient’s participation in the study will be recorded in the 
eCRF. Trade name and international nonproprietary name (if available), indication, and start and 
end dates of the administered medication are to be recorded. Medications used by the patient and 
therapeutic procedures completed by the patient will be recorded in the eCRF (see Sections 8.2
and 8.3 for a list of excluded and permitted concomitant medications).
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9.5.5.1
Background MG Therapy 
Eligible patients will have received MG background therapy (Table 8.c) before screening. Once 
randomized into the study, patients will remain on background therapy, as managed by their 
principal investigator, in accordance with local institutional practices, and in alignment with the 
study protocol, throughout study participation. Allowed background therapy is defined as no more 
than a cholinesterase inhibitor ± corticosteroid ± 1 steroid-sparing immunosuppressive drug 
(limited to azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, or 
cyclophosphamide). Patients must be on at least one allowed background medication. Background 
MG therapy ongoing at the time of screening will be recorded in the eCRF, as well as any changes 
to this therapy.
9.5.6
Physical Examination
A complete physical examination as well as a symptom-directed physical examination with 
assessments for MG signs and symptoms will be completed in accordance with standard of care at 
the times specified in the SOE (Appendix A). Women of childbearing potential should be asked 
about their menstrual history at each visit. A serum pregnancy test should be conducted for 
delayed menses (see Section 9.5.10).
9.5.7
Height and Weight
Height will be measured during screening only (within 28 days before the first dose of TAK-079).
Weight will be measured during screening and at Weeks 10, 16, and 32 as outlined in Appendix A.
9.5.8
Vital Signs
Vital signs (body temperature, respiratory rate, heart rate, and blood pressure) will be evaluated at 
visits specified in Appendix A and recorded both on the source documentation and in the eCRF. In 
addition, vital signs should be assessed at any time it is clinically warranted, ie, patient exhibits 
signs or symptoms of ISR, CRS, or hypersensitivity reactions. As indicated in Appendix A, vital 
signs are to be assessed before each study dose and 2 hours (±10 minutes) postdose after the first 
and second TAK-079/placebo dose. 
Clinically significant values, as determined by the principal investigator, must be documented as 
an AE and closely monitored for follow-up. 
9.5.9
12-Lead ECG
A single 12-lead ECG is to be performed at the screening visit (for assessment of eligibility) and at 
Weeks 10 and 16 of the SFP, and 32 of the LFP and will be read locally. Additional ECGs may be 
done per investigator discretion. 
Each ECG recording should be performed according to standard institutional practice. 
NOTE: Any ECG finding that is judged by the investigator as clinically significant (except at the 
screening visit) is considered an AE; as such, clinically significant findings are to be recorded on 
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the source documentation and in the eCRF, and the patient should undergo continued monitoring 
as described in Section 10.1.2.
9.5.10
Pregnancy Test
A serum pregnancy (human chorionic gonadotropin [hCG]) test will be completed for all female 
patients; this test will be performed at screening and during the SFP and must be negative for the 
patient to be randomized and to continue in the study. 
A urine pregnancy test will be completed for all female patients before the first dose of 
TAK-079/placebo and at Week 5 of the dosing period. If the subject reports delayed menses a 
serum pregnancy test should be completed and a negative result obtained before dosing with the 
study drug.
All study pregnancy testing may be conducted at a designated local laboratory as determined and 
confirmed by the sponsor, with appropriate laboratory documentation provided in advance of 
study testing.
9.5.10.1
Definition of Women of Childbearing Potential
A woman of childbearing potential is a sexually mature woman who: 

Has not undergone a hysterectomy or bilateral oophorectomy, or 

Is not postmenopausal. A postmenopausal state is defined as no menses for 12 months without 
an alternative medical cause.
9.5.10.2
Timing of Pregnancy Testing 
Women of childbearing potential must have pregnancy testing completed in accordance with the 
timing outlined as follows: 

Before Initial Study Dosing: 
–
Screening period: a negative serum pregnancy test (hCG <5 mIU/mL).
–
Baseline: (Either Day 1 prior to initial study dosing, or 1 day before study dosing) a 
negative urine pregnancy test with a sensitivity of at least 50 mIU/mL. If the urine test is 
indeterminate, a serum pregnancy test is mandatory.

During Study Enrollment:
–
At Week 5, before dosing (urine pregnancy test).
–
During SFP, and LFP as outlined in Appendix A (serum pregnancy test).
–
If a menstrual period is delayed (serum pregnancy test). 
–
Additional pregnancy tests to be conducted as requested by the IRB and/or as required by 
local regulations. 
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9.5.11
AEs
Monitoring of AEs, serious and nonserious, will be conducted throughout the study as specified in 
Appendix A. Refer to Section 10.0 for details regarding definitions, documentation, and reporting 
of AEs and SAEs. 
9.5.12
Clinical Laboratory Evaluations
Hematology, serum chemistry, and serology assessments will be performed locally, with reference 
ranges provided in the electronic data capture (EDC) system. Clinical laboratory evaluations will 
be performed according to the SOE in Appendix A throughout the study. 
Instructions for handling and shipping clinical laboratory samples are provided in the study 
laboratory manual.
9.5.12.1
Clinical Chemistry and Hematology
Blood samples for analysis of the clinical chemistry and hematology parameters shown in 
Table 9.a will be obtained as specified in the SOE (Appendix A).
Table 9.a
Clinical Chemistry and Hematology Tests
Hematology
Serum Chemistry
Hematocrit
Hemoglobin
Leukocytes with differential
Total lymphocyte count
Neutrophils (ANC)
Platelet (count)
Coombs test (both direct and 
indirect)
Serum pregnancy test
Albumin
Alkaline phosphatase (ALP)
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Bilirubin (total)
Blood urea nitrogen (BUN)
Calcium
Carbon dioxide (CO2)
Creatinine
Chloride
Glucose
Lactate dehydrogenase (LDH)
Potassium
Sodium
ANC: absolute neutrophil count.
9.5.13
Disease Assessment
The study principal investigator or appropriately trained, delegated, study site staff will assess 
each patient for disease activity based on the following MG disease activity scales outlined in the 
following sections and in accordance with the SOE in Appendix A. 
Further details for completing the disease assessment scales are provided in the rater manual and 
associated training materials. 
9.5.13.1
MG-ADL Score
The MG-ADL is a validated, 8-question patient-reported outcome measure of MG symptoms 
[35,36]. The MG-ADL assesses relevant MG symptoms and their functional impact on the patient. 
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The patient will assess functional disability secondary to ocular (2 items), bulbar (3 items), 
respiratory (1 item), and gross motor or limb impairment (2 items). Each item is individually 
graded from 0 (normal) to 3 (severe). The total MG-ADL score ranges from 0 to 24 points, with 
higher scores indicating greater functional impairment and disability.
A 2-point reduction in the MG-ADL total score is considered a clinically meaningful 
improvement. 
9.5.13.2
MGII Score
The MGII is a novel and validated measure of MG severity, with demonstrated feasibility, 
reliability, and construct validity [37,38]. The MGII score was developed using patient input and 
consists of 6 physician-examination and 22 patient-reported items. The MGII has less floor effect 
(ie, more dynamic range at the lower end of the scale) than other commonly used measures and is 
therefore more sensitive to detect change. The total score ranges from 0 to 84 (with higher scores 
indicating worse MG disease activity), and a group-level reduction by 8 points reflects the minimal 
clinically important difference.
9.5.13.3
MGC Score
The MGC scale is a validated patient- and physician-reported 10-item assessment tool for 
evaluating the signs and symptoms of MG. Physician assessment includes assessment for ptosis 
(upward gaze), double vision on lateral gaze, eye closure, neck flexion or extension, shoulder 
abduction, and hip flexion; patient assessment includes self-report of talking, chewing, 
swallowing, and breathing. Items are scored based on 4 potential levels of impact: normal, mild, 
moderate, or severe. The total score ranges from 0 to 50, with higher scores indicating a greater 
impact of MG on functional activities [39-41].
A 3-point reduction in the MGC total score is considered a clinically meaningful improvement.
9.5.13.4
QMG Score for Disease Severity
The QMG score is a physician-reported, validated, 13-item disease-severity assessment tool. The 
QMG score evaluates muscle strength based on quantitative testing of sentinel muscle groups: 
ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and 
respiratory (1 item). Each item is graded on a scale of 0 to 3, with 3 being the most severe. The 
total score ranges from 0 to 39, with higher scores representing a greater disease burden [42,43].
A 3-point reduction in the QMG total score is considered a clinically meaningful improvement.
9.5.13.5
MG-QoL15r
The MG-QoL15r is a validated tool containing 15 patient-reported items about the patient’s 
perception of impairment and disability and the degree to which the patient tolerates disease 
manifestations [44-46]. The total score ranges from 0 to 30, with higher scores indicating worse 
MG disease activity.
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9.5.13.6
Patient Global Impression of Change
The Patient Global Impression of Change (PGIC) is an anchor scale used to aid the interpretation 
of the above MG disease activity instruments (MG-ADL, MGII, MGC, QMG and MG-QoL15r). 
The PGIC may be used in analyses of meaningful change and other psychometric properties and 
performance characteristics of these instruments.
9.5.13.7
Patient Global Impression of Severity
The Patient Global Impression of Severity (PGIS) is an anchor scale used to aid the interpretation 
of the above MG disease activity instruments (MG-ADL, MGII, MGC, QMG and MG-QoL15r). 
The PGIS may be used in analyses of meaningful change and other psychometric properties and 
performance characteristics of these instruments.
9.5.13.8
Quantification of Ig
Serum samples for IgM, IgG, and IgA will be obtained at screening and throughout the study at the 
time points specified in Appendix A; testing will be performed at the central laboratory.
9.5.14
Biomarker, Pharmacodynamic, and PK Samples
Samples are collected by venipuncture or indwelling catheter at the time points detailed in the SOE 
(Appendix A) for the measurement of serum concentrations of TAK-079 and biomarker 
assessments. Samples will be tested at a central laboratory.
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9.5.14.1
Primary Specimen Collection
Table 9.b
Primary Specimen Collection
Specimen Name in Schedule of 
Procedures
Primary 
Specimen
Description of Intended Use
Sample Collection
Serum sample for autoantibodies 
Serum
Antibody level
Mandatory 
Blood sample for flow cytometry
Blood
CD19+ counts
Mandatory a
Blood sample for pharmacodynamics
Blood
Pharmacodynamic (changes in 
CD38+ cells) 
Mandatory
Blood sample for immunoprofiling
Blood
Broad immune cell changes
Mandatory
Serum sample for circulating 
biomarkers
Serum
Biomarker measurements
Mandatory
Serum sample for quantitative 
IgA/IgM/IgG
Serum
Ig measurements
Mandatory
Serum sample for immunogenicity 
assessments
Serum
Immunogenicity assessments
Mandatory
Serum sample for TAK-079 PK
Serum
PK measurements
Mandatory
Serum sample for vaccine-induced 
protective antibodies
Serum
Vaccine-induced protective 
antibodies
Mandatory
Serum sample for HBV, HCV, and 
HIV
Serum
Study eligibility
Mandatory
Blood sample for HCV RNA PCR
Blood
Study eligibility
Mandatory b
HBV: hepatitis B virus; HCV: hepatitis C virus; Ig: immunoglobulin; PCR: polymerase chain reaction; PK: 
pharmacokinetics.
a CD19 evaluation to be performed only in patients with prior exposure to rituximab.
b To be performed only for patients who have received curative treatment for prior chronic HCV infection.
9.5.15
PK Measurements
Serum samples for the measurement of concentrations of TAK-079 will be collected at multiple 
time points as specified in the SOE in Appendix A.
The timing of samples may be modified during the study on the basis of emerging PK data if a 
change in the sampling scheme is considered necessary to better characterize the PK profile of 
TAK-079. Additional PK samples may be requested if deemed necessary by the medical monitor 
for specific events of clinical interest or AEs. 
Details regarding the preparation, handling, and shipping of the PK samples are provided in the 
laboratory manual.
9.5.16
Pharmacodynamic/Biomarker Measurements
In this study, several biomarkers will be assessed to test for correlation with safety, PK, and, if 
possible, with efficacy. These biomarkers will be used to identify patients who have a higher 
probability of response or adverse reactions to TAK-079. The biomarker sample analysis will be 
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performed if or when required. Because new techniques continue to be developed, the method and 
laboratory that will be recommended for the biomarker analysis cannot be anticipated. Samples for 
pharmacodynamic measurements will be collected as detailed in Appendix A.
If a patient is exhibiting signs or symptoms possibly assessed as CRS by the investigator, a blood 
draw should be performed for central evaluation that could include, but is not limited to, immune 
markers and cytokine markers. Further details are provided in the laboratory manual.
9.5.16.1
Autoantibodies
Serum samples will be collected to detect anti-AChR and anti-MuSK antibodies as outlined in 
Appendix A and analyzed by a central laboratory. 
9.5.16.2
Pharmacodynamics
Blood samples will be collected to analyze CD38+ expression and monitor changes in immune 
cells by flow cytometry before, during, and at the end of treatment. These evaluations will be 
performed at a central laboratory. 
9.5.16.3
Circulating Biomarkers
Serum samples for cytokines/chemokines will be collected before, during, and at the end of 
treatment to help identify patients who have a higher probability of response or of experiencing 
adverse reactions to TAK-079.
9.5.16.4
Immunoprofiling
Blood samples for immunoprofiling will be collected for profiling of immune cells before, during, 
and at the end of treatment. These blood samples will be analyzed for the presence and changes of 
immune cells by flow or mass cytometry. 
9.5.16.5
Vaccine-Induced Protective Antibodies
Serum samples for vaccine-induced protective antibodies (measles, mumps, rubella, tetanus, and 
diphtheria) will be collected before, during, and at the end of treatment. 
9.5.17
Immunogenicity Sample Collection
Serum samples for the measurement of anti–TAK-079 antibody (antidrug antibody and ADA are 
exchangeable terms in this protocol) will be collected at multiple time points as specified in the 
SOE in Appendix A.
The samples must be taken before each dosing. Details regarding the preparation, handling, and 
shipping of the immunogenicity samples are provided in the laboratory manual. Positive ADA 
screening samples will be further tested for true positivity and titer by the study central laboratory.
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9.6
End of Safety Follow-up Assessments
End of SFP clinical parameters, as outlined in Table 9.c, will be assessed at Week 16 of the SFP 
(see SOE in Appendix A). If clinical presentation and parameters do not meet the end of SFP 
criteria, and are deemed by the principal investigator as study related, the study-related parameters 
not meeting end-of-study criteria will continue to be assessed in the LFP until they normalize or 
return to baseline. 
Table 9.c
End of Safety Follow-Up Period Clinical Parameters
Safety Parameter Laboratory 
Investigations
End-of-Study Criteria
Continuation to Long-term Follow-up
Neutrophils
≥LLN or ≥study baseline levels, 
or abnormal levels that are not 
directly related to dosing of 
investigational product.
<LLN and <study baseline levels that are 
directly related to dosing of investigational 
product.
Platelets
Total lymphocyte count
Hgb
IgG, IgA, and IgM levels 
Events of clinical interest
TAK-079–related 
hypersensitivity reaction (IRR, 
allergic reaction, or anaphylaxis) 
(See Section 8.6.1).
Clinical symptoms related to 
hypersensitivity reaction 
resolved.
Clinical symptoms related to hypersensitivity 
reaction ongoing.
TAK-079-related CRS (See 
Section 8.6.2).
Clinical symptoms related to 
CRS reaction resolved.
Clinical symptoms related to CRS reaction 
ongoing.
Systemic infection
Any ≥Grade 2 a systemic infection that is not 
resolved.
CRS: cytokine release syndrome; CTCAE: Common Terminology Criteria for Adverse Events; Hgb: hemoglobin; Ig: 
immunoglobulin; IRR: infusion-related reaction; LLN: lower limit of normal; NCI: National Cancer Institute. 
a Laboratory and infection grading are based on NCI CTCAE v4.03.
9.7
Completion of Study Treatment (for Individual Patients)
Patients will be considered to have completed study treatment once they have completed the 
8-week dosing period.
9.8
Completion of Study (for Individual Patients)
A patient will be considered to have completed the study once they have completed the dosing 
period and at completion of the Week 20 or Week 32 end-of-study visit of the LFP (for patients 
randomized to placebo or TAK-079, respectively). 
9.9
Discontinuation of Treatment With Study Drug
Study drug must be permanently discontinued for patients meeting any of the following criteria:

Withdrawal by patient.
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
Pregnancy.
Treatment with study drug may also be discontinued for any of the following reasons:

AE/SAE.

Protocol deviation. 

Symptomatic deterioration. 

Unsatisfactory therapeutic response. 

Study terminated by sponsor.

Lost to follow-up.

Other.
Once study drug has been discontinued, all study procedures outlined for the end-of-treatment visit 
will be completed as specified in the SOE in Appendix A. The primary reason for study drug 
discontinuation will be recorded on the eCRF.
In addition, study drug should also be discontinued if the patient meets the criteria outlined in 
Section 8.4.1.
9.10
Withdrawal of Patients From Study
A patient will be withdrawn from the study for any of the following reasons:

Death.

Study terminated by sponsor.

Withdrawal by patient.

Lost to follow-up.

Other.
The consequence of a patient withdrawing consent from further treatment and follow-up is that no 
new information will be collected from the withdrawn patient and added to the existing data or any 
database. However, every effort will be made to follow all patients for safety. Data collected 
during patient consent, however, must be included in the database.
9.11
Study Compliance
TAK-079/placebo will be administered or dispensed only to eligible patients under the supervision 
of the investigator or identified subinvestigator(s). The appropriate study personnel will maintain 
records of study drug receipt and dispensing.
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9.12
Coronavirus Disease 2019–Related Procedural Changes
The following information provides guidance regarding changes to the study procedures that could 
be implemented for study participants or study sites affected by the coronavirus disease 2019 
(COVID-19) public health emergency. This guidance takes references from the Food and Drug 
Association (FDA) Guidance on Conduct of Clinical Trials of Medical Products during 
COVID-19 Public Health Emergency - Guidance for Industry, Investigators, and Institutional 
Review Boards, March 2020, updated 04 December 2020, and the European Medicines Agency 
(EMA) Guidance on the Management of Clinical Trials During the COVID-19 (Coronavirus) 
Pandemic, Version 3 (28 April 2020).
As the COVID-19 pandemic may peak in different regions at different times and restrictions 
implemented by local laws and recommendations may vary, any decision on procedural changes 
should be made on a case-by-case basis by the principal investigator in consultation with the study 
team and the medical team as needed, while maintaining patient safety and confidentiality as the 
priority.
Procedural changes due to COVID-19 may include the following:

Informed consent procedure: If necessary, informed consent from a potential or current trial 
participant may be obtained via electronic informed consent capabilities, or an electronic 
face-to-face consent interview when these individuals are unable to travel to the site.

During the COVID-19 public health emergency, remote visits may be conducted by phone (eg, 
collection of AEs and safety monitoring), video conferencing (Telehealth with the physician or 
Telemedicine or other platform acceptable to the physician and patient) or site staff visiting the 
participant’s residence. Local visits and Telemedicine must comply with national and local 
laws and regulations. The type of alternative visit must be recorded on the eCRF. The 
investigator may use their judgement to determine the appropriateness of a remote visit as an 
alternative visit in advance (for example, if no significant issues arise that may necessitate a 
hands-on physical exam).

“Remote visits” via virtual communications may be performed as a safety check on the 
patient’s well-being.

For home healthcare visits, collection of clinical laboratory samples (blood specimen 
collection or other diagnostic tests) may be performed by the investigator, qualified site staff or 
qualified home healthcare provider who can visit the study participant’s residence. These may 
be obtained the day before a scheduled visit (see Appendix A).

ECG procedures: For home healthcare visits, ECGs may be performed by a qualified health 
care professional who is authorized/certified to perform such tests routinely.

Patient visits at screening, Weeks 1-4, 8, 12, 16, 20, and 32 must be done with the patient 
present at the investigative site. Other visits may be conducted at the clinic or by optional home 
healthcare visits (or a hybrid of Telehealth/Telemedicine with home healthcare) to extend 
flexibility to patients during COVID-19 public health emergency. Home healthcare visits will 
be documented in the study records and eCRF. As per the investigator’s judgment, if there are 
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no concerns raised by the symptom-directed physical, vital signs measurements will not be 
required to be collected at the Week14 visit during the COVID-19 pandemic. QMG, MGC and 
the physician examination portion of MGII may be omitted if performing a remote visit. 

For possible dosing visits at home, the investigator or qualified site staff must evaluate the 
patient either remotely or at the patient’s residence prior to dose administration. A patient 
should have previously received 4 doses of study drug at the clinic site unless otherwise 
approved by the sponsor. Safety parameters for dosing decisions (Table 8.d) must be evaluated 
as in a regular in-clinic visit. Dose administration must be performed by a qualified healthcare 
provider.

Safety labs (eg, complete blood count, chemistry, liver function tests) may be obtained at a 
clinic local to the patient’s home with sponsor approval.

Deviations from the protocol-specified procedures will be recorded as related to COVID-19.

The assessment of forced vital capacity for the QMG test may be omitted for 
COVID-19-related reasons.

Patients who discontinued from screening due to COVID-19–related factors but were 
otherwise qualified to participate in the trial may be rescreened if the sponsor’s clinician 
agrees.

Missed or delayed clinic visits or subject withdrawals due to COVID-19 must be recorded on 
the eCRF.

Withdrawal: If a patient chooses to withdraw from study participation due to personal concerns 
related to the COVID-19 pandemic (other than a COVID-19–related AE), this should be 
specified as the reason for patient withdrawal in the eCRF.
10.0
ADVERSE EVENTS
10.1
Definitions
10.1.1
Pretreatment Event Definition
A pretreatment event (PTE) is any untoward medical occurrence in a patient who has signed 
informed consent to participate in a study but before administration of any study medication; it 
does not necessarily have to have a causal relationship with study participation.
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10.1.2
AE Definition
AE means any untoward medical occurrence in a patient administered a pharmaceutical product; 
the untoward medical occurrence does not necessarily have a causal relationship with this 
treatment.
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal (investigational) 
product whether or not it is related to the medicinal product.
An untoward finding generally may:

Indicate a new diagnosis or unexpected worsening of a preexisting condition. (Intermittent 
events for preexisting conditions or underlying disease should not be considered PTEs or 
AEs.)

Necessitate therapeutic intervention.

Require an invasive diagnostic procedure.

Require discontinuation or a change in dose of study medication or a concomitant medication.

Be considered unfavorable by the investigator for any reason.
Diagnoses versus signs and symptoms:

Each event should be recorded to represent a single diagnosis. Accompanying signs (including 
abnormal laboratory values or ECG findings) or symptoms should NOT be recorded as 
additional AEs. If a diagnosis is unknown, sign(s) or symptom(s) should be recorded 
appropriately as a PTE(s) or an AE(s).
Laboratory values and ECG findings:

Changes in laboratory values or ECG parameters maybe considered AEs if they are judged to 
be clinically significant, ie, if some action or intervention is required or if the investigator 
judges the change to be beyond the range of normal physiologic fluctuation. A laboratory retest 
and/or continued monitoring of an abnormal value are not considered an intervention. In 
addition, repeated or additional noninvasive testing for verification, evaluation or monitoring 
of an abnormality is not considered an intervention.

If abnormal laboratory values or ECG findings are the result of pathology for which there is an 
overall diagnosis (eg, increased creatinine in renal failure), the diagnosis only should be 
reported appropriately as an AE.
Preexisting conditions:

A preexisting condition (present at the time of signing of informed consent) is considered a 
concurrent medical history condition and should NOT be recorded as a PTE or AE. A baseline 
evaluation (eg, laboratory test, ECG, x-ray) should NOT be recorded as a PTE unless related to 
a study procedure. However, if the patient experiences a worsening or complication of such a 
concurrent medical history condition, the worsening or complication should be recorded 
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appropriately as a PTE (worsening or complication occurs before start of study medication) or 
an AE (worsening or complication occurs after start of study medication). Investigators should 
ensure that the event term recorded captures the change in the condition, eg, “worsening of…”.

If a patient has a preexisting episodic condition (eg, asthma, epilepsy), any occurrence of an 
episode should only be captured as an PTE/AE if the episodes become more frequent, serious, 
or severe in nature; that is, investigators should ensure that the AE term recorded captures the 
change from baseline in the condition, eg “worsening of…”.

If a patient has a degenerative concurrent condition (eg, cataracts, rheumatoid arthritis), 
worsening of the condition should only be captured as a PTE/AE if occurring to a greater 
extent than that which would be expected. Again, investigators should ensure that the AE term 
recorded captures the change in the condition, eg, “worsening of…”.
Worsening of AEs:

If the patient experiences a worsening or complication of a PTE after the first administration of 
study medication or a worsening or complication of an AE after any change in study 
medication, the worsening or complication should be recorded as a new AE. Investigators 
should ensure that the AE term recorded captures the change in the condition, eg, “worsening 
of…”.
Changes in severity of AEs:

If the patient experiences a change in the severity of an AE that is not associated with a change 
in study medication, the event should be captured once with the maximum severity recorded.
Preplanned surgeries or procedures:

Preplanned procedures (surgeries or therapies) that were scheduled before signing of informed 
consent are not considered AEs. However, if a preplanned procedure is performed early (eg, as 
an emergency) because of worsening of the preexisting condition, the worsening of the 
condition should be captured appropriately as an AE. Complications resulting from any 
planned surgery should be reported as AEs.
Elective surgeries or procedures:

Elective procedures performed where there is no change in the patient’s medical condition 
should not be recorded as AEs but should be documented in the patient’s source documents. 
Complications resulting from an elective surgery should be reported as AEs.
Overdose:

An overdose is defined as a known deliberate or accidental administration of investigational 
drug, to or by a study patient, at a dose above that which is assigned to that individual patient 
according to the study protocol. 

All cases of overdose (with or without associated AEs) are to be documented on the Overdose 
page of the eCRF to capture this important safety information consistently in the database. AEs 
associated with an overdose will be documented on the AE CRF(s) according to Section 10.5.
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
SAEs of overdose should be reported according to the procedure outlined in Section 10.2.

If an overdose does occur, close monitoring and supportive treatment as medically required.
10.1.3
SAE Definition
SAE means any untoward medical occurrence that at any dose:

Results in death.

Is life-threatening (refers to an AE in which the patient was at risk of death at the time of the 
event. It does not refer to an event which hypothetically might have caused death if it were 
more severe).

Requires inpatient hospitalization or prolongation of an existing hospitalization.

Results in persistent or significant disability or incapacity.

Is a congenital anomaly/birth defect.

Is a medically important event that satisfies any of the following:

May require intervention to prevent items 1 through 5 above.

May expose the patient to danger, even though the event is not immediately 
life-threatening or fatal or does not result in hospitalization.

Includes any event or synonym described in the Takeda Medically Significant AE List 
(Table 10.a).
Table 10.a
Takeda Medically Significant Adverse Event List
Term
Acute respiratory failure/acute respiratory 
distress syndrome
Hepatic necrosis
Acute liver failure
Torsade de pointes/ventricular fibrillation/ventricular 
tachycardia
Anaphylactic shock
Acute renal failure
Malignant hypertension
Pulmonary hypertension
Convulsive seizures
Pulmonary fibrosis
Agranulocytosis
Confirmed or suspected endotoxin shock
Aplastic anemia
Confirmed or suspected transmission of infectious agent by a 
medicinal product
Toxic epidermal necrolysis/Stevens-Johnson 
syndrome
Neuroleptic malignant syndrome/malignant hyperthermia
Spontaneous abortion/stillbirth and fetal death

Note: Some clinical centers may only be able to provide certain rescue therapies (eg, IVIg) via 
inpatient hospitalization. Therefore, the hospital admission itself (in an otherwise clinically 
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stable patient) specifically for access and administration of rescue therapy does not count 
automatically as an SAE, unless there are other circumstances that fulfill SAE criteria.
AEs that fulfill 1 or more of the serious criteria above are to be considered SAEs and should be 
reported and followed up in the same manner.
As there is no MG or neurologic specific grading scale, in this study intensity for each AE, 
including any laboratory abnormality, will be determined using the NCI CTCAE, version 4.03, 
effective 27 November 2017 [47]. Use of the CTCAE criteria scale is aligned with the 
international consensus guidance for the management of MG [48] which is supported by the 
American Academy of Neurology (aan/Guidelines/home/GuidelineDetail/823 Accessed 21 Aug 
2019) and the Myasthenia Gravis Foundation of America 
(myastheniagravisnews/2018/02/01/panel-of-myasthenia-gravis-experts-propose-guidelines-for-t
reatment-and-care/ Accessed 21 Aug 2019). Especially at lower grades of toxicity, laboratory 
parameters are similar between the CTCAE and WHO toxicity criteria; note in this study the 
threshold for holding study drug is at a low grade (see Table 8.d), therefore either scale could be 
applicable. The CTCAE criteria, however, also allows for more precise grading of severity of AEs 
reported with biologics such as infections and infusion related reactions (hypersensitivity and 
anaphylaxis) as compared to the WHO toxicity grading scale where criterion for these are lacking. 
In addition, the CTCAE criteria has very thorough criteria for Neuro and Neuromuscular AEs 
which again is quite sparse in the WHO criteria. For these reasons, rather than try to use 2 separate 
scales, the CTCAE criteria will be used in this study.
Clarification should be made between an SAE and an AE that is considered severe in intensity 
(Grade 3 or 4) because the terms serious and severe are NOT synonymous. The general term 
severe is often used to describe the intensity (severity) of a specific event; the event itself, however, 
may be of relatively minor medical significance (such as a Grade 3 headache). This is NOT the 
same as serious, which is based on patient/event outcome or action criteria described above and is 
usually associated with events that pose a threat to a patient’s life or ability to function. A severe 
AE (Grade 3 or 4) does not necessarily need to be considered serious. For example, a white blood 
cell count of 1000/mm3 to less than 2000/mm3 is considered Grade 3 (severe) but may not be 
considered serious. Seriousness (not intensity) serves as a guide for defining regulatory reporting 
obligations.
10.2
Procedures for Recording and Reporting AEs and SAEs
All AEs spontaneously reported by the patient or in response to an open question from study 
personnel or revealed by observation, physical examination, or other diagnostic procedures will be 
recorded on the appropriate page of the eCRF (see Section 10.3 for the period of observation). Any 
clinically relevant deterioration in laboratory assessments or other clinical finding is considered an 
AE. When possible, signs and symptoms indicating a common underlying pathology should be 
noted as a single comprehensive event.
Regardless of causality, SAEs must be reported (see Section 10.3 for the period of observation) by 
the investigator to the Takeda Global Pharmacovigilance department or designee within 24 hours 
of becoming aware of the event. This will be done by transmitting an electronic data capture (EDC) 
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SAE report. If transmission of an EDC SAE report is not feasible within 24 hours, then a facsimile 
of the completed Takeda paper-based SAE form should be sent (please see fax numbers below). In 
case of fax, site personnel need to confirm successful transmission of all pages and include an 
email address on the fax cover sheet so that an acknowledgment of receipt can be returned via 
e-mail within 1 business day. Email submission of SAE forms with an attachment in portable 
document format should only be used in the case where fax is not possible and EDC is not feasible 
within 24 hours of receiving the event. In case of email, site personnel need to confirm successful 
transmission by awaiting an acknowledgment of the receipt via email within 1 business day. If 
SAEs are reported via fax or by email, EDC must be updated as soon as possible with the 
appropriate information.
The SAE form should be transmitted within 24 hours to the attention of the contact listed as 
follows:
SAE Reporting Contact Information
Cognizant
United States and Canada Toll-free fax #: 1-800-963-6290
Rest of World fax#: +1-202-315-3560
Email: takedaoncocases@cognizant.com
If information not available at the time of the first report becomes available at a later date, then the 
investigator will transmit a follow-up EDC SAE report (or a paper-based SAE form if an EDC 
SAE report is not feasible) or provide other documentation immediately within 24 hours of receipt. 
Copies of any relevant data from the hospital notes (eg, ECGs, laboratory tests, discharge 
summary, postmortem results) should be sent to the addressee, if requested.
All SAEs should be followed up until resolution or permanent outcome of the event. The timelines 
and procedure for follow-up reports are the same as those for the initial report.
Planned hospital admissions or surgical procedures for an illness or disease that existed before the 
patient was enrolled in the study are not to be considered AEs unless the condition deteriorated in 
an unexpected manner during the study; eg, surgery was performed earlier or later than planned.
For both serious and nonserious AEs, the investigator must determine both the severity (toxicity 
grade) of the event and the relationship of the event to study drug administration. 
Severity (toxicity grade) for each AE, including any lab abnormality, will be determined using the 
NCI CTCAE, version 4.03, effective 27 November 2017 [47]. 
Relationship of the event to study drug administration (ie, its causality) will be determined by the 
investigator responding yes (related) or no (unrelated) to this question: Is there a reasonable 
possibility that the AE is associated with the study drug?
10.3
Monitoring of AEs and Period of Observation
AEs, both nonserious and serious, will be monitored throughout the study as follows: 

AEs will be reported from the signing of informed consent through the SFP and recorded in the 
eCRF. AEs ongoing at the Week 16 visit of the SFP should be monitored through the LFP until 
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they are resolved, return to baseline, or are clearly determined to be due to a patient’s stable or 
chronic condition or intercurrent illness(es). Study-drug related AEs/SAEs with onset after the 
SFP will be collected through the LFP.

SAEs will be reported to the Takeda Global Pharmacovigilance department or designee from 
the signing of informed consent through the SFP and recorded in the eCRF. After this period, 
during the LFP, only related SAEs must be reported to the Takeda Global Pharmacovigilance 
department or designee. SAEs should be monitored until they are resolved or are clearly 
determined to be due to a patient’s stable or chronic condition or intercurrent illness(es).
10.4
Procedures for Reporting Drug Exposure During Pregnancy and Birth Events
If a woman becomes pregnant or suspects that she is pregnant while participating in this study, she 
must inform the investigator immediately and permanently discontinue study drug. The sponsor 
must also be contacted immediately by sending a completed pregnancy form to the Takeda Global 
Pharmacovigilance department or designee. The pregnancy must be followed for the final 
pregnancy outcome.
If a female partner of a male patient becomes pregnant during the male patient’s participation in 
this study, the sponsor must also be contacted immediately by sending a completed pregnancy 
form to the Takeda Global Pharmacovigilance department or designee. Every effort should be 
made to follow the pregnancy for the final pregnancy outcome.
10.5
Procedures for Reporting Including Overdose
All cases of overdose (with or without associated AEs) will be documented on an Overdose page 
of the eCRF to capture this important safety information consistently in the database. AEs 
associated with an overdose will be documented on the AE eCRF. SAEs of overdose should be 
reported according to the procedure outlined in Section 10.2.
10.6
Safety Reporting to Investigators, IRBs or IECs, and Regulatory Authorities
The sponsor will be responsible for reporting all suspected unexpected serious adverse reactions 
(SUSARs) and any other applicable SAEs to regulatory authorities, investigators, and IRBs and 
IECs, as applicable, in accordance with national regulations in the countries where the study is 
conducted. Relative to the first awareness of the event by/or further provision to the sponsor or 
sponsor’s designee, SUSARs will be submitted to the regulatory authorities as expedited reports 
within 7 days for fatal and life-threatening events and within 15 days for other serious events, 
unless otherwise required by national regulations. The sponsor will also prepare an expedited 
report for other safety issues where these might materially alter the current benefit-risk assessment 
of an investigational medicinal product or that would be sufficient to consider changes in the 
investigational medicinal product’s administration or in the overall conduct of the study. The 
investigational site also will forward a copy of all expedited reports to his or her IRB or IEC in 
accordance with national regulations. 
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11.0
STUDY-SPECIFIC COMMITTEES
In accordance with Takeda standard operating procedures, each clinical trial is evaluated to 
determine whether a data safety monitoring board (DSMB) should be convened. Applicable 
regulation and guidance (including the guidance set forth by the US FDA as described in the 
Guidance for Clinical Trial Sponsors: Establishment and Operation of Clinical Trial Data 
Monitoring Committees, fda.gov/downloads/RegulatoryInformation/Guidances/ucm127073.pdf, 
Accessed 24 July 2019) are used to evaluate each trial in terms of potential confounding factors 
that complicate evaluation of the study safety and/or efficacy data, and potential risks of the study 
design or treatment to study participants.
A DSMB is not indicated at this time for this study given that Takeda’s standards and processes, 
which include continuous review and evaluation of safety data reported from all participating sites 
through the conduct of the study, are appropriate for the ongoing monitoring of patient safety and 
data integrity (see Section 6.2). However, the decision to convene a DSMB could be made at any 
time during the conduct of Study TAK-079-1005.
Though a formal DSMB will not be formed, internal reviews of available safety information will 
be conducted. Key safety data will be reviewed and evaluated by sponsor representatives for 
possible study conduct recommendation(s). The sponsor representatives will make decisions 
regarding dosing and/or scheduling, which will be discussed with investigators for decision for 
alignment.
12.0
DATA HANDLING AND RECORDKEEPING 
The full details of procedures for data handling will be documented in the data management plan. 
If selected for coding, AEs, medical history, and concurrent conditions will be coded using the 
MedDRA. Drugs will be coded using the World Health Organization (WHO) Drug Dictionary.
12.1
eCRFs
Completed eCRFs are required for each patient who signs an ICF.
The sponsor or its designee will supply investigative sites with access to eCRFs and will make 
arrangements to train appropriate site staff in the use of the eCRF. These forms are used to transmit 
the information collected in the performance of this study to the sponsor, CRO partners, and 
regulatory authorities. Investigative sites must complete eCRFs in English.
After completion of the entry process, computer logic checks will be run to identify items such as 
inconsistent dates, missing data, and questionable values. Queries may be issued by Takeda 
personnel (or designee) and will be answered by the site.
Any change of, modification of, or addition to the data on the eCRFs should be made by the 
investigator or appropriate site personnel. Corrections to eCRFs are recorded in an audit trail that 
captures the old information, the new information, identification of the person making the 
correction, the date the correction was made, and the reason for the change.
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The principal investigator must review the eCRFs for completeness and accuracy and must sign 
and date the appropriate eCRFs as indicated. Furthermore, the principal investigator must retain 
full responsibility for the accuracy and authenticity of all data entered on the eCRFs.
eCRFs will be reviewed for completeness and acceptability at the study site during periodic visits 
by study monitors. The sponsor (or designee) will be permitted to review the patient’s medical and 
hospital records pertinent to the study to ensure accuracy of the eCRFs. The completed eCRFs are 
the sole property of the sponsor and should not be made available in any form to third parties, 
except for authorized representatives of appropriate governmental health or regulatory authorities, 
without written permission of the sponsor.
12.2
Record Retention
The investigator agrees to keep the records stipulated in Section 12.1 and those documents that 
include (but are not limited to) the study-specific documents, the identification log of all 
participating patients, medical records, temporary media such as thermal-sensitive paper, source 
worksheets, all original signed and dated ICFs, patient authorization forms regarding the use of 
personal health information (if separate from the ICFs), electronic copies of eCRFs including the 
audit trail, and detailed records of drug disposition to enable evaluations or audits from regulatory 
authorities and the sponsor (or designees). Any source documentation printed on degradable 
thermal-sensitive paper should be photocopied by the site and filed with the original in the 
patient’s chart to ensure long-term legibility. Furthermore, ICH E6 Section 4.9.5 requires the 
investigator to retain essential documents specified in ICH E6 (Section 8) until at least 2 years after 
the last approval of a marketing application for a specified drug indication being investigated or, if 
an application is not approved, until at least 2 years after the investigation is discontinued and 
regulatory authorities are notified. In addition, ICH E6 Section 4.9.5 states that the study records 
should be retained until an amount of time specified by applicable regulatory requirements or for a 
time specified in the clinical study site agreement between the investigator and sponsor.
Refer to the clinical study site agreement for the sponsor’s requirements for record retention. The 
investigator should contact and receive written approval from the sponsor before disposing of any 
such documents.
13.0
STATISTICAL METHODS
13.1
Statistical and Analytical Plans
A statistical analysis plan will be prepared and finalized before database lock. This document will 
provide further details regarding the definition of analysis variables and analysis methodology to 
address all study objectives.
13.1.1
Analysis Sets
Full analysis set: all enrolled patients. In efficacy analyses, only patients with both baseline and at 
least 1 valid postbaseline value will be included. 
Safety analysis set: patients who have received at least 1 dose of study drug. 
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PK analysis set: patients who have received at least 1 dose and have at least 1 measurable 
TAK-079 serum concentration.
Pharmacodynamic analysis set: patients who have a baseline and at least 1 postbaseline sample 
assessment. 
Immunogenicity analysis set: patients from the safety population who have a baseline and at least 
1 postbaseline immunogenicity sample assessment.
13.1.2
Analysis of Demographics and Other Baseline Characteristics
Patient demographic and baseline characteristics will be summarized descriptively. Variables to be 
analyzed include sex, age, race, medical history, prior medications/therapies, ECG findings, and 
other parameters as appropriate. For continuous variables, descriptive statistics (number, mean, 
standard deviation, median, minimum, and maximum) will be provided. For categorical variables, 
patient counts and percentages will be provided. Categories for missing data will be presented as 
needed.
13.1.3
Efficacy Analysis
Efficacy is not the primary endpoint for this study. Secondary efficacy measures will include:

Score change from baseline for the following:
–
MG-ADL score
–
QMG score
–
MGC score

Change from baseline in anti-AChR antibody or anti-MuSK antibody levels.

Percentage of patients meeting minimal clinically important difference criteria in the 
respective MG clinical impairment scales (MG-ADL, QMG, MGC).
Exploratory efficacy measures will include: 

Score change from baseline in the MGII score.

Duration of a clinically meaningful effect on MG disease severity (in all the clinical disease 
impairment scales: MG-ADL, QMG, MGC, MGII). 

Percentage of patients meeting minimal clinically important difference criteria in the MGII 
scale. 

Frequency and proportion of patients requiring rescue therapy
Efficacy endpoints will be summarized by descriptive statistics and presented by treatment group. 
Where appropriate, efficacy endpoints may be analyzed with the following methods:

Binary endpoints will be analyzed using a Fisher’s exact test.
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
Change from baseline endpoints measured repeatedly over time will be analyzed using a 
mixed-model repeated-measures analysis, which includes treatment, visit, and 
(treatment × visit) interaction terms as the factors, with baseline values as covariates. 
All tests of treatment effects will be conducted at a 2-sided α level of 0.05, and 95% CIs for the 
differences in proportions and least squares means will be provided. No inferential hypothesis was 
tested in these endpoints, so CIs and p-values are not adjusted for multiplicity.
All efficacy analyses will be performed using the full analysis set.
13.1.4
PK Analysis
Descriptive summary of the concentration-time profile of serum TAK-079 will be provided. PK 
parameters will include Ctrough. Data permitting, additional parameters eg, Cmax, AUC after last 
dose, and half-life may be reported. A population PK model may be developed. If developed, the 
population PK model will be reported separately. PK/pharmacodynamic analyses of selected 
pharmacodynamic and/or efficacy measures may be conducted as data permit. Any population 
PK/pharmacodynamic analysis if conducted will be reported separately.
13.1.5
Immunogenicity Analyses 
TAK-079 immunogenicity status (ADA incidence) will be analyzed and summarized using 
descriptive statistics, as applicable, and using the immunogenicity analysis set. The effect of 
immunogenicity on PK, pharmacodynamics, safety, and efficacy may be explored. 
Immunogenicity analyses will be based on available data from patients with a baseline assessment 
and at least 1 postbaseline immunogenicity assessment. 
13.1.6
Safety Analysis
Safety will be evaluated by the frequency of AEs, severity and types of AEs, and by changes from 
baseline in patients’ vital signs, weight, and clinical laboratory results using the safety analysis set. 
Exposure to study drug and reasons for discontinuation will be tabulated. 
TEAEs that occur after administration of the first dose of study drug and through the end of the 
SFP period will be tabulated. 
AEs will be tabulated according to the MedDRA, and data will be summarized using Preferred 
Term and primary System Organ Class. All safety analyses will be performed using the safety 
analysis population.
In this study, Grade 2 or greater medication related toxicities will be monitored starting from the 
first 12 safety-evaluable patients and then every 12 safety-evaluable patients. If the stopping 
bounds of ≥3/12, and ≥5/24 have been achieved, accrual to the study will be suspended to allow for 
a blinded investigation of the safety profile. After consideration by the study team, which could 
include the safety management team as appropriate, especially if case unblinding is necessary, a 
decision will be made as to whether accrual can be resumed. The AE grading limits are based on 
the International Consensus Guidelines for the Management of Myasthenia Gravis where the aim 
is no more than grade 1 CTCAE medication side effects [48]. The statistical bounds are based on a 
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Bayesian strategy to monitor outcomes in clinical trials. If the stopping rule is met, there is 80% 
probability that the true toxicity rate is greater than 10% with a prior beta distribution with 
parameters 0.2 and 1.8 for the binomially distributed toxicity rate [49].
Takeda clinicians will conduct reviews of SAEs and related clinical parameters to ensure 
consistency with an acceptable benefit-risk ratio throughout the study. If >2 patients experience 
the same SAE, the study will be suspended to allow for a blinded investigation by the study team 
which may include the safety management team as noted above; after which a decision will be 
made to whether accrual can be resumed.
13.2
Interim Analysis and Criteria for Early Termination
No interim analysis is planned.
13.3
Determination of Sample Size
Approximately 36 patients are planned to be randomized to treatment in a ratio of 1:1:1 (TAK-079 
300 mg, TAK-079 600 mg, or placebo). This study is exploratory and not powered to address any 
predefined hypothesis. 
14.0
QUALITY CONTROL AND QUALITY ASSURANCE
14.1
Study-Site Monitoring Visits
Monitoring visits to the study site will be made periodically during the study to ensure that all 
aspects of the protocol are followed. Source documents will be reviewed for verification of data 
recorded on the eCRFs. Source documents are defined as original documents, data, and records. 
The investigator and institution guarantee access to source documents by the sponsor or its 
designee (CRO) and by the IRB or IEC.
In the event a monitor cannot visit the site in a timely manner due to the COVID-19 pandemic,
alternative monitoring approaches such as remote source data verification or telephone contact 
may be used to ensure data quality and integrity and maintain patient safety. Alternative 
monitoring approaches should be used only where allowed by applicable local regulations and 
permitted by the IRB/IEC.
All aspects of the study and its documentation will be subject to review by the sponsor or designee 
including, but not limited to, the investigator’s binder, study medication, patient medical records, 
informed consent documentation, documentation of patient authorization to use personal health 
information (if separate from the ICFs), and eCRFs and associated source documents. It is 
important that the investigator and other study personnel are available during the monitoring visits 
and that sufficient time is devoted to the process.
14.2
Protocol Deviations
The investigator should not deviate from the protocol, except where necessary to eliminate an 
immediate hazard to study patients. Should other unexpected circumstances arise that will require 
deviation from protocol-specified procedures, the investigator should consult with the sponsor or 
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designee (and IRB or IEC, as required) to determine the appropriate course of action. There will be 
no exemptions (a prospectively approved deviation) from the inclusion or exclusion criteria.
The site should document all protocol deviations in the patient’s source documents. In the event of 
a significant deviation, the site should notify the sponsor or its designee (and IRB or EC, as 
required). Significant deviations include, but are not limited to, those that involve fraud or 
misconduct, increase the health risk to the patient, or confound interpretation of the primary study 
assessment.
The sponsor will assess any protocol deviation; if it is likely to affect to a significant degree the 
safety and rights of a patient or the reliability and robustness of the data generated, it may be 
reported to regulatory authorities as a serious breach of GCP and the protocol.
14.3
Quality Assurance Audits and Regulatory Agency Inspections
The study site also may be subject to quality assurance audits by the sponsor or designees. In this 
circumstance, the sponsor-designated auditor will contact the site in advance to arrange an 
auditing visit. The auditor may ask to visit the facilities where laboratory samples are collected, 
where the medication is stored and prepared, and any other facility used during the study. In 
addition, there is the possibility that this study may be inspected by regulatory agencies, including 
those of foreign governments (eg, US FDA, the United Kingdom [UK] Medicines and Healthcare 
products Regulatory Agency [MHRA], the Pharmaceuticals and Medical Devices Agency of 
Japan [PMDA]). If the study site is contacted for an inspection by a regulatory body, the sponsor 
should be notified immediately. The investigator and institution guarantee access for quality 
assurance auditors to all study documents as described in Section 14.1.
15.0
ETHICAL ASPECTS OF THE STUDY
This study will be conducted with the highest respect for the individual participants (ie, patients) 
according to the protocol, the ethical principles that have their origin in the Declaration of Helsinki, 
and the ICH Harmonized Tripartite Guideline for GCP. Each investigator will conduct the study 
according to applicable local or regional regulatory requirements and align his or her conduct in 
accordance with the responsibilities of the investigator that are listed in Appendix B. The 
principles of Helsinki are addressed through the protocol and through appendices containing 
requirements for informed consent and investigator responsibilities.
15.1
IRB and/or IEC Approval
IRBs and IECs must be constituted according to the applicable state and federal/local requirements 
of each participating region. The sponsor or designee will require documentation noting all names 
and titles of members who make up the respective IRB or IEC. If any member of the IRB or IEC 
has direct participation in this study, written notification regarding his or her abstinence from 
voting must also be obtained. American sites unwilling to provide names and titles of all members 
because of privacy and conflict of interest concerns should instead provide a Federalwide 
Assurance number or comparable number assigned by the US Department of Health and Human 
Services.
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The sponsor or designee will supply relevant documents for submission to the respective IRB or 
IEC for the protocol’s review and approval. This protocol, the IB, a copy of the ICF, and, if 
applicable, patient recruitment materials and advertisements and other documents required by all 
applicable laws and regulations must be submitted to a central or local IRB or IEC for approval. 
The IRB’s or IEC’s written approval of the protocol and patient informed consent must be 
obtained and submitted to the sponsor or designee before commencement of the study, ie, before 
shipment of the sponsor-supplied drug or study-specific screening activity. The IRB or IEC 
approval must refer to the study by its exact protocol title, number, and version date; identify 
versions of other documents (eg, ICF) reviewed; and state the approval date. If required by country 
or regional regulations or procedures, approval from the competent regulatory authority will be 
obtained before commencement of the study or implementation of a substantial amendment. The 
sponsor will ship drug once the sponsor has confirmed the adequacy of site regulatory 
documentation and, when applicable, the sponsor has received permission from the competent 
authority to begin the study. Until the site receives notification, no protocol activities, including 
screening, may occur.
Sites must adhere to all requirements stipulated by their respective IRB or IEC. This may include 
notification to the IRB or IEC regarding protocol amendments, updates to the ICF, recruitment 
materials intended for viewing by patients, local safety reporting requirements, reports and 
updates regarding the ongoing review of the study at intervals specified by the respective IRB or 
IEC, and submission of the investigator’s final status report to IRB or IEC. All IRB and IEC 
approvals and relevant documentation for these items must be provided to the sponsor (or 
designee).
Patient incentives should not exert undue influence for participation. Payments to patients must be 
approved by the IRB or IEC and sponsor.
15.2
Patient Information, Informed Consent, and Patient Authorization
Written consent documents will embody the elements of informed consent as described in the 
Declaration of Helsinki and the ICH Guidelines for GCP and will be in accordance with all 
applicable laws and regulations. The ICF, patient authorization form (if applicable), and patient 
information sheet (if applicable) describe the planned and permitted uses, transfers, and 
disclosures of the patient’s personal and personal health information for purposes of conducting 
the study. The ICF and the patient information sheet (if applicable) further explain the nature of the 
study, its objectives, and potential risks and benefits, and the date informed consent is given. The 
ICF will detail the requirements of the participant and the fact that he or she is free to withdraw at 
any time without giving a reason and without prejudice to his or her further medical care.
The investigator is responsible for the preparation, content, and IRB or IEC approval of the ICF 
and, if applicable, the patient authorization form. The ICF, patient authorization form (if 
applicable), and patient information sheet (if applicable) must be approved by both the IRB or IEC 
and the sponsor before use.
The ICF, patient authorization form (if applicable), and patient information sheet (if applicable) 
must be written in a language fully comprehensible to the prospective patient. It is the 
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responsibility of the investigator to explain the detailed elements of the ICF, patient authorization 
form (if applicable), and patient information sheet (if applicable) to the patient. Information should 
be given in both oral and written form whenever possible and in the manner deemed appropriate by 
the IRB or IEC. If the patient is not capable of rendering adequate written informed consent, the 
patient’s legally acceptable representative may provide such consent for the patient in accordance 
with applicable laws and regulations.
The patient, or the patient’s legally acceptable representative, must be given ample opportunity to 
(1) inquire about details of the study and (2) decide whether to participate in the study. If the 
patient, or the patient’s legally acceptable representative, determines that he or she will participate 
in the study, then the ICF and patient authorization form (if applicable) must be signed and dated 
by the patient, or the patient’s legally acceptable representative, at the time of consent and before 
the patient enters into the study. The patient or the patient’s legally acceptable representative 
should be instructed to sign using their legal names, not nicknames, using a ballpoint pen with 
either blue or black ink. The investigator must also sign and date the ICF and patient authorization 
(if applicable) at the time of consent and before the patient enters into the study; however, the 
sponsor may allow a designee of the investigator to sign to the extent permitted by applicable law.
Once signed, the original ICF, patient authorization form (if applicable), and patient information 
sheet (if applicable) will be stored in the investigator’s site file. The investigator must document 
the date the patient signs the informed consent in the patient’s medical record. Copies of the signed 
ICF, the signed patient authorization form (if applicable), and patient information sheet (if 
applicable) shall be given to the patient.
All revised ICFs must be reviewed and signed by relevant patients or the relevant patient’s legally 
acceptable representative in the same manner as the original informed consent. The date the 
revised consent was obtained should be recorded in the patient’s medical record, and the patient 
should receive a copy of the revised ICF.
15.3
Patient Confidentiality
The sponsor and designees affirm and uphold the principle of the patient’s right to protection 
against invasion of privacy. Throughout this study, a patient’s source data will be linked to the 
sponsor’s clinical study database or documentation only via a unique identification number. As 
permitted by all applicable laws and regulations, limited patient attributes, such as sex, age, or date 
of birth, and patient initials may be used to verify the patient and accuracy of the patient’s unique 
identification number.
To comply with ICH Guidelines for GCP and to verify compliance with this protocol, the sponsor 
requires the investigator to permit its monitor or designee’s monitor, representatives from any 
regulatory authority (eg, US FDA, UK MHRA, Japan PMDA), the sponsor’s designated auditors, 
and the appropriate IRBs and IECs to review the patient’s original medical records (source data or 
documents) including, but not limited to, laboratory test result reports, ECG reports, admission and 
discharge summaries for hospital admissions occurring during a patient’s study participation, and 
autopsy reports. Access to a patient’s original medical records requires the specific authorization 
of the patient as part of the informed consent process (see Section 15.2).
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Copies of any patient source documents that are provided to the sponsor must have certain 
identifying personal information removed, eg, patient name, address, and other identifier fields not 
collected on the patient’s eCRF.
15.4
Publication, Disclosure, and Clinical Study Registration Policy
15.4.1
Publication 
The investigator is obliged to provide the sponsor with complete test results and all data derived by 
the investigator from the study. During and after the study, only the sponsor may make study 
information available to other study investigators or to regulatory agencies, except as required by 
law or regulation. Except as otherwise allowable in the clinical study site agreement, any public 
disclosure (including publicly accessible websites) related to the protocol or study results, other 
than study recruitment materials and advertisements, is the sole responsibility of the sponsor.
The sponsor may publish any data and information from the study (including data and information 
generated by the investigator) without the consent of the investigator. Manuscript authorship for 
any peer-reviewed publication will appropriately reflect contributions to the production and 
review of the document. All publications and presentations must be prepared in accordance with 
this section and the clinical study site agreement. In the event of any discrepancy between the 
protocol and the clinical study site agreement, the clinical study site agreement will prevail.
15.4.2
Clinical Study Registration
To ensure that information on clinical studies reaches the public in a timely manner and to comply 
with applicable laws, regulations, and guidance, Takeda will, at a minimum, register interventional 
clinical studies it sponsors anywhere in the world on ClinicalTrials.gov or other publicly 
accessible websites on or before start of study, as defined by Takeda policy/standards. Takeda 
contact information, along with investigator’s city, state (for Americas investigators), country, and 
recruiting status will be registered and available for public viewing. 
As needed, Takeda and investigator/site contact information may be made public to support 
participant access to studies via registries. In certain situations/registries, Takeda may assist 
participants or potential participants in finding a clinical study by helping them locate study sites 
closest to their homes by providing the investigator name, address, and phone number via 
email/phone or other methods preferred by callers requesting study information. Once patients 
receive investigator contact information, they may call the site requesting enrollment into the 
study. The investigative sites are encouraged to handle the study inquiries according to their 
established patient screening process. If the caller asks additional questions beyond the topic of 
study enrollment, they should be referred to the sponsor. 
Any investigator who objects to Takeda providing this information to callers must provide Takeda 
with a written notice requesting that their information not be listed on the registry site. 
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15.4.3
Clinical Study Results Disclosure
Takeda will post the results of clinical studies on ClinicalTrials.gov, and other publicly accessible 
websites (including the Takeda corporate site) and registries, as required by Takeda 
policy/standards, applicable laws, and/or regulations. 
15.4.4
Data Sharing
The sponsor is committed to responsible sharing of clinical data with the goal of advancing 
medical science and improving patient care. Qualified independent researchers will be permitted 
to use data collected from patients during the study to conduct additional scientific research, which 
may be unrelated to the study drug or the patient’s disease. The data provided to external 
researchers will not include information that identifies patients personally.
15.5
Insurance and Compensation for Injury
Each patient in the study must be insured in accordance with the regulations applicable to the site 
where the patient is participating. If a local underwriter is required, then the sponsor or sponsor’s 
designee will obtain clinical study insurance against the risk of injury to clinical study patients. 
Refer to the clinical study site agreement regarding the sponsor’s policy on patient compensation 
and treatment for injury. If the investigator has questions regarding this policy, he or she should 
contact the sponsor or sponsor’s designee.
16.0
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30. Bugelski PJ, Achuthanandam R, Capocasale RJ, Treacy G, Bouman-Thio E. Monoclonal 
antibody-induced cytokine-release syndrome. Expert Rev Clin Immunol 2009;5(5):499-521.
31. RITUXAN (rituximab) [prescribing information]. San Francisco, CA: Genentech, Inc., 2013.
32. Winkler U, Jensen M, Manzke O, Schulz H, Diehl V, Engert A. Cytokine-release syndrome in 
patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment 
with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood 
1999;94(7):2217-24.
33. Rituxan (rituximab) injection. Prescribing Information. South San Francisco, CA, US: 
Genentech, Inc., Revised January 2019.
34. Chari A, Mateos M, Van de Donk N, Kaufman J, Moreau P, Oriol A, et al. Subcutaneous 
Daratumumab in Patients with Relapsed or Refractory Multiple Myeloma: Part 2 Safety and 
Efficacy Update of the Open-Label, Multicenter, Phase 1b Study (PAVO). Blood 
2018;132(Suppl 1). 1995.
35. Wolfe GI, Herbelin L, Nations SP, Foster B, Bryan WW, Barohn RJ. Myasthenia gravis 
activities of daily living profile. Neurology 1999;52(7):1487-9.
36. Muppidi S, Wolfe GI, Conaway M, Burns TM, Mg C, Mg-Qol15 Study G. MG-ADL: still a 
relevant outcome measure. Muscle Nerve 2011;44(5):727-31.
37. Barnett C, Bril V, Kapral M, Kulkarni AV, Davis AM. Myasthenia Gravis Impairment Index: 
Responsiveness, meaningful change, and relative efficiency. Neurology 2017;89(23):2357-64.
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CONFIDENTIAL
38. Barnett C, Bril V, Kapral M, Kulkarni A, Davis AM. Development and validation of the 
Myasthenia Gravis Impairment Index. Neurology 2016;87(9):879-86.
39. Burns TM. The MG composite: an outcome measure for myasthenia gravis for use in clinical 
trials and everyday practice. Ann N Y Acad Sci 2012;1274:99-106.
40. Sadjadi R, Conaway M, Cutter G, Sanders DB, Burns TM, Group MGCM-QS. Psychometric 
evaluation of the myasthenia gravis composite using Rasch analysis. Muscle Nerve 
2012;45(6):820-5.
41. Benatar M, Sanders DB, Burns TM, Cutter GR, Guptill JT, Baggi F, et al. Recommendations 
for myasthenia gravis clinical trials. Muscle Nerve 2012;45(6):909-17.
42. Katzberg HD, Barnett C, Merkies IS, Bril V. Minimal clinically important difference in 
myasthenia gravis: outcomes from a randomized trial. Muscle Nerve 2014;49(5):661-5.
43. Barohn RJ, McIntire D, Herbelin L, Wolfe GI, Nations S, Bryan WW. Reliability testing of the 
quantitative myasthenia gravis score. Ann N Y Acad Sci 1998;841:769-72.
44. Burns TM, Grouse CK, Conaway MR, Sanders DB, The mg c, mg-qol15 Study g. Construct 
and concurrent validation of the MG-QOL15 in the practice setting. Muscle Nerve 
2010;41(2):219-26.
45. 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(6):1015-22.
46. Burns TM, Grouse CK, Wolfe GI, Conaway MR, Sanders DB, Composite MG, et al. The 
MG-QOL15 for following the health-related quality of life of patients with myasthenia gravis. 
Muscle Nerve 2011;43(1):14-8.
47. Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03. U.S. Department 
of Health and Human Services National Cancer Institute. 14 June 2010.
48. 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(4):419-25.
49. Thall PF, Sung HG. Some extensions and applications of a Bayesian strategy for monitoring 
multiple outcomes in clinical trials. Statistics in Medicine 1998;17(14):1563-80.
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Appendix A
Schedule of Events
Study Procedures a
Screen
ing
Treatment Period
Safety
Follow-up Period (SFP)
Long-term
Follow-up Period (LFP)
Period
Length: 8 weeks
Week b
Days 
-28 to 
-1
1
2
3
4
5
6
7
8
10
12
14
16 c
20 d
24
28
32
Window
±2 days
±2 days
±2 days
Informed consent e
X
Eligibility criteria f
X
Demographics
X
Complete medical history, 
including prior therapy
X
Complete physical examination 
X
X
X
Symptom-directed physical 
examination g
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECG h
X
X
X
X
Vital signs i
X
X
X
X
X
X
X
X
X
X
X
X
X
Investigator predosing criteria 
assessment
X
X
X
X
X
X
X
Height (cm) 
X
Weight (kg)
X
X
X
X
Blood type assessment
X
Laboratory Assessments
Serum pregnancy test h 
X
X
X
X
Urine pregnancy test h,j,m
X
X
Hematology h,k,m
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Clinical chemistry h,k,m
X
X
X
X
X
Direct/indirect Coombs test h,m
X
X
X
X
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Appendix A
Schedule of Events
Study Procedures a
Screen
ing
Treatment Period
Safety
Follow-up Period (SFP)
Long-term
Follow-up Period (LFP)
Period
Length: 8 weeks
Week b
Days 
-28 to 
-1
1
2
3
4
5
6
7
8
10
12
14
16 c
20 d
24
28
32
Window
±2 days
±2 days
±2 days
T-cell interferon-γ release assay 
(TIGRA)
X
Serum sample for anti-AChR or 
anti-MuSK antibodies h,l,m
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood sample for immunoprofiling 
h,m
X
X
X
X
X
X
Blood sample for CD19 assay n
X
Serum sample for circulating 
biomarkers h,m,o,p
X
X
X
X
X
X
Serum sample for quantitative 
IgA/IgM/IgG h,m,q
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum sample for TAK-079 PK h,m,p
X
X
X
X
X
X
X
X
X
X
X
X
Blood sample for 
pharmacodynamic biomarkers h,m
X
X
X
X
X
X
Serum sample for immunogenicity 
(eg, ADA) h,m
X
X
X
X
X
X
X
X
X
Serum sample for vaccine-induced 
protective antibodies h, m
X
X
X
X
X
Samples for HBV, HCV, and HIV 
assessment
X
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CONFIDENTIAL
Appendix A
Schedule of Events
Study Procedures a
Screen
ing
Treatment Period
Safety
Follow-up Period (SFP)
Long-term
Follow-up Period (LFP)
Period
Length: 8 weeks
Week b
Days 
-28 to 
-1
1
2
3
4
5
6
7
8
10
12
14
16 c
20 d
24
28
32
Window
±2 days
±2 days
±2 days
Disease Assessment tests h
MG-ADL score
X
X
X
X
X
X
X
X
X
X
X
X
X
MGII score r
X
X
X
X
X
X
X
X
X
X
X
X
MGC score s
X
X
X
X
X
X
X
X
X
X
X
X
QMG score s
X
X
X
X
X
X
X
X
X
X
X
X
MG-QoL15r
X
X
X
X
X
X
X
X
X
X
X
X
PGIS
X
X
X
X
X
X
X
X
X
X
X
X
PGIC
X
X
X
Study Therapy Administration
Premedication dosing t
X
X
X
X
X
X
X
X
TAK-079, SC u
X
X
X
X
X
X
X
X
Postdose medication v
X
AE reporting w
New onset AEs recorded from the signing of the ICF through the SFP; SAEs collected from the signing of the ICF through the 
SFP; unresolved AEs/SAEs as of Week 16 and study drug-related AEs/SAEs with onset after SFP collected through the LFP
Concomitant medications/ 
procedures monitoring
Recorded from signing of the ICF through SFP
Recorded only for concomitant 
medications/procedures related 
to underlying disease
AChR: acetylcholine receptor; ADA: antidrug antibodies; AE: adverse event; CRS: cytokine release syndrome; COVID-19: coronavirus disease 2019; ECG: 
electrocardiogram; eCRF: electronic case report form; HBV: hepatitis B virus; HCV: hepatitis C virus; ICF: informed consent form; Ig: Immunoglobulin; IRB: 
institutional review board; IVIg: intravenous immunoglobulin; LFP: long-term follow-up period; MG: myasthenia gravis; MG-ADL: Myasthenia Gravis-Activities 
of Daily Living; MGC: Myasthenia Gravis Composite; MGII: Myasthenia Gravis Impairment Index; MG-QoL15r; Myasthenia Gravis Quality of Life Scale; 
MuSK: muscle-specific tyrosine kinase; PGIC: Patient Global Impression of Change; PGIS: Patient Global Impression of Severity; PK: pharmacokinetic; QMG: 
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Study No. TAK-079-1005
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02 February 2021
CONFIDENTIAL
Appendix A
Schedule of Events
Study Procedures a
Screen
ing
Treatment Period
Safety
Follow-up Period (SFP)
Long-term
Follow-up Period (LFP)
Period
Length: 8 weeks
Week b
Days 
-28 to 
-1
1
2
3
4
5
6
7
8
10
12
14
16 c
20 d
24
28
32
Window
±2 days
±2 days
±2 days
Quantitative Myasthenia Gravis; SAE: serious adverse event; SC: subcutaneous; SFP: safety follow-up period; TEAE: treatment-emergent adverse event.
a Patients may undergo additional laboratory assessments and observations as necessary based on the principal investigator’s best medical judgment, and as 
warranted by exhibited clinical signs or symptoms at each study clinic visit. 
b Patient visits at screening, Weeks 1-4, 8, 12, 16, 20, and 32 must be done with the patient present at the investigative site. Other visits may be conducted at the 
clinic or by optional home healthcare visits (or a hybrid of Telehealth/Telemedicine with home healthcare) to extend flexibility to patients during COVID-19 public 
health emergency. Home healthcare visits will be documented in the study records and eCRF.
c Patients will be unblinded after Week 16. Clinical parameters below the levels in Table 8.d for continued dosing, including ongoing drug-related AEs, at Week 16 
should be monitored until the parameters/AEs are resolved, return to baseline, or are clearly determined to be due to a patient’s stable or chronic condition or 
intercurrent illness(es).
d The Week 20 visit of the LFP will be the end-of-study visit for patients randomized to placebo. Patients randomized to placebo will require only a 
symptom-directed physical examination at this visit.
e Informed consent must be documented before initiating any screening procedures associated with the study.
f Screening period is 28 days (ie, Day -28 to Day -1). Confirmation of patient eligibility by a Takeda project clinician or designee is required before enrollment and 
before receiving study drug. See Section 9.5 for additional time allowance for extenuating circumstances, to include but not be limited to, need for screening 
retesting, as granted on approval by Takeda or designee.
g Physical examinations are to be symptom- and MG disease–directed with significant clinical findings noted as AEs. In LFP, needed only if there were ongoing 
drug-related AEs at the Week 16 assessment. Women of childbearing potential should be asked about their menstrual history at each visit. A serum pregnancy test 
should be conducted for delayed menses (see Section 9.5.10).
h Assessments may be performed on the day before or the day of the indicated visit before dosing.
i Vital signs (temperature, blood pressure, respiratory rate, and heart rate) are measured before all TAK-079 administrations and 2 hours (±10 minutes) postdose 
after the first and second TAK-079/placebo dose. In addition, vital signs should be assessed at any time it is clinically warranted. As per the investigator’s judgment, 
if there are no concerns raised by the symptom-directed physical, vital signs measurements will not be required to be collected at the Week14 visit during the 
COVID-19 pandemic.
j The results of urine pregnancy tests must be available and negative before TAK-079 is administered. A serum pregnancy test should be completed if the patient's 
menstrual period is delayed, or if the IRB requests, and a negative result obtained before dosing with the study drug (see Section 9.5.10). Serum pregnancy testing 
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TAK-079
Study No. TAK-079-1005
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02 February 2021
CONFIDENTIAL
Appendix A
Schedule of Events
Study Procedures a
Screen
ing
Treatment Period
Safety
Follow-up Period (SFP)
Long-term
Follow-up Period (LFP)
Period
Length: 8 weeks
Week b
Days 
-28 to 
-1
1
2
3
4
5
6
7
8
10
12
14
16 c
20 d
24
28
32
Window
±2 days
±2 days
±2 days
may be used in place of urine pregnancy testing with prior permission from the sponsor.
k Hematology and chemistry laboratory samples will be collected locally. Local laboratory evaluations may be done more frequently at the investigator’s discretion 
(eg, for acute management of TEAEs) and may be used for dosing decisions.
l Clinical laboratory evaluations for disease assessments (anti-AChR and anti-MuSK antibodies) will be tested centrally.
m Samples collected before TAK-079 administration. 
n CD19 evaluation to be performed only in patients with prior exposure to rituximab; CD19 counts must be within the normal range at screening to be eligible. 
o Circulating biomarkers may include assessment of complement C3 and C4 levels. Sample is also drawn for cytokine markers. Additional samples of cytokine 
markers are to be drawn if CRS is suspected.
p Additional PK and biomarker sampling may be requested.
q Quantitative immunoglobulins will be tested at a central laboratory; thus, results will not be available before each weekly dose. However, per standard medical 
practice, investigators should review the results once available and take appropriate clinical action, which may include but is not limited to withholding study drug 
and treatment with IVIg, for example, in the setting of a severe infection.
r Physician examination portion of this assessment may be omitted if performing a remote visit.
s Procedure may be omitted if performing a remote visit. The assessment of forced vital capacity for QMG test may be omitted for COVID-19-related reasons (see 
Section 9.12).
t Premedication and postdose medication before and after TAK-079 administration as outlined in Section 8.1.
u Time and anatomical site should be recorded for each injection. Patients will be closely monitored in the clinic for at least 2 hours after the first and second 
TAK-079 dose; before discharge from the clinic, the possible signs and symptoms of anaphylactic reactions and CRS should be reviewed with patients.
v Postdose medication should be given 2 hours (±15 minutes) after the first injection of the first dose and 1 day after the first dose of study drug in the morning.
Postdose medication may be given with subsequent doses if clinically indicated and under the discretion of the principal investigator (see Section 8.1.2).
w Assessments for AEs are to include a symptomatic examination per standard medical practice.
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CONFIDENTIAL
Appendix B
Clinical Signs and Symptoms of Cytokine Release Syndrome
Organ System
Symptoms
Constitutional
Fever with or without rigors, malaise, fatigue, anorexia, myalgias, arthralgia, nausea, 
vomiting, headache
Skin
Rash
Gastrointestinal
Nausea, vomiting, diarrhea
Respiratory
Tachypnea, hypoxemia
Cardiovascular
Tachycardia, widened pulse pressure, hypotension, increased cardiac output (early), 
potentially diminished cardiac output (late)
Coagulation
Elevated D-dimer, hypofibrinogenemia with or without bleeding
Renal
Azotemia
Hepatic
Transaminitis, hyperbilirubinemia
Neurologic
Headache, mental status changes, confusion, delirium, word-finding difficulty or frank 
aphasia, hallucinations, tremor, dysmetria, altered gait, seizures 
Source: Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, et al. Current concepts in the diagnosis and 
management of cytokine release syndrome. Blood 2014;124(2):188-95 [20].
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Appendix C
Grading System for Cytokine Release Syndrome
Grade
Toxicity
Grade 1
Symptoms are not life-threatening and require symptomatic treatment only, eg, fever, 
nausea, fatigue, headache, myalgias, malaise)
Grade 2
Symptoms require and respond to moderate intervention
Oxygen requirement <40%, or
Hypotension responsive to fluids or low dose of 1 vasopressor, or 
Grade 2 organ toxicity
Grade 3
Symptoms require and respond to aggressive intervention
Oxygen requirement ≥40%, or
Hypotension requiring high dose or multiple vasopressors, or
Grade 3 organ toxicity, or 
Grade 4 transaminitis
Grade 4
Life-threatening symptoms
Requirements for ventilator support, or
Grade 4 organ toxicity (excluding transaminitis)
Grade 5
Death
Source: Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, et al. Current concepts in the diagnosis and 
management of cytokine release syndrome. Blood 2014;124(2):188-95 [20].
Grades 2 to 4 refer to the Common Terminology Criteria for Adverse Events, version 4.03 grading.
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Appendix D
Responsibilities of the Investigator
Clinical research studies sponsored by the sponsor are subject to ICH GCP and all the applicable 
local laws and regulations. The responsibilities imposed on investigators by the FDA are 
summarized in the Statement of Investigator (Form FDA 1572), which must be completed and 
signed before the investigator may participate in this study.
The investigator agrees to assume the following responsibilities by signing a Form FDA 1572:
1. Conduct the study in accordance with the protocol.
2. Personally conduct or supervise the staff who will assist in the protocol.
3. If the investigator/institution retains the services of any individual or party to perform 
study-related duties and functions, the investigator/institution should ensure that this 
individual or party is qualified to perform those study-related duties and functions and should 
implement procedures to ensure the integrity of the study-related duties and functions 
performed and any data generated.
4. Ensure that study-related procedures, including study-specific (nonroutine/nonstandard panel) 
screening assessments, are NOT performed on potential patients before the receipt of written 
approval from relevant governing bodies/authorities.
5. Ensure that all colleagues and employees assisting in the conduct of the study are informed of 
these obligations.
6. Secure prior approval of the study and any changes by an appropriate IRB/IEC that conform to 
21 CFR Part 56, ICH and local regulatory requirements.
7. Ensure that the IRB/IEC will be responsible for initial review, continuing review, and approval 
of the protocol. Promptly report to the IRB/IEC all changes in research activity and all 
anticipated risks to patients. Make at least yearly reports on the progress of the study to the 
IRB/IEC, and issue a final report within 3 months of study completion.
8. Ensure that requirements for informed consent, as outlined in 21 CFR Part 50, ICH and local 
regulations, are met.
9. Obtain valid informed consent from each patient who participates in the study, and document 
the date of consent in the patient’s medical chart. Valid informed consent is the most current 
version approved by the IRB/IEC. Each ICF should contain a patient authorization section that 
describes the uses and disclosures of a patient’s personal information (including personal 
health information) that will take place in connection with the study. If an ICF does not include 
such a patient authorization, then the investigator must obtain a separate patient authorization 
form from each patient or the patient’s legally acceptable representative.
10. Prepare and maintain adequate case histories of all persons entered into the study, including 
eCRFs, hospital records, laboratory results, etc, and maintain these data for a minimum of 2 
years following notification by the sponsor that all investigations have been discontinued or 
that the regulatory authority has approved the marketing application. The investigator should 
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CONFIDENTIAL
contact and receive written approval from the sponsor before disposing of any such 
documents.
11. Allow possible inspection and copying by the regulatory authority of GCP-specified essential 
documents.
12. Maintain current records of the receipt, administration, and disposition of sponsor-supplied 
drugs, and return all unused sponsor-supplied drugs to the sponsor. 
13. Report adverse reactions to the sponsor promptly. In the event of an SAE, notify the sponsor 
within 24 hours.
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CONFIDENTIAL
Appendix E
Investigator Consent to Use of Personal Information
Takeda will collect and retain personal information of the investigator, including his or her name, 
address, and other identifying personal information. In addition, the investigator’s personal 
information may be transferred to other parties located in countries throughout the world (eg, the 
UK, US, and Japan), including the following:

Takeda, its affiliates, and licensing partners.

Business partners assisting Takeda, its affiliates, and licensing partners.

Regulatory agencies and other health authorities.

IRBs and IECs.
The investigator’s personal information may be retained, processed, and transferred by Takeda 
and these other parties for research purposes including the following:

Assessment of the suitability of the investigator for the study and/or other clinical studies.

Management, monitoring, inspection, and audit of the study.

Analysis, review, and verification of the study results.

Safety reporting and pharmacovigilance relating to the study.

Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to the study.

Preparation and submission of regulatory filings, correspondence, and communications to 
regulatory agencies relating to other medications used in other clinical studies that may contain 
the same chemical compound present in the study medication.

Inspections and investigations by regulatory authorities relating to the study.

Self-inspection and internal audit within Takeda, its affiliates, and licensing partners.

Archiving and audit of study records.

Posting investigator site contact information, study details, and results on publicly accessible 
clinical study registries, databases, and websites.
The investigator’s personal information may be transferred to other countries that do not have data 
protection laws that offer the same level of protection as data protection laws in the investigator’s 
own country.
The investigator acknowledges and consents to the use of his or her personal information by 
Takeda and other parties for the purposes described above.
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CONFIDENTIAL
Appendix F
MG-ADL Score
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

 
 
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MG-ADL - United States/English 
MG-ADL_AU1.1_eng-USori.docx 
MG Activities of Daily Living (MG-ADL) profile 

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	
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	*
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



 
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TAK-079
Study No. TAK-079-1005
Page 99 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
Appendix G
MGII Score
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

Constant or present 
most of the day
INSTRUCTIONS:
Please answer the following questions regarding your symptoms. Only consider those that you think are 
related to myasthenia. Check the answer that best describes your symptoms over the past 2 weeks.
1. Double vision throughout the day
Have you experienced episodes of 
double vision?  If yes, at what time 
do they occur (on average)?
No Double 
Vision   
Episodes only in 
the evenings
Episodes starting in 
the afternoons
2. Double vision with activities
Have you experienced double vision 
with activities such as reading, driving, 
watching TV or using a computer?  If 
yes, how long does it take (on average) 
before the double vision occurs?
No Double 
Vision   
After more than 
1 hour
After less than 1 hour, 
but not immediately
Constant double vision 
or it starts immediately
3. Severity of double vision
Have you experienced double vision? 
If yes, how severe has it been (at 
your worst)?
No Double 
Vision   
Mild: it doesn’t 
affect my daily 
activities
It affects my activities 
but no need to cover 
one eye
I need to cover 
one eye to be able 
to function
4. Eyelid droping throghout the day
Have you experienced drooping of 
your eyelid(s)? If yes, when does it 
occur (on average)?
No eyelid 
drooping     
Only in the 
evenings
Drooping starts in the 
afternoons
Constant drooping or 
present most of the day
5. Eyelid droping with activities
6. Severity of eyelid droping
Have you experienced drooping of your 
eyelid(s) with activities such as reading, 
driving, watching TV or using a com-
puter?  If yes, how long does it take (on 
average) before the drooping occurs?
Have you experienced drooping of 
your eyelids? If yes, how severe has it 
been (at your worst)?
No eyelid 
drooping     
After more than 
1 hour
After less than 1 hour, 
but not immediately
Constant drooping or it 
starts immediately
No eyelid 
drooping     
Mild: it doesn’t 
affect my vision
It affects my vision 
but no need to lift my 
eyelid
I need to lift my eyelid 
or tilt my head to be 
able to see
MG Impairment Index (MGII)
TM - Patient Questionaire
 PROBLEMS WITH YOUR EYES: Please answer regarding the past 2 weks.
ID: _______________ 
Date:______________
  0 
      1 
2  
               3
  0 
      1 
2  
               3
  0 
      1 
2  
               3
  0 
      1 
2  
               3
  0 
      1 
2  
               3
  0 
      1 
2  
               3
MGII. V1.0. English- Canada
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

 PROBLEMS EATING: Please answer regarding the past 2 weeks.
7. Difficulty swallowing
Have you experienced difficulty 
swallowing? How severe has it 
been (at your worst)?
No 
swallowing 
problems
Occasional episodes 
of choking/coughing 
with food or liquids
Liquids return 
through my nose, 
but no problems 
with solid food
Difficulty 
swallowing hard 
food, requiring a 
change in diet
Unable to 
swallow or 
using a feeding 
tube
8. Chewing different types of food
Have you experienced difficulty 
chewing? How severe has it been 
(at your worst)?
No difficulty 
chewing  
Difficulty chewing 
hard foods (e.g. 
steak, raw carrots)
Difficulty chewing soft 
foods (e.g. hard boiled 
egg)
Unable to chew (eating 
only liquids or feeding 
tube)
9. Chewing tiredness/fatigue
At your worst, how long does it 
take to develop fatigue or tiredness 
in your jaw?
No difficulty 
chewing  
Difficulty chewing 
at the end of the 
meal
Difficulty chewing from 
the beginning of the 
meal
Unable to chew (eating 
only liquids or feeding 
tube)
 PROBLEMS SPEAKING AND BREATHING: Please answer regarding the past 2 weeks.
10. Voice changes through the day
Have you experienced episodes of 
nasal, hoarse or weak voice? When 
do they occur on average?
No voice 
changes      
Voice changes only 
in the evenings
Voice changes 
starting in the 
afternoons
Constant voice 
changes or present 
most of the day
11. Voice changes with prolonged conversation
How long can you talk (on    
average), before developing voice 
changes, such as nasal, hoarse or 
weak voice? (Normal conversation, 
with pauses for other speakers)
No voice 
changes      
Voice changes 
after more than 30 
minutes
Voice changes after 
less than 30 minutes, 
but not immediately
Constant voice changes 
or they start immediately 
(less than 1 minute)
12. Severity of voice changes
At your worst, how severe have 
your voice changes been? (Nasal, 
hoarse, weak voice)
No voice 
changes      
Mild changes: my 
voice is mostly 
clear
Moderate changes: 
it can be hard to 
understand me
Severe changes: 
it is impossible to 
understand me
ID: _____________
  0 
    1 
  2  
  3
  0 
    1 
  2  
  3
  0     
1              
  2              
  3 
4
  0 
    1 
  2  
  3
  0 
    1 
  2  
  3
  0 
    1 
  2  
  3
MG Impairment Index (MGII)
TM - Patient Questionaire
MGII. V1.0. English- Canada
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

ID: _____________
 PROBLEMS SPEAKING AND BREATHING (Cont.): Please answer regarding the past 2 weeks.
13. Speech clarity through the day
Have you experienced difficulty 
pronouncing words or slurred 
speech? When does it occur on 
average?
No episodes of 
slurred speech   
Slurred speech 
only in the 
evenings
Slurred speech 
starting in the 
afternoons
Constant slurring, or 
present most 
of the day
14. Speech clarity with prolonged conversation
How long can you talk (on    
average), before developing 
slurred speech? (Normal 
conversation, with pauses for other 
speakers)
15. Severity of speech changes
At your worst, how severe have 
your speech changes been? (Slur-
ring, difficulty pronouncing words)
No episodes of 
slurred speech    
Mild slurring: 
It is easy to 
understand me
Moderate slurring: There 
are some difficulties 
understanding me
Severe slurring: 
it is impossible to 
understand me
No episodes of    
slurred speech   
Slurred speech 
after 30 minutes
Slurred speech after 
less than 30 minutes, 
but not immediately
Constant slurring, or 
it starts immediately  
(less than 1 minute)
16. Difficulty breathing
Have you experienced shortness 
of breath that is caused by
myasthenia?  (i.e. not caused 
by asthma, or other lung/heart 
disease) If yes, when has it 
occurred (at your worst)?
No shortness of 
breath (except 
for strenuous 
exercise)
With moderate 
effort (e.g. walking 
several blocks at my 
own pace)
With minimal 
effort (e.g. getting 
dressed, walking 
inside the house)
At rest or when 
lying on my
 back
Requiring 
assisted
 ventilation
 GENERALIZED SYMPTOMS: Please answer regarding the past 2 weeks.
17. Overall physical tiredness
Have you experienced overall 
physical tiredness caused by 
myasthenia gravis? (i.e. not by 
sleeplessness, depression or 
other medical conditions) 
No physical 
tiredness           
Overall physical 
tiredness in the 
evenings
Overall physical 
tiredness starting in 
the afternoons
Constant physical 
tiredness, or present 
most of the day
  0 
    1 
   2  
  3
  0 
    1 
   2  
  3
  0 
    1 
   2  
  3
  0     
1              
  2              
3 
4
  0 
    1 
   2  
  3
MG Impairment Index (MGII)
TM - Patient Questionaire
MGII. V1.0. English- Canada
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

ID: ____________
18. Arm weakness severity
Have you experienced weakness 
in your arms? If yes, how severe 
has it been (at your worst)?
No arm 
weakness      
Mild weakness 
(e.g. difficulty 
lifting heavy 
objects)
Moderate weakness 
(e.g. difficulty lifting arms 
above the shoulders, but 
I can do it)
Severe weakness 
(unable to lift arms 
above the shoulders)
19. Arm weakness with prolonged use
Have you experienced weakness 
in your arms after prolonged use? 
When does it happen (on 
average)?
20. Leg weakness severity
Have you experienced weakness in 
your legs? If yes, how severe has it 
been (at your worst)?
No leg
weakness     
Mild weakness (e.g. 
difficulty standing 
from a squat or from 
tying my shoes)
Moderate weakness 
(e.g difficulty standing  
from a chair, I need to 
push up with my arms)
Severe weakness 
(e.g unable to stand 
from a chair without 
assistance)
No arm 
weakness      
Weakness when 
keeping arms up for 
long (e.g. washing 
or drying my hair)
Weakness with prolonged 
activities at shoulder level 
(organizing objects on a 
shelf, holding a phone to 
the ear)
Weakness with 
minimal effort (e.g. 
desk work, chopping 
vegetables)
GENERALIZED SYMPTOMS: Please answer regarding the past 2 weeks. 
21. Leg weakness with prolonged use
Have you experienced weakness 
in your legs after prolonged use? 
When does it happen (on 
average)?
No leg
weakness     
Weakness when 
walking more than 
10 blocks at my own 
pace
Weakness when 
walking less than 10 
blocks at my own pace
Constant weakness 
or with minimal effort 
(standing, walking 
inside the house)
22. Neck weakness
Have you experienced weakness 
in your neck? When does it happen 
(on average)?
No neck
weakness     
Weakness only in 
the evenings
Weakness starting in 
the afternoons
Constant weakness 
or present most of the 
day
  0 
  1 
   2  
  3
  0 
   1 
   2  
   3
  0 
   1 
   2  
   3
  0 
   1 
   2  
   3
  0 
   1 
   2  
   3
MG Impairment Index (MGII)
TM - Patient Questionaire
MGII. V1.0. English- Canada
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

MG Impairment Index (MGII) - Examination  
ID:_________________ 
Date:________________
0
1
2
3
Score
E1. Diplopia
No Diplopia
Diplopia in only 1 
direction. 
Diplopia in 2 
directions.
Diplopia in ≥3 direc-
tions OR in primary 
gaze.
E2. Ptosis
No ptosis
Ptosis between 10-60 
seconds.
Spontaneous 
ptosis or in less than 
10 seconds.
E3. Lower Facial 
Strength
Normal strength
Can resist with 
cheeks, but air 
escapes through lips.
Unable to seal lips 
or provide resis-
tance with cheeks.
E4. Arm Endurance
Holds arms for 180 
seconds.
Holds arms for 91-
179 seconds.
Holds arms for 30-
90 seconds.
Holds arms for < 30 
seconds.
E5. Leg Endurance
Holds leg for 90 
seconds.
Holds leg for 40-89 
seconds.
Holds leg for 16-39 
seconds.
Holds leg for ≤ 15 
seconds.
E6. Neck 
Endurance
Holds head for 60 
seconds.
Holds head for 35-59 
seconds.
Holds head for 11-
34 seconds.
Holds head for ≤ 10 
seconds.
This sheet refers to the physical examination. Detailed instructions are found in the instruction 
manual. You will need a stopwatch.
MGII. V1.0. English- Canada
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TAK-079
Study No. TAK-079-1005
Page 100 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
Appendix H
MGC Score
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

MG composite scale 
Ptosis, upward ease 
>45 seconds = 0 11-45 seconds = 1
1-10 seconds = 2
Immediate = 3 
(physician examination) 
Double vision on lateral 
>45 seconds = 0 11-45 seconds = 1
1-10 seconds = 3
Immediate = 4 
Gaze, left or right 
(physician examination) 
Eye closure 
Normal = 0 
Mild weakness (can 
Moderate weakness 
Severe weakness 
(physician examination) 
be forced open with 
(can be forced open 
(unable to keep  
effort) = 0 
easily) = 1 
eye closed) = 2 
Talking   
Normal = 0 
Intermittent slurring 
Constant slurring or 
Difficult to 
(patient history) 
or nasal speech = 2 
nasal but can be  
understand 
understood = 4 
speech = 6 
Chewing 
Normal = 0 
Fatigue with solid 
Fatigue with soft 
Gastric tube = 6 
(patient history) 
food = 2  
food = 4 
Swallowing 
Normal = 0 
Rare episode of   
Frequent trouble  
Gastric tube = 6 
(patient history) 
choking or trouble 
swallowing, for example 
swallowing = 2  
necessitating change in 
diet = 5 
Breathing (thought to 
Normal = 0 
Shortness of breath 
Shortness of breath at 
Ventilator  
be caused by MG) 
with exertion = 2  
rest = 4  
dependence = 9 
Neck flexion or  
Normal = 0 
Mild weakness = 1 
Moderate weakness 
Severe weakness 
extension (weakest) 
(i.e., ~50% weak, ±15%) = 4 
(physician examination) 
= 3 
Shoulder abduction 
Normal = 0 
Mild weakness = 2 
Moderate weakness 
Severe weakness 
(physician examination) 
(i.e., ~50% weak, ±15%) = 5 
= 4 
Hip flexion 
Normal = 0 
Mild weakness = 2 
Moderate weakness 
Severe weakness 
(physician examination) 
(i.e., ~50% weak, ±15%) = 5 
= 4 
TOTAL
_________ 
Note: Please note that “moderate weakness” for neck and limb items should be construed as weakness that equals 
roughly 50% ± 15% of expected normal strength. Any weakness milder than that would be “mild,” and any
weakness more severe than that would be classified as “severe.”
Patient ID #: _ 
Date:_
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TAK-079
Study No. TAK-079-1005
Page 101 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
Appendix I
QMG Score
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

© 1997 UT Southwestern Medical Center, Dallas 
 
QMG - United States/English – Original version 
QMG_AU2.1_eng-USori.docx 
 
 
 
 
Test Item 
None 
Mild 
Moderate 
Severe 
Score 
Grade 
0 
1 
2 
3 
Raw 
Scale 
Double vision on lateral gaze  
Right or left (circle one), secs 
61 
11-60 
1-10 
Spontaneous 
 
 
Ptosis (upward gaze) 
61 
11-60 
1-10 
Spontaneous 
 
 
Facial muscles 
Normal lid  
closure 
Complete, weak,  
some resistance 
Complete, without  
resistance 
Incomplete 
 
 
Swallowing 4 oz 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 
degrees sitting), seconds 
240 
90-239 
10-89 
0-9 
 
 
Left arm outstretched (90  
degrees sitting), seconds 
240 
90-239 
10-89 
0-9 
 
 
Forced Vital Capacity 
 
> 80 
65-79 
50-64 
<50 
 
 
Rt- hand grip, kg 
Men 
Women 
 
> 45 
> 30 
 
15-44 
10-29 
 
5-14 
5-9 
 
0-4 
0-4 
 
 
Lt- hand grip, kg 
Men 
Women 
 
> 35 
> 25 
 
15-34 
10-24 
 
5-14 
5-9 
 
0-4 
0-4 
 
 
Head lifted (45 degrees supine
seconds 
120 
30-119 
1-29 
0 
 
 
Right leg outstretched (45  
degrees supine), seconds 
100 
31-99 
1-30 
0 
 
 
Left leg outstretched (45 
 degrees supine), seconds 
100 
31-99 
1-30 
0 
 
 
                                                                                         
 
                                                                                                                               TOTAL QMG SCORE : 
 
 
 
 
 
QMG form 
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TAK-079
Study No. TAK-079-1005
Page 102 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
Appendix J
MG-QoL15r
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Patient ID #: __________ 
Date: __________
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TAK-079
Study No. TAK-079-1005
Page 103 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
Appendix K
PGIC
Property of Takeda: For non-commercial use only and subject to the applicable Terms of Use

PGIC Questionaire
Regarding your myasthenia gravis, how has your functioning changed 
since you started taking study medication? 
Much beter
Moderately beter
A litle beter
No change
A litle worse
Moderately worse
one box only
Much worse
Patient ID:_
Date:_
version as of 9/4/2019
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TAK-079
Study No. TAK-079-1005
Page 104 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
Appendix L
PGIS
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PGIS Questionnaire
How much has your myasthenia gravis affected your functioning
in the past 7 days? 
Not at all
Patient ID:______________
Date:__________________
A little bit
Somewhat
Quite a bit
Very much
one box only
version as of 9/4/2019
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TAK-079
Study No. TAK-079-1005
Page 105 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
Appendix M
Protocol History
Date
Amendment Number
Type
Region
02 February 2021
Amendment 4
Substantial
Global
28 September 2020
Amendment 3
Substantial
Global
05 March 2020
Amendment 2
Substantial
Global
18 October 2019
Amendment 1
Nonsubstantial
Global
05 September 2019
Initial Protocol
Not applicable
Global
Protocol Amendment 3 Summary and Rationale
The primary reason for this amendment was to add contingency plans for the coronavirus disease 
2019 (COVID-19) pandemic by incorporating flexibility for study participants and investigators, 
while continuing to maintain patient safety and study integrity as per local site regulations. Other 
minor changes and clarifications to the protocol are summarized below.
Protocol Amendment 3
Summary of Changes Since the Last Version of the Approved Protocol
Sections Affected by Change
Description of Each Change and Rationale
Location
Description 
Rationale
Section 2.0 STUDY SUMMARY
Statistical Considerations: Updated 
text in the synopsis for the primary 
endpoint analysis to be consistent 
with the body of the protocol.
To harmonize the analysis of the 
safety data between the synopsis and 
body of the protocol.
Section 2.0 STUDY SUMMARY 
Section 5.2.3 Exploratory Endpoints 
Amended the wording for the 
exploratory endpoint of 
pharmacokinetics (PK) from "PK of 
TAK-079 in combination with the 
background therapy. PK parameters 
include but are not limited to Cmax, 
AUC, and tmax (time of first 
occurrence of Cmax) to read: "Serum 
concentration-time profile of 
TAK-079 PK parameters will 
include, but are not limited to Ctrough
over time."
Clarify PK endpoint.
Added exploratory endpoint: Change 
in serum immunoglobulin levels.
The reduction in immunoglobulin 
levels is an important 
pharmacodynamic indicator of 
TAK-079 effect.
Added antidrug antibody (ADA) as 
an immunogenicity assessment and 
removed ADA as a biomarker.
To clarify that ADA is an 
immunogenicity assessment and not 
a biomarker of disease activity.
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TAK-079
Study No. TAK-079-1005
Page 106 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
Protocol Amendment 3
Summary of Changes Since the Last Version of the Approved Protocol
Sections Affected by Change
Description of Each Change and Rationale
Location
Description 
Rationale
Section 2.0 STUDY SUMMARY
Section 7.2 Exclusion Criteria 
Exclusion Criterion #4: Revised to 
exclude patients if there is an 
expectation that any rescue therapy 
may be needed between screening 
and dosing.
To clarify that a patient’s underlying 
MG should be stable enough that the 
need for rescue therapy is not 
expected before dosing. 
Section 2.0 STUDY SUMMARY
Section 13.1.3 Efficacy Analysis 
Statistical Considerations:
Changed "Secondary Efficacy 
Endpoints" to read: "Efficacy 
Endpoint Analyses."
Revised text to specify how different 
types of secondary efficacy 
endpoints (binary vs continuous) 
will be analyzed.
To clarify statistical analyses.
Section 13.1.4 PK Analysis 
PK analysis description made clearer 
and more concise.
To clarify the PK analysis to better 
reflect the information that will be 
obtained from the PK sampling 
schedule in this study.
Section 2.0 STUDY SUMMARY
Section 13.3 Determination of Sample 
Size 
Amended the sample-size 
justification to remove the statement 
describing a power calculation for 
the secondary efficacy endpoints.
To further clarify that this study is an 
exploratory study and not powered 
to test any predefined statistical 
hypothesis at a formal α level. 
Statistical tests will be not be 
inferential and will not be adjusted 
for multiplicity.
Section 4.4 Benefits and Risks 
Assessment 
New section added summarizing the 
potential risks and benefits of 
TAK-079.
Added in response to a health 
authority request.
Section 5.1.3 Exploratory Objectives 
Removed "in combination with 
background therapy" from the 
exploratory objectives of the PK and 
pharmacodynamics of TAK-079.
To clarify that the PK and
pharmacodynamics of TAK-079 will 
be determined regardless of 
background therapy received.
Section 8.1 Study Drug 
Administration 
Added clarifying statements that first 
dose assessments detailed in Table 
8.d may be satisfied by screening.
To clarify that on Day 1 of dosing, 
these laboratory studies would have 
been recently obtained in the absence 
of recently administered study drug. 
For other doses, the window is 
expanded to allow obtaining labs the 
day before (rather than restricted to 
24 hours before the study visit) for 
flexibility in obtaining laboratory 
results, especially in light of 
operational complexities due to 
coronavirus disease 2019 
(COVID-19).
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TAK-079
Study No. TAK-079-1005
Page 107 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
Protocol Amendment 3
Summary of Changes Since the Last Version of the Approved Protocol
Sections Affected by Change
Description of Each Change and Rationale
Location
Description 
Rationale
Section 8.1.2 Postdose Medication 
The dose of methylprednisone was 
corrected from <20 mg to read ≤20 
mg.
To correct typographical error.
Section 8.2 Excluded Concomitant 
Medications and Procedures, Table
8.b Excluded Concomitant 
Medications 
Added footnote b to the categories of 
intravenous immunoglobulin, 
plasmapheresis/plasma exchange, 
and subcutaneous immunoglobulin: 
"Patients for whom any therapy 
(besides the allowed standard 
background therapies for MG) is 
reasonably expected between 
screening and dosing are excluded 
from study participation."
To align with text in Exclusion 
Criterion No 4.
Corrected exclusion criteria for 
dosing of rituximab, belimumab, 
eculizumab, or any monoclonal 
antibody for immunomodulation 
restricted from ≤6 months "before 
the screening visit" to read "before 
the first dosing."
To align with text in Exclusion 
Criterion No 6. 
Section 8.4.1 Assessment and Criteria 
for Terminating Patient Dosing, Table 
8.d Summary of Subsequent Dosing 
Criteria 
Safety Parameter: Total lymphocyte 
count:
Continue Dosing: Corrected 
"≥500/mm3" to read: "≥500/mm3 or 
≥90% of the baseline level."
Dose Hold: Corrected "<500/mm3" 
to read:" <500/mm3 and <90% of the 
baseline level."
Allows for minor fluctuations in the 
cell counts for patients on 
background therapy who may also 
have low baseline values. This 
criterion is based on emerging 
information from ongoing clinical 
studies with TAK-079.
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TAK-079
Study No. TAK-079-1005
Page 108 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
Protocol Amendment 3
Summary of Changes Since the Last Version of the Approved Protocol
Sections Affected by Change
Description of Each Change and Rationale
Location
Description 
Rationale
Amended footnote c from 
"Laboratory grading is based on 
CTCAE v4.03" to read: "Laboratory 
and infection grading are based on 
CTCAE v4.03.
Added footnote c to: row labeled 
"Platelets" for Thrombocytopenia 
≤Grade 2c and Thrombocytopenia 
≤Grade 3c; row labeled 
"Hypersensitivity (allergic reaction 
or anaphylaxis)e" for ≤Grade 2c, and 
row labeled "Systemic infection" for 
Grade 2c and ≥Grade 3c
Removed footnote f from Systemic 
infection Grade 2c and ≥Grade 3c.
To clarify that all laboratory and 
infection grades listed in the table are 
based on Common Terminology 
Criteria for Adverse Events
(CTCAE) v4.03 criteria.
Section 8.5.1 Pregnancy, Lactations, 
and Contraception 
Changed Section heading to include 
"Contraception" and added Table 8.e
(methods of contraception for female 
patients) and Table 8.f (methods of 
contraception for male patients) to 
match with contraception method 
recommendations provided in the 
informed consent form.
Text added in response to a request 
from a health authority.
Section 8.6.1.1 Management 
Recommendations for 
Hypersensitivity Reactions 
First sentence: Change ISR to IRR. 
Correct typo.
Add "Signs and symptoms of 
systemic hypersensitivity reactions 
include rash, urticaria, fever, and/or 
bronchospasms."
To describe the clinical presentation 
of an infusion reaction. 
Remove examples of Grade 1, Grade 
2, and Grade 3 hypersensitivity 
reactions.
Add text in parenthesis after Grade 3 
or greater: "(including any diagnosis 
of anaphylaxis according to 
Sampson [24])."
To avoid confusion with definition 
of CTCAE v4.03 grades and criteria 
for diagnosis of anaphylaxis. 
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TAK-079
Study No. TAK-079-1005
Page 109 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
Protocol Amendment 3
Summary of Changes Since the Last Version of the Approved Protocol
Sections Affected by Change
Description of Each Change and Rationale
Location
Description 
Rationale
Table 8.d Summary of Subsequent 
Dosing Criteria
Table 8.d: Revised wording:
Hypersensitivity (IRR, allergic 
reaction, or anaphylaxis (See Section 
8.6.1). NOTE: IRR, allergic reaction, 
and anaphylaxis are each classified 
according to CTCAE v4.03. 
Anaphylaxis is diagnosed according 
to Sampson et al [19].
Continue Dosing: ≤Grade 2 
Dose Discontinuation: ≥Grade 3 or 
any signs or symptoms of an 
anaphylactic reaction [19].
CRS (See Section 8.6.2)
NOTE: CRS is classified in 
accordance with Lee et al [20].
Continue Dosing: Grade 1 with 
symptomatic treatment allowed in 
accordance with Lee et al [20].
Dose Discontinuation: ≥Grade 2.
Remove Table footnotes e and f as 
information is redundant with 
information provided in table.
Make dosing criteria for 
hypersensitivity and CRS in table
consistent with text in Section 8.6.1
and Section 8.6.2
Section 9.12 COVID-19 Related 
Procedural Changes 
Added new section (Section 9.12) 
and text regarding contingency plans 
for the COVID-19 pandemic 
ongoing during the clinical study.
New section to mitigate the impact 
of the COVID-19 pandemic to 
ensure the rights, safety, and 
well-being of patients, the safety of 
clinical trial staff, maintain 
compliance with Good Clinical 
Practice, maintain study integrity, 
and patient privacy.
Section 9.5.10.2 Timing of Pregnancy 
Testing
Changed timing of pregnancy testing 
before initial study dosing at baseline 
from "within 24 hours before the 
start of study drug" to read: "Either 
Day 1 prior to initial study dosing, or 
1 day before study dosing."
To clarify the timing of pregnancy 
testing at baseline.
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TAK-079
Study No. TAK-079-1005
Page 110 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
Protocol Amendment 3
Summary of Changes Since the Last Version of the Approved Protocol
Sections Affected by Change
Description of Each Change and Rationale
Location
Description 
Rationale
Section 9.6 End of Safety Follow-up 
Period Assessments, Table 9.c End of 
Safety Follow-Up Period Clinical 
Parameters 
Table 9.c: Revised criteria for 
neutrophils, platelets, total 
lymphocyte count, and Hgb as 
follows:
End-of-Study Criteria: ≥LLN or 
≥study baseline levels, or abnormal 
levels that are not directly related to 
dosing of investigational product.
Continuation to Long-term 
Follow-up: <LLN and < study 
baseline levels that are directly 
related to dosing of investigational 
product.
To clarify the end-of-study criteria 
and long-term follow-up parameters 
by correcting errors and unclear 
wording.
TAK-079-related hypersensitivity 
reaction (IRR, allergic reaction, or 
anaphylaxis) (See Section 8.6.1)
End-of-Study Criteria: Clinical 
symptoms related to hypersensitivity 
reaction resolved.
Continuation to Long-term 
Follow-up: Clinical symptoms 
related to hypersensitivity reaction 
ongoing.
TAK-079-related CRS (See Section 
8.6.2)
End-of-Study Criteria: Clinical 
symptoms related to CRS reaction 
resolved. 
Continuation to Long-term 
Follow-up: Clinical symptoms 
related to CRS reaction ongoing.
Revised criteria for systemic 
infection as follows:
Continuation to Long-term 
Follow-up: Any ≥Grade 2 b
systemic infection that is not 
resolved.
Footnote a: added "see Section 8.6.2 
for details" for definitions of 
CTCAE grades.
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TAK-079
Study No. TAK-079-1005
Page 111 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
Protocol Amendment 3
Summary of Changes Since the Last Version of the Approved Protocol
Sections Affected by Change
Description of Each Change and Rationale
Location
Description 
Rationale
Section 10.1.3 SAE Definition 
Added: Note: Some clinical centers 
may only be able to provide certain 
rescue therapies (eg, IVIg) via 
inpatient hospitalization. Therefore, 
the hospital admission itself (in an 
otherwise clinically stable patient) 
specifically for access and 
administration of rescue therapy 
does not count automatically as an 
SAE, unless there are other 
circumstances that fulfill SAE
criteria.
Added clarification that inpatient 
stay for rescue therapy does not 
automatically count as a serious 
adverse event (SAE).
Section 13.1.1 Analysis Sets 
The definition of the PK analysis set 
has been clarified to read “Patients 
who have received at least 1 dose and 
have at least 1 measurable TAK-079 
serum concentration.”
Clarification.
Section 13.1.5 Immunogenicity 
Analyses
Added "pharmacodynamics" to the 
statement that reads: The effect of 
immunogenicity on PK, 
pharmacodynamics, safety, and 
efficacy may be explored.
Correction.
Section 14.1 Study-Site Monitoring 
Visits 
Added 2nd paragraph of text 
regarding contingency plans for 
Study-Site Monitoring Visits 
conducted during the COVID-19 
pandemic.
Text added per Sponsor's COVID-19 
guidelines.
Appendix A Schedule of Events
Removed serum sample collection 
for immunogenicity (eg, ADA) at 
Weeks 3, 5, and 7.
Serum samples do not need to be 
collected every week.
Reordered all footnotes due to the
addition of 4 footnotes (b, h, r, and 
s).
N/A
Added footnote b to table row 
labeled "Week" to allow for remote 
visits at certain time points.
Added per COVID-19 guidelines to 
allow flexibility for remote visits.
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TAK-079
Study No. TAK-079-1005
Page 112 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
Protocol Amendment 3
Summary of Changes Since the Last Version of the Approved Protocol
Sections Affected by Change
Description of Each Change and Rationale
Location
Description 
Rationale
Appendix A continued...
Added footnote letter h to table rows 
labeled: 12-lead ECG; serum 
pregnancy test; urine pregnancy test; 
hematology; clinical chemistry; 
direct/indirect Coombs test; serum 
sample for anti-AChR or anti-MuSK 
antibodies; blood sample for 
immunoprofiling; serum sample for 
circulating biomarkers; serum 
sample for quantitative 
IgA/IgM/IgG; serum sample for 
TAK-079 PK; serum sample for 
immunogenicity (eg, ADA); serum 
sample for vaccine-induced 
protective antibodies; 
pharmacodynamic biomarkers; and 
Disease assessment tests.
To indicate that assessments may be 
performed on the day before or the 
day of the indicated visit before 
dosing.
Added text to table footnote i to state 
that vital signs measurements will 
not be required at the Week 14 visit 
during the COVID-19 pandemic 
visit as long as there are no concerns 
raised by the symptom-directed 
physical.
Added per COVID-19 guidelines to 
allow flexibility for remote visits.
Added text to footnote j and added 
footnote “j” designator to table row 
labeled urine pregnancy test to 
indicate that serum pregnancy 
testing may be used in place of urine 
pregnancy testing with prior 
permission from the sponsor.
To clarify that the intent of the 
protocol is not to exclude use of 
more accurate serum pregnancy tests 
if this is logistically feasible for a 
site.
Added footnote letter m to table rows 
labeled: urine pregnancy test, 
hematology; clinical chemistry; 
direct/indirect Coombs test, and 
serum sample for vaccine-induced 
protective antibodies.
To ensure that samples are collected 
before TAK-079 administration
Added footnote r to table row labeled 
Myasthenia Gravis Impairment 
Index (MGII) score to indicate that 
the Physician examination portion of 
the MGII score may be omitted if 
performing a remote visit.
Added per COVID-19 guidelines to 
allow flexibility for remote visits.
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TAK-079
Study No. TAK-079-1005
Page 113 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
Protocol Amendment 3
Summary of Changes Since the Last Version of the Approved Protocol
Sections Affected by Change
Description of Each Change and Rationale
Location
Description 
Rationale
Added footnote s to table rows 
labeled Myasthenia Gravis 
Composite (MGC) and Quantitative 
Myasthenia Gravis (QMG) scores to 
indicate that the MGC and QMG 
may be omitted if performing a 
remote visit.
Added per COVID-19 guidelines to 
allow flexibility for remote visits.
Appendix I QMG Score
Updated the version of the QMG 
form from v2.0 to v2.1.
Minor version update to the QMG 
form, which includes a vertical 
border in the column header 
separating “Raw” and “Scale” 
scores. 
Rationale for Amendment 2
The objective of Amendment 2 was to remove language regarding details of storage conditions 
outlined in the Rationale for Amendment 1. This was because the storage conditions may vary by 
region and do not require further specification in the study protocol.
Additionally, changes to inclusion and exclusion criteria were made to provide better definitions, 
clarification of intent and removal of vague language. Updates to the Takeda serious adverse event 
reporting process, which now includes an acknowledgment of receipt, have been made in Section 
10.2.
Minor grammatical, editorial, formatting, and administrative changes not affecting the conduct of 
the study are included for clarification and administrative purposes only. 
Changes in Amendment 2
1. Updated Inclusion Criterion 7 to clarify the intent to exclude only pulse steroid therapy. 
Dosing of corticosteroids with oral therapy every other day is as acceptable as daily. 
2. Updated Exclusion Criterion 8 to exclude only those receiving live vaccines and not inactive 
vaccines. 
3. Updated Exclusion Criterion 12 to clarify the intent not to exclude a minor, benign, resolved, 
localized herpes simplex infection not requiring systemic therapy. 
4. Updated Exclusion Criterion 13f to change “lower limit of normal” to “5 g/L.” As a result of 
this edit, subjects are excluded if the IgG is less than 5 g/L (500 mg/dL) at screening.
5. Updated Exclusion Criterion 16 to clarify the intent to exclude subjects with active hepatitis C 
and not those who have been fully cured of the disease. Additionally, more stringent criteria 
are used to exclude subjects with hepatitis B infection. 
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TAK-079
Study No. TAK-079-1005
Page 114 of 114
Protocol Incorporating Amendment No. 4
02 February 2021
CONFIDENTIAL
6. Updated the serious adverse event reporting procedure in Section 10.2 to include an 
acknowledgement of receipt. 
7. Added a global fax number to the SAE Reporting Contact Information.
8. Descriptors for circulating biomarker samples and quantitative IgA/IgM/IgG samples have 
been changed from blood to serum in the schedule of events.
9. Updated the version number of the QMG scoring assessment tool (to Version 2.0; previously 
Version 1.0) which fixes a typographical error in the definition of severe forced vital capacity 
(FVC) (in Version 2 FVC is <50; in Version 1 FVC was ≤50).
10. Serum samples for hepatitis B, hepatitis C, and HIV have been added to the Section 9.0 
Primary Specimen Collection Table.
11. Added serum pregnancy test at Week 32.
12. Eligibility criteria regarding immunosuppressive drugs now requires a stable dose for at least 3 
months before screening. Stable dosing of azathioprine will remain at 6 months prior to 
screening.
Rationale for Amendment 1
The objective of this amendment was to remove language specifying that the site pharmacist is to 
be unblinded. The reason for this change is because the storage conditions for the placebo 
formulation were changed to be the same as for the active drug (both now refrigerated at 5°C, 
whereas previously the placebo was to be stored frozen at -20°C). This avoids the need for an 
unblinded site pharmacist. Therefore, all site personnel, including the site pharmacist, are to be 
blinded as to treatment assignments.
Additionally, a protocol subsection is added to provide information regarding potential 
interference with serological testing.
Minor grammatical, editorial, formatting, and administrative changes not affecting the conduct of 
the study are included for clarification and administrative purposes only. 
Changes in Amendment 1 
1. Removal of language specifying that the site pharmacist is to be unblinded, as was previously 
detailed in Section 8.7.2 and Section 8.7.4. As a result of this edit, all site staff will be blinded 
as to treatment assignment through study Week 16.
2. The addition of a protocol subsection 8.5.3 to provide clarification regarding potential 
interference with serological testing
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