Clinical trial NCT04278924
Conditions: Primary Immune Thrombocytopenia
Keywords: Drug Therapy
Sponsor: Takeda
Start date: 2020-11-09; Completion date: 2024-04-29
Enrollment: 41 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Primary immune thrombocytopenia (ITP) is a rare disease that results in low levels of platelets - the cells that help blood clot.

The main aim of the study is to check for side effects from taking TAK-079 at three different dose levels. Another aim is to learn if TAK-079 can increase the platelet count in people with ITP.

In addition to receiving stable background therapy for ITP, participants will receive an injection of either TAK-079 or a placebo once a week for 2 months. A placebo looks like TAK-079 but will not have any medicine in it. After treatment, all participants will be followed-up for another 2 months.

Then, participants who received TAK-079 will continue to be followed-up for an extra 4 months. Participants who received the placebo and would like to receive TAK-079 may be able to do this in an extension period in the study.

Detailed description:
The drug being tested in this study is called TAK-079. TAK-079 is being tested to treat people who have primary immune thrombocytopenia (ITP). This study will evaluate the safety and biologic activity of TAK-079 or matching placebo in combination with stable ITP background therapy.

The study will enroll approximately 36 to 54 participants. In Part A of the study, participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups. Those who received placebo in this period will have the choice to receive TAK-079 after a safety follow-up period and will be randomized to one of the two open-label TAK-079 treatment arms. An unblinded safety review will take place once a minimum of 24 evaluable participants are available for analysis in Part A to decide whether to open enrollment into Part B.

In Part B participants will be randomly assigned to one of two treatment groups. Those who received placebo in this period will have the choice to receive study drug after a safety follow-up period in a single open-label TAK-079 treatment arm.

This multi-center trial will be conducted worldwide. All participants will be followed for at least 8 weeks in a Safety Follow-up Period, and a 16-week Long-term Follow-up Period after the 8 weeks of treatment.

Arms: arm 1: Participants received TAK-079 placebo-matching injection subcutaneously (SC), once weekly (QW) for 8 weeks. Following treatment participants were followed up for 8 weeks in a double blinded short follow-up period (SFP) up to Week 16. Participants who opted to receive treatment with TAK-079 were then randomized to receive TAK-079, SC injection, QW for 8 weeks in Open-label Extension (OLE) Period of Part A or Part B. Participants who did not opt to receive treatment with TAK-079 were followed up for another 16 weeks in an unblinded long follow-up period (LFP) up to Week 32. arm 2: Participants received TAK-079 100 mg, SC injection, QW for 8 weeks. Following treatment participants were followed up for 8 weeks in a double blinded SFP up to Week 16. Participants who opted to receive treatment with TAK-079 were then randomized to receive TAK-079, SC injection, QW for 8 weeks in OLE Period of Part A or Part B. Participants who did not opt to receive treatment with TAK-079 were followed up for another 16 weeks in an unblinded LFP up to Week 32. arm 3: Participants received TAK-079 300 mg, SC injection, QW for 8 weeks. Following treatment participants were followed up for 8 weeks in a double blinded SFP up to Week 16. Participants who opted to receive treatment with TAK-079 were then randomized to receive TAK-079, SC injection, QW for 8 weeks in OLE Period of Part A or Part B. Participants who did not opt to receive treatment with TAK-079 were followed up for another 16 weeks in an unblinded LFP up to Week 32. arm 4: Participants received TAK-079 600 mg, SC injection, QW for 8 weeks. Following treatment participants were followed up for 8 weeks in a double blinded SFP up to Week 16. Participants who opted to receive treatment with TAK-079 were then randomized to receive TAK-079, SC injection, QW for 8 weeks in OLE Period of Part A or Part B. Participants who did not opt to receive treatment with TAK-079 were followed up for another 16 weeks in an unblinded LFP up to Week 32. arm 5: Participants who received placebo in double-blind Part A and opted to receive treatment with TAK-079 were randomized to receive TAK-079 100 mg, SC injection, QW for 8 weeks in OLE Period of Part A. Following treatment participants were followed up for 8 weeks in a SFP and then for another 16 weeks in a LFP. arm 6: Participants who received placebo in double-blind Part A and opted to receive treatment with TAK-079 were randomized to receive TAK-079 300 mg, SC injection, QW for 8 weeks in OLE Period of Part A. Following treatment participants were followed up for 8 weeks in a SFP and then for another 16 weeks in a LFP. arm 7: Participants who received placebo in double-blind Part B and opted to receive treatment with TAK-079 received TAK-079 600 mg, SC injection, QW for 8 weeks in OLE Period of Part B. Following treatment participants were followed up for 8 weeks in a SFP and then for another 16 weeks in a LFP.
Interventions: intervention 1: Placebo intervention 2: TAK-079
Intervention descriptions: intervention 1: TAK-079 placebo-matching SC injection. intervention 2: TAK-079 SC injection.

Protocol documents:
Prot_000.pdf: 
For non-commercial use only


PROTOCOL
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Safety, 
Tolerability, and Efficacy of TAK-079 in Patients With Persistent/Chronic Primary 
Immune Thrombocytopenia
Sponsor:
Takeda Development Center Americas, Inc. 
95 Hayden Avenue, 
Lexington, MA 02421 USA
Study Number:
TAK-079-1004
EudraCT Number:
2019-004103-12
Compound:
TAK-079
Date:
28 April 2022
Amendment Number:
5
Amendment History
Date
Amendment Number
Type
Region
28 April 2022
Amendment 5
Substantial
Global
05 May 2021
Amendment 4
Substantial
Global
18 December 2020
Amendment 3
Substantial
Global
7 October 2020
Amendment 2
Substantial
Global
26 December 2019
Amendment 1
Nonsubstantial
Global
06 November 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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1.0
ADMINISTRATIVE INFORMATION
1.1
Contacts 
A separate contact information list will be provided to each site.
Serious adverse event (SAE) 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 manual.
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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 also to protect the 
rights, safety, privacy, and well-being of study subject/patients in accordance with the following:

The ethical principles that have their origin in the Declaration of Helsinki.

ICH, E6 (R2) GCP: Consolidated Guideline.

All applicable laws and regulations, including, without limitation, data privacy laws and 
regulations.

Regulatory requirements for reporting SAEs defined in Section 10.0 of this protocol.

Terms outlined in the clinical study site agreement. 

Responsibilities of the investigator (Appendix E). 
I further authorize that my personal information may be processed and transferred in accordance 
with the uses contemplated in Appendix F 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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1.3
Protocol Amendment 5 Summary of Changes
Protocol Amendment 5 Summary and Rationale 
This section describes the changes in reference to the protocol incorporating Amendment 5. The 
primary reason for this amendment is to update the number of patients enrolled in each study part, 
to modify the prophylactic drug coadministration, to clarify the criteria for opening study Part B, 
. 
In this amendment, minor grammatical, editorial, formatting, and administrative changes not 
affecting the conduct of the study are included for clarification and administrative purposes only.
Change 
Number
Protocol Amendment 5
Summary of Changes Since the Last Version of the Approved Protocol
Sections Affected by Change
Description of Each Change and Rationale
Location
Description 
Rationale
1.
Section 2.0 STUDY SUMMARY
Section 4.2.1 Rationale for Dosing 
Regimen
Section 6.1.1 Part A Overview
Section 6.1.3 Part B Overview
Figure 6.b Study Schematic: Part A 
and B, Main Study
Section 6.2 Number of Patients
Table 8.a Dosing Regimens
Section 13.3 Determination of Sample 
Size
Defined the minimum
number of patients enrolled in 
each treatment arm in both 
Part A and Part B.
Number of patients 
changed to expedite 
safety review of Part A.
2.
Section 4.2.1 Rationale for Dosing 
Regimen
Added a note to indicate that 
the information reflects the 
data used to support the 
dosing rationale included in 
the original protocol (dated 
06 November 2019).
Edited to indicate the 
data from which the dose 
justification for this 
protocol were based.
3.
Section 4.2.1 Rationale for Dosing 
Regimen
Section 8.7.2
Deleted references to the 
current TAK-079 
investigator’s brochure (IB).
As the dose justification 
section was written 
based on data that has 
since been updated, the 
references to the current 
TAK-079 IB are 
removed.
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Change 
Number
Protocol Amendment 5
Summary of Changes Since the Last Version of the Approved Protocol
Sections Affected by Change
Description of Each Change and Rationale
Location
Description 
Rationale
8.
Section 2.0 STUDY SUMMARY
Section 4.2.1 Rationale for Dosing 
Regimen
Section 6.1 Overview of Study Design
Section 6.1.2 Assessment and Criteria 
for Opening Part B Enrollment (New 
section)
Section 6.1.3 Part B Overview
Section 13.2 Interim Analyses
Added information
discussing the criteria for 
assessment of unblinded 
safety data for a minimum of 
24 evaluable Part A patients 
in order to determine whether 
enrollment in Part B will be 
opened; discussed the internal 
Safety Review Committee 
that will be responsible for 
analysis of the unblinded 
data. Updated information 
about the interim analysis of 
data from Parts A and B 
accordingly.
Clarified the procedures 
to be undertaken to 
determine if Part B of the 
study will proceed.
9.
Section 2.0 STUDY SUMMARY
Section 6.2 Number of Patients
Updated the total number of 
patients in the study overall 
(36 to 54), total number of 
study sites (50), and location 
of the study sites (North 
America, Europe, and 
Asia-Pacific).
Number of sites and 
locations expanded to 
recruit patients from 
more areas. Subjects 
from the Asia-Pacific 
region will be included 
in Part B to collect 
ethnicity-specific 
information. Number of 
patients decreased due to 
enrollment rates and 
patient availability.
10.
Section 2.0 STUDY SUMMARY
Section 7.2 Exclusion Criteria
Updated exclusion criterion 
10 to also exclude patients 
with significant ocular 
medical conditions; updated 
exclusion criterion 12 to also 
exclude patients in vaccine 
studies; adjusted exclusion 
criterion 13 to clarify timing; 
clarified exclusion criterion 
17 for identification of 
patients with hepatitis B or C.
Ensure investigators 
exclude patients with 
significant ocular 
conditions and patients 
participating in any 
vaccine studies. Provide 
clarification for 
investigators on the 
timeline for inclusion of 
patients with localized 
herpes simplex 
infections. Provide 
clarification regarding 
the tests used to identify 
patients with hepatitis B 
or C.
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TABLE OF CONTENTS
1.0
ADMINISTRATIVE INFORMATION ...........................................................................2
1.1
Contacts.....................................................................................................................2
1.2
Approval....................................................................................................................3
1.3
Protocol Amendment 5 Summary of Changes............................................................5
2.0
STUDY SUMMARY ....................................................................................................18
3.0
STUDY REFERENCE INFORMATION ......................................................................24
3.1
Study-Related Responsibilities.................................................................................24
3.2
List of Abbreviations ...............................................................................................25
3.3
Corporate Identification...........................................................................................26
4.0
INTRODUCTION.........................................................................................................27
4.1
Background .............................................................................................................27
4.2
Rationale for the Proposed Study.............................................................................28
4.2.1
Rationale for Dosing Regimen.........................................................................28
4.3
Benefits and Risks Assessment ................................................................................35
5.0
STUDY OBJECTIVES AND ENDPOINTS..................................................................35
5.1
Objectives................................................................................................................35
5.1.1
Primary Objective............................................................................................35
5.1.2
Secondary Objective........................................................................................35
5.1.3
....................................................................................36
5.2
Endpoints.................................................................................................................36
5.2.1
Primary Endpoints ...........................................................................................36
5.2.2
Secondary Endpoints .......................................................................................36
5.2.3
.....................................................................................37
6.0
STUDY DESIGN..........................................................................................................37
6.1
Overview of Study Design.......................................................................................37
6.1.1
Part A Overview..............................................................................................40
6.1.2
Assessment and Criteria for Opening Part B Enrollment ..................................42
6.1.3
Part B Overview ..............................................................................................43
6.2
Number of Patients ..................................................................................................43
6.3
Duration of Study ....................................................................................................44
6.3.1
Duration of an Individual Patient’s Study Participation....................................44
6.3.2
End of Study/Study Completion Definition and Planned Reporting..................44
6.3.3
Time Frames for Primary and Secondary Endpoints to Support Disclosures.....44
6.3.4
Total Study Duration .......................................................................................44
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7.0
STUDY POPULATION................................................................................................44
7.1
Inclusion Criteria .....................................................................................................44
7.2
Exclusion Criteria ....................................................................................................45
8.0
STUDY DRUG .............................................................................................................47
8.1
Study Drug Administration......................................................................................47
8.2
Prophylactic Coadministration Regimen ..................................................................48
8.2.1
Prophylactic Coadministration Regimen for First Study Drug Dosing Events 
(Main Study and OLE).....................................................................................49
8.2.2
Prophylactic Coadministration Regimen for Study Drug Dosing Events 
Subsequent to First Dosing Events...................................................................49
8.2.3
Postdose Medication........................................................................................50
8.2.4
Additional Considerations for Patients with Respiratory Complications...........50
8.2.5
Rescue Therapy ...............................................................................................51
8.3
Excluded Concomitant Medications and Procedures ................................................51
8.4
Permitted Concomitant Medication..........................................................................52
8.5
Study Stopping Rules...............................................................................................53
8.5.1
Assessment and Criteria for Terminating Patient Dosing..................................53
8.6
Precautions and Restrictions ....................................................................................56
8.6.1
Pregnancy, Lactation, and Contraception .........................................................56
8.6.2
Drug Interactions.............................................................................................57
8.6.3
Interference With Serological Testing..............................................................58
8.7
Management of Clinical Events ...............................................................................58
8.7.1
................................................58
8.7.2
.................................................................................................................60
8.7.3
........................................................................................62
8.7.4
.........................................................................................................63
8.7.5
.................................................................................................................63
8.7.6
........................................................................63
8.7.7
Overdose .........................................................................................................64
8.8
Description of Investigational Agents ......................................................................64
8.8.1
Study Drug: TAK-079 .....................................................................................64
8.8.2
Clinical Study Drug Blinding...........................................................................65
8.8.3
Randomized Code Creation and Storage..........................................................66
8.8.4
Clinical Study Blind Maintenance/Unblinding Procedure.................................66
8.8.5
Destruction of Sponsor-Supplied Drugs ...........................................................66
9.0
STUDY CONDUCT......................................................................................................67
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9.1
Study Personnel and Organizations..........................................................................67
9.2
Arrangements for Recruitment of Patients................................................................67
9.3
Treatment Group Assignments.................................................................................68
9.4
Study Procedures.....................................................................................................68
9.4.1
Informed Consent ............................................................................................68
9.4.2
Inclusion and Exclusion...................................................................................68
9.4.3
Patient Demographics......................................................................................69
9.4.4
Medical History...............................................................................................69
9.4.5
Concomitant Medications and Procedures........................................................69
9.4.6
Physical Examination ......................................................................................70
9.4.7
Patient Height and Weight ...............................................................................70
9.4.8
Vital Signs.......................................................................................................70
9.4.9
12-Lead ECG...................................................................................................70
9.4.10
Pregnancy Test ................................................................................................70
9.4.11
AEs .................................................................................................................71
9.4.12
Clinical Laboratory Evaluations.......................................................................72
9.4.13
..............................................73
9.4.14
............................................................................................74
9.4.15
...................................................74
9.4.16
.................................................................75
9.4.17
.............................................75
9.4.18
............................................................75
9.5
Special Study Visit Days/Periods.............................................................................76
9.5.1
Study Week 16 ................................................................................................76
9.5.2
Study Week 20 ................................................................................................76
9.5.3
Study Week 32 ................................................................................................76
9.5.4
OLE Dosing Period (EW1 to EW8) .................................................................76
9.5.5
EW16 ..............................................................................................................77
9.5.6
EW32 ..............................................................................................................77
9.6
End of Safety Follow-up Assessments .....................................................................77
9.7
Completion of Study Treatment (for Individual Patients) .........................................78
9.8
Completion of Study (for Individual Patients)..........................................................78
9.9
Discontinuation of Treatment With Study Drug and Patient Replacement................78
9.10
Withdrawal of Patients From Study .........................................................................79
9.11
Study Compliance....................................................................................................79
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9.12
COVID-19–Related Procedural Changes .................................................................80
10.0
ADVERSE EVENTS ....................................................................................................81
10.1
Definitions...............................................................................................................81
10.1.1
Pretreatment Event Definition..........................................................................81
10.1.2
AE Definition ..................................................................................................81
10.1.3
SAE Definition................................................................................................83
10.2
Procedures for Recording and Reporting AEs and SAEs..........................................84
10.3
Monitoring of AEs and Period of Observation .........................................................86
10.4
Procedures for Reporting Drug Exposure During Pregnancy and Birth Events.........86
10.5
Procedures for Reporting (Including Overdose) .......................................................86
10.6
Safety Reporting to Investigators, IRBs or IECs, and Regulatory Authorities...........86
11.0
STUDY-SPECIFIC COMMITTEES .............................................................................87
12.0
DATA HANDLING AND RECORDKEEPING............................................................87
12.1
eCRFs......................................................................................................................87
12.2
Record Retention .....................................................................................................88
13.0
STATISTICAL METHODS..........................................................................................89
13.1
Statistical and Analytical Plans ................................................................................89
13.1.1
Analysis Sets ...................................................................................................89
13.1.2
Analysis of Demographics and Other Baseline Characteristics.........................89
13.1.3
Efficacy Analysis.............................................................................................89
13.1.4
.....................................................................................................90
13.1.5
.............................................................................90
13.1.6
................................................................................90
13.1.7
Safety Analysis................................................................................................90
13.2
Interim Analyses......................................................................................................90
13.3
Determination of Sample Size..................................................................................91
14.0
QUALITY CONTROL AND QUALITY ASSURANCE...............................................91
14.1
Study-Site Monitoring Visits ...................................................................................91
14.2
Protocol Deviations..................................................................................................92
14.3
Quality Assurance Audits and Regulatory Agency Inspections ................................92
15.0
ETHICAL ASPECTS OF THE STUDY........................................................................92
15.1
IRB and/or IEC Approval ........................................................................................92
15.2
Subject Information, Informed Consent, and Subject Authorization .........................93
15.3
Subject Confidentiality ............................................................................................94
15.4
Publication, Disclosure, and Clinical Trial Registration Policy.................................95
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15.4.1
Publication.......................................................................................................95
15.4.2
Clinical Trial Registration................................................................................95
15.4.3
Clinical Trial Results Disclosure......................................................................96
15.4.4
Data Sharing....................................................................................................96
15.5
Insurance and Compensation for Injury....................................................................96
16.0
REFERENCES..............................................................................................................97
LIST OF IN-TEXT TABLES
Table 8.a
Dosing Regimens...............................................................................................48
Table 8.b
Prophylactic Coadministration Regimen for First Study Drug Dosing Events.....49
Table 8.c
Prophylactic Coadministration Regimen for Study Drug Dosing Events Other 
Than First Dosing Events...................................................................................50
Table 8.d
Excluded Concomitant Medications ...................................................................52
Table 8.e
Permitted Concomitant Medications...................................................................53
Table 8.f
Summary of Subsequent Dosing Criteria............................................................55
Table 8.g
Highly Effective and Other Effective Methods of Contraception for Female 
Patients ..............................................................................................................57
Table 8.h
Highly Effective and Other Effective Methods of Contraception for Male 
Patients ..............................................................................................................57
Table 9.a
Clinical Chemistry and Hematology Evaluations................................................72
Table 9.b
Primary Specimen Collection.............................................................................73
Table 9.c
Clinical Parameters for End of Safety Follow-up Period.....................................78
LIST OF IN-TEXT FIGURES
Figure 4.a
Change in Serum Baseline of Total IgA, IgG, and IgM in Healthy Subjects .......31
Figure 4.b
Serum Levels of Total IgA, IgG, and IgM in Patients With RRMM ...................32
Figure 4.c
Pharmacodynamic Effects of TAK-079 on Plasma Cells in Bone Marrow 
Aspirate Samples From Patients With RRMM ...................................................34
Figure 6.a
Study Schema: Overview ...................................................................................38
Figure 6.b
Study Schematic: Part A and B, Main Study ......................................................39
Figure 6.c
Schematic for the OLE Periods ..........................................................................40
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LIST OF APPENDICES
Appendix A
Part A and B Main Study Schedule of Events...................................................100
Appendix B
Schedule of Events: OLE-A and OLE-B ..........................................................107
Appendix C
..........................112
Appendix D
.............................................113
Appendix E
Responsibilities of the Investigator...................................................................114
Appendix F
Investigator Consent to Use of Personal Information........................................116
Appendix G
..........................................................................................117
Appendix H
..........................................................................................................118
Appendix I
Protocol History...............................................................................................119
Appendix J
.............................................................................134
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2.0
STUDY SUMMARY
Name of Sponsor(s): 
Takeda Development Center Americas, Inc.
Compound: TAK-079
Title of Protocol: 
A Phase 2, Randomized, Double-blind, Placebo-Controlled 
Study to Evaluate Safety, Tolerability, and Efficacy of 
TAK-079 in Patients With Persistent/Chronic Primary 
Immune Thrombocytopenia
EudraCT No.: 2019-004103-12
Study Number: TAK-079-1004
Phase: 2
Study Design:
This is a randomized double-blind, placebo-controlled, phase 2 study designed to assess the safety, tolerability, and 
efficacy of TAK-079 in patients with persistent/chronic primary immune thrombocytopenia (ITP). This study is 
organized in 2 parts, Part A and Part B.
Part A
In Part A, patients are randomized to 1 of 3 study arms (including placebo) for a double-blind 8-week dosing period 
and 8-week blinded safety follow-up period (SFP). 

Arm A1: Matching placebo added to stable background therapy (n = 8 - 12 patients)

Arm A2: TAK-079 100 mg added to stable background therapy (n = 8 - 12 patients).

Arm A3: TAK-079 300 mg added to stable background therapy (n = 8 - 12 patients)
Safety assessments, including safety laboratory tests, will be performed each week before subsequent dosing. Patients 
may have study drug (TAK-079 or matching placebo) doses modified (eg, withheld or delayed) for safety reasons. 
Platelet levels will be assessed on Day 3 of Week 1 (2 days after the first dose) and on each weekly visit, before 
administration of the subsequent doses.
After an 8-week dosing period, patients will be followed for an 8-week blinded SFP. At the completion of SFP, study 
dosing will be unblinded and patients who were dosed with TAK-079, will continue to a 16-week long-term follow-up 
period (LFP) for continued observation of safety and efficacy. Those patients previously randomized to placebo will 
have the option to continue on to LFP or continue on to the open-label extension (OLE) phase.
Part A Open-label Extension
Additional laboratory evaluations and assessments will be performed at the Week 16 visit to ensure that the OLE 
eligibility criteria are met for those patients continuing on to OLE. The first dosing day in Part A open-label extension 
(OLE-A) phase (on Extension Week 1 [EW1]) is to occur less than 4 weeks after the Week 16 visit.
In OLE-A, patients will be randomly assigned to 1 of the following study arms:

Arm A1-E1: TAK-079 100 mg added to stable, standard background therapy.

Arm A1-E2: TAK-079 300 mg added to stable, standard background therapy.
Patients in Arms A1-E1 and A1-E2 will proceed through the 8-month protocol in an open-label fashion (2 months of 
open-label dosing, 2 months of open-label SFP, and 4 months of LFP).
Part B
Part B enrollment will not be initiated until a decision to continue on to Part B is determined based on an unblinded 
safety data review after a minimum of 24 patients (8 patients per arm) exit the dosing period with a minimum of 4 
study doses. 
In Part B, a minimum of 12 and up to approximately 18 eligible patients will be randomized after screening in a 
double-blind 1:2 ratio to 1 of the following treatment groups:

Arm B1: Matching placebo added to stable, standard background therapy (n = 4 - 6).
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
Arm B2: TAK-079 600 mg added to stable, standard background therapy (n = 8 - 12).
Similar to Part A, safety assessments, including safety laboratory tests, will be performed each week before 
subsequent dosing. Patients may have study drug (TAK-079 or matching placebo) doses modified (eg, withheld or 
delayed) for safety reasons. Platelet levels will be assessed on Day 3 of Week 1 (2 days after the first dose) and on each 
weekly visit, before administration of the subsequent doses.
After an 8-week dosing period, patients will be followed for an 8-week blinded SFP. At the completion of SFP, study 
dosing will be unblinded and patients who were dosed TAK-079, will continue to a 16-week LFP for continued 
observation of safety and efficacy. Those patients previously randomized to placebo will have the option to continue 
on to LFP or continue on to the OLE.
Part B Open-label Extension
Additional laboratory evaluations and assessments will be performed at the Week 16 visit (at the end of Part B) to 
ensure all OLE eligibility criteria are met for those patients continuing on to OLE. The first dosing day in Part B 
open-label extension (OLE-B) phase (on EW1) is to occur less than 4 weeks after the Week 16 visit.
In OLE-B, patients will be assigned to TAK-079 600 mg added to stable, standard background therapy (Arm B1-E). 
Patients in Arms B1-E will proceed through the 8-month protocol in an open-label fashion (2 months of open-label 
dosing, 2 months of open-label SFP, and 4 months of LFP).
Note: At any point in the study, patients may receive rescue therapy, defined as additional dosing of concomitant 
medications, administered in accordance with institutional practices or the physician’s best medical judgment, to 
control and manage ITP. Patients who receive rescue therapy during the dosing period will stop study treatment and 
enter the SFP, unless the patient is administered a specific dosing period–permitted rescue treatment as defined in 
Section 8.2.5. Additional assessments and evaluations may be performed as deemed necessary by local institutional 
practices and the primary investigator.
Primary Objectives:
The primary objective is to evaluate the safety and tolerability of TAK-079 in patients with persistent/chronic primary 
ITP.
Secondary Objectives:
The secondary objective is to assess the effects of TAK-079 on platelet counts in patients with persistent/chronic 
primary ITP.
Patient Population: Patients ≥18 years of age with persistent/chronic primary ITP.
Number of Patients:
Part A: at least 24 and up to 36 patients, randomized as 
follows:
Matching placebo a: 8 - 12 patients
TAK-079 100 mg a: 8 - 12 patients.
TAK-079 300 mg a: 8 - 12 patients
Part B: at least 12 and up to 18 patients randomized as 
follows: 
Matching placebo a: 4 - 6 patients
TAK-079 600 mg a: 8 - 12 patients.
a To be dosed in combination with principal investigator–
directed ITP standard background therapy.
Number of Sites: 
Approximately 50 study sites in North America, 
Europe, and Asia-Pacific.
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Dose Level(s):
Part A: 
Matching placebo a
TAK-079 100 mg a
TAK-079 300 mg a
OLE-A:
TAK-079 100 mg a
TAK-079 300 mg a
Part B:
Matching placebo a
TAK-079 600 mg a
OLE-B:
TAK-079 600 mg a
a To be dosed in combination with principal investigator–
directed ITP standard background therapy.
Route of Administration:
TAK-079/matching placebo will be administered 
through subcutaneous injections.
Duration of Treatment: 
Once weekly for 8 weeks. For those eligible placebo 
patients choosing to continue to an OLE, there is also 
8 weeks of dosing. 
Period of Evaluation: 
Main dosing period (Part A and Part B): 8 weeks
SFP: 8 weeks
LFP: 16 weeks
Main Criteria for Inclusion:
1.
Age 18 years or older and able and willing to comply with study procedures.
2.
Diagnosed with ITP that has persisted for ≥3 months, diagnosed in accordance to The American Society of 
Hematology 2011 Evidence-based Practice Guideline for Immune Thrombocytopenia or the International 
Consensus Report on The Investigation and Management of Primary Immune Thrombocytopenia as locally 
applicable.
3.
Has a mean platelet count of <30,000/µL (and individually ≤35,000/µL) on at least 2 measurements at least 
1 week apart during screening.
4.
Diagnosis of ITP supported by a prior response to an ITP therapy (other than a thrombopoietin receptor agonist) 
that achieved a platelet count of ≥50,000/µL.
5.
If receiving standard background treatment for ITP, treatment should be stable in dose and frequency for at least 4 
weeks before dosing. 
a)
Permitted standard background treatments may include: 1 oral corticosteroid; ±1 immunosuppressant from 
the following list: azathioprine, danazol, dapsone, cyclosporine, mycophenolate mofetil, mycophenolate 
sodium; ±1 thrombopoietin receptor agonist (romiplostim, eltrombopag, avatrombopag); ± fostamatinib. 
Corticosteroids, including dexamethasone, must be given as oral, daily or every-other-day therapy as 
opposed to pulse therapy.
b)
The dose of any permitted standard background therapy must be expected to remain stable through the study, 
unless dose reduction is required due to toxicities.
6.
Female patients of childbearing potential are required to have a negative pregnancy test. Both female patients of 
childbearing potential and male patients must practice an effective, reliable, and approved contraceptive regimen 
during the study and 
, whichever is longer, after discontinuation of treatment.
7.
Voluntary written consent must be given before performance of any study-related procedure that is not part of 
standard medical care, with the understanding that consent may be withdrawn by the patient at any time without 
prejudice to future medical care.
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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.
18. Has a history of severe allergic or anaphylactic reactions to recombinant proteins or excipients used in the 
TAK-079/placebo formulation.
Main Criteria for Evaluation and Analyses:
The primary endpoint is the percentage of patients with treatment-emergent adverse events (TEAEs) including Grade 
3 or higher events, serious adverse events, and adverse events (AEs) leading to TAK-079 discontinuation. 
The secondary efficacy endpoints assess the effects of TAK-079 administration on the changes in platelet count, 
through the following 4 endpoints:
1.
Percentage of patients with a platelet response. Platelet response is defined as a platelet count ≥50,000/µL and 
≥20,000/µL above baseline on at least 2 visits without a dosing period–permitted rescue treatment in the previous 
4 weeks and without any other previous rescue therapy.
2.
The percentage of patients with a complete platelet response. Complete platelet response is defined as a 
platelet count ≥100,000/µL on at least 2 visits without a dosing period–permitted rescue treatment in the previous 
4 weeks and without any other previous rescue therapy.
3.
The percentage of patients with a clinically meaningful platelet response. A clinically meaningful platelet 
response is defined as a platelet count ≥20,000/µL above baseline on at least 2 visits without a dosing period–
permitted rescue treatment in the previous 4 weeks and without any other previous rescue therapy.
4.
The percentage of patients with a hemostatic platelet response. A hemostatic platelet response is defined for 
patients with a baseline platelet count of <15,000/µL who achieve a platelet count of ≥30,000/µL and ≥20,000/µL 
above baseline on at least 2 visits without a dosing period–permitted rescue treatment in the previous 4 weeks and 
without any other previous rescue therapy.
Statistical Considerations:
Safety analysis: The safety analysis 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. 
AEs that occur after administration of the first dose of TAK-079 or placebo and through the end of the SFP will be 
tabulated and followed until resolution. 
Related AEs and coronavirus disease 2019 (COVID-19)-related AEs that occur during the LFP will also be 
summarized.
AEs will be tabulated according to the latest version of 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 set.
Efficacy Analysis:
Efficacy endpoints will be summarized by descriptive statistics and presented by treatment group as well as by study 
Part. Where appropriate, efficacy endpoints may be analyzed with the following methods:

The number and percentage of subjects attaining each type of response will be summarized by treatment group. 
Binary responder endpoints will be analyzed using a Fisher exact test.

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.
Interim Analyses
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One unblinded safety review and one interim analysis will be conducted before the final database lock of this study.
Unblinded Safety Review: An unblinded safety review will take place once a minimum of 24 evaluable patients are 
available for analysis in Part A. For the purposes of this unblinded safety review, an evaluable patient is defined as a 
patient who exits the dosing period in Part A having received a minimum of 4 study doses, regardless of the reason for 
exit (eg, completion of Part A dosing period, early discontinuation, study drug discontinuation). This unblinded safety 
review will include all unblinded safety data from all patients from Part A available at the data-cut (data up to the 
Week 16 visit). 
Interim Analysis: After all patients in Part B (Arms B1 and B2) complete the blinded SFP (complete the Week 16 
visit), an unblinded interim analysis with Part A and Part B data will take place to evaluate safety and efficacy. If it is 
deemed not appropriate to continue onto Part B after the unblinded safety review, then this interim analysis will not be 
conducted.
Sample Size Justification:
This study is exploratory and not powered to address any predefined hypothesis. 
Part A: At least 24 and up to 36 patients will be randomized in a ratio of 1:1:1 to treatment groups (TAK-079 100 mg, 
TAK-079 300 mg, or matching placebo).
Part B: At least 12 and up to 18 patients will be randomized 1:2 to treatment groups (matching placebo or TAK-079 
600 mg). 
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3.0
STUDY REFERENCE INFORMATION
3.1
Study-Related Responsibilities
The sponsor will perform all study-related activities with the exception of those identified in the 
clinical supplier list in the study manual. The identified vendors will perform specific 
study-related activities either in full or in partnership with the sponsor.
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3.2
List of Abbreviations
AE
adverse event
anti-D
anti-D immunoglobulin
AUC
area under the concentration-time curve
CFR
Code for Federal Regulations
Cmax
maximum observed concentration 
COPD
chronic obstructive pulmonary disease
COVID-19
coronavirus disease 2019
CrCl
creatinine clearance
CRO
contract research organization 
CRS
cytokine release syndrome 
CTCAE
Common Terminology Criteria for Adverse Events 
eCRF
electronic clinical report form
DSMB
data safety monitoring board 
ECG
electrocardiogram
EDC
electronic data capture 
EW
extension week
FDA
Food and Drug Administration
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 
ISR
injection site reaction
ITP
primary immune thrombocytopenia
IV
intravenous
IVIg
intravenous immunoglobulin
IXRS
interactive voice/web response system 
LFP
long-term follow-up period 
LLN
lower limit of normal
mAb
monoclonal antibody 
MedDRA
Medical Dictionary for Regulatory Activities 
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MHRA
Medicines and Healthcare products Regulatory Agency
NK
natural killer 
NOAEL
no-observed-adverse-effect level
OLE
open-label extension
OLE-A, B
Part A, B open-label extension
PCR
polymerase chain reaction
PMDA
Pharmaceuticals and Medical Devices Agency of Japan 
PPD
purified protein derivative
PTE
pretreatment event 
QW
once weekly
RBC
red blood cell
RRMM
relapsed/refractory multiple myeloma
SAE
serious adverse event
SC
subcutaneous 
SFP
safety follow-up period 
SLE
systemic lupus erythematosus
SUSAR
serious adverse reaction 
TB
tuberculosis
TEAE
treatment-emergent adverse event
TIGRA
T-cell interferon-γ release assay
TNF-α
tumor necrosis factor-alpha
TPO-RA
thrombopoietin receptor agonist
UK
United Kingdom
ULN
upper limit of normal
US
United States
3.3
Corporate Identification 
Takeda
Takeda Development Center Americas, Inc.
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4.0
INTRODUCTION
4.1
Background
Primary immune thrombocytopenia (ITP) is a rare autoimmune disease characterized by 
autoantibody-mediated destruction of platelets. The annual incidence of ITP is approximately 1 to 
5 per 100,000 adults and prevalence in the United States (US) is 8 per 100,000 children and 12 per 
100,000 adults (Terrell et al. 2012). The main clinical manifestation of ITP is thrombocytopenia 
(platelet count <100,000/µL) with normal platelet morphology in the absence of other hematologic 
findings (such as abnormalities in the coagulation cascade, appearance of schistocytes or abnormal 
leukocytes). While many patients may be asymptomatic, thrombocytopenia causes bleeding in 
most patients. Bleeding may manifest in a spectrum of petechiae, nonpalpable purpura, epistaxis, 
and severe hemorrhage. The greatest risk of severe bleeding occurs when the platelet count drops 
below 10,000 to 20,000/µL. Finally, fatigue and associated reduced quality of life are common 
features of ITP; however, the mechanisms of these effects are not well-understood (Hill and 
Newland 2015; McMillan et al. 2008; Newton et al. 2011).
ITP is caused by autoantibodies directed against platelet surface glycoproteins on platelets or 
megakaryocytes. Production of autoantibodies involves both autoreactive CD4-positive T helper 
cells and splenic macrophages as antigen-presenting cells (Chong 2009; Kuwana et al. 2009; Patel 
et al. 2008; Sukati et al. 2007). Autoantibodies against glycoproteins Ib/IX, Ia/IIa, IV, and V have 
been described, and epitope spreading is known to occur (Cines and Blanchette 2002). The 
presence of multiple antibodies against different epitopes may predict more severe disease. 
Platelets coated with autoantibodies are cleared by macrophages in the spleen and liver. 
Treatment for ITP is divided into first-line and second-line treatments (Provan et al. 2010). 
First-line treatments include corticosteroids, intravenous immunoglobulin (IVIg) and anti-D 
immunoglobulin (anti-D). These agents generally work by decreasing platelet destruction. 
Second-line therapies include immunosuppressants that function to decrease the production of 
autoantibodies. Medical therapy includes azathioprine, cyclophosphamide, cyclosporin A, danazol, 
dapsone, mycophenolate mofetil, and rituximab. These drugs are limited by variable efficacy, 
toxicities, and transient response. Other forms of therapy are splenectomy and the use of 
thrombopoietin receptor agonists (TPO-RAs). Splenectomy, although highly efficacious, is 
associated with a high complication rate (Kojouri et al. 2004), and in many practice settings is 
deferred because of the surgical risk and patient and physician preference. 
TPO-RAs (romiplostim, eltrombopag, and avatrombopag), which increase platelet production by 
stimulation of megakaryocytes, are also highly efficacious, but often require chronic treatment and 
are associated with an increase in bone marrow reticulin formation, which has been described for 
both romiplostim and eltrombopag (Bussel et al. 2009; Kuter et al. 2008) while abnormalities in 
liver function tests have been observed in 11% of patients on eltrombopag (Cheng et al. 2011). 
Eltrombopag has a boxed warning for severe and potentially life-threatening hepatotoxicity. 
Additionally, wide swings in the platelet count can be seen with TPO-RAs, with platelet counts 
reaching the 700,000 to 1 million/µL range. Fostamatinib, a tyrosine kinase inhibitor which 
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reduces phagocytosis of autoantibody-coated platelets, is a therapy of modest effect reserved for 
refractory patients who fail second-line therapies (Bussel et al. 2018). 
Approximately 20% of patients do not respond to the therapeutic approaches listed above (Provan 
et al. 2010). There is a need for a novel therapy in ITP which could provide deeper and sustained 
responses with a favorable safety profile to help achieve a hemostatic platelet count and improve 
patients’ quality of life.
4.2
Rationale for the Proposed Study
TAK-079 is a fully human anti-CD38 immunoglobulin (Ig) G1 monoclonal antibody (mAb), 
which depletes cells expressing high levels of target by apoptosis, antibody-dependent 
cell-mediated cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular 
phagocytosis. CD38 is a cell surface molecule that is expressed at high levels on short- and 
long-lived plasma cells, plasmablasts and natural killer (NK) cells, and is induced on activated B-
and T-cells. Depletion of plasma cells and plasmablasts would lead to a reduction in the levels of 
immunoglobulins (Ig) and pathogenic autoantibodies, thereby reducing the 
autoantibody-mediated destruction of platelets and improving the platelet count. 
TAK-079 is therefore being proposed as a potential treatment for ITP in adult patients.
TAK-079 is in early-stage clinical development for the treatment of hematologic malignancies and 
autoimmune diseases. The clinical development plan is based on a comprehensive review of the 
available nonclinical and clinical data with TAK-079 and other anti-CD38 monoclonal antibodies, 
and the ongoing investigation of the biology of several possible indications. TAK-079 has been 
evaluated in a thorough, comprehensive nonclinical safety program comprising single- and 
repeat-dose toxicology studies in cynomolgus monkeys of up to 13 weeks in duration. In these 
studies, TAK-079 has demonstrated an acceptable safety profile and dose-dependent 
pharmacodynamic effects consistent with the mode of action, supporting continuing clinical 
development (see Module 2.6.2 and TAK-079 Investigator’s Brochure [IB]). 
4.2.1
Rationale for Dosing Regimen
This study is organized in 2 parts (Part A and an optional Part B, each consisting of the main study 
and open-label extension [OLE] phases, see Section 6.0, Figure 6.a, Figure 6.b, and Figure 6.c for 
details). In Part A of this study, doses of 100 and 300 mg of TAK-079 or matching placebo will be 
administered by subcutaneous (SC) injection in a double-blinded study design. Each study arm 
will enroll at least 8 and up to 12 patients (for a total of 24 to 36 patients across 3 dosing arms of 
Part A). The study drug or matching placebo is administered once weekly (QW) during the 8-week 
dosing period, for a maximum 8 study doses. After a minimum of 24 patients (8 patients per arm) 
exit the Part A dosing period with a minimum of 4 study doses, an unblinded safety data review 
will be performed (see Section 6.1.2 for details) to decide whether to move forward with study Part 
B. Part A enrollment will end once Part B enrollment is initiated. Part B consists of a dosing cohort 
of TAK-079 600 mg and a placebo arm. A total of 12 - 18 patients will be enrolled and randomized, 
with a ratio of 2:1, into the TAK-079 600 mg and the placebo arm. Similar to Part A, patients in 
Part B will receive study drug by SC injection in a double-blinded manner QW during the 8-week 
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dosing period, for a maximum 8 study doses. Within each study part (Part A and B), an OLE phase 
will be available for all placebo patients who wish to obtain access to active study drug following 
the completion of the main study dosing period and a 2-month safety follow-up period (SFP). 
Please note the information presented below reflects the data used to support the dosing rationale 
included in the original protocol (dated 06 November 2019).
The criteria for selecting the doses and schedule of TAK-079 for treating patients with ITP was 
based upon identifying previously well-tolerated doses that demonstrated pertinent 
pharmacodynamic activity. The clinical experience to date has demonstrated that TAK-079 is safe 
and well tolerated in 3 different populations (ie, healthy subjects, patients with relapsed/refractory 
multiple myeloma [RRMM], and patients with systemic lupus erythematosus [SLE]) and across a 
broad range of doses (up to 1200 mg), vascular concentrations and exposures. 
In healthy subjects in Study TAK-079_101, single SC doses of TAK-079 up to 0.6 mg/kg (fixed 
dose equivalent of approximately 45 mg) were well tolerated, adverse events (AEs) were mild to 
moderate in intensity, with most of the AEs being mild. There were no serious AEs (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 the administration of TAK-079 (see TAK-079 IB).
In the ongoing study in RRMM, 33 patients in total have been enrolled across 5 dose-escalation 
cohorts (4 patients in 45 mg; 3 patients in 135 mg; 12 patients in 300 mg; 12 patients in 600 mg and 
2 patients in 1200 mg). A maximum duration of exposure is 12 cycles as of September 2019, for a 
patient in each of the 135 mg and 300 mg cohorts, respectively. The maximum tolerated dose has 
not been identified and no dose-limiting toxicities have been reported. At the IB data-cut off (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 toxicities, 
injection site reactions (ISRs), or systemic infusion reactions. No drug-related SAEs, AEs that led 
to study discontinuation, or on-study deaths, have been reported. As of June 2019, with additional 
enrollment to the 300 mg and 600 mg dose cohorts, TAK-079 continues to be safe and well 
tolerated, and no new safety concerns have been identified. The most commonly reported (at least 
20% of all patients) treatment-emergent AEs (TEAEs) by Preferred Term regardless of causality at 
doses up to 600 mg include anemia, decreased appetite, fatigue, headache, hypertension, and 
insomnia. All AEs have been scored according to the Common Terminology Criteria for Adverse 
Events (CTCAE) scale as Grade 1 or 2 other than 2 events that were reported as drug-related Grade 
3 events (decreased neutrophil count and anemia [in 1 patient each]), both of which were transient. 
In the ongoing study in SLE, 8 patients have been enrolled and treated with 45 mg TAK-079 or 
placebo (in a blinded manner). As of the IB data cutoff (N = 3 patients) from March 2019, 1 patient 
has reported 2 TEAEs: nausea and headache (both events Grade 1). No infusion reactions, 
cytokine release syndrome (CRS) or ISRs have been reported.
Three AEs were observed in the repeat-dose, 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 
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Figure 4.a
Change in Serum Baseline of Total IgA, IgG, and IgM in Healthy Subjects
Ig: immunoglobulin; IV: intravenous(ly); SC: subcutaneous(ly); SEM: standard error of measurement. 
Serum samples obtained following a single administration of TAK-079 or placebo, administered either as 0.003 to 
0.06 mg/kg IV or 0.03 to 0.6 mg/kg as an SC injection. 
Symbols represent the mean change for the cohort and error bars represent the SEM.
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Figure 4.c
Pharmacodynamic Effects of TAK-079 on Plasma Cells in Bone Marrow 
Aspirate Samples From Patients With RRMM
RRMM: relapsed refractory multiple myeloma. 
Target occupancy (blue lines, percent 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), at doses of TAK-079 at 45, 135, 300, or 600 mg dosed weekly 
for 8 weeks; followed by biweekly for 8 weeks; then monthly until disease progression. Target occupancy and plasma 
cell levels were quantified by flow cytometry and the data represent individual patients.
Case reports exist of successfully treating antibody-driven diseases with anti-CD38 therapy using 
the same dose and schedule as in patients with 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-RBC antibodies following an ABO-mismatched allogenic bone marrow transplant 
for myelodysplastic syndrome (Chapuy et al. 2018). Similarly, daratumumab at the myeloma dose 
was used successfully in a pediatric patient with anti-RBC antibodies following bone marrow 
transplantation (Tolbert 2016). Lastly, a case of antibody-mediated rejection following renal 
transplantation for postinfectious membranoproliferative glomerulonephritis was treated 
successfully with 7 weekly doses of myeloma-dose of daratumumab following failure of 
bortezomib and rituximab therapy in a patient with a normal bone marrow (less than 1% plasma 
cells) and concurrently treated with tacrolimus and prednisone (Anand et al. 2017). 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 patients without myeloma who 
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Figure 6.b
Study Schematic: Part A and B, Main Study
AE: adverse event; COVID-19: coronavirus disease 2019; LFP: long-term follow-up period; SFP: safety follow-up 
period; W: week.
a Unresolved AEs as of Week 16 and related AEs/serious AEs with onset after SFP will be collected through the 
LFP. COVID-19 infection and COVID-19 vaccination-related AEs will be collected through the LFP regardless of 
causality.
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Figure 6.c
Schematic for the OLE Periods
AE: adverse event; COVID-19: coronavirus disease 2019; EW: extension week; LFP: long-term follow-up period;
OLE: open-label extension; SFP: safety follow-up period.
a Unresolved AEs as of Week 16 and related AEs/serious AEs with onset after SFP will be collected through the LFP. 
COVID-19 infection and COVID-19 vaccination-related AEs will be collected through the LFP regardless of 
causality.
6.1.1
Part A Overview 
After screening, at least 24 and up to 36 eligible patients will be randomized in a double-blind 
1:1:1 ratio to 1 of the following groups (see Figure 6.b):

Arm A1: Matching placebo added to stable background therapy (n = 8 - 12 patients).
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
Arm A2: TAK-079 100 mg added to stable background therapy (n = 8 - 12 patients).

Arm A3: TAK-079 300 mg added to stable background therapy (n = 8 - 12 patients).
TAK-079 or matching placebo will be administered via SC injection QW for 8 weeks (see Section 
8.1 for more details). Safety assessments, including safety laboratory tests, will be performed each 
week before subsequent dosing. Patients may have study drug (TAK-079 or matching placebo) 
doses modified (eg, withheld or delayed) for safety reasons (see further details on dose 
modification/stopping criteria in Section 8.5). Platelet levels will be assessed on Day 3 of Week 1 
(2 days after the first dose) and on each weekly visit, before administration of the subsequent 
doses.
After completing the 8-week dosing period, patients will enter a blinded SFP, completing safety 
and laboratory assessments every 2 weeks for 2 months. 
At the completion of SFP (Week 16 visit), patients will be unblinded. 
Patients who were dosed with TAK-079 (Arms A2 and A3) will be followed monthly for 4 months 
in an LFP to check platelet counts and to monitor for any ongoing drug-related AEs at the end of 
the SFP. Patients who were dosed with matching placebo (Arm A1) will be eligible for the Part A 
open-label extension (OLE-A) phase (see Section 6.1.1.1) for access to study drug. Placebo 
patients who opt not to participate in the OLE-A will end the study at the Week 20 visit of the LFP.
6.1.1.1
Part A Open-label Extension Phase
For patients who obtained placebo in Part A and who wish to continue in the OLE-A for access to 
study drug, laboratory evaluations will be obtained at the Week 16 visit (at the end of Part A) to 
ensure inclusion/exclusion criteria continue to be met as follows:
OLE Inclusion Criteria:
1. Platelet count at Week 16 or later of less than 50,000/µL and continued need for additional 
medical treatment in the opinion of the investigator.
2. For female patients of childbearing potential, a continued negative urine pregnancy test.
3. Meets all continued dosing criteria as in Table 8.f.
4. Continues to meet criteria for background concomitant medications as defined as follows: 
1 oral corticosteroid (as daily or every-other-day therapy); ±1 immunosuppressant from the 
following list: azathioprine, danazol, dapsone, cyclosporine, mycophenolate mofetil, 
mycophenolate sodium; ±1 TPO-RA (romiplostim, eltrombopag, avatrombopag); 
±fostamatinib. Background therapy should be stable for 4 weeks before the first day of dosing 
in the OLE.
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OLE Exclusion Criteria:
1. Experiencing 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), that poses an added risk for the patient, or could confound the assessment 
of the patient.
2. Use of any rescue therapy in the 2 weeks preceding the first day of dosing in the OLE.
3. Has had an opportunistic infection since dosing, or is currently undergoing 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 is allowed, as long as the lesion has resolved without 
systemic therapy prior to the first day of dosing in the OLE.
The first dosing day in OLE-A (on Extension Week 1 [EW1]; see Schedule of Events [SOE] in 
Appendix B) is to occur less than 4 weeks after the Week 16 visit. In OLE-A, patients will be 
randomly assigned to 1 of the following study arms (see Figure 6.c):

Arm A1-E1: TAK-079 100 mg added to stable, standard background therapy.

Arm A1-E2: TAK-079 300 mg added to stable, standard background therapy.
Patients in Arms A1-E1 and A1-E2 will proceed through the 8-month protocol in an open-label 
fashion (2 months open-label dosing, 2 months open-label SFP, 4 months LFP). 
6.1.2
Assessment and Criteria for Opening Part B Enrollment 
An unblinded safety review will take place once a minimum of 24 evaluable patients are available 
for analysis in Part A. For the purposes of this unblinded safety review, an evaluable patient is 
defined as a patient who exits the dosing period in Part A having received a minimum of 4 study 
doses, regardless of the reason for exit (eg, completion of Part A dosing period, early 
discontinuation, study drug discontinuation). This unblinded safety review will include all 
unblinded safety data from all patients from Part A available at the data-cut (data up to the Week 
16 visit). The purpose of the safety review is to inform the decision of whether to open enrollment 
to Part B, and based on the unblinded safety review the study may: (1) advance enrollment to Part 
B at the protocol-defined dose level, (2) advance enrollment to Part B at a lower dose level than the 
Part B protocol-defined level, (3) continue or expand enrollment in Part A, or (4) enact early 
termination of the study. Enrollment into Part A will end once Part B enrollment begins. 
An internal, independent Safety Review Committee (SRC) will be established to review unblinded 
study safety data. The SRC may also review unblinded efficacy data from all patients from Part A 
available at the data-cut. The decision to advance to Part B will be based on the unblinded study 
safety data.
Members of the SRC will be separated from the clinical study team upon receiving unblinded data 
and until after all patients enrolled in Part A complete the blinded portion of the study and are 
individually unblinded. During the time of SRC review, enrollment into Part A may be kept open. 
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Details of the SRC membership, responsibilities, and safety review criteria will be presented in the 
SRC Charter.
6.1.3
Part B Overview 
Once at least 24 patients in Part A (8 patients in each arm) have received at least 4 study doses, an 
unblinded safety review with all unblinded safety data available at the data-cut (data up to the 
Week 16 visit) across all Part A patients will be conducted by the Safety Review Committee to 
decide whether to open enrollment into Part B (see Section 6.1.2 for more details). In Part B, a 
minimum of 12 and up to 18 eligible patients will be randomized after screening in a double-blind 
1:2 ratio to 1 of the following groups (see Figure 6.b):

Arm B1: Matching placebo added to stable, standard background therapy (n = 4 - 6).

Arm B2: TAK-079 600 mg added to stable, standard background therapy (n = 8 - 12).
The Schedule of Events/visits will continue as in Part A.
As in Part A, patients will be unblinded at the end of the SFP (Week 16 visit). Patients who were 
dosed with TAK-079 (Arm B2) will be followed monthly for 4 months in the LFP. Patients dosed 
with matching placebo (Arm B1) will be eligible for Part B open-label extension (OLE-B) phase 
for access to study drug (see Section 6.1.3.1). Placebo patients who opt not to participate in the 
OLE-B will end the study at the Week 20 visit.
6.1.3.1
Part B Open-label Extension Phase
For patients who obtained placebo in Part B who wish to continue in the OLE-B for access to study 
drug, laboratory evaluations will be obtained at the Week 16 visit (at the end of Part B) to ensure 
satisfaction of the OLE inclusion/exclusion criteria (as outlined in Section 6.1.1.1). The first 
dosing day in OLE-B (on EW1; see SOE in Appendix B) is to occur approximately less than 4 
weeks after the Week 16 visit. In the OLE-B, patients will be offered (see Figure 6.c):

Arm B1-E: TAK-079 600 mg added to stable, standard background therapy. 
Patients in Arm B1-E will proceed through the 8-month protocol in an open-label fashion 
(2 months open-label dosing, 2 months open-label SFP, 4 months LFP).
6.2
Number of Patients
Approximately 36 to 54 patients with persistent/chronic primary ITP (ie, approximately 24 - 36 
patients in Part A and 12 – 18 patients in Part B) will be randomized from approximately 50 study 
sites in the North America, Europe, and Asia-Pacific. 
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6.3
Duration of Study
6.3.1
Duration of an Individual Patient’s Study Participation
Patients randomized in Part A or Part B to TAK-079 will be treated for a maximum of 8 weeks and 
will be followed for an 8-week blinded SFP, and a 16-week unblinded LFP. Maximum total study 
participation will last 8 months from the initial day of study dosing. 
Patients randomized to 8-week placebo dosing during either Part A or Part B, will have the option 
to continue on to their respective OLE phases (OLE-A or OLE-B) during which they will complete 
a maximum of 8 weeks of dosing with TAK-079, 8 weeks of SFP, and 16 weeks of LFP for a 
maximum total study participation of 13 months (including 4 weeks of interim time before the start 
of the OLE) from the initial day of the first dosing period. Patients who received placebo in either 
Part A or Part B who do not continue to an OLE will end the study at Week 20 in the LFP, for a 
maximum study participation of 5 months.
6.3.2
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 32 for TAK-079 patients, Week 20 for 
placebo patients who chose not to enter the OLE, or EW32 for placebo patients who participated in 
the OLE), as shown in Appendix A and Appendix B. 
6.3.3
Time Frames for Primary and Secondary Endpoints to Support Disclosures
Refer to Section 15.4 for disclosure information for all primary and secondary endpoints.
6.3.4
Total Study Duration
It is anticipated that this study will end after all randomized patients have attended the 
end-of-study visit (ie, Week 32 for TAK-079 patients, Week 20 for placebo patients who chose not 
to enter the OLE or EW32 for placebo patients who participated in the OLE) as shown in 
Appendix A and Appendix B. It is expected that the full duration of the study will last for 
approximately 36 months (including the OLE), should Part B be activated, and 24 months if Part B 
is not activated.
7.0
STUDY POPULATION
7.1
Inclusion Criteria
Each patient must meet all the following inclusion criteria to be to be randomized to treatment:
1. Age 18 years or older and able and willing to comply with study procedures.
2. Diagnosed with ITP that has persisted for ≥3 months, diagnosed in accordance to The 
American Society of Hematology 2011 Evidence-based Practice Guideline for Immune 
Thrombocytopenia (Neunert et al. 2011) or the International Consensus Report on The 
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Investigation and Management of Primary Immune Thrombocytopenia (Provan et al. 2010) as 
locally applicable.
3. Has a mean platelet count of <30,000/µL (and individually ≤35,000/µL) on at least 
2 measurements at least 1 week apart during screening.
4. Diagnosis of ITP supported by a prior response to an ITP therapy (other than a TPO-RA) that 
achieved a platelet count of ≥50,000/µL.
5. If receiving standard background treatment for ITP, treatment should be stable in dose and 
frequency for at least 4 weeks before dosing. 
a) Permitted standard background treatments may include: 1 oral corticosteroid; 
±1 immunosuppressant from the following list: azathioprine, danazol, dapsone, 
cyclosporine, mycophenolate mofetil, mycophenolate sodium; ±1 TPO-RA (romiplostim, 
eltrombopag, avatrombopag); ± fostamatinib. Corticosteroids, including dexamethasone, 
must be given as oral, daily or every-other-day therapy as opposed to pulse therapy.
b) The dose of any permitted standard background therapy must be expected to remain stable 
through the study, unless dose reduction is required because of toxicities.
6. Female patients of childbearing potential are required to have a negative pregnancy test. Both 
female patients of childbearing potential and male patients must practice an effective, reliable, 
and approved contraceptive regimen during the study and 
, 
whichever is longer, after discontinuation of treatment (see Section 8.6.1). 
7. Voluntary written consent must be given before performance of any study-related procedure 
not part of standard medical care, with the understanding that consent may be withdrawn by 
the patient at any time without prejudice to future medical care.
7.2
Exclusion Criteria
Patients meeting any of the following exclusion criteria are not to be randomized to treatment.
1. Use of anticoagulants or any drug with antiplatelet effect (such as aspirin) within 3 weeks 
before screening.
2. History of any thrombotic or embolic event within 12 months before screening.
3. History of splenectomy within 3 months before screening.
4. Use of IVIg, subcutaneous immunoglobulin or anti-D immunoglobulin treatment within 
4 weeks of screening, or an expectation that any therapy besides the patient’s standard 
background therapies may be used for treatment of thrombocytopenia (eg, a rescue therapy) 
between screening and dosing.
5. Diagnosed with chronic obstructive pulmonary disease (COPD) or asthma, and a 
prebronchodilatory 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. Use of rituximab or any mAb for immunomodulation within 4 months before first dosing. 
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b) Patients with an indeterminate TIGRA result must meet the following criteria:
–
Has a negative PPD skin test (defined as <5 mm induration).
–
Is 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).
16. Has a serious medical or psychiatric illness that could, in the investigator’s opinion, potentially 
interfere with the completion of treatment according to this protocol.
17. Has hepatitis B (a positive test result for hepatitis B surface antigen [HBsAg], or hepatitis B 
core antibody [anti-Hbc]), or Hepatitis C (positive HCV RNA), 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.
18. Has 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 study Day 1 to begin dosing of TAK-079 or placebo in 
accordance to their randomized assigned treatment. Before TAK-079/placebo administration, 
patients will receive premedication as listed in Section 8.2.1 and will complete safety assessments 
as outlined in Table 8.f and Appendix A. Both the patient and physician will be blinded to 
treatment. 
Patients will receive study drug via SC injection, QW, for 8 weeks as outlined in Table 8.a and the 
SOE in Appendix A. As study treatment will generally require multiple SC injections to 
administer the full dose, the Week 1 dose (and the dose on EW1 of the OLE; see Section 9.5.4 and 
Appendix B) will be administered by giving each SC injection 30 minutes apart 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.f. For 
the first dose in the main study or the OLE, laboratory assessments in Table 8.f may be evaluated 
using results obtained at screening or the Week 16 visit, respectively. Otherwise, laboratory results 
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clinical site due to regional drug availability or local regulations, the medication may be supplied 
by the sponsor.
On the basis of emerging safety data, the sponsor may adjust pre- and postdose medication 
regimen to ensure patient safety. If modifications are needed, investigators will be notified 
via written communication of any required modifications to the pre-and postdose 
medication regimen.
8.2.1
Prophylactic Coadministration Regimen for First Study Drug Dosing Events 
(Main Study and OLE)
For the first dosing event in the main study (W1 Day 1) and the OLE (EW1 Day 1), the regimen 
outlined in Table 8.b should be followed for the prevention of a possible 
 
 Considering the timing of the risk of 
 after study drug dosing, this will ensure that 
therapeutic levels of prophylactic medications are present at the time of expected maximum 
exposure of study drug.
Table 8.b
Prophylactic Coadministration Regimen for First Study Drug Dosing Events 
Medication
X
None
None
X
X
X
X
X
X
None
X
X
8.2.2
Prophylactic Coadministration Regimen for Study Drug Dosing Events 
Subsequent to First Dosing Events
On each dosing day other than W1 Day 1 or EW1 Day 1, patients are to be premedicated with 
 
 1 to 3 hours before 
mezagitamab administration as outlined in Table 8.c.
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On the basis of emerging data, the Takeda physician/designee may modify treatments 
administered pre- or post–TAK-079/placebo injection to ensure patient safety.
8.2.5
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 
ITP conditions.
Rescue medications may include, but are not limited to, high-dose corticosteroids, IVIg, and 
increasing or adding background therapies. Rescue therapy given during the dosing period 
generally will result in the discontinuation from study dosing and advancement to the SFP.
However, one of the following dosing period–permitted rescue treatments is allowed as a bridge 
therapy for safety reasons (especially at the beginning of the study), since it may take several 
weeks before TAK-079 begins to have an effect on platelet levels:
Rescue with one of the above will allow patients to continue treatment with study drug and not be 
discontinued from the dosing period. Since these dosing period–permitted rescue therapies are 
typically expected to have a duration of effect of 4 weeks or less, a long-term effect on platelet 
levels is not anticipated. A second rescue treatment, however, will result in dosing period 
discontinuation.
8.3
Excluded Concomitant Medications and Procedures
Excluded concomitant medications are summarized in Table 8.d. 
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Table 8.d
Excluded Concomitant Medications
Category or Agent
Exclusion Criteria
(Exclusion Criteria Must Be Upheld Throughout Study Participation, 
in Addition to the Time Points Indicated Below)
Anticoagulants 
(to include any medicinal agent with 
antiplatelet effects)
Restricted from ≤3 weeks before obtaining screening laboratory samples, as 
outlined in Appendix A.
Intravenous or subcutaneous 
immunoglobulins or anti-D 
immunoglobulins
Restricted from ≤4 weeks before obtaining screening laboratory samples, as 
outlined in Appendix A. IVIg may be given as part of a single, dosing 
period–permitted rescue treatment as described in Section 8.2.5
Rituximab or any monoclonal 
antibody for immunomodulation not 
otherwise specified
Restricted within 4 months before first dosing.
Note: Patients with prior rituximab exposure must have CD19 counts within 
normal range at the time of screening visit.
Immunosuppressants 
(eg, cyclophosphamide, vincristine)
Unless otherwise stated, restricted from ≤6 months before dosing, as 
outlined in Appendix A.
Note: See Table 8.e for permitted oral immunosuppressants.
Live vaccinations
Restricted from ≤4 weeks before obtaining screening laboratory samples, as 
outlined in Appendix A.
8.4
Permitted Concomitant Medication 
Stable dosing of concomitant background therapy, based on standard background treatment for 
ITP, is permitted throughout study participation, if the therapy regimen has remained stable in 
dose and frequency for ≥4 weeks before initiating study dosing. The dose of any permitted 
standard background therapy must be expected to remain stable through the study, unless dose 
reduction is required because of toxicities. Permitted standard background treatments may include 
1 oral corticosteroid; ±1 permitted oral immunosuppressant from the following list: azathioprine, 
danazol, dapsone, cyclosporine, mycophenolate mofetil, mycophenolate sodium; ±1 TPO-RA 
(romiplostim, eltrombopag, avatrombopag); ±fostamatinib (see Table 8.e).
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Table 8.e
Permitted Concomitant Medications
Medications
Criteria
(Criteria Are to Be Maintained Throughout the Study)
Immunosuppressants
Therapy must be stable in dose and frequency for at least 4 weeks before dosing.
Azathioprine
Danazol
Dapsone
Cyclosporine
Mycophenolate mofetil
Mycophenolate sodium
Oral corticosteroids
Therapy must be stable in dose and frequency for at least 4 weeks before dosing.
Oral corticosteroids may be given as part of a dosing period rescue treatment as 
described in Section 8.2.5.
Thrombopoietin receptor 
agonist(s)
(eg, romiplostim, 
eltrombopag, 
avatrombopag)
Therapy must be stable in dose and frequency for at least 4 weeks before dosing.
Fostamatinib
Therapy must be stable in dose and frequency for at least 4 weeks before dosing.
8.5
Study Stopping Rules
Takeda clinicians/designee will provide ongoing safety oversight and surveillance throughout the 
entire study. 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 (see Section 6.1.2). On the 
basis of outcomes of the Takeda safety reviews and in accordance with predefined criteria, 
decisions about the dosing regimen and/or study conduct are to be made and implemented.
8.5.1
Assessment and Criteria for Terminating Patient Dosing
Investigators will evaluate patients before each dose for the parameters outlined in Table 8.f. 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.f, 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 (or Appendix B, if during the OLE).
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.
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
The patient receives rescue medication that is not a dosing period–permitted treatment as 
described in Section 8.2.5.

If study dosing is held for 2 consecutive doses because of safety concerns or conditions 
outlined in Table 8.f.

The patient chooses to withdraw from study dosing.

The patient has a confirmed pregnancy.
NOTE: If 2 or more patients discontinue study drug dosing on the basis of the dose discontinuation 
criteria in Table 8.f, 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 immunoglobulin 
levels (IgG, IgA, and IgM) will be evaluated during the dosing period at a central laboratory. If any 
of these are >50% below the lower limit of normal (LLN), the investigator should manage as 
clinically appropriate on the basis of signs and symptoms the patient is experiencing. If IgG levels 
are below the LLN and the patient is experiencing a severe infection, IVIg may be administered, 
per physician discretion according to standard practice. If IVIg is given as a rescue treatment as 
described in Section 8.2.5, the patient may continue with dosing of the study drug; otherwise, the 
patient will be discontinued from the dosing period of the study and enter the SFP.
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Table 8.f
Summary of Subsequent Dosing Criteria
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Table 8.g
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 postvasectomy), must agree to 1 of the 
following:

Agree to practice effective barrier contraception (Table 8.h) during the entire study dosing 
period and through 
*, 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.h
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, using 2 barrier methods at the same time is recommended.
* Note that the half-life of TAK-079 has not yet been determined. On the basis of conservative 
information in the literature regarding the half-life of IgG1 as well as other IgG1 human 
monoclonal antibodies (Mankarious et al. 1988; Suzuki et al. 2010) a conservative time frame to 
continue contraception would be 
. 
8.6.2
Drug Interactions
Nonclinical drug interaction studies have not been conducted with TAK-079. However, as 
TAK-079 is a fully human IgG1 mAb, the risk of drug-drug interactions is low.
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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 
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.
8.8.2
Clinical Study Drug Blinding
The assignment of study patients to 1 of 3 study arms in Part A or 1 or 2 study arms in Part B 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 8.8.4.
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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.
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 
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, central laboratory(ies), coordinating investigator(s), 
the interactive response technology provider, and CRO team may be found in the Study Manual. 
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 
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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.
9.4.3
Patient Demographics
Patient demographic characteristics will be collected at screening and will include age, sex, race, 
and ethnicity (optional depending on country).
9.4.4
Medical History
A complete medical history is compiled for each patient during the screening period and includes 
assessment and documentation of prior medical history, comorbidities, and concomitant 
treatments. This includes assessments of current ITP signs and symptoms, as evaluated and scored 
by disease activity tools, and previous and current ITP therapies. The complete medical history 
should include history of eye disease or ophthalmic clinical symptoms (including allergic 
reactions). If an eye exam has been conducted within the previous year, a copy of the records from 
the exam should be provided to the site as source documentation. Coronavirus disease 2019 
(COVID-19) infection and vaccination prior to the study should be recorded as part of medical 
history. 
9.4.5
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 SFP 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 8.3 and 
8.4 for a list of excluded and permitted concomitant medications).
COVID-19 vaccination and COVID-19 treatments received during the study through LFP will be 
recorded as concomitant medications.
9.4.5.1
Background ITP Therapy
Eligible patients must have protocol-compliant ITP background therapy in accordance to criteria 
outlined in Table 8.d and Table 8.e. Once randomized into the study, patients will remain on 
protocol-compliant background therapy, as managed by their principal investigator, in accordance 
with local institutional practices, throughout study participation. Patients should remain on their 
stable dose of standard background therapy throughout the study unless dose reduction is required 
due to toxicities. Permitted standard background treatments may include 1 oral corticosteroid; ±1 
oral immunosuppressant from the following list: azathioprine, danazol, dapsone, cyclosporine, 
mycophenolate mofetil, mycophenolate sodium; ±1 TPO-RA (romiplostim, eltrombopag, 
avatrombopag); ±fostamatinib. Background ITP therapy at the time of screening and throughout 
study participation will be recorded in the eCRF. 
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9.4.6
Physical Examination
A complete physical examination as well as a symptom-directed physical examination with 
assessments for ITP signs and symptoms will be completed in accordance with standard of care at 
the times specified in the SOE (see Appendix A and Appendix B). 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 9.4.10).
9.4.7
Patient 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 during Weeks 10, 16, and 32 as outlined in 
Appendix A and EW10, EW16, and EW32, as outlined in Appendix B. 
9.4.8
Vital Signs
Vital signs (body temperature, respiratory rate, heart rate, and blood pressure) will be evaluated at 
visits specified in Appendix A and Appendix B, 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 
 
 As indicated in 
Appendix A and Appendix B, vital signs are to be assessed before each study dose 
 
. 
Clinically significant values, as determined by the principal investigator, must be documented as 
an AE and closely monitored for follow-up.
9.4.9
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 in both the main study and OLE (as outlined in Appendix A and 
Appendix B), 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 
the source documentation and in the eCRF, and the patient should undergo continued monitoring 
as described in Section 10.1.2.
9.4.10
Pregnancy Test
A serum pregnancy (human chorionic gonadotropin [hCG]) test will be completed for female 
patients of childbearing potential; this test will be performed at screening, during the SFP 
(ie, Weeks 10 and 16), and during the LFP (Week 32); results must be negative for the patient to be 
randomized and to continue in the study. Likewise in the OLE, serum pregnancy tests will be 
performed at EW10, EW16, and EW32.
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A urine pregnancy test will be completed for all female patients of childbearing potential before 
the first dose of TAK-079/placebo and at Week 5 of the dosing period. In the OLE, a urine 
pregnancy test will be completed on EW1 before the first dose of TAK-079 and at EW5 of the 
OLE 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.
9.4.10.1
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.
9.4.10.2
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 before 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 (and EW5), before dosing (urine pregnancy test).
–
During SFP and LFP, as outlined in Appendix A and Appendix B (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.
9.4.11
AEs
Monitoring of AEs, serious and nonserious, will be conducted throughout the study as specified in 
Appendix A and Appendix B. Refer to Section 10.0 for details regarding definitions, 
documentation, and reporting of AEs and SAEs. 
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Table 9.c
Clinical Parameters for End of Safety Follow-up Period
Safety Parameter Laboratory 
Investigations
End-of-Study Criteria
Continuation to Long-term Follow-up
Neutrophils
≥LLN or ≥study baseline levels 
or low levels that are not 
directly related to dosing of 
investigational product.
<LLN and <study baseline levels that is 
directly related to dosing of investigational 
product.
Total lymphocyte count
Hgb
IgG, IgA, and IgM levels 
Events of clinical interest a
; CTCAE: Common Terminology Criteria for Adverse Events; Hgb: hemoglobin; Ig: 
immunoglobulin; 
; LLN: lower limit of normal.
.
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 of the main study.
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 following, as relevant: 

The Week 20 end-of-study visit of the LFP, for patients originally randomized to placebo who 
chose not to enter an OLE.

The Week 32 end-of-study visit of the LFP, for patients originally randomized to TAK-079.

The EW32 visit of the OLE LFP, for patients originally randomized to placebo who 
participated in the OLE, completing the dosing period, SFP, and LFP of the OLE.
9.9
Discontinuation of Treatment With Study Drug and Patient Replacement
Study drug must be permanently discontinued for patients meeting any of the following criteria:

Withdrawal by patient.

Pregnancy.
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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.

Withdrawal by patient.

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 (see Appendix A). and Appendix B). 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 8.5.1.
Patients who discontinue/withdraw prematurely from study drug dosing for reasons other than 
safety may be replaced at the discretion of the sponsor.
9.10
Withdrawal of Patients From Study
A patient may 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 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
COVID-19–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 COVID-19 public health 
emergency. This guidance takes references from the US Food and Drug Administration (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 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 judgment 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 trial participant’s residence. These may 
be obtained the day before a scheduled visit (see Appendix A and Appendix B).

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 (except for the second platelet count determination), Week 1, Week 
2, Week 3, Week 4, Week 10, Week 16, Week 20 (only for placebo patients not advancing to 
the OLE), and Week 32 of the main study and EW1, EW2, EW3, EW4, EW10, EW16, and 
EW32 of the OLE 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 
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COVID-19 public health emergency. Home healthcare visits will be documented in the study 
records and eCRF.

For 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 3 to 4 doses of study drug at the clinic site unless otherwise approved by 
the sponsor. Safety parameters for dosing decisions (Table 8.f) 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.

Patients who discontinued from screening or run-in period 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.
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.
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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, that is, 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 
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…”).
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
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.

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:
1. Results in death.
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2. 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).
3. Requires inpatient hospitalization or prolongation of an existing hospitalization.
4. Results in persistent or significant disability or incapacity.
5. Is a congenital anomaly/birth defect.
6. 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.
Note: Some clinical centers may only be able to provide certain dosing period–permitted 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.
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. An inpatient hospitalization specifically for the 
access and administration of rescue therapy for thrombocytopenia, as described in Section 8.2.5, in 
an otherwise clinically stable patient is not considered a fulfillment of criterion 2, above.
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.
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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 EDC 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 laboratory abnormality, will be determined 
using the National Cancer Institute CTCAE, Version 4.03, effective 14 June 2010. The criteria are 
provided in the study manual.
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?
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COVID-19 vaccination-related AEs will be confirmed by the investigator and flagged in the AE 
eCRF form.
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 
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).

COVID-19 infection and COVID-19 vaccination-related AEs will be recorded from the 
signing of informed consent through LFP regardless of causality.
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 
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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.
11.0
STUDY-SPECIFIC COMMITTEES
In accordance with Takeda standard operating procedures, each clinical study 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 study 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. However, the decision to convene a DSMB could be made at any time during the 
conduct of Study TAK-079-1004.
Although a formal DSMB will not be formed, internal reviews of available safety information by 
an internal independent SRC will be conducted prior to initiation of Part B and as needed. 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 
Medical Dictionary for Regulatory Activities (MedDRA). Drugs will be coded using the World 
Health Organization Drug Dictionary.
12.1
eCRFs 
Completed eCRFs are required for each patient that 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.
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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.
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.
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Unblinded Safety Review: An unblinded safety review will take place once a minimum of 24 
evaluable patients are available for analysis in Part A. For the purposes of this unblinded safety 
review, an evaluable patient is defined as a patient who exits the dosing period in Part A having 
received a minimum of 4 study doses, regardless of the reason for exit (eg, completion of Part A 
dosing period, early discontinuation, study drug discontinuation). This unblinded safety review 
will include all unblinded safety data from all patients from Part A available at the data-cut (data 
up to the Week 16 visit). For additional information, see Section 6.1.2. 
Interim Analysis: After all patients in Part B (Arms B1 and B2) complete the blinded SFP 
(complete the Week 16 visit), an unblinded interim analysis with Part A and Part B data will take 
place to evaluate safety and efficacy. If it is deemed not appropriate to continue onto Part B after 
the unblinded safety review, then this interim analysis will not be conducted.
13.3
Determination of Sample Size
This study is exploratory and not powered to address any predefined hypothesis.
In Part A, at least 24 and up to approximately 36 patients will be randomized in a ratio of 1:1:1 to 
treatment groups (TAK-079 100 mg, TAK-079 300 mg, or matching placebo).
In Part B, a minimum of 12 and up to approximately 18 patients will be randomized 1:2 to 
treatment groups (matching placebo or TAK-079 600 mg). 
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 (ie, 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 
(as long as blinding is not jeopardized) 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 review of 
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.
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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 
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 IEC, 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, the 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 Harmonised 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 E. 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 
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voting must also be obtained. Those 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.
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 notify the site 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 trial. 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
Subject Information, Informed Consent, and Subject 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, subject authorization form (if applicable), and subject 
information sheet (if applicable) describe the planned and permitted uses, transfers, and 
disclosures of the subject’s personal and personal health information for purposes of conducting 
the study. The ICF and the subject 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.
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The investigator is responsible for the preparation, content, and IRB or IEC approval of the ICF 
and, if applicable, the subject authorization form. The ICF, subject authorization form (if 
applicable), and subject information sheet (if applicable) must be approved by both the IRB or IEC 
and the sponsor before use.
The ICF, subject authorization form (if applicable), and subject information sheet (if applicable) 
must be written in a language fully comprehensible to the prospective subject. It is the 
responsibility of the investigator to explain the detailed elements of the ICF, subject authorization 
form (if applicable), and subject information sheet (if applicable) to the subject. 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 subject is not capable of rendering adequate written informed 
consent, then the subject’s legally acceptable representative may provide such consent for the 
subject in accordance with applicable laws and regulations.
The subject, or the subject’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 
subject, or the subject’s legally acceptable representative, determines that he or she will participate 
in the study, then the ICF and subject authorization form (if applicable) must be signed and dated 
by the subject, or the subject’s legally acceptable representative, at the time of consent and before 
the subject enters into the study. The subject or the subject’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 subject authorization 
(if applicable) at the time of consent and before the subject 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, subject authorization form (if applicable), and subject information 
sheet (if applicable) will be stored in the investigator’s site file. The investigator must document 
the date the subject signs the informed consent in the subject’s medical record. Copies of the 
signed ICF, the signed subject authorization form (if applicable), and subject information sheet (if 
applicable) shall be given to the subject.
All revised ICFs must be reviewed and signed by relevant subjects or the relevant subject’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 subject’s medical record, and the subject 
should receive a copy of the revised ICF.
15.3
Subject Confidentiality
The sponsor and designees affirm and uphold the principle of the subject’s right to protection 
against invasion of privacy. Throughout this study, a subject’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 subject attributes, such as sex, age, or date 
of birth, and subject initials may be used to verify the subject and accuracy of the subject’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 
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regulatory authority (eg, US FDA, UK MHRA, Japan PMDA), the sponsor’s designated auditors, 
and the appropriate IRBs and IECs to review the subject’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 subject’s study participation, and 
autopsy reports. Access to a subject’s original medical records requires the specific authorization 
of the subject as part of the informed consent process (see Section 15.2).
Copies of any subject source documents that are provided to the sponsor must have certain 
identifying personal information removed (eg, subject name, address, and other identifier fields 
not collected on the subject’s eCRF).
15.4
Publication, Disclosure, and Clinical Trial 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 Trial Registration
To ensure that information on clinical trials reaches the public in a timely manner and to comply 
with applicable laws, regulations, and guidance, Takeda will, at a minimum, register interventional 
clinical trials 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 trials via registries. In certain situations/registries, Takeda may assist 
participants or potential participants in finding a clinical trial by helping them locate trial sites 
closest to their homes by providing the investigator name, address, and phone number via 
email/phone or other methods preferred by callers requesting trial information. Once subjects 
receive investigator contact information, they may call the site requesting enrollment into the trial. 
The investigative sites are encouraged to handle the trial inquiries according to their established 
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subject screening process. If the caller asks additional questions beyond the topic of trial 
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. 
15.4.3
Clinical Trial Results Disclosure
Takeda will post the results of clinical trials on ClinicalTrials.gov, clinicaltrialsregister.eu, 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 subject in the study must be insured in accordance with the regulations applicable to the site 
where the subject 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 subjects. 
Refer to the clinical study site agreement regarding the sponsor’s policy on subject compensation 
and treatment for injury. If the investigator has questions regarding this policy, he or she should 
contact the sponsor or sponsor’s designee.
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Appendix C
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Appendix E
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 
trial-related duties and functions, the investigator/institution should ensure that this individual 
or party is qualified to perform those trial-related duties and functions and should implement 
procedures to ensure the integrity of the trial-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 subjects 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 Code for Federal Regulations (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 subjects. 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 subject who participates in the study, and document 
the date of consent in the subject’s medical chart. Valid informed consent is the most current 
version approved by the IRB/IEC. Each ICF should contain a subject authorization section that 
describes the uses and disclosures of a subject’s personal information (including personal 
health information) that will take place in connection with the study. If an ICF does not include 
such a subject authorization, then the investigator must obtain a separate subject authorization 
form from each subject or the subject’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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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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Appendix F
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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Appendix G
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Appendix H
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ITP‐PAQ v1.0 (05 September 2017) 
US (English) 
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ITP‐PAQ v1.0 (05 September 2017) 
US (English) 
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ITP‐PAQ v1.0 (05 September 2017) 
US (English) 
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ITP‐PAQ v1.0 (05 September 2017) 
US (English) 
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ITP‐PAQ v1.0 (05 September 2017) 
US (English) 
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ITP‐PAQ v1.0 (05 September 2017) 
US (English) 
For non-commercial use only


ITP‐PAQ v1.0 (05 September 2017) 
US (English) 
For non-commercial use only


ITP‐PAQ v1.0 (05 September 2017) 
US (English) 
For non-commercial use only


ITP‐PAQ v1.0 (05 September 2017) 
US (English) 
For non-commercial use only


ITP‐PAQ v1.0 (05 September 2017) 
US (English) 
For non-commercial use only


TAK-079
Study No. TAK-079-1004
Page 119 of 144
Protocol Incorporating Amendment No. 5
28 April 2022
CONFIDENTIAL
Appendix I
Protocol History
Date
Amendment Number
Type
Region
28 April 2022
Amendment 5
Substantial
Global
05 May 2021
Amendment 4
Substantial
Global
18 December 2020
Amendment 3
Substantial
Global
7 October 2020
Amendment 2
Substantial
Global
26 December 2019
Amendment 1
Nonsubstantial
Global
06 November 2019
Initial protocol
Not applicable
Global
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TAK-079
Study No. TAK-079-1004
Page 120 of 144
Protocol Incorporating Amendment No. 5
28 April 2022
CONFIDENTIAL
Protocol Amendment 4 and Rationale
This section describes the changes in reference to the protocol incorporating Amendment 4. The 
primary reason for this amendment is to change the legal entity name for the sponsor to Takeda 
Development Center Americas, Inc. Other changes are outlined in the table below.
Change 
Number
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
1
Title Page
2.0 STUDY SUMMARY
Changed legal entity name for the 
sponsor from Millennium 
Pharmaceuticals, Inc (MPI), 40 
Lansdowne Street, Cambridge, MA 
02139 to: Takeda Development Center 
Americas, Inc, 95 Hayden Avenue, 
Lexington, MA 02421, USA.
New legal entity name for 
sponsor.
2
3.3 Corporate Identification
Changed corporate identification from 
Millennium Pharmaceuticals, Inc. a 
wholly owned subsidiary of Takeda to 
read: Takeda, Takeda Development 
Center Americas, Inc.
New legal entity name for 
sponsor.
3
6.2 Number of Patients
Changed US, Canada to North America
To be consistent with 
Synopsis.
4
Table 8.c Permitted 
Concomitant Medications 
Table header for second column 
changed from “Criteria Are to Be 
Maintained from Screening to 
Completion of Study Dosing Phase” to 
read: “Criteria Are to Be Maintained 
Throughout the Study”
Correction.
5
10.1.3 SAE Definition
Under 6. Is a MEDICALLY 
IMPORTANT EVENT:
Removed “Includes any event or 
synonym described in the Takeda 
Medically Significant AE List (see 
Table 10.a).”
Removed Table 10.a
To be consistent with 
updated protocol template.
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TAK-079
Study No. TAK-079-1004
Page 124 of 144
Protocol Incorporating Amendment No. 5
28 April 2022
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, Part A and B Main 
Study Schedule of Events, footnote b
Footnote b added to row labeled 
“Week”: “Patient visits at screening, 
Weeks 1-4, Week 10, Week 16, 
Week 20 (only for placebo patients 
not advancing to the OLE), and 
Week 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.”
To clarify which visits must be 
conducted with patient present and 
which visits may be conducted in the 
clinic or by optional home healthcare 
visits.
Appendix B Schedule of Events: 
OLE-A and OLE-B, footnote b.
Footnote b added to row labeled 
“Week”: “Patient visits at EW1, 
EW2, EW3, EW4, EW10, EW16, 
and EW32 of the OLE 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.”
To clarify which visits must be 
conducted with patient present and 
which visits may be conducted in the 
clinic or by optional home healthcare 
visits.
Appendix I Protocol History
Changes in Amendment 2 added.
Added according to template 
guidelines.
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TAK-079
Study No. TAK-079-1004
Page 125 of 144
Protocol Incorporating Amendment No. 5
28 April 2022
CONFIDENTIAL
Protocol Amendment 2 and Rationale
The primary reasons for Amendment 2 were to:

Provide clarifications regarding inclusion/exclusion criteria for platelet counts and prior 
high-dose pulse steroid therapy. These changes will provide for a more efficient screening 
process while continuing to ensure inclusion of patients with stable platelet counts below 
30,000/µL.

Allow patients to receive predefined rescue therapies during the dosing period without 
automatic discontinuation from study drug dosing and advancement to the safety follow-up 
period (SFP). As it may take several weeks for TAK-079 to increase platelet counts, this 
change enables investigators to provide a limited bridge therapy for safety purposes.

Clarify the eligibility criteria for the open-label extension (OLE)-A and OLE-B and enhance 
access to the OLE for placebo patients who receive rescue therapies during the study.

Address feedback from a health authority by providing a specific protocol section on the risks 
and benefits of TAK-079, and by specifying the allowable contraception methods.

Add contingency plans for the COVID-19 pandemic by incorporating flexibility for study 
participants, investigators, and study-site monitors while continuing to maintain patient safety 
and study integrity as per local site regulations.
In this amendment, minor grammatical, editorial, formatting, and administrative changes not 
affecting the conduct of the study were included for clarification and administrative purposes only.
Protocol Amendment 2
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
Changed definition of platelet 
response to exclude counts for 
patients who received a 
nonpermitted rescue therapy and 
counts from patients who had 
received a rescue therapy in the 
previous 4 weeks.
Evaluation of the secondary endpoints 
4 weeks after a dosing period–
permitted rescue treatment is allowed 
since the duration of effect is typically 
less than 4 weeks. Any other rescue 
therapy prevents further evaluation of 
the secondary endpoints.
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TAK-079
Study No. TAK-079-1004
Page 127 of 144
Protocol Incorporating Amendment No. 5
28 April 2022
CONFIDENTIAL
Protocol Amendment 2
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 7.1 Inclusion Criteria
Table 8.c Permitted Concomitant 
Medications
#5 Inclusion Criterion: Removed 
text that restricted high-dose 
pulse steroid therapy 14 days 
before dosing and clarified that 
every-other-day dosing of oral 
corticosteroid therapy is allowed.
High-dose pulse steroid therapy may 
confound platelet counts for longer 
than 14 days and is not consistent with 
the dosing period–permitted rescue 
therapies. Also clarifies that stable 
background therapy with daily or 
every-other-day corticosteroids is 
allowed, as the intent was not to 
exclude this group of patients.
Section 2.0 Study Summary
Section 7.2 Exclusion Criteria
#4 Exclusion Criterion: Revised 
to exclude patients if there is an 
expectation that any rescue 
therapy may be needed between 
screening and dosing.
Clarifies that a patient’s platelet count 
should be stable enough that the need 
for a rescue therapy is not expected 
before dosing.
Section 2.0 Study Summary
Section 7.2 Exclusion Criteria
Section 8.2 Excluded Concomitant 
Medications and Procedures
#9 Exclusion Criterion: Revised 
vaccination restriction to live 
vaccines only.
Patients who receive TAK-079 or any 
other immunosuppressive drug, such 
as corticosteroids, may be placed at 
increased risk of infection from a live 
vaccine. This risk is not present with 
inactive vaccines. It is recommended 
to continue with vaccinations with 
inactive vaccines as these may confer 
protective benefit.
Section 2.0 Study Summary
Section 7.2 Exclusion Criteria
Appendix B Schedule of Events: 
OLE-A and OLE-B
#13 Exclusion Criterion: 
Definition updated to clarify 
parameters for patients with 
herpes simplex infection.
Most local herpes lesions are benign 
and do not require any specific 
systemic treatment; infections of this 
type that have resolved do not pose any 
risk to the patient with study drug 
treatment.
Section 2.0 Study Summary
Section 7.2 Exclusion Criteria
Appendix B Schedule of Events: 
OLE-A and OLE-B
#17 Exclusion Criterion: 
Revised to allow patients cured 
of hepatitis C.
Patients who have been fully cured of 
hepatitis C are no longer at risk of 
worsening of infection by 
immunosuppressive agents. 
Additionally, the hepatitis B core Ab 
test is used to exclude patients with 
possible latent/occult hepatitis B to 
prevent the theoretical possibility of 
reactivation.
Section 2.0 Study Summary
Section 13.1.3 Efficacy Analysis
Specified how different types of 
secondary efficacy endpoints 
(binary vs continuous) will be 
analyzed.
Clarifies statistical analyses.
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TAK-079
Study No. TAK-079-1004
Page 133 of 144
Protocol Incorporating Amendment No. 5
28 April 2022
CONFIDENTIAL
Protocol Amendment 1 and Rationale
This document describes the changes to the protocol incorporating Amendment 01. The primary 
reason for this amendment is to address United States (US) Food and Drug Administration (FDA) 
feedback on the primary immune thrombocytopenia (ITP) Investigational New Drug (IND).This 
feedback indicated that all patients should have either phenotype or genotype testing prior to study 
drug treatment with no exceptions. This is because there is a potential that TAK-079 may affect 
blood bank serologic testing should a patient require a red blood cell (RBC) transfusion. While the 
informed consent form specified that this test is required for all patients, the language in the 
protocol was inconsistent with this. This amendment revises the protocol language to accurately 
reflect that the RBC phenotype or genotype assessment is required for study participation. 

Extended RBC antigen typing (assessed by phenotyping or genotyping) is required before 
initiation of study dosing.

Correction of FEV1 to be defined as forced expiratory volume in 1 second; previously 
erroneously defined as forced expiratory volume in 1 minute.

Correction of Appendix B Schedule of Events: OLE-A and OLE-B; indicating postmedication 
dosing is to be conducted during EW1, previously it was erroneously indicated to be performed 
during EW1D3.
Minor grammatical, editorial, formatting, and administrative changes not affecting the conduct of 
the study are included for clarification and administrative purposes only.
For non-commercial use only


TAK-079
Study No. TAK-079-1004
Page 134 of 144
Protocol Incorporating Amendment No. 5
28 April 2022
CONFIDENTIAL
Appendix J
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Study No. TAK-079-1004
Page 135 of 144
Protocol Incorporating Amendment No. 5
28 April 2022
CONFIDENTIAL
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Study No. TAK-079-1004
Page 136 of 144
Protocol Incorporating Amendment No. 5
28 April 2022
CONFIDENTIAL
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Study No. TAK-079-1004
Page 137 of 144
Protocol Incorporating Amendment No. 5
28 April 2022
CONFIDENTIAL
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Study No. TAK-079-1004
Page 138 of 144
Protocol Incorporating Amendment No. 5
28 April 2022
CONFIDENTIAL
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Study No. TAK-079-1004
Page 139 of 144
Protocol Incorporating Amendment No. 5
28 April 2022
CONFIDENTIAL
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Study No. TAK-079-1004
Page 140 of 144
Protocol Incorporating Amendment No. 5
28 April 2022
CONFIDENTIAL
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Study No. TAK-079-1004
Page 141 of 144
Protocol Incorporating Amendment No. 5
28 April 2022
CONFIDENTIAL
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SAP_001.pdf: 
F or n o n- c o m m er ci al u s e o nl y


S T A TI S TI C A L A N A L Y SI S P L A N  
St u d y N u m ber: T A K- 0 7 9- 1 0 0 4 
St u d y Titl e: A P hase 2, Ra n d o mize d, D o u ble- Bli n d, Place b o- C o ntr olle d St u d y t o E v al uate Safet y, 
T olera bilit y, a n d Efficac y of T A K- 0 7 9 i n Patie nts Wit h Persiste nt/ C hr o nic Pri mar y I m m u ne 
T hr o m b oc yt o p e nia 
P hase: 2 
Versi o n: A me n d me nt 3. 0 
Date: 1 6 Ma y 2 0 2 4 
Pre pare d b y: 
 
 Base d o n: 
Pr ot oc ol Versi o n a n d D ate: 
A me n d me nt 5, 2 8 A pril 2 0 2 2 
C O N FI D E N TI A L P R O P E R T Y O F T A K E D A 
T his d o c u me nt is a c o nfi d e nti al d o c u me nt of T a ke d a. Acce pta nce of t his d oc u me nt c o nstit utes t he a gree me nt b y 
t he reci pie nt t hat n o i nf or mati o n c o ntai ne d herei n will b e p u blis he d or discl ose d wit h o ut writte n a ut h orizati o n 
fr o m T a k e d a. 
F or n o n- c o m m er ci al u s e o nl y


 
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R E VI SI O N HI S T O R Y  
 
Versi o n 
D ate 
P ri m ar y R ati o n ale f o r R e visi o n 
Ori gi nal versi o n 
0 5- A P R- 2 0 2 1 
N ot a p plica ble 
A me n d me nt 1. 0 
2 9- A U G- 2 0 2 2 
Pr ot oc ol a me n d me nt 
A me n d me nt 2. 0 
0 1- D E C- 2 0 2 3 
T o clarif y statistical met h o ds as o utli ne d i n Secti o n 9. 1 
A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4 
T o a d dress fee d bac k fr o m i nteri m a nal ysis a n d dr y-r u n re vie w of t he 
ta bles, listi n gs a n d fi g ures 
 
 
 
 
 
 
 
 
 
 
F or n o n- c o m m er ci al u s e o nl y


 
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P a g e 3 of 4 0  
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1 6- M A Y- 2 0 2 4  
 
 
T a ble of C o nte nts 
1. 0  
O BJ E C TI V E S A N D E N D P OI N T S ..................................................................................... 9  
1. 1  
St u d y O bjecti ves ............................................................................................................ 9  
1. 1. 1  
Pri mar y O bj ecti ve ................................................................................................. 9  
1. 1. 2  
Sec o n dar y O bjecti ve ............................................................................................. 9  
1. 1. 3  
 .......................................................................................... 9 
1. 2  
E n d p oi nts ....................................................................................................................... 9  
1. 2. 1  
Pri mar y E n d p oi nt .................................................................................................. 9  
1. 2. 2  
Sec o n dar y E n d p oi nts ............................................................................................. 9  
1. 2. 3  
 ........................................................................................ 1 0 
2. 0  
S T U D Y D E SI G N .............................................................................................................. 1 1  
2. 1  
O ver vie w of St u d y Desi g n ........................................................................................... 1 1  
2. 2  
Pr ot oc ol Fi g ure 6.a St u d y Sc he m a: O ver vie w............................................................. 1 1  
2. 3  
Pr ot oc ol Fi g ure 6. b St u d y Sc he m atic: Part A a n d B, Mai n St u d y ............................... 1 2  
2. 4  
Pr ot oc ol Fi g ure 6.c Sc h e matic f or t he O L E Peri o ds ................................................... 1 3  
2. 5  
Part A O ver vie w .......................................................................................................... 1 4  
2. 6  
Part B O ver vie w .......................................................................................................... 1 4  
2. 7  
I nteri m A nal yses .......................................................................................................... 1 5 
2. 8  
N u m ber of Patie nts ...................................................................................................... 1 6  
2. 9  
D urati o n of St u d y ........................................................................................................ 1 6  
3. 0  
S T A TI S TI C A L H Y P O T H E S E S A N D D E CI SI O N R U L E S ............................................ 1 6  
3. 1  
Statistical H y p ot heses .................................................................................................. 1 6  
3. 2  
M ulti plicit y A dj ust me nt .............................................................................................. 1 6  
4. 0  
S A M P L E- SI Z E D E T E R MI N A TI O N ................................................................................ 1 6  
5. 0  
A N A L Y SI S S E T S ............................................................................................................. 1 7  
5. 1  
E nr olle d Set ................................................................................................................. 1 7  
5. 2  
F ull A nal ysis Set .......................................................................................................... 1 7  
5. 3  
Safet y A nal ysis Set ...................................................................................................... 1 7  
5. 4  
 ........................................................................................................... 1 7 
5. 5  
 ........................................................................................................... 1 7 
5. 6  
 ...................................................................................... 1 7 
6. 0  
S T A TI S TI C A L A N A L Y SI S ............................................................................................. 1 7  
6. 1  
Ge neral C o nsi derati o ns ................................................................................................ 1 7  
6. 1. 1  
Ge neral Pri nci ples ............................................................................................... 1 7  
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6. 1. 2  
L o n git u di nal M o deli n g of C ha n ge fr o m Baseli ne .............................................. 1 8  
6. 1. 3  
A nal ysis of Bi nar y Efficac y E n d p oi nts ............................................................... 1 9  
6. 1. 4  
Ha n dli n g of Treat m e nt Misall ocati o ns ................................................................ 1 9  
6. 2  
Dis p ositi o n of S u bjects ................................................................................................ 1 9  
6. 3  
De m o gra p hic a n d Ot her Baseli ne C haracteristics ....................................................... 1 9  
6. 3. 1  
De m o gra p hic C haract eristi cs .............................................................................. 1 9  
6. 3. 2  
Baseli ne C haracteristics ...................................................................................... 2 0  
6. 3. 3  
Me dical Hist or y ................................................................................................... 2 0  
6. 4  
C o nc o mita nt Me dicati o ns a n d Pr oce d ures .................................................................. 2 0  
6. 5  
Efficac y A nal ysis ......................................................................................................... 2 1  
6. 5. 1  
Pri mar y E n d p oi nt A nal ysis ................................................................................. 2 1  
6. 5. 2  
Sec o n dar y E n d p oi nts A n al ysis ............................................................................ 2 1  
6. 5. 3  
 .......................................................................... 2 2 
6. 5. 4  
S u b gr o u p A n al ys es .............................................................................................. 2 7  
6. 6  
Safet y A nal ysis ............................................................................................................ 2 7  
6. 6. 1  
A d verse E v e nts .................................................................................................... 2 7  
6. 6. 2  
Cli nical La b orat or y E val uati o ns.......................................................................... 3 0  
6. 6. 3  
Vital Si g ns ........................................................................................................... 3 0  
6. 6. 4  
1 2- Lea d E C Gs ..................................................................................................... 3 1  
6. 6. 5  
Pre g n a nc y T est .................................................................................................... 3 1  
6. 6. 6  
E xte nt of E x p os ure a n d C o m plia nce ................................................................... 3 1  
6. 7  
 ................................. 3 1 
6. 7. 1  
 ................................................................................... 3 1 
6. 7. 2  
 ....................................................... 3 2 
6. 8  
 ............................................................................................ 3 3 
6. 9  
I nteri m A nal yses .......................................................................................................... 3 4 
7. 0  
R E F E R E N C E S .................................................................................................................. 3 4  
8. 0  
C H A N G E S T O P R O T O C O L P L A N N E D A N A L Y S E S .................................................. 3 4  
9. 0  
A P P E N DI X ....................................................................................................................... 3 5  
9. 1  
C ha n ges fr o m t he Pre vi o us V ersi o n of t he S A P .......................................................... 3 5  
9. 2  
Data Ha n dli n g C o n ve nti o ns......................................................................................... 3 5  
9. 2. 1  
Defi niti o n of Bas eli ne ......................................................................................... 3 5  
9. 2. 2  
Defi niti o n of St u d y Da ys .................................................................................... 3 5  
9. 2. 3  
Defi niti o n of A nal ysis Visits ............................................................................... 3 6  
9. 2. 4  
Resc ue T hera pies a n d Per mitt e d Resc ue Treat me nt ........................................... 3 6  
9. 2. 5  
Pri or I T P Me di cati o ns ......................................................................................... 3 6  
F or n o n- c o m m er ci al u s e o nl y


 
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9. 2. 6  
T E A Es Occ urri n g d uri n g D osi n g a n d S F P Peri o d, L F P p eri o d .......................... 3 7  
9. 3  
A nal ysis S oft w are ........................................................................................................ 3 8  
9. 4  
Criteria f or I d e ntificati o n of Mar ke dl y A b n or mal Val ues ........................................... 3 8  
9. 5  
 ..................................................................................... 3 9 
 
F or n o n- c o m m er ci al u s e o nl y


 
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LI S T O F I N- T E X T T A B L E S 
Ta ble 1  N u m ber of Wee ks Eac h Visit C o vers i n Calc ulati n g D urati o n of a Cli nicall y M ea ni n gf ul 
Effect ..................................................................................................................... 2 3  
Ta ble 2 I m m u n o ge nicit y Stat us Defi niti o n ................................................................................... 3 4  
Ta ble 3 C ha n ges fr o m t he Pre vi o us Versi o n of t h e S A P .............................................................. 3 5  
Ta ble 4 Pri or I T P Me dicati o ns a n d Cate g or y ................................................................................ 3 6  
Ta ble 5 
 .................................................. 3 9 
 
 
F or n o n- c o m m er ci al u s e o nl y


 
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A B B R E VI A TI O N S 
A D A 
a nti- dr u g a nti b o d y 
A E 
a d verse e ve nt 
B MI 
b o d y mass i n d e x 
CI 
c o nfi d e nce i nter val 
C O VI D- 1 9 
c or o na vir us disease 2 0 1 9 
C T C A E 
C o m m o n T er mi n ol o g y Criteri a f or A d verse E ve nts 
C tr o u g h 
tr o u g h c o nce ntrati o n 
E C G 
electr ocar di o gra m 
e C R F 
electr o nic case re p ort f or m 
E W 
e xte nsi o n wee k 
I g A 
i m m u n o gl o b uli n A 
I g G 
i m m u n o gl o b uli n G 
I g M 
i m m u n o gl o b uli n M 
 
 
 
 
I T P 
i m m u ne t hr o m b o c yt o pe nia 
 
 
L F P 
l o n g-ter m f oll o w- u p p eri o d 
M A V 
mar ke dl y a b n or mal val ues 
Me d D R A  
Me dical Dicti o nar y f or Re g ul at or y Acti vities  
M M R M  
mi xe d effects m o d el f or re peate d meas ures 
N K 
nat ural killer 
O L E 
o p e n la b el e xte nsi o n 
P B 
plas ma blast 
 
 
 
 
P R O 
Patie nt Re p orte d O utc o mes 
P T 
preferre d t er m ( M e d D R A) 
P T E  
pre-treat me nt e ve nt 
S A E 
seri o us a d verse e ve nt 
S A P 
statistical a nal ysis pla n 
S C 
s u bc uta ne o us 
S D 
sta n dar d de viati o n 
S F P 
safet y f oll o w- u p peri o d 
F or n o n- c o m m er ci al u s e o nl y


 
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S O C 
S yste m Or ga n Class 
S R C  
Safet y Re vie w C o m mitt ee 
T E A E 
treat me nt-e mer ge nt a d verse e ve nt 
W H O 
W orl d Healt h Or ga nizati o n 
F or n o n- c o m m er ci al u s e o nl y


 
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1. 0  
O B J E C TI V E S A N D E N D P OI N T S 
1. 1  
St u d y O bjecti ves 
1. 1. 1  
Pri m ar y O bjecti ve 
T he pri m ary o bjective is t o ev al u ate t he s afety a n d t oler a bility of T A K- 0 7 9 i n p atie nts wit h 
persiste nt/c hr o nic pri m ary I T P. 
1. 1. 2  
Sec o n d ar y O bjecti ve 
T he sec o n d ary o bjective is t o assess t he effects of T A K- 0 7 9 a d mi nistr ati o n o n pl atelet c o u nts i n 
p atie nts wit h persiste nt/c hr o nic pri m ary I T P. 
1. 1. 3  
 
 
 
 
 
 
 
 
 
 
 
 
1. 2  
E n d p oi nts 
1. 2. 1  
Pri m ar y E n d p oi nt 
T he pri m ary e n d p oi nt is t he perce nt a g e of p atie nts wit h T E A Es i ncl u di n g Gr a de 3 or hi g her 
eve nts, S A Es, a n d A Es le a di n g t o T A K- 0 7 9 disc o nti n u ati o n. 
1. 2. 2  
Sec o n d ar y E n d p oi nts 
T he sec o n d ary e n d p oi nt assesses t he effects of T A K- 0 7 9 a d mi nistr ati o n o n c h a n ges i n t he 
pl atelet c o u nt, t hr o u g h t he f oll o wi n g 4 e n d p oi nts: 
1. N u m ber a n d p erce nt a ge of p atie nts wit h a pl atelet res p o nse. Pl atelet res p o nse is defi ne d 
a d osi n g peri o d- per mitte d resc ue tre at me nt i n t he previ o us 4 weeks, wit h o ut pre mat ure 
F or n o n- c o m m er ci al u s e o nl y


F or n o n- c o m m er ci al u s e o nl y


F or n o n- c o m m er ci al u s e o nl y


 
T A K- 0 7 9- 1 0 0 4 
P a g e 1 2 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
 
2. 3  
Pr ot oc ol Fi g ure 6. b St u d y Sc he m atic: P art A a n d B, M ai n St u d y 
 
A E: a d verse eve nt; C O VI D- 1 9: c or o n avir us dise ase 2 0 1 9; L F P: l o n g-ter m f oll o w- u p p eri o d; S F P: s afety f oll o w- u p 
p eri o d; W: week. 
a U nres olve d A Es as of Week 1 6 a n d rel ate d A Es/seri o us A Es wit h o nset after S F P will be c ollecte d t hr o u g h t h e L F P. 
C O VI D- 1 9 i nfecti o n a n d C O VI D- 1 9 v a cci n ati o n-rel ate d A Es will be c oll ecte d t hr o u g h t h e L F P re g ar dless of c a us ality. 
F or n o n- c o m m er ci al u s e o nl y


 
T A K- 0 7 9- 1 0 0 4 
P a g e 1 3 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
 
2. 4  
 Pr ot oc ol Fi g ure 6. c Sc he m atic f or t he O L E Peri o ds 
 
A E: a d verse eve nt; C O VI D- 1 9: c or o n avir us dise ase 2 0 1 9; E W: exte nsi o n week; L F P: l o n g-ter m f oll o w- u p peri o d; 
O L E: o pe n-l a b el exte nsi o n; S F P: s afety f oll o w- u p p eri o d. 
a U nres olve d A Es as of Week 1 6 a n d rel ate d A Es/seri o us A Es wit h o nset after S F P will b e c oll ecte d t hr o u g h t he L F P. 
C O VI D- 1 9 i nfecti o n a n d C O VI D- 1 9 v a cci n ati o n-rel ate d A Es will be c oll ecte d t hr o u g h t h e L F P re g ar dless of c a us ality. 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 1 4 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
2. 5  
P art A O ver vi e w 
After scree ni n g, at le ast 2 4 u p t o 3 6 eli gi ble p ati e nts will be r a n d o miz e d i n a d o u ble-
bli n d 1: 1: 1 r ati o t o 1 of t he f oll o wi n g gr o u ps (see Pr ot oc ol Fi g ure 2. b): 
 Ar m A 1 : M atc hi n g pl ace b o a d de d t o st a ble b ack gr o u n d t her a py ( n = 8 - 1 2 p atie nts). 
 Ar m A 2 : T A K- 0 7 9 1 0 0 m g a d de d t o st a ble b ack gr o u n d t her a py ( n = 8 - 1 2 p atie nts). 
 Ar m A 3 : T A K- 0 7 9 3 0 0 m g a d de d t o st a ble b a ck gr o u n d t her a py ( n = 8 - 1 2 p atie nts). 
T A K- 0 7 9 or m atc hi n g pl ace b o will be a d mi nistere d vi a S C i njecti o n Q W f or 8 weeks (see 
Pr ot oc ol Secti o n 8. 1 f or m ore det ails). S afety assess me nts, i ncl u di n g s afety l a b or at ory tests, 
will be perf or me d e ac h w eek b ef ore s u bse q ue nt d osi n g. P atie nts m ay h ave st u dy dr u g ( T A K-
0 7 9 or m atc hi n g pl ace b o) d os es m o difie d (e g, wit h hel d or del aye d) f or s af ety re as o ns (see 
f urt her det ails o n d ose m o dific ati o n/st o p pi n g criteri a i n pr ot oc ol Secti o n 8. 5). Pl atel et levels 
will be assesse d o n D ay 3 of Week 1 ( 2 d ays after t he first d ose) a n d o n e a c h weekly visit, 
bef ore a d mi nistr ati o n of t he s u bse q ue nt d oses. 
After c o m pleti n g t he 8- w eek d osi n g peri o d, p atie nts will e nter a bli n de d S F P, c o m pleti n g s afety 
a n d l a b or at ory assess me nts every 2 weeks f or 2 m o nt hs. 
At t he c o m pleti o n of S F P ( Week 1 6 visit), p atie nts will be u n bli n de d. 
P atie nts w h o were d ose d wit h T A K- 0 7 9 ( Ar ms A 2 a n d A 3) will be f oll o we d m o nt hly f or 4 
m o nt hs i n a n L F P t o c heck pl atelet c o u nts a n d t o m o nit or f or a ny o n g oi n g dr u g-rel ate d A Es at 
t he e n d of t he S F P. P atie nts w h o were d ose d wit h m atc hi n g pl ace b o ( Ar m A 1) will be eli gi ble 
f or t he P art A o pe n-l a bel exte nsi o n ( O L E- A) p h as e (see pr ot oc ol  Secti o n 6. 1. 1. 1) f or access t o 
st u dy dr u g. Pl ace b o p atie nts w h o o pt n ot t o p artici p at e i n t he O L E- A will e n d t he st u dy at t he 
Week 2 0 visit of t he L F P. 
 F or p atie nts w h o o bt ai ne d pl ace b o i n P art A a n d w h o wis h t o c o nti n ue i n t he O L E- A f or 
access t o st u dy dr u g, l a b or at ory ev al u ati o ns will be o bt ai ne d at t he Week 1 6 visit ( at t he e n d 
of P art A) t o e ns ure i ncl usi o n/excl usi o n criteri a s pecifie d i n Pr ot oc ol Secti o n 6. 1. 1. 1 
c o nti n ue t o be met. 
T he first d osi n g d ay i n O L E- A ( o n E xte nsi o n Week 1, [ E W 1], see Sc he d ule of E ve nts [ S O E] 
i n pr ot oc ol  A p pe n dix B) is t o occ ur less t h a n 4 weeks after t he Week 1 6 visit. I n O L E- A, 
p atie nts will be r a n d o mly assi g ne d t o 1 of t he f oll o wi n g st u dy ar ms (s ee Pr ot oc ol  Fi g ure 
6.c): 
 Ar m A 1- E 1:  T A K- 0 7 9 1 0 0 m g a d d e d t o st a ble, st a n d ar d b ack gr o u n d t her a p y. 
 Ar m A 1- E 2:  T A K- 0 7 9 3 0 0 m g a d d e d t o st a ble, st a n d ar d b ack gr o u n d t her a p y. 
P atie nts i n Ar ms A 1- E 1 a n d A 1- E 2 will pr ocee d t hr o u g h t he 8- m o nt h pr ot oc ol i n a n o pe n-
l a bel f as hi o n ( 2 m o nt hs o pe n-l a bel d osi n g, 2 m o nt hs o pe n-l a bel S F P, 4 m o nt hs L F P). 
2. 6  
P art B O ver vie w 
O nce at le ast 2 4 p atie nts i n P art A ( 8 p ati e nts i n e ac h ar m) h ave receive d at le ast 4 st u dy 
d oses, a n u n bli n de d s afety revie w wit h all u n bli n de d s afety d at a av ail a ble at t he d at a-c ut 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 1 5 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
( d at a u p t o t he Week 1 6 visit) acr oss all P art A p atie nts will be c o n d ucte d by t he S afety 
Revie w C o m mittee t o deci de w het her t o o pe n e nr oll me nt i nt o P art B (see pr ot oc ol  Secti o n 
6. 1. 2 f or m ore det ails). I n a d diti o n, t here will be a li mite d re vie w of u n bli n de d effi cac y d ata 
relate d t o t he sec o n dar y efficac y e n d p oi nts b y a n i n de pe n de nt Saf et y R e vie w C o m mittee 
( S R C). T he p ur p ose of t h e safet y re vie w is t o i nf or m t he decisi o n of w het her t o o pe n 
e nr oll me nt t o Part B, a n d base d o n t he u n bli n de d s afet y re vie w t he st u d y m a y: ( 1) a d v a nce 
e nr oll me nt t o Part B at t he pr ot oc ol- defi ne d d ose l e vel ( T A K 0 7 9 at 6 0 0 m g s q wee kl y), ( 2) 
a d va nce e nr oll me nt t o Part B at a  d ose le vel l o wer t ha n t he Part B pr ot oc ol- defi ne d le v el, ( 3) 
c o nti n ue or e x pa n d e nr oll m e nt i n Part A, or ( 4) e n act earl y t er mi nati o n of t he st u d y.  
I n P art B, a mi ni m u m of 1 2 a n d u p t o 1 8 eli gi ble p atie nts will be r a n d o mize d aft er 
scree ni n g i n a d o u ble- bli n d 1: 2 r ati o t o 1 of t he f oll o wi n g gr o u ps (see Pr ot oc ol  Fi g ure 
6. b): 
 Ar m B 1:  M atc hi n g pl ace b o a d de d t o st a ble, st a n d ar d b ack gr o u n d t her a py ( n = 4 - 6). 
 Ar m B 2:  T A K- 0 7 9 6 0 0 m g a d de d t o st a ble, st a n d ar d b ack gr o u n d t her a py ( n 
= 8 - 1 2).  T his is t he pr ot oc ol- defi ne d os e le vel a n d will be re place d b y t he 
fi nal S R C rec o m m e n de d d ose le vel. 
 
T he sc he d ule of eve nts/visits will c o nti n ue as i n P art A. 
As i n P art A, p atie nts will be u n bli n de d at t he e n d of t he S F P ( Week 1 6 visit). P atie nts w h o 
were d ose d wit h T A K- 0 7 9 ( Ar m B 2) will be f oll o we d m o nt hly f or 4 m o nt hs i n t he L F P. 
P atie nts d ose d wit h m atc hi n g pl ace b o ( Ar m B 1) will be eli gi ble f or P art B o pe n-l a bel 
exte nsi o n ( O L E- B) p h ase f or a ccess t o st u dy dr u g. Pl ace b o p atie nts w h o o pt n ot t o 
p artici p ate i n t he O L E- B will e n d t he st u dy at t he Week 2 0 visit. 
F or p atie nts w h o o bt ai ne d pl ace b o i n P art B w h o wis h t o c o nti n ue i n t he O L E- B f or access 
t o st u dy dr u g, l a b or at ory ev al u ati o ns will be o bt ai ne d at t he Week 1 6 visit ( at t he e n d of 
P art B) t o e ns ur e s atisf acti o n of t he O L E i ncl usi o n/excl usi o n criteri a ( as o utli ne d i n 
Pr ot oc ol  Secti o n 6. 1. 1. 1). T he first d osi n g d ay i n O L E- B ( o n E W 1, see S O E i n Pr ot oc ol  
A p pe n dix B) is t o occ ur a p pr oxi m ately less t h a n 4 weeks after t he Week 1 6 visit. I n t he 
O L E- B, p atie nts will be offere d (see Pr ot oc ol Fi g ure 6.c): 
 Ar m B 1- E:  T A K- 0 7 9 6 0 0 m g a d de d t o st a ble, st a n d ar d b ack gr o u n d t her a p y. 
P atie nts i n Ar m B 1- E will pr ocee d t hr o u g h t he 8- m o nt h pr ot oc ol i n a n o pe n-l a bel 
f as hi o n ( 2 m o nt hs o pe n-l a bel d osi n g, 2 m o nt hs o pe n-l a bel S F P, 4 m o nt hs L F P). 
2. 7  
I nteri m A n al yses 
O ne u n bli n de d s afety revie w wit h a li mite d assess me nt of efficac y  a n d o n e i nteri m a n alysis 
will be c o n d ucte d bef ore t he fi n al d at a b as e l ock of t his st u dy. 
U n bli n de d S afety Revie w:  A n u n bli n de d s afety revie w b y a n i n de p e n de nt safet y re vie w 
c o m mittee will t ake pl ace o nce a mi ni m u m of 2 4 ev al u a bl e p atie nts are av ail a ble f or a n alysis 
i n P art A. F or t he p ur p oses of t his u n bli n de d s afety revie w, a n ev al u a ble p atie nt is defi ne d as 
a p atie nt w h o exits t he d osi n g peri o d i n P art A h avi n g receive d a mi ni m u m of 4 st u dy d oses, 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 1 6 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
re g ar dless of t he re as o n f or exit (e g, c o m pleti o n of P art A d osi n g peri o d, e arly 
disc o nti n u ati o n, st u dy dr u g disc o nti n u ati o n). T his u n bli n de d s afety revie w will i ncl u de all 
u n bli n de d s afety d at a fr o m all p atie nts fr o m P art A av ail a ble at t he d at a-c ut ( d at a u p t o t he 
Week 1 6 visit). Li mite d assess me nt of effi cac y will als o be perf or me d at t he u n bli n de d safet y 
re vie w. T h e pri mar y st u d y tea m will re mai n bli n de d t o treat me nt assi g n me nt. 
I nteri m A n alysis: After all p atie nts i n P art B ( Ar ms B 1 a n d B 2) c o m plete t h e bli n de d S F P 
(c o m plete t he Week 1 6 visit), a n u n bli n de d i nteri m a n alysis wit h P art A a n d P art B d at a will 
t ake pl ace b y t he pri mar y st u d y tea m  t o ev al u ate s afety a n d effic acy. If it is dee me d n ot 
a p pr o pri ate t o c o nti n ue o nt o P art B after t he u n bli n de d s afety revie w, t he n t his i nteri m 
a n alysis will n ot be c o n d ucte d.   
2. 8  
N u m ber of P atie nts 
A p pr oxi m ately 3 6 t o 5 4 p atie nts wit h persiste nt/c hr o nic pri m ary I T P (ie, a p pr oxi m ately 2 4 - 3 6 
p atie nts i n P art A a n d 1 2 1 8 p atie nts i n P art B) will be r a n d o mize d fr o m a p pr oxi m ately 5 0 
st u dy sites i n t he N ort h A meric a, E ur o pe, a n d Asi a- P acific re gi o ns. 
2. 9  
D ur ati o n of St u d y 
P atie nts r a n d o mize d i n P art A or P art B t o T A K- 0 7 9 will be tre ate d f or a m axi m u m of 
8 weeks a n d will be f oll o we d f or a n 8- week bli n de d S F P, a n d a 1 6- week u n bli n de d 
L F P. M axi m u m t ot al st u dy p artici p ati o n will l ast 8 m o nt hs fr o m t he i niti al d ay of 
st u dy d osi n g. 
P atie nts r a n d o mize d t o 8- week pl ace b o d osi n g d uri n g eit her P art A or P art B, will h ave t he 
o pti o n t o c o nti n ue o n t o t heir res pective O L E p h ases ( O L E- A or O L E- B) d uri n g w hic h t hey 
will c o m plete a m axi m u m of 8 weeks of d osi n g wit h T A K- 0 7 9, 8 weeks of S F P, a n d 1 6 weeks 
of L F P f or a m axi m u m t ot al st u dy p artici p ati o n of 1 3 m o nt hs (i ncl u di n g 4 w eeks of i nteri m 
ti me bef ore t he st art of t he O L E) fr o m t he i niti al d ay of t he first d osi n g peri o d. P atie nts w h o 
receive d pl ace b o i n eit her P art A or P art B w h o d o n ot c o nti n ue t o a n O L E will e n d t he 
st u dy at Week 2 0 i n t he L F P, f or a m axi m u m st u dy p artici p ati o n of 5 m o nt hs. 
3. 0  
S T A TI S TI C A L H Y P O T H E S E S A N D D E CI SI O N R U L E S 
3. 1  
St atistic al H y p ot heses 
N o tests of statistical h y p ot heses are pla n ne d. 
3. 2  
M ulti plicit y A dj ust me nt 
N o m ulti plicit y a dj ust me nts are pla n ne d. 
4. 0  
S A M P L E- SI Z E D E T E R MI N A TI O N 
I n P art A, at le ast 2 4 a n d u p t o a p pr oxi m ately 3 6 p atie nts will be r a n d o mize d i n a r ati o of 
1: 1: 1 t o tre at me nt gr o u ps ( T A K- 0 7 9 1 0 0 m g, T A K- 0 7 9 3 0 0 m g, or m atc hi n g pl ace b o). 
I n P art B, a mi ni m u m of 1 2 a n d u p t o a p pr oxi m ately 1 8 p atie nts will be r a n d o mize d i n a r ati o 
1: 2 t o tre at me nt gr o u ps ( m atc hi n g pl ace b o or T A K- 0 7 9 6 0 0 m g). 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 1 7 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
5. 0  
A N A L Y SI S S E T S 
T he a nal ysis sets will be defi ne d i n t he mai n st u d y p hase a n d will i ncl u de t he f oll o wi n g: 
5. 1  
E nr olle d Set 
S u bjects w h o are ra n d o miz e d. 
5. 2  
F ull A n al ysis Set 
S u bjects w h o are ra n d o miz e d a n d recei v e d at least 1 d ose of st u d y dr u g. 
5. 3  
S afet y A n al ysis Set 
S u bjects w h o recei ve d at least 1 d ose of st u d y dr u g. 
5. 4  
 
 
 
5. 5  
 
 
 
5. 6  
 
 
 
6. 0  
S T A TI S TI C A L A N A L Y SI S 
6. 1  
Ge ner al C o nsi der ati o ns 
6. 1. 1  
Ge ner al Pri nci ples 
C o nti n u o us data will be s u m marize d usi n g n u m ber of patie nts ( N), mea n, sta n dar d 
de viati o n ( S D), me dia n, mi ni m u m, a n d ma xi m u m, w here a p pr o priat e. W here i n dicate d, t he 
c oeffi cie nt of variati o n ( % C V) a n d ge o m etric mea n ma y als o be i ncl u de d i n t he s u m mar y 
of c o nti n u o us data. 
 
 F or n o n- P K 
data, arit h metic mea ns, ge o metric mea ns, a n d me dia ns will be prese nte d t o 1 m ore deci m al 
place t ha n t he rec or de d d ata, a n d S Ds will be pres e nte d t o 2 m ore deci mal places t ha n t he 
rec or d e d data, w here a p pr o priate. 
Cate g orical data will be s u m marize d usi n g t he n u m ber a n d perce nt of p atie nts f or eac h 
cate g or y, w h ere a p pr o priate. Perce nta ges will be re p orte d t o 1 deci mal place. 
C o nfi de nce i nter v als ( CIs) will be 2-si de d at t he 9 5 % le vel a n d will be pres e nte d t o t he sa me 
n u m ber of deci mal places as t he c orres p o n di n g s u m mar y statistic ( mea n or perce nt a ge). 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 1 8 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
S u m maries will be prese nte d b y st u d y part a n d treat me nt gr o u p ( place b o [ Part A, Part B, 
c o m bi ne d], T A K- 0 7 9 1 0 0 m g, T A K- 0 7 9 3 0 0 m g, T A K- 0 7 9 6 0 0 m g) a n d b y visit w here 
-
t he T A K- 0 7 9 1 0 0 m g, 
3 0 0 m g, a n d 6 0 0 m g treat m e nt gr o u ps ma y b e dis pla ye d i n selecte d s u m m aries. 
T he O L E p has e will be s u m marize d se paratel y fr o m t he mai n st u d y. I n a d diti o n, descri pti ve 
s u m maries of p o ole d dat a fr o m t he O L E p hase a n d t he mai n st u d y ma y be prese nte d. 
6. 1. 2  
L o n git u di n al M o deli n g of C h a n ge fr o m B aseli ne 
F or selecte d efficac y e n d p oi nts, a mi x e d effects m o del f or re p eate d m eas ures ( M M R M) 
will be use d t o a nal yze differe nces i n c ha n ge fr o m baseli ne bet wee n eac h T A K- 0 7 9 ar m 
a n d place b o at eac h sc he d ule d p ost baseli ne visit u p t o Wee k 1 6 of t he mai n st u d y. T he 
a nal ysis f or eac h e n d p oi nt descri be d i n Secti o n  6. 5. 2  a n d Secti o n 6. 5. 3  will i n dicate 
w het her a n M M R M a n al ysis is pla n ne d. 
 St atistic al m o del. T he M M R M a nal ysis will o nl y use data u p t o t he Wee k 1 6 visit of 
t he mai n st u d y, a n d t he m o del will i ncl u de treat me nt, visit, a n d treat me nt- b y- visit 
i nteracti o n ter ms as t he fact ors a n d a dj uste d b y b aseli ne val ue a n d b aseli ne- b y- visit 
i nteracti o n. T he K e n war d- R o ger met h o d f or calc ulati n g d e n o mi nat or de grees of 
free d o m will be use d. T h e u nstr uct ure d c o vari a nce will be use d as t he d efa ult 
str uct ure f or t h e m o del. If t here are c o n ver ge nce iss ues, a first or der a ut ore gressi ve 
c o varia n ce str uct ure will be use d. 
 I nterc urre nt eve nts a n d missi n g d at a. If a s u bject recei v es resc ue t hera p y or pre mat urel y 
disc o nti n ues fr o m st u d y dr u g, a n y assess me nts o btai ne d t hereafter will be e x cl u de d fr o m 
t he M M R M a nal ysis. I n a d diti o n, a n y assess me nts o btai ne d wit hi n 4 wee ks after a 
per mitte d d osi n g- p eri o d resc ue treat m e nt will be e x cl u de d fr o m t he M M R M a nal ysis. T his 
a p pr oac h all o ws esti mati o n of t he treat me nt effect u n der t h e h y p ot hetical sit uati o n i n w hic h 
t he d osi n g s c he d ule is a d here d t o wit h o ut us e of resc ue t hera p y or ot her per mitte d resc ue 
treat me nts. Base d o n t he missi n g at ra n d o m ass u m pti o n, t he M M R M a nal ysis will be 
perf or me d usi n g o bs er ve d case data o nl y. A sec o n dar y M M R M a nal ysis will als o be 
perf or me d as descri be d a b o ve, wit h t he a d diti o nal r ule t hat a n y assess me nts o btai ne d 
wit hi n 4 wee ks after a n y a d mi nistrati o n of s yste mi c c ortic oster oi ds gi ve n at d oses of > 2 0 
m g pre d nis o n e ( or e q ui vale nt, i e, met h yl pre d nis ol o ne, de x a met has o ne, pre d nis ol o ne, 
c ortis o ne, h y dr oc ortis o ne, ster oi ds) will be e x cl u de d fr o m t he dat a f or a nal ysis. 
 S u m m aries. T he M M R M esti mate d mea n c h a n ge fr o m baseli ne al o n g wit h sta n dar d 
err or a n d CI, will be s u m marize d f or eac h visit b y treat me nt gr o u p. Esti mate d 
differe n ces of mea ns b et wee n eac h T A K- 0 7 9 ar m a n d t he place b o ar m as well as 
sta n dar d err ors a n d CIs f or t he differe nces will be pr o vi de d. O bser v e d val u es a n d c ha n ge 
fr o m baseli ne at all sc he d ule d p ost baseli ne visits will be s u m marize d se paratel y f or t he 
mai n st u d y a n d t he O L E p hase. T he M M R M esti mate d mea n c h a n ge fr o m baseli ne a n d 
sta n dar d err or at eac h sc h e d ule d visit will be pl ott e d b y treat me nt gr o u p. T h e o bser ve d 
mea n c ha n ge fr o m b aseli ne will als o be pl otte d. 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 1 9 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
6. 1. 3  
A n al ysis of Bi n ar y Effic ac y E n d p oi nts 
Bi nar y e n d p oi nts will be prese nte d usi n g c o u nts a n d perce nt a ges b y treat me nt gr o u p. T he 
perce nt a ge a n d c orres p o n di n g Cl o p per- Pears o n CI will be s u m marize d b y treat me nt gr o u p. 
T he differe nce i n perce nt a ge bet w ee n eac h T A K- 0 7 9 ar m a n d t he place b o ar m as well as 
t he Mietti ne n- N ur mi ne n CI will be s u m marize d. T he c orres p o n di n g p- val ue base d o n 
- 0 7 9 ar ms a n d place b o.  
6. 1. 4  
H a n dli n g of Tre at me nt Mis all oc ati o ns 
F or a n al ys es of safet y, efficac y, 
, p atie nts will be a nal yz e d 
acc or di n g t o act ual treat m e nt recei v e d. 
6. 2  
Dis p ositi o n of S u bjects 
Scree n fail ures will be s u m marize d, i ncl u di n g n u m ber of s u bjects, de m o gra p hics, a n d pri mar y 
reas o n f or faile d s cree ni n g. 
A d diti o nal s u m maries a n d listi n gs, base d o n t he e nr olle d set, will i ncl u de: 
 S u m mar y of dis p ositi o n i n t he mai n st u d y a n d o p e n-la bel e xte nsi o n peri o d i n 
ter ms of s u bjects w h o c o m plete d d osi n g wit h t he i n vesti gati o nal st u d y dr u g, 
s u bjects w h o pre mat urel y disc o nti n ue d fr o m i n vesti gati o nal st u d y dr u g, pri mar y 
reas o n f or disc o nti n uati o n fr o m i n vesti gati o nal st u d y dr u g, s u bjects w h o 
pre mat urel y disc o nti n ue d fr o m t he st u d y, a n d s u bjects w h o c o m plete d t he st u d y, 
as well as pri mar y reas o n f or disc o nti n uati o n fr o m st u d y. 
 Listi n g of s u bject dis p ositi o n i ncl u di n g date of first d ose, date of last d ose, 
d urati o n of treat me nt, t he reas o n f or pre mat ure dis c o nti n uati o n of i n vesti gati o nal 
st u d y dr u g, a n d t h e reas o n f or pre mat ure disc o nti n uati o n of st u d y. 
 S u m mar y of n u m b er of s u bjects i n eac h a nal ysis s et. 
 S u m mar y b y c o u ntr y a n d site. 
 S u m mar y a n d listi n g of si g nifica nt pr ot oc ol de viati o ns. 
 Listi n g of de viati o ns fr o m i ncl usi o n/e xcl usi o n criteria.
 
 Listi n g of pr ot oc ol d e viati o ns relate d t o C O VI D- 1 9, i ncl u di n g visits 
i m pacte d b y C O VI D- 1 9. 
6. 3  
De m o gr a p hic a n d Ot her B aseli ne C h ar acteristi cs 
6. 3. 1  
De m o gr a p hic C h ar acteristics 
De m o gra p hic c haracteristics will be s u m marize d a n d liste d usi n g t he safet y 
a nal ysis s et. Varia bl es t o b e prese nte d i ncl u de a ge, se x, c o u ntr y, et h nicit y, a n d 
race. 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 2 0 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
6. 3. 2  
B aseli ne C h ar acteristi cs 
Baseli ne c haracteristi cs will be s u m marize d a n d liste d usi n g t he safet y a nal ysis set. 
Varia bles t o be prese nt e d i ncl u de: 
 Wei g ht, hei g ht, b o d y m ass i n de x ( B MI) a n d fe male re pr o d u cti ve s yst e m stat us. 
 I T P diseas e hist or y 
 Pri or me dicati o ns relate d t o I T P as rec or de d i n t he e C R F as des cri be d i n Secti o n 9. 2. 5. 
All me dical hist or y d ata relate d t o st u d y disease will be i ncl u de d i n listi n gs. Me dicati o ns will 
be c o de d usi n g t he W orl d Healt h Or ga nizati o n ( W H O) Dr u g Dicti o nar y. 
6. 3. 3  
Me dic al Hist or y 
Me dical hist or y refers t o si g nifica nt c o n diti o ns or diseases t hat st o p pe d at or pri or t o 
i nf or me d c o nse nt or are o n g oi n g at i nf or me d c o nse nt. Me dical hist or y will be c o de d usi n g 
t he Me dical Dicti o nar y f or Re g ul at or y Acti vities ( Me d D R A, versi o n 2 3. 0 or hi g her) a n d 
will be s u m marize d usi n g S yste m Or ga n Class ( S O C) a n d Me d D R A preferre d ter m ( P T). 
T he ta ble will be s orte d i n al p ha betical or d er b y S O C. Wit hi n a S O C, P Ts are s orte d i n 
decreasi n g fre q ue nc y bas e d o n t he t otal n u m ber of s u bjects. T he n u m ber a n d perce nt a ge of 
s u bjects wit h a n y si g nifica nt me dical hist or y will be s u m marize d f or eac h S O C a n d P T. T he 
de n o mi nat or use d f or cal c ulati n g t he p erce nta ges will be t he t otal n u m ber of s u bjects 
i ncl u de d i n eac h treat me nt gr o u p. F or t he ta bles, if a s u bject re p orts t he sa me P T m ulti ple 
ti mes, t he n t hat P T will be c o u nte d o nl y o nce f or t hat s u bject. Si milarl y, if a s u bject re p orts 
m ulti ple c o n diti o ns wit hi n t he sa me S O C, t he n t hat S O C will be c o u nte d o nl y o nce f or t hat 
s u bject. All me dical hist or y d ata will be prese nte d i n listi n gs. S u m maries a n d listi n gs will 
use t he safet y a nal ysis set. 
Me dical hist or y relat e d t o I T P will be prese nte d as part of baseli ne c haract eristics. 
6. 4  
C o nc o mit a nt Me dic ati o ns a n d Pr oce d ures 
Me dicati o ns use d b y pati e nts a n d t hera p e uti c pr oce d ures c o m plet e d b y pati e nts, fr o m 2 8 
da ys b ef ore t he first d os e of st u d y me dicati o n ( T A K- 0 7 9 or place b o) t hr o u g h t he e n d of t he 
me dicati o ns a n d c o nc o mita nt pr oce d ures a n d will be s u m marize d a n d liste d usi n g t he safet y 
a nal ysis s et. F or s u bjects w h o partici pate i n t he O L E p hase of t he st u d y, c o nc o mita nt 
me dicati o ns a n d pr oce d ures occ urri n g after rec o ns e nti n g t o partici p ati o n i n t he O L E will be 
i ncl u de d i n s u m maries f or t he O L E p hase. Me dicati o ns will be c o de d usi n g t he W H O Dr u g 
Dicti o nar y. 
Missi n g or partial dat es will n ot be i m p ut e d. C o nser vati vel y, a me di cati o n or pr oce d ure 
will be classifie d as c o n c o mita nt if t he a vail a ble i nf or mati o n a b o ut t he e n d date is 
i ns ufficie nt t o deter mi ne w het her it occ urre d d uri n g t he re p orti n g peri o d. 
A se parate s u m mar y f or C O VI D- 1 9 relate d me dicati o ns a n d pr oce d ures ma y be pr o vi de d. 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 2 1 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
6. 5  
Effic ac y A n al ysis 
T he f ull a nal ysis set will be use d f or a nal yses of efficac y e n d p oi nts. 
6. 5. 1  
Pri m ar y E n d p oi nt A n al ysis 
N ot a p plica ble, as t he st u d y has n o pri mar y efficac y e n d p oi nts. 
6. 5. 2  
Sec o n d ar y E n d p oi nts A n al ysis 
T he sec o n d ar y e n d p oi nts are t he f oll o wi n g 4 t y pes of bi nar y res p o ns es, as d efi ne d i n Secti o n 
1. 2. 2. T hese will be e v al uate d at Wee k 1 6 a n d W ee k 3 2. 
1.  Platelet res p o nse 
2.  C o m plete platelet res p o nse 
3.  Cli nicall y m ea ni n gf ul platelet res p o nse 
4.  He m ostatic platelet res p o nse 
Eac h of t he 4 t y p es of res p o nses re q uires s p ecific platelet c o u nts e x presse d n u mericall y, as 
defi ne d i n Secti o n 1. 2. 2, t o be attai ne d o n at least 2 visits w here n o ne of t h e f oll o wi n g 
occ urre d: 
 T he s u bject recei ve d resc ue t h era p y at a n y ti me pri or t o t he visit. 
 T he s u bject recei ve d a d osi n g- peri o d per mitte d res c ue treat me nt wit hi n 4 wee ks 
pri or t o t he visit. 
 T he s u bject pre m at urel y disc o nti n ue d fr o m st u d y dr u g pri or t o t he visit. 
 T he platelet c o u nt is missi n g at t he visit. 
T he n u m ber a n d p erce nta ge of s u bjects attai ni n g eac h t y pe of res p o nse b y Wee k 1 6 i n t he 
mai n st u d y will be s u m mariz e d b y treat me nt gr o u p. Bi nar y a nal yses will b e perf or me d 
f oll o wi n g t he met h o ds s p ecifie d i n Secti o n 6. 1. 3. CIs f or perce nta ges will be prese nt e d. 
Differe nces i n p erce nta ges at Wee k 1 6 a n d CIs f or t he differe nces bet wee n eac h T A K- 0 7 9 
ar m a n d place b o c o m bi n e d will be prese nte d f or t he mai n st u d y. I n a d diti o n, f or T A K- 0 7 9 
s u bjects i n t he mai n st u d y, t he n u m ber a n d perce nta ge of s u bjects attai ni n g eac h t y pe of 
res p o nse b y Wee k 3 2 will be prese nte d al o n g wit h CIs f or t he perce nta ges. F or s u bjects i n 
t he O L E, t he n u m ber a n d perce nt a ge of s u bjects attai ni n g eac h t y pe of res p o nse b y Wee k 1 6 
a n d b y Wee k 3 2 will be prese nte d al o n g wit h CIs f or t he perce nta ges. As a s u p p orti ve 
a nal ysis f or t he sec o n dar y e n d p oi nts, M M R M a nal yses of c ha n ge fr o m bas eli ne i n pl atelet 
c o u nts t o Wee k 1 6 will be perf or me d f oll o wi n g t h e met h o ds s pecifie d Secti o n  6.1.2. 
If a n u ne x pecte d differe nce bet w ee n Part A a n d Part B Place b o is o bser ve d, a d diti o nal 
a nal ys es ma y be p erf or me d base d o n Part A a n d Part B, se p aratel y. 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 2 2 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
6. 5. 3  
 
6. 5. 3. 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
F or n o n- c o m m er ci al u s e o nl y


F or n o n- c o m m er ci al u s e o nl y


F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 2 5 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
  
 
 
 
6. 5. 3. 4  
 
 
 
 
 
.  
 
 
 
6. 5. 3. 5  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 2 6 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
6. 5. 3. 6  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
6. 5. 3. 7  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 2 7 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
 
 
 
 
. 
6. 5. 4  
S u b gr o u p A n al yses 
S u b gr o u p a n al ys es are n ot pl a n ne d. 
6. 6  
S afet y A n al ysis 
Safet y will be e val uate d b y t he fre q u e nc y of T E A Es, se verit y a n d t y pes of T E A Es, a n d b y 
c ha n ges fr o m baseli ne i n vit al si g ns, wei g ht, a n d cli nical la b orat or y res ults usi n g t he 
safet y a n al ysis set. 
E x p os ure t o i n vesti gati o nal st u d y dr u g will be ta b ulate d. 
T o assess t he i m pact of c o nti n ge nc y m eas ures ta ke n o n safet y res ults of partici pati n g patie nts 
d uri n g t he C O VI D- 1 9 p a n de mic, t he alt er nati ve met h o d(s) of safet y assess me nts (e. g., 
la b orat or y e v al uati o ns, vital si g ns, a n d/ or E C G) d u e t o C O VI D- 1 9 ma y b e liste d or 
s u m marize d if data per mits.  
6. 6. 1  
A d verse E ve nts 
All pretreat me nt e ve nts ( P T Es) a n d A Es will be c o de d b y S O C a n d P T usi n g Me d D R A 
( versi o n 2 3. 0 or later) a n d will be liste d f or patie nts i n t he safet y a nal ysis s et. A E i nte nsit y is 
deter mi ne d b y t he C T C A E scale versi o n 4. 0 3. 
A pretreat me nt e ve nt ( P T E) is a n y u nt o war d me di cal occ urre n ce i n a p atie nt w h o has 
si g ne d i nf or me d c o nse nt t o partici pate i n a st u d y b ut bef ore a d mi nistrati o n of a n y st u d y 
me dicati o n; it d oes n ot necessaril y h a ve t o ha v e a ca usal relati o ns hi p wit h st u d y 
partici pati o n. 
A treat me nt-e mer ge nt a d verse e v e nt ( T E A E) is defi ne d as a n A E ha vi n g a start date a n d 
ti me e q ual t o or later t ha n t he start date a n d ti me of t he first d ose of st u d y dr u g. If t he st art 
date of t he A E e q uals t he start date of t he first treat me nt a n d eit her t he start ti me of t he A E 
or t he start ti me of t he treat m e nt is missi n g, t he n t he A E will c o u nt as a T E A E. A Es wit h 
partiall y missi n g o ns et d ates will be c o u nte d as T E A Es if t he m o nt h (if a v aila ble) a n d t he 
year are e q ual t o or later t ha n t he m o nt h a n d year of t he date of first d ose. A Es wit h a 
c o m pletel y missi n g start date will be c o u nte d as T E A Es.  
F or s u bjects i n O L E, T E A Es will be s u m marize d se parat el y f or t he mai n st u d y a n d t h e O L E. 
T he f oll o wi n g s u m maries f or T E A Es will be pres e nte d b y treat me nt gr o u p f or t he d osi n g, S F P, 
a n d L F P peri o d. D osi n g, S F P, a n d L F P peri o d T E A Es are d efi ne d i n Secti o n 9. 2. 6 : 
 O verall T E A Es i ncl u di n g s u m maries of a n y T E A E, a n y T E A Es relate d t o st u d y 
dr u g, a n y seri o us T E A Es, a n y seri o us T E A Es relate d t o st u d y dr u g, a n y Gra de 3 
F or n o n- c o m m er ci al u s e o nl y


F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 2 9 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
le vel will be less t ha n or e q ual t o t he s u m of t he s u bject c o u nts acr oss all a d verse e v e nts 
wit hi n t hat S O C. 
F or t he s u m mar y of T E A Es b y S O C, P T, a n d ma xi m u m t o xicit y, if a s u bject e x perie nces 
m ore t ha n 1 e pis o de of a partic ular c o de d a d verse e ve nt, t he s u bject will be c o u nte d o nl y 
o nce b y t he ma xi m u m se verit y of t he e pis o de ( preferre d ter m). Si milarl y, if a s u bject has 
m ore t ha n 1 a d verse e v e nt wit hi n a S O C, t he s u bject will be c o u nte d o nl y o nce b y t h e 
ma xi m u m se verit y i n t hat S O C. Missi n g t o xicit y gra des will be i m p ute d as gra de 3 
(se vere). 
A Es wit h missi n g ca usal relati o ns hi p will be classifie d as relate d t o st u d y dr u g. 
All A Es will be liste d b y treat me nt, s u bject i de ntifier a n d o nset dat e of t he A E. T he listi n g will 
c o ntai n: s u bject i de ntifier, a ge, se x, race, A E ( preferre d t er m a n d re p orte d t er m), rel ati o ns hi p 
t o st u d y dr u g, o nset date, e n d date or w het her t h e e ve nt was o n g oi n g, d urati o n, se verit y, acti o n 
ta ke n c o ncer ni n g st u d y dr u g, t he o utc o me, a n d w h et her t he a d v erse e ve nt w as a n S A E. 
S pecial listi n gs f or S A Es, I R Rs, I S Rs, T E A Es lea di n g t o disc o nti n uati o n of i n vesti gati o nal 
st u d y dr u g, a n d T E A Es l ea di n g t o deat h will als o be prese nt e d. I S Rs a n d I R Rs are 
assesse d b y t he i n vesti gat ors a n d rec or de d i n t he e C R F. 
A Es wit h start dates t hat are c o m plet el y or partiall y missi n g will be i m p ute d as f oll o ws: 
 If m o nt h a n d year are k n o w n b ut da y is missi n g 
o  If m o nt h a n d year are t he sa me as m o nt h a n d year of first d ose date, t he n 
first d ose date will be use d. 
o  If m o nt h a n d year are later t ha n first d ose d ate, t h e n first da y of t he m o nt h 
will be use d. 
 If year is k n o w n b ut da y a n d m o nt h are missi n g 
o  If year e q uals year of first d ose date, t he n first d os e date will be use d. 
o  If year is great er t ha n year of first d ose dat e, t he n 1st of J a n uar y of t he 
year will be use d. 
 If all are missi n g, t he n t h e first d ose date will be use d. 
After i m p utati o n, if t he st o p dates are c o m plete, all i m p ute d dates are c hec k e d a gai nst t he 
st o p dates t o e ns ure t hat start dates d o n ot occ ur after st o p dates. If a n i m p ute d start date 
occ urs after t he st o p dat e, t he n c ha n ge t h e i m p ute d start date t o be t he sa m e as t he st o p 
date. W he n t he start date a n d t he st o p date are b ot h i nc o m plete f or a s u bject, t he start date 
will be i m p ute d first. 
A d verse e ve nts wit h st o p dates t hat are c o m pl etel y or partiall y missi n g will be i m p ute d as 
f oll o ws: 
 
 necessar y. 
 If m o nt h a n d year are k n o w n b ut da y is missi n g, t he last da y of t he m o nt h will be use d. 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 3 0 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
 If year is k n o w n, b ut da y a n d m o nt h are missi n g 
o  If t he year is e q ual t o or less t ha n t he year of last d ose, t he n 3 1st of Dece m b er 
will be use d. 
o  If t he year is great er t ha n t he year of l ast d ose, t he n 1st of J a n uar y will be us e d. 
 If all are missi n g, t he n 3 1st of Dece m b er of t he year of last d ose will be use d. 
If a s u bject dies, t h e n use deat h date f or A E st o p d ate. After i m p utati o n, all i m p ute d dates 
are c h ec k e d a gai nst start dates t o e ns ure t hat st o p dates d o n ot occ ur bef ore start dates. If a n 
i m p ute d st o p date occ urs pri or t o t he start date, t he n c ha n ge t he i m p ute d st o p date t o be t he 
sa me as t he start d ate. 
T o assess of t he i m pact of C O VI D- 1 9 o n t he s afet y of p artici pati n g s u bjects, a listi n g of 
C O VI D- 1 9 relate d T E A Es will be pr o vi de d. 
6. 6. 2  
Cli nic al L a b or at or y E v al u ati o ns 
All la b orat or y val ues will be c o n verte d t o sta n dar dize d SI u nits a n d s u m marize d i n ta bles 
a n d listi n gs b y treat m e nt gr o u ps. If a la b v al ue is re p orte d usi n g a n o n- n u m eric q ualifier 
(e. g., less t ha n ( <) a cert ai n val ue, or greater t ha n ( >) a certai n v al ue), t he gi ve n n u meric 
val ue will be use d i n t he s u m m ar y statistics, i g n ori n g t he n o n- n u meric q ualifier. 
T he f oll o wi n g s u m maries f or la b orat or y test res ults will be prese nte d b y treat me nt gr o u p: 
 Act ual val ue a n d c ha n ge fr o m baseli ne val u es at eac h sc he d ul e d assess me nt. 
 S hift ta bles f or t he c ha n ge fr o m Baseli ne t o eac h p ost- baseli ne ti me p oi nt will be 
prese nte d. F or t hes e ta bles, eac h s u bject will be cat e g orize d as l o w, n or mal, or hi g h 
f or t he baseli ne v al ue, a n d l o w, n or mal, or hi g h f or eac h p ost- b aseli ne ti me p oi nt, 
acc or di n g t o t h e l ocal la b orat or y refere n ce ra n ges. T he n u m ber of s u bjects as well as 
perce nt a ges i n eac h of t he c o m bi nati o ns of s hifts will be prese nte d. 
 Mar ke dl y a b n or mal val u es ( M A Vs) as defi ne d b y t he criteria i n Secti o n  9. 4 will be 
s u m marize d b y treat me nt gr o u p. T he n u m ber a n d perce nt a ge of s u bjects wit h 
M A Vs o bser ve d p ost- bas eli ne i n eac h of t he a p plica ble la b orat or y para meters will 
be prese nte d. 
All cli nical la b orat or y data will be prese nte d i n SI u nits i n data listi n gs. 
6. 6. 3  
Vit al Si g ns 
T he act ual v al ues a n d c h a n ges fr o m bas eli ne of vital si g n para meters a n d wei g ht at eac h 
sc he d ule d visit will be s u m marize d b y treat me nt gr o u p. Vital si g n val u es will als o be prese nte d 
i n listi n gs. 
P ost- d ose vital si g n M A Vs as defi ne d i n Secti o n 9. 4 will be ta b ulate d. If a s u bject has a 
p ost- d ose M A V f or a partic ular vital si g n para meter, all visits f or t hat s u bject f or t hat 
para meter will be liste d. T he n u m ber a n d p erce nta ge of s u bjects wit h at least 1 p ost- d ose 
mar ke dl y a b n or m al vital si g ns meas ure me nt will be s u m marize d. T he ma p pi n g of t he 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 3 1 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
s u bjects w h o meet t he M A V criteri a will be liste d as a ta ble. All o bser vati o ns, i ncl u di n g 
o nes at u nsc he d ule d visits, will be i ncl u de d i n t he M A V e val uati o n a n d s u m maries if 
M A V criteria are satisfie d. 
6. 6. 4  
1 2- Le a d E C Gs 
E C G varia bles at sc h e d ul e d visits a n d t heir c ha n ges fr o m baseli ne will be s u m marize d b y 
n u m ber a n d perce nt a ge of s u bjects i n eac h of t he a p pr o priate cate g ories ( N or mal; 
A b n or mal, N ot Cli nicall y Si g nifica nt; A b n or mal, Cli nicall y Si g nifica nt) at t he sc he d ule d 
visit relati ve t o t he baseli ne stat us. All E C G res ults will be prese nte d i n listi n gs. 
6. 6. 5  
Pre g n a nc y Test 
Cli nical la b orat or y sa m ple c ollecti o n a n d res ults f or pre g na n c y tests will be prese nt e d i n a 
se parat e listi n g. 
6. 6. 6  
E xte nt of E x p os ure a n d C o m pli a nce 
T he t otal n u m ber of d oses ta ke n, a n d t he t otal a m o u nt of d oses ta ke n will be s u m marize d 
descri pti vel y b y treat m e nt gr o u p, se p aratel y f or t h e mai n st u d y a n d T A K- 0 7 9 
a d mi nistrati o n i n t he O L E peri o d f or pre vi o us place b o s u bjects. 
Treat me nt c o m plia nce will be s u m marize d i n ter ms of t he perce nt of sc h e d ule d d oses 
recei v e d, defi n e d f or eac h s u bject as: [( Act ual t otal n u m ber of d os es ta k e n) ÷ ( Pla ne d 
n u m ber of d oses ta k e n)] * 1 0 0. 
T he date a n d ti me of eac h d ose f or eac h s u bject will be re p orte d i n a d ata listi n g. 
T he i m pact of t he C O VI D- 1 9 o n e x p os ure a n d c o m plia nce will be s u m marize d i n ter ms of t he 
perce nt of sc he d ule d d os es misse d f or eac h s u bject d ue t o eac h of t h e f oll o wi n g reas o n: 
 S u bject dia g n ose d wit h C O VI D- 1 9 
 S u bject discreti o n d ue t o C O VI D- 1 9 
 Tra vel restricti o ns d ue t o C O VI D- 1 9 
 I n v esti gati ve sit e accessi bilit y (site cl os ure, site visit restricti o ns, or site 
staff u na vaila bilit y) d ue t o C O VI D- 1 9 
 
All C O VI D- 1 9 i m pacts o n d ose a d mi nistrati o n are i ncl u de d i n t he C O VI D- 1 9 i m pact listi n g.
 
6. 7  
 
6. 7. 1  
 
 
 
 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 3 2 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6. 7. 2  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 3 3 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6. 8  
 
 
 
 
 
 
 
 
 
 
 
 
 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 3 4 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
 Ta ble 2 
 
6. 9  
I nteri m A n al yses 
O ne u n bli n de d safet y re vie w wit h a li mite d efficac y re vie w a n d o ne i nteri m a nal ysis will be 
c o n d ucte d bef ore t h e fi nal data base l oc k of t his st u d y as d escri be d i n Secti o n 2. 7. 
7. 0  
R E F E R E N C E S 
N ot a p plica ble. 
8. 0  
C H A N G E S T O P R O T O C O L P L A N N E D A N A L Y S E S 
will be use d f or bi nar y e n d p oi nt a nal ysis i nstea d. 
F or n o n- c o m m er ci al u s e o nl y


F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 3 6 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
Da y 1 a n d D a y - 1 bei n g t he da y pri or t o St u d y Da y 1. St u d y d a ys pri or t o t he first d os e of 
st u d y dr u g will be calc ulate d as: [ date of i nterest  date of first d ose of st u d y dr u g]. St u d y 
da ys o n or aft er t he first d ose of st u d y dr u g will be calc ul ate d as: [ date of i nterest  date of 
first d ose of st u d y dr u g + 1]. 
Si milarl y, O L E St u d y D a y 1 is defi n e d as t he da y o n w hic h a s u bject is a d mi nistere d t heir first 
d ose of st u d y dr u g i n t he O L E p h ase, a n d ot her O L E st u d y da ys are d efi ne d relati ve t o O L E 
St u d y Da y 1.  
9. 2. 3  
Defi niti o n of A n al ysis Visits 
Visit desi g nat ors are pre defi ne d val ues t h at a p pear as part of t h e visit ta b i n t he electr o nic 
case re p ort f or m (e C R F). T he detaile d st u d y visit wi n d o ws ca n be f o u n d i n Pr ot oc ol 
A p pe n di x A a n d A p pe n di x B. S u m m aries a n d a nal yses b y visit will use t he n o mi nal wee k 
ass ociate d wit h eac h visit as rec or de d o n t he e C R F.  
9. 2. 4  
Resc ue T her a pies a n d Per mitte d Resc u e Tre at me nt 
Resc ue t hera pies will be re vie we d b y cli nicia ns pri or t o t he data base l o c k t o c o nfir m b ot h 
resc ue t h era pies a n d d osi n g- p er mitte d res c ue treat me nts. D osi n g- p er mitte d resc ue treat m e nts 
are s pecific resc ue treat m e nts gi ve n o nce d uri n g t h e d osi n g p eri o d t hat were all o we d per 
pr ot oc ol a n d di d n ot re q uire t he disc o nti n uati o n of st u d y treat me nt. T hese will be classifie d 
i nt o t he t hree all o we d cat e g ories: platelet tra nsf usi o n, a si n gle d os e of I VI g u p t o 1 g/ k g, or a n 
a d diti o nal 2 0 m g of pre d nis o n e ( or e q ui vale nt) per da y f or u p t o 7 d a ys.  
A n i nitial re vie w will occ ur pri or t o data bas e freez e pri or t o Part B u n bli n di n g (f or data u p t o 
Wee k 1 6) a n d after t he P art B u n bli n di n g (f or L F P a n d O L E d ata) b ot h f or t he i nteri m 
a nal ysis, a n d a gai n p eri o dicall y t o re vie w ne w dat a e ntries u ntil data bas e l oc k. 
9. 2. 5  
Pri o r I T P Me dic ati o ns 
Pri or I T P me dicati o ns are f urt her classifie d acc or di n g t o t he cate g ories i n Ta ble 4. All pri or 
I T P me dicati o ns will be re vie we d b y cli nicia ns pri or t o data base l o c k a n d cl assifie d. I n t he 
s u m mar y ta bl e, t he n u m b er a n d perce nta ges of s u bjects i n eac h pri or I T P me dicati o n cate g or y, 
as well as t he n u m ber a n d perce nt a ge of s u bjects recei vi n g eac h pri or I T P me dicati o n will be 
s u m marize d b y treat me nt gr o u p.  
I n a d diti o n, pri or I T P me dicati o ns t hat are o n- g oi n g at t he s u b
st u d y. T he n u m ber a n d p erce nt a ges of s u bjects i n eac h I T P me di cati o n cate g or y, as well as t he 
n u m ber a n d perce nt a ge of s u bjects recei vi n g eac h I T P me dicati o n will be s u m marize d b y 
treat me nt gr o u p.  
Ta ble 4 Pri or I T P Me dic ati o ns a n d Cate g or y 
M E DI C A TI O N C A T E G O R Y 
S T A N D A R DI Z E D M E DI C A TI O N N A M E 
I m m u n os u p pressa nts 
A Z A T HI O P RI N E 
CI C L O S P O RI N 
M E T H O T R E X A T E 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 3 7 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
M Y C O P H E N O L A T E M O F E TI L  
M Y C O P H E N O LI C A CI D 
T A C R O LI M U S 
C Y C L O P H O S P H A MI D E 
VI N B L A S TI N E 
VI N C RI S TI N E 
VI N D E SI N E 
 
C ortic oster oi ds 
M E T H Y L P R E D NI S O L O N E 
C O R TI S O N E 
D E X A M E T H A S O N E 
P R E D NI S O L O N E 
P R E D NI S O N E 
H Y D R O C O R TI S O N E 
S T E R OI D S 
 
T hr o m b o p oieti n Rece pt or A g o nists   
R O MI P L O S TI M 
E L T R O M B O P A G 
A V A T R O M B O P A G 
H E T R O M B O P A G O L A MI N E 
H E T R O M B O P A G 
 
Rit u xi ma b 
RI T U XI M A B 
 
F osta mati ni b 
F O S T A M A TI NI B 
 
I VI G 
I M M U N O G L O B U LI N S N O S 
A N TI- D I M M U N O G L O B U LI N 
 
I m m u n osti m ula nts 
I N T E R F E R O N A L F A- 2 B 
O P R E L V E KI N 
 
Ot her I T P 
A L E M T U Z U M A B 
D A N A Z O L 
D A P S O N E 
C O L C HI CI N E 
A N TI T H Y M O C Y T E I M M U N O G L O B U LI N 
PI L O S A; F O R S Y T HI A S U S P E N S A; G L Y C Y R R HI Z A S P P.;I N DI G O; P A E O NI A X 
 
 
 
9. 2. 6  
T E A Es Occ urri n g d uri n g D osi n g a n d S F P Peri o d, L F P peri o d 
T he f oll o wi n g will a p pl y f or b ot h mai n st u d y a n d O L E p h ases: 
 T E A Es occ urri n g d uri n g D osi n g a n d S F P peri o d are defi n e d as T E A Es wit h a start 
date o n or bef ore t he d ate of Wee k 1 6 visit date. F or place b o s u bjects e nteri n g t he 
O L E p h ase, t he S F P peri o d i ncl u des T E A Es occ urri n g pri or t o t he O L E treat me nt st art 
date. 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 3 8 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
 T E A Es occ urri n g d uri n g L F P p eri o d are defi ne d as T E A Es wit h a start date after t he 
date of Wee k 1 6 visit dat e. 
 
9. 3  
A n al ysis S oft w are 
All statistical a nal yses will be c o n d ucte d usi n g S A S ®  Versi o n 9. 4 or hi g her. 
9. 4  
Criteri a f or I de ntific ati o n of M ar ke dl y A b n or m al V al ues 
He m at ol o g y  
 
P a r a meter 
L o w A b n o r m al 
Hi g h A b n or m al 
 
He m o gl o bi n 
< 8 0 g/ L 
> 1. 2 × U L N 
 
He mat o crit 
W B C 
Platelet c o u nt 
T otal l y m p h oc yte c o u nt 
Ne utr o p hils 
< 2 4 % 
< 1. 5 × 1 0 9/ L 
< 5 0 × 1 0 9/ L 
< 0. 5 × 1 0 9/ L 
< 1 × 1 0 9/ L 
> 1. 2 × U L N 
> 1. 5 × U L N 
> 6 0 0 × 1 0 9/ L 
> 1. 5 × U L N 
> 8 × 1 0 9/ L 
 
L L N =l o wer li mit of n or mal, U L N = u p per li mit of n or mal, W B C = w hite bl o o d cell. 
Ser u m C he mistr y 
 
P a r a meter 
L o w A b n o r m al 
Hi g h A b n or m al 
A L T 
-- 
> 3 × U L N 
A S T 
-- 
> 3 × U L N 
Al kali ne p h os p hatas e 
-- 
> 3 × U L N 
T otal bilir u bi n 
-- 
 
A L T a n d t otal bilir u bi n 
-- 
A L T > 3 × U L N a n d T B > 2 × U L N 
A S T a n d t otal bilir u bi n 
 
A S T > 3 × U L N a n d T B > 2 × U L N 
Al b u mi n 
< 2 5 g/ L 
-- 
Creati ni ne 
-- 
 
Gl uc ose 
< 2. 8 m m ol/ L 
> 1 9. 4 m m ol/ L 
C hl ori d e 
S o di u m 
P otassi u m 
Bl o o d urea nitr o ge n 
< 7 5 m m ol/ L 
< 1 3 0 m m ol/ L 
< 3. 0 m m ol/ L 
-- 
> 1 2 6 m m ol/ L 
> 1 5 0 m m ol/ L 
> 6. 0 m m ol/ L 
> 1 0. 7 m m ol/ L 
Calci u m 
< 1. 7 5 m m ol/ L 
> 2. 8 8 m m ol/ L 
Car b o n di o xi de 
< 1 9 m m ol/ L 
> 2 9 m m ol/ L 
Lactate d e h y dr o ge nase 
< 1 0 5 U/ L 
> 3 3 3 U/ L 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 3 9 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
A L T =ala ni ne a mi n otra nsferas e, A S T =as p artat e a mi n otra nsferase, L L N =l o wer li mit of n or mal, U L N = u p p er li mit of 
n or mal. T B =t otal bilir u bi n. 
 
Vit al Si g ns 
P a r a meter 
U nit 
L o w A b n o r m al 
Hi g h A b n o r m al 
P ulse 
b p m 
< 5 0 
> 1 2 0 
S yst olic bl o o d press ure 
m m H g 
< 8 5 
> 1 8 0 
Diast olic bl o o d press ure 
m m H g 
< 5 0 
> 1 1 0 
B o d y te m perat ure 
° C 
< 3 5. 6 
> 3 7. 7 
 
9. 5  
 
 
F or n o n- c o m m er ci al u s e o nl y


T A K- 0 7 9- 1 0 0 4 
P a g e 4 0 of 4 0  
St atistic al A n al ysis Pl a n Fi n al A me n d me nt 3. 0 
1 6- M A Y- 2 0 2 4  
 
C O N FI D E N TI A L  
F or n o n- c o m m er ci al u s e o nl y


F or n o n- c o m m er ci al u s e o nl y