Conditions: Polymyositis Dermatomyositis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 51
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the efficacy of ustekinumab in participants with active polymyositis (PM)/dermatomyositis (DM) despite receiving 1 or more standard-of-care treatments (for example, glucocorticoids and/or immunomodulators).

Detailed description:

Arms:
arm 1: Participants will receive body weight-range based IV dosing of approximately 6 milligram per kilogram (mg/kg) of ustekinumab at Week 0 followed by ustekinumab 90 milligram (mg) subcutaneously (SC) at Week 8 and every 8 Weeks (q8w) administrations through Week 72. At Week 24, participants will receive IV dosing of placebo. arm 2: Participants will receive IV dosing of placebo at Week 0 followed by placebo SC administrations at Weeks 8,16 and 24. At Week 24, participants will receive body weight-range based IV dosing of approximately 6 mg/kg of ustekinumab, followed by ustekinumab 90 mg SC q8w administrations Week 32 through Week 72.

Interventions: intervention 1: Ustekinumab 6 mg/kg intervention 2: Ustekinumab 90 mg intervention 3: Placebo IV intervention 4: Placebo SC
Intervention descriptions: intervention 1: Participants will receive body weight-range based IV dosing of 6 mg/kg of ustekinumab at Week 0 in Group 1 and at Week 24 in Group 2. intervention 2: Participants will receive ustekinumab 90 mg SC at Week 8 and every 8 Weeks (q8w) through Week 72 in Group 1 and q8w Week 32 through Week 72 in Group 2. intervention 3: Participants will receive IV dosing of placebo at Week 24 in Group 1 and at Week 0 in Group 2. intervention 4: Participants will receive SC dosing of placebo at Weeks 8,16 and 24.

Protocol document:
Prot_000.pdf: 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
1 
Status: Approved, Date:  β9 November β0β1
Janssen Pharmaceutical K.K.*
Clinical Protocol
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group
Study of Ustekinumab in Participants With Active Polymyositis and Dermatomyositis
Who Have Not Adequately Responded to One or More Standard-of-care Treatments
Protocol CNTO1275DMY3001; Phase 3
AMENDMENT 3
STELARA® (ustekinumab) 
*This study is being conducted by Janssen Pharmaceutical K.K. in Japan. The term “sponsor” is used
throughout the protocol to represent Janssen Pharmaceutical K.K. The sponsor is identified on the
Protocol Supplementary Information, which will be provided as a separate document.
Status: 
Approved
Date: 
β9 November β0β1
Prepared by: Janssen Pharmaceutical K.K.
EDMS number: 
EDMS-ERI-17γ744989, 4.0
GCP Compliance:  This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory
requirements. 
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company
customarily holds close and treats as confidential. The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or
otherwise.
NCT03981744


STELARA® (ustekinumab) 
 
 
Clinical Protocol CNTO1β75DMYγ001 Amendment γ
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
β
Status: Approved, Date:  β9 November β0β1
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment γ 
β9 November β0β1
Amendment β 
4 June β0β0
Amendment 1 
1γ Au  g β019
Original Protocol 
1γ Feb β019
Amendment 3 (30 Nov 2021)
Overall Rationale for the Amendment: The overall reason for the amendment is to align with internal
standard on study estimands based on the latest considerations on statistical analyses.
Section number
and Name
Description of Change 
Brief Rationale
1.1. 
Synopsis
 Tertiary Endpoints,
 PM/DM Disease Activity
γ. OBJECTIVES AND
ENDPOINTS
 Tertiary Endpoints,
 PM/DM Disease Activity 
Added text on tertiary endpoints of PM/DM
disease activity.
Text was revised to clarify
tertiary endpoints of PM/DM
disease activity.
1.1 
Synopsis 
 OVERALL DESIGN
4.1. Overall Design
6.γ. Measures to Minimize
Bias: Randomization and
Blinding,
 Blinding 
Updated and added text on unblinding
timing.
Text was revised to change the
unblinding timing.
1.1 
Synopsis
 Primary Efficacy Analysis
7.1. Discontinuation of Study
Drug
9.4.1.1. 
Primary Endpoint
Analysis
9.4.1.1.1. Primary Estimand
Added intercurrent events (ICEs) to the study 
estimands, rephrased the primary estimand 
sections, and deleted treatment failure. 
 
To align with internal
standard, text was revised to
clarify the study estimands,
introduce the ICE to the study
estimands and re-phrase the
primary estimand sections.
Meanwhile, incorporate the
treatment failure rules into the
ICE handlin  g rules.
1.1 
Synopsis  
 Secondary Efficacy Analyses 
9.4.1.β. 
Secondary Efficacy 
Analyses 
Added strategies to address the ICEs for 
secondary efficacy. 
Text was added to clarify
strategies to address the ICEs
for secondary efficacy
analyses.
9.4.1.1. 
Primary Endpoint 
Analysis 
Updated text on missing data. 
Text was revised to address
the ICEs.
9.4.1.1.β. Estimands other than 
the primar y estimand 
Updated text on sensitivity/supplemental 
analyses. 
Text was revised to add
supplemental estimand.
9.4.β. 
Safety Analyses 
 Adverse Events 
Added text on AEs of COVID-19. 
Text was added to capture
AEs of COVID-19 during the
COVID-19 pandemic.
Throughout the protocol 
Minor grammatical formatting or spelling 
changes were made.
Minor errors were noted.


STELARA® (ustekinumab) 
 
 
Clinical Protocol CNTO1β75DMYγ001 Amendment γ
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
γ
Status: Approved, Date:  β9 November β0β1
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................. 2 
TABLE OF CONTENTS .......................................................................................................................... 3 
LIST OF IN-TEXT TABLES AND FIGURES ............................................................................................ 5 
1. 
PROTOCOL SUMMARY ................................................................................................................ 6 
1.1. 
Synopsis ..................................................................................................................................... 6 
1.2. 
Schema .................................................................................................................................... 14
1.3. 
Schedule of Activities (SoA) ...................................................................................................... 15
2. 
INTRODUCTION .......................................................................................................................... 20
2.1. 
Study Rationale......................................................................................................................... 21
2.2. 
Background............................................................................................................................... 21
2.3. 
Benefit/Risk Assessment ........................................................................................................... 23
3. 
OBJECTIVES AND ENDPOINTS ................................................................................................. 24
4. 
STUDY DESIGN ........................................................................................................................... 26
4.1. 
Overall Design .......................................................................................................................... 26
4.2. 
Scientific Rationale for Study Design ......................................................................................... 28
4.2.1. 
Study-Specific Ethical Design Considerations ........................................................................ 28
4.3. 
Justification for Dose ................................................................................................................. 29
4.4. 
End of Study Definition .............................................................................................................. 29
5. 
STUDY POPULATION ................................................................................................................. 29
5.1. 
Inclusion Criteria ....................................................................................................................... 30
5.2. 
Exclusion Criteria ...................................................................................................................... 34
5.3. 
Lifestyle Considerations ............................................................................................................ 39
5.4. 
Screen Failures ......................................................................................................................... 40
6. 
STUDY DRUG .............................................................................................................................. 41
6.1. 
Study Drugs Administered ......................................................................................................... 41
6.2. 
Preparation/Handling/Storage/Accountability ............................................................................. 44
6.3. 
Measures to Minimize Bias: Randomization and Blinding .......................................................... 44
6.4. 
Study Drug Compliance ............................................................................................................ 45
6.5. 
Concomitant Therapy ................................................................................................................ 46
6.5.1. 
Prestudy and Concomitant Medications Through Week 80 ..................................................... 47
6.5.2. 
Glucocorticoid Therapy .......................................................................................................... 47
6.5.3. 
Non-biologic Immunomodulators ............................................................................................ 48
6.5.4. 
Topical Medications ............................................................................................................... 48
6.5.5. 
Rescue Medication ................................................................................................................ 48
6.6. 
Prohibited Therapies ................................................................................................................. 49
7. 
DISCONTINUATION OF STUDY DRUG AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL ........................................................................................... 50
7.1. 
Discontinuation of Study Drug ................................................................................................... 50
7.2. 
Participant Discontinuation/Withdrawal From the Study ............................................................. 51
7.2.1. 
Withdrawal From the Use of Research Samples .................................................................... 52
7.3. 
Lost to Follow-up ....................................................................................................................... 52
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................ 52
8.1. 
Efficacy Assessments ............................................................................................................... 54
8.1.1. 
Efficacy Evaluations ............................................................................................................... 54
8.1.1.1. 
Physician Global Activity ..................................................................................................... 54
8.1.1.2. 
Patient Global Activity ......................................................................................................... 54
8.1.1.3. 
Manual Muscle Testing ....................................................................................................... 54


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8.1.1.4. 
Muscle Enzymes................................................................................................................. 54
8.1.1.5. 
Extramuscular Assessment (Myositis Disease Activity Assessment Tool) ............................ 54
8.1.1.6. 
Physical Function (Health Assessment Questionnaire Disability Index)................................ 55
8.1.1.7. 
Functional Index-2 .............................................................................................................. 55
8.1.1.8. 
36-item Short Form ............................................................................................................. 55
8.1.2. 
Endpoint Definitions ............................................................................................................... 55
8.1.2.1. 
IMACS TIS ......................................................................................................................... 55
8.1.2.2. 
Disease Worsening ............................................................................................................. 56
8.2. 
Safety Assessments .................................................................................................................. 56
8.2.1. 
Physical Examination ............................................................................................................. 56
8.2.2. 
Vital Signs ............................................................................................................................. 57
8.2.3. 
Electrocardiogram .................................................................................................................. 57
8.2.4. 
Clinical Safety Laboratory Assessments ................................................................................. 57
8.2.5. 
Interstitial Lung Diseases and Respiratory Muscle.................................................................. 57
8.2.6. 
Pregnancy ............................................................................................................................. 58
8.2.7. 
Infections ............................................................................................................................... 58
8.2.7.1. 
Tuberculosis ....................................................................................................................... 58
8.2.8. 
Infusion- or Injection-site Reactions........................................................................................ 58
8.3. 
Adverse Events and Serious Adverse Events ............................................................................ 58
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event
Information ............................................................................................................................ 59
8.3.2. 
Method of Detecting Adverse Events and Serious Adverse Events ......................................... 59
8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events ..................................................... 59
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events ........................................... 60
8.3.5. 
Pregnancy ............................................................................................................................. 60
8.3.6. 
Infections ............................................................................................................................... 60
8.3.6.1. 
Tuberculosis ....................................................................................................................... 60
8.3.7. 
Infusion- or Injection-site Reactions........................................................................................ 61
8.4. 
Events of Special Interest .......................................................................................................... 61
8.5. 
Treatment of Overdose ............................................................................................................. 61
8.6. 
Pharmacokinetics and Immunogenicity ...................................................................................... 61
8.6.1. 
Evaluations ............................................................................................................................ 62
8.6.2. 
Analytical Procedures ............................................................................................................ 62
8.6.3. 
Pharmacokinetic Parameters and Evaluations........................................................................ 62
8.6.4. 
Immunogenicity Assessments (Anti-ustekinumab Antibodies) ................................................. 62
8.7. 
Genetics ................................................................................................................................... 62
8.8. 
Biomarkers ............................................................................................................................... 63
9. 
STATISTICAL CONSIDERATIONS .............................................................................................. 64
9.1. 
Statistical Hypotheses ............................................................................................................... 64
9.2. 
Sample Size Determination ....................................................................................................... 64
9.3. 
Populations for Analyses ........................................................................................................... 66
9.4. 
Statistical Analyses ................................................................................................................... 67
9.4.1. 
Efficacy Analyses ................................................................................................................... 67
9.4.1.1. 
Primary Endpoint Analysis .................................................................................................. 67
9.4.1.1.1. 
Primary Estimand ............................................................................................................ 67
9.4.1.1.2. 
Estimands other than the primary estimand ..................................................................... 69
9.4.1.1.3. 
Subgroup Analyses ......................................................................................................... 69
9.4.1.2. 
Secondary Efficacy Analyses .............................................................................................. 69
9.4.2. 
Safety Analyses ..................................................................................................................... 69
9.4.3. 
Other Analyses ...................................................................................................................... 71
9.5. 
Interim Analysis......................................................................................................................... 72
9.5.1. 
Independent Data Monitoring Committee ............................................................................... 72
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ........................... 74
10.1. 
Appendix 1: Abbreviations and Trademarks .............................................................................. 74
10.2. 
Appendix 2: Regulatory, Ethical, and Study Oversight Considerations ....................................... 76
REGULATORY AND ETHICAL CONSIDERATIONS ....................................................................... 76


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FINANCIAL DISCLOSURE .............................................................................................................. 79
INFORMED CONSENT PROCESS ................................................................................................. 79
DATA PROTECTION ...................................................................................................................... 80
LONG-TERM RETENTION OF SAMPLES FOR ADDITIONAL FUTURE RESEARCH ..................... 81
COMMITTEES STRUCTURE .......................................................................................................... 81
PUBLICATION POLICY/DISSEMINATION OF CLINICAL STUDY DATA ......................................... 81
DATA QUALITY ASSURANCE ........................................................................................................ 83
CASE REPORT FORM COMPLETION ........................................................................................... 83
SOURCE DOCUMENTS ................................................................................................................. 83
MONITORING ................................................................................................................................. 84
ON-SITE AUDITS............................................................................................................................ 85
RECORD RETENTION ................................................................................................................... 85
STUDY AND SITE CLOSURE ......................................................................................................... 86
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting .......................................................................................................... 87
ADVERSE EVENT DEFINITIONS AND CLASSIFICATIONS ........................................................... 87
ATTRIBUTION DEFINITIONS ......................................................................................................... 88
SEVERITY CRITERIA ..................................................................................................................... 88
SPECIAL REPORTING SITUATIONS ............................................................................................. 89
PROCEDURES ............................................................................................................................... 89
CONTACTING SPONSOR REGARDING SAFETY.......................................................................... 90
PRODUCT QUALITY COMPLAINT HANDLING .............................................................................. 90
10.4. 
Appendix 4: Clinical Laboratory Tests........................................................................................ 92
10.5. 
Appendix 5: Contraceptive and Barrier Guidance and Collection of Pregnancy Information ........ 94
10.6. 
Appendix 6: Medical Device Incidents: Definition and Procedures for Recording,
Evaluating, Follow-up, and Reporting ........................................................................................ 97
10.7. 
Appendix 7: Cancer Screening Test .......................................................................................... 99
10.8. 
Appendix 8: Hepatitis B Virus Screening ................................................................................. 100
10.9. 
Appendix 9: Protocol Amendment History................................................................................ 101
11. REFERENCES ........................................................................................................................... 112
INVESTIGATOR AGREEMENT .......................................................................................................... 114
LIST OF IN-TEXT TABLES AND FIGURES 
TABLES
Table 1: 
Prestudy and Concomitant Glucocorticoid Use Through Week 80 ........................................ 47
Table 2: 
Glucocorticoid Tapering Schedule (Daily Dose [mg] of Prednisolone or Equivalent) .............. 48
Table 3: 
Overview of IMACS DOI Response Rates at Week 24 in Selected Studies ........................... 65
Table 4: 
Meta-analysis Using Random-effect and Fixed-effect Models: Pooled IMACS DOI
Response Rates at Week 24 and Their 95% CIs .................................................................. 65
Table 5: 
Meta-analysis Using Bayesian Model With Non-informative Prior: Posterior Summary
of IMACS DOI Response Rates at Week 24 ......................................................................... 65
Table 6: 
Overview of the Drop-out Rates in a Few Recent Ustekinumab Clinical Trials....................... 66
Table 7: 
Power for a Fixed Sample Size (50 Participants in Total) at Alpha=0.05 (2-sided) to
Detect a Significant Treatment Difference in the Proportion of Participants With
IMACS TIS Response at Week 24 Assuming a Drop-out Rate of 5% .................................... 66
FIGURES
Figure 1: Schematic Overview of the Study ......................................................................................... 14


STELARA® (ustekinumab) 
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1.
PROTOCOL SUMMARY
1.1. 
Synopsis
A Phase γ, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of
Ustekinumab in Participants With Active Polymyositis and Dermatomyositis Who Have Not Adequately
Responded to One or More Standard-of-care Treatments 
STELARA® (ustekinumab) is a fully human G1 kappa monoclonal antibody that binds with high affinity
and specificity to the shared p40 subunit of human interleukin (IL)-1β and IL-βγ cytokines. The binding of
ustekinumab to the IL-1β/βγp40 subunit blocks the binding of IL-1β or IL-βγ to the IL-1βRȕ1 receptor on
the surface of natural killer and cluster of differentiation (CD)4+ T cells, inhibiting IL-1β- and IL-βγ-
specific intracellular signaling and subsequent activation and cytokine production. Abnormal regulation of
IL-1β and IL-βγ has been associated with multiple immune-mediated diseases including polymyositis
(PM)/dermatomyositis (DM). Therefore, inhibition of IL-1β and IL-βγ has the potential to be effective in
the treatment of PM/DM.
OBJECTIVES AND ENDPOINTS
Objectives
Primary Objective
The primary objective is to evaluate the efficacy of ustekinumab in participants with active PM/DM despite
receiving 1 or more standard-of-care treatments (eg, glucocorticoids and/or immunomodulators).
Secondary Objectives
The secondary objectives are to evaluate the following in participants with active PM/DM despite receiving
1 or more standard-of-care treatments (eg, glucocorticoids and/or immunomodulators):

Improvement in organ-specific (musculoskeletal, mucocutaneous, etc) measures of PM/DM disease
activity

Reduction in PM/DM worsening
Tertiary Objectives
The tertiary objectives are to evaluate:

Safety and tolerability

Pharmacokinetics (PK) and immunogenicity

Pharmacodynamic and response biomarkers of ustekinumab treatment

Effect on health-related quality of life and physical function
Endpoints
Primary Endpoint
The primary endpoint is the proportion of participants who achieve Minimal Improvement in International
Myositis Assessment and Clinical Studies Total Improvement Score (IMACS TIS) at Week β4.


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Secondary Endpoints
The secondary endpoints are: 
 
Mean change from baseline in Functional Index-β (FI-β) at Week β4
 
The proportion of participants who experience disease worsening through Week β4 based on
consensus criteria for worsening
 
Mean change from baseline in Manual Muscle Testing (MMT)-8 at Week β4
 
Mean change from baseline in Physician Global Activity (PhGA) at Week β4
 
Mean change from baseline in Extramuscular Assessment (Myositis Disease Activity Assessment Tool
[MDAAT]-Extramuscular Global Assessment) at Week β4
 
Mean change from baseline in muscle enzymes (creatine kinase [CK], alanine aminotransferase [ALT],
aspartate aminotransferase [AST], lactate dehydrogenase [LDH], and aldolase) at Week β4
Tertiary Endpoints 
PM/DM Disease Activity
 
The proportion of participants who achieve Minimal Improvement in IMACS TIS over time 
 
The proportion of participants who achieve Moderate Improvement in IMACS TIS over time
 
The proportion of participants who achieve Major Improvement in IMACS TIS over time
 
IMACS TIS score over time
 
Mean change from baseline in PhGA over time
 
The proportion of participants with improvement in PhGA over time
 
Mean change from baseline in MMT-8 over time
 
The proportion of participants with improvement in MMT-8 over time
 
Mean change from baseline in Muscle enzymes (CK, ALT, AST, LDH, and aldolase) over time
 
The proportion of participants with improvement in Muscle enzymes (CK, ALT, AST, LDH, and
aldolase) over time
 
Mean change from baseline in MDAAT over time 
 
The proportion of participants with improvement in MDAAT over time 
 
Mean change from baseline in FI-β over time
 
The proportion of participants who reduce the use of systemic glucocorticoid from baseline at Week β4
 
The proportion of participants who reduce the use of systemic glucocorticoid from baseline and
achieve Minimal Improvement in IMACS ITS at Week β4
 
Time to worsening in participants who experience disease worsening through Week β4 based on
consensus criteria for worsening
Patient-reported Outcomes
 
Mean change from baseline in Patient Global Activity (PtGA) at Week β4
 
The proportion of participants with improvement in PtGA at Week β4


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 
Mean change from baseline in Physical Function (Health Assessment Questionnaire Disability Index
[HAQ-DI]) at Week β4
 
The proportion of participants with improvement in Physical Function (HAQ-DI) at Week β4
 
Mean change from baseline in γ6-item short form (SF-γ6) including individual domains and
component summary (PCS, MCS) scores at Week β4
 
The proportion of participants with improvement in SF-γ6 including individual domains and
component summary (PCS, MCS) scores at Week β4
 
Mean change from baseline in PtGA over time
 
The proportion of participants with improvement in PtGA over time
 
Mean change from baseline in Physical Function (HAQ-DI) over time
 
The proportion of participants with improvement in Physical Function (HAQ-DI) over time
 
Mean change from baseline in SF-γ6 including individual domains and component summary (PCS,
MCS) scores over time
 
The proportion of participants with improvement in SF-γ6 including individual domains and
component summary (PCS, MCS) scores over time
Pharmacokinetics and Immunogenicity
 
Summary of serum ustekinumab concentrations
 
Incidence of anti-ustekinumab antibodies
Biomarkers
 
Biomarkers of ustekinumab treatment response over time
Hypothesis
Treatment with ustekinumab is superior to placebo in participants with active PM/DM despite receiving 1
or more standard-of-care treatments as measured by the proportion of participants achieving IMACS TIS
at Week β4.
OVERALL DESIGN
This is a randomized, double-blind, placebo-controlled, multicenter, interventional study in participants
≥18 years and ≤75 years of age with active PM/DM despite receiving 1 or more standard-of-care treatments
(eg, glucocorticoids and/or immunomodulators) to evaluate the efficacy, safety, and tolerability of
ustekinumab in addition to standard-of-care background therapy. 
The total duration of the study is up to 94 weeks, consisting of γ study periods: a ≤6-week screening period
(rescreening is permitted once per participant), a 7β-week study drug administration period, and 16-week
follow-up period.
Approximately 50 participants will be randomly assigned in a 1:1 ratio to receive either ustekinumab or
matching placebo with the following treatment administrations: 
 
Week 0: Body weight-range based intravenous (IV) administration of ustekinumab (~6 mg/kg) or
placebo
 
Week 8 and Week 16: subcutaneous (SC) administration of 90 mg ustekinumab or placebo 


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 
Week β4: Placebo group participants crossover to receive body weight-range based IV administration
of ustekinumab (~6 mg/kg) and placebo SC and ustekinumab group participants receive placebo IV
and continue with SC administration of 90 mg ustekinumab
 
Week γβ, Week 40, Week 48, Week 56, Week 64, and Week 7β: SC administration of 90 mg
ustekinumab
A placebo comparator (in addition to standard-of-care background therapy) will be used in this study
through Week β4 to allow for blinded, placebo-controlled evaluation of the efficacy and safety of
ustekinumab in participants with PM/DM. 
Randomization will be stratified by disease subset (PM/DM) and baseline treatment level (glucocorticoid
dose [≥0.5 mg/kg/day or <0.5 mg/kg/day of prednisolone or equivalent]) using permuted block central
randomization. 
Four database locks (DBLs) will occur at Week β4, Week 5β, Week 7β, and Week 88. In addition to these
4 DBLs, one DBL will occur for the interim analysis of futility. Investigative study sites and participants
will remain blinded to initial treatment assignment until the DBL at Week 5β. After the Week β4 DBL, the
data will be unblinded to sponsor for analysis while participants are still participating in the study.
Identification of sponsor personnel who will have access to the unblinded participant data during the period
from the Week β4 DBL to the Week 5β DBL will be documented prior to unblinding to sponsor. After
Week β4, participants who are randomized to placebo group will crossover to receive ustekinumab and all
the participants will enter the cross-over administration phase to allow for evaluation of the long-term
efficacy and safety of ustekinumab. 
An external independent data monitoring committee (IDMC) will be commissioned for this study.
A futility analysis will be carried out after β0 participants complete Week β4 visit. The analysis will be
performed in an unblinded fashion by the IDMC based primarily on Week β4 efficacy data. The details of
the futility analysis will be included in the interim analysis plan.
The end of study is considered as the last follow-up assessment at Week 88 for the last participant in the
study.
NUMBER OF PARTICIPANTS
Approximately 50 participants are planned to be enrolled in the study.
INTERVENTION GROUPS AND DURATION
Following randomization at Week 0, participants assigned to the active treatment group will receive an
initial body weight-range based IV dose ~6 mg/kg of ustekinumab (ustekinumab β60 mg weight ≤55 kg;
ustekinumab γ90 mg weight >55 kg and ≤85 kg; ustekinumab 5β0 mg weight >85 kg), and participants
who were randomized to placebo will receive a single IV dose of placebo. Starting at Week 8, participants
will receive SC dosing with either placebo or ustekinumab 90 mg q8w through Week β4. At Week β4,
participants receiving placebo will crossover to receive body weight-range based IV administration of
ustekinumab. Starting at Week γβ, all participants will receive ustekinumab 90 mg SC q8w through
Week 7β.
Week 0 up to Week 16 
Group 1: Participants will receive body weight-range based IV dosing of ~6 mg/kg of ustekinumab at
Week 0 followed by ustekinumab 90 mg SC administrations at Weeks 8 and 16.
Group 2: Participants will receive IV dosing of placebo at Week 0 followed by placebo SC administrations
at Weeks 8 and 16. 


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Week 24 
Group 1: Participants will receive IV dosing of placebo and ustekinumab 90 mg SC administration.
Group 2: Participants will receive body weight-range based IV dosing of ~6 mg/kg of ustekinumab and
placebo SC administration. 
Week 32 up to Week 72
Groups 1 and 2: Participants will receive ustekinumab 90 mg SC q8w administrations through Week 7β.
EFFICACY EVALUATIONS
Measures of global disease activity: PhGA and PtGA for global evaluation of the patient's overall disease
activity at the time of assessment using a 10 cm Visual Analogue Scale (VAS).
Measures of muscle: Manual Muscle Testing (MMT) to assess muscle strength, muscle enzymes to measure
the serum activities of muscle-associated enzymes including CK, the transaminases (ALT, AST), LDH, and
aldolase, MDAAT to measure the degree of disease activity of extramuscular organ systems and muscle,
and FI-β for assessing muscle endurance in participants with PM/DM.
Patient-reported outcomes (PROs): Health Assessment Questionnaire Disability Index (HAQ-DI) for
physical function and SF-γ6 survey to assess generic health-related quality of life (HRQOL).
PHARMACOKINETIC AND IMMUNOGENICITY EVALUATIONS
 
Summary of serum ustekinumab concentrations and presence of anti-ustekinumab antibodies 
 
Pharmacokinetics (PK)-efficacy relationships for primary and selected key secondary endpoints
 
If data allow, population PK and population PK-pharmacodynamics (PD) analysis on primary and/or
selected key secondary efficacy endpoints
PHARMACOGENOMIC EVALUATIONS
A pharmacogenomic blood (whole blood deoxyribonucleic acid [DNA]) will be collected from participants
who consent separately to this component of the study to allow for pharmacogenomic research, as necessary.
Participant participation in pharmacogenomic research is optional.
BIOMARKER EVALUATIONS 
Assessments will be performed to identify biomarkers that are relevant to ustekinumab treatment. These
may include but not limited to, immune, inflammatory and other soluble protein markers, gene expression
markers in ribonucleic acid (RNA), phenotypic and functional cellular markers and, for patients who
complete the optional DNA informed consent, DNA markers related to susceptibility and polymorphisms.
 
Ig isotype profile (IgG, IgM, IgA levels)
 
IL-1β/IL-17/IL-βγ (eg, messenger RNA [mRNA], Soluble Protein [Serum])
 
Anti-aminoacyl-transfer RNA (tRNA) synthetases (Jo-1, PL-7, PL-1β, EJ, OJ, KS)
 
Anti-Mi-β, anti-SRP, anti-TIF1-Ȗ, anti-NXP-β, anti-MDA5, anti-SAE, anti-HMGCR
 
Type I, II, and III interferons (IFNs)
 
Other inflammation-related molecules and autoantibody profile


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SAFETY EVALUATIONS
Safety evaluations will include assessment of adverse event (AEs), concomitant medications, pregnancy
testing, administration reactions, serum chemistry, hematology and blood coagulation laboratory tests, vital
signs, ECG, general physical examinations, and TB testing. In addition, HIV, hepatitis B, and hepatitis C,
will be required at screening. The presence of interstitial lung disease (ILD) and respiratory muscle
weakness will be evaluated using x-ray, chest high-resolution computer tomography (HRCT), blood gas
analysis (partial pressure of oxygen in arterial blood [PaOβ] and partial pressure of carbon dioxide in arterial
blood [PaCOβ]), and pulmonary function test (PFT) (vital capacity [VC], forced vital capacity [FVC],
diffusing capacity of the lungs for carbon monoxide [DLCO], maximal inspiratory pressure [MIP], maximal
expiratory pressure [MEP], and maximal voluntary ventilation [MVV]). All participants must be monitored
with SpOβ and laboratory data (KL-6 and SP-D) regularly during the study.
STATISTICAL METHODS
Simple descriptive summary statistics, such as sample size (n), mean, standard deviation (SD), median,
interquartile (IQ) range, minimum, and maximum for continuous variables, and counts and percentages for
discrete variables will be used to summarize most data.
In addition, graphical data displays (eg, line plots) and participant listings may also be used to
summarize/present the data.
In general, all statistical tests will be performed at a β-sided significance level of α=0.05.
Sample Size Determination
The sample size calculation is based upon the primary endpoint, the proportion of participants who achieve
IMACS TIS response at Week β4. To determine the effect size versus placebo used for calculating the
sample size, meta-analyses were conducted for the synthesis of the evidence. Considering the primary
endpoint evaluated at Week β4 in Japanese patients, a dropout rate of 5% is accommodated for sample size
calculation. Particularly focusing on the effect size of 40% which is considered a reasonable estimate of
effect size, a sample size of 50 participants is projected to give 8β.β% power to detect a significant
difference in response rate compared with placebo (assuming β5% and 65% response rates in placebo and
ustekinumab, respectively with the 5% dropout rate in β4 weeks, which translates to 40% absolute increase
over placebo or an odds ratio of 5.57) with an alpha level of 0.05 (β-sided). 
Efficacy Analysis
It is considered that the effectiveness of ustekinumab treatment in adult patients with PM/DM will be
demonstrated if the ustekinumab group is shown to be superior to placebo group for the primary efficacy
analysis in this study.
Primary Efficacy Analysis
The primary endpoint of this study is the proportion of participants who achieve IMACS TIS response at
Week β4. The Primary Estimand will be targeted for the primary endpoint. The Primary Estimand for the
primary endpoint is defined by the following:
 
Study intervention: 
 
Ustekinumab (~6 mg/kg IV at Week 0, and 90 mg SC q8w through Week β4) 
 
Placebo (IV at Week 0 and SC q8w through Week β4)
 
Population: Subjects with active PM/DM despite receiving one or more standard-of-care treatments.
 
Variable/endpoint: IMACS TIS binary response variable at Week β4, where a responder is defined
as a participant who achieves IMACS TIS response at Week β4 and does not have a prohibited change


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in PM/DM medications. A participant who has a prohibited change in PM/DM medications or
discontinues treatment for any reason including COVID-19 infection but excluding other COVID-19
reasons is considered a non-responder.
 
Population-level summary: Odds ratio for the proportion of subjects achieving IMACS TIS response
at Week β4 between the ustekinumab and placebo intervention groups.
 
ICEs and their corresponding strategies:
ICEs
Analysis Strategy for
Addressing Intercurrent Events
1. A prohibited change in PM/DM 
medications prior to Week β4  
Composite Strategy: A subject with this intercurrent
event is considered as a non-responder after this event, the
occurrence of this intercurrent event being captured in the
variable definition.
 
β. Discontinuation of study intervention
for any reason, including COVID-19
infection but excluding other
COVID-19 reasons
γ. Discontinuation of study intervention 
due to COVID-19 related reasons 
(excluding COVID-19 infection) 
Hypothetical Strategy: This intercurrent event is
addressed with a hypothetical strategy, as if the
intercurrent event would not have occurred.
 
Logistic regression adjusting for β stratification factors, disease subset (PM or DM) and baseline treatment
level (glucocorticoid dose [≥0.5 mg/kg/day or <0.5 mg/kg/day of prednisolone or equivalent]) will be used
to analyze the primary endpoint. If the above logistic regression model does not converge, the binomial test
will be conducted without adjusting for the β stratification factors. The magnitude of the effect will be
estimated by the odds ratio in IMACS TIS response between the ustekinumab and placebo groups and the
95% confidence interval will be provided. 
Secondary Efficacy Analyses
All endpoints other than the primary endpoint of this study are not prospectively powered and all p-values
reported for the secondary endpoints will be considered nominal.
 
Treatment comparison in time to worsening through Week β4 will be done using a log-rank test.
Kaplan-Meier estimates will be provided for each treatment group. Analysis for time to worsening will
be repeated adjusting for β stratification factors using a proportional hazards model. In the analyses
for time-to-event endpoints, subjects with ICE 1-β will be handled with Composite Strategy and
subjects with ICE γ will be handled with Treatment Policy Strategy (the observed data will be used
regardless of whether or not this ICE had occurred).
 
Analyses comparing the β treatment arms will be performed using a logistic model similar to primary
analysis with the binary outcome related to individual core set measures at Week β4. The primary
estimand approaches dealing with ICEs will be applied to these analyses.
 
All other efficacy endpoints will be summarized over time by treatment group. Treatment comparisons
will be performed using a mixed-effect model repeated measure (MMRM) model where there are
repeated continuous measurements or a logistic model where there is a dichotomous response variable.
The primary estimand approaches dealing with ICEs will be applied to these analyses also and the
detailed methods of analysis and the data-handling rules will be provided in the statistical analysis plan
(SAP).
Safety Analyses
All safety analyses will be based on the population of participants who receive at least 1 dose of either study
drug; participants will be summarized by the treatment they receive. Adverse events, serious adverse event


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(SAEs), reasonably related AEs, and AEs by severity will be summarized by treatment group. More
specification of other special interesting event such as malignancies, serious infections, serious
cardiovascular events and ILD will be described in the SAP. However, a summary table will not be provided
if the number of events is too few to provide meaningful summary. The laboratory parameters and change
from baseline in selected laboratory parameters (hematology and chemistry), and the number of participants
with abnormal laboratory parameters (hematology and chemistry) based on National Cancer Institute (NCI)
Common Terminology Criteria for Adverse Events (CTCAE) toxicity grading will be summarized by
treatment group. Listings of SAEs will also be provided. 
Other Analyses
Pharmacokinetic Analyses 
Serum ustekinumab concentrations will be summarized over time. Descriptive statistics, including
arithmetic mean, SD, median, IQ range, minimum, and maximum will be calculated at each sampling time
point. All concentrations below the lowest quantifiable sample concentration of the assay (BQL) or missing
data will be labeled as such in the concentration data listing or statistical analysis system (SAS) dataset.
The BQL concentrations will be treated as zero in the summary statistics.
If feasible, population PK analysis of ustekinumab may be performed using nonlinear mixed-effects
modeling. Data may be combined with those of other selected studies to support a relevant structural model.
Details will be given in a population PK analysis plan and the results of the population PK analysis will be
presented in a separate report.
Biomarkers Analyses 
Biomarker analyses performed may include but not limited to serum analysis for levels of IFNs as well as
molecular pathway profiling for evidence of IL-1β and IL-βγ pathway modulation. The biomarkers
analyzed may include inflammatory markers, RNA, autoantibodies, T, B, and natural killer (NK) cell
immunophenotyping, and other categories of biomarkers potentially involved in the development and the
progression of PM/DM.
Biomarker results will be summarized in a separate technical report.
Genetic (DNA) analyses will be conducted only in participants who sign the optional DNA consent form.
These analyses will be summarized in a separate technical report.
Immunogenicity Analyses 
The incidence of anti-ustekinumab antibodies and the impact of antibodies on serum ustekinumab
concentrations will be summarized for all participants who receive at least 1 dose of ustekinumab and have
appropriate samples for detection of antibodies to ustekinumab (ie, participants with at least 1 sample
obtained after their first dose of ustekinumab). The incidence of neutralizing antibodies (NAbs) to
ustekinumab will be summarized for participants who are positive for antibodies to ustekinumab and have
samples evaluable for NAbs to ustekinumab.
Pharmacokinetic/Pharmacodynamic Analyses 
The relationship between serum ustekinumab concentration and efficacy measures for primary and selected
key secondary endpoints will be analyzed graphically. In addition, population PK/PD modeling may be
performed to characterize the relationship between serum ustekinumab exposure and efficacy measures.
Further details will be provided in a population PK/PD analysis plan and the results will be provided in a
separate report.


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Interim Analysis 
A futility analysis based on the primary endpoint of IMACS TIS at Week β4 will be conducted when
β0 participants (40% of the originally planned total sample size) have completed the Week β4 visit. The
whole study may be stopped for futility when the conditional power (ie, the probability of success at the
end of the study, given the data at the interim analysis) is less than a prespecified cutoff. The prespecified
cutoff value will be 0.β0. For the futility analysis, the treatment assignment information will be unblinded
to IDMC and independent statistical support group for the β0 participants included in the interim analysis
only (the treatment assignment for the remaining participants will remain blinded at this time). The details
will be stated in interim analysis charter.
The simulation study demonstrates that this futility analysis will result in a slight loss in power (≤0.6%)
when the treatment effect is expected to be 40% assuming the response rate in the placebo group as β5%
and Type I error rate will not inflate (α=0.05, β-sided) for the primary endpoint analysis. 
1.2. 
Schema
Figure 1: 
Schematic Overview of the Study








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a. 
Screening visit must be performed no more than 6 weeks prior to the randomization visit (Week 0). Participants may be hospitalized to treat PM/DM.
b. 
It is strongly recommended that participants who permanently discontinue study drug, but do not withdraw from study participation, be followed at all subsequent
study visits through Week 80. 
Participants, who permanently discontinue study drug administrations on or before the Week 7β visit, but do not withdraw from study participation, must undergo
procedures for safety follow-up visits (postdiscontinuation) as outlined for the end of trial (EO-Treatment) visit as soon as possible on or before next scheduled
visit.
Participants, who permanently discontinue study drug administrations on or before the Week 7β visit, and withdraw from study participation, must undergo
procedures for safety follow-up visits (postdiscontinuation) as outlined for the end of trial (EO-Treatment) visit as soon as possible on or before next scheduled
visit, and must return approximately 8 weeks after last study drug administration to undergo procedures for safety follow-up visits (8 weeks postdiscontinuation) as
outlined for the end of trial (EO-Treatment). If the interval between postdiscontinuation visit and 8 weeks postdiscontinuation visit is less than two weeks, can skip
8 weeks postdiscontinuation.
c. 
Participants, who discontinue study drug administrations on or before the Week 7β visit, and withdraw from study participation, must return approximately 16
weeks after last study drug administration to undergo procedures for safety follow-up visits as outlined for the end of trial (EO-Trial) visit.
d. 
Administration of study drug and visit window should be within ±7 days of the scheduled visit date. Unless otherwise specified, all assessments (except for
injection-site evaluation) are to be completed prior to study drug administration.
e. 
Participants will sign informed consent forms for participation in the study CNTO1β75DMYγ001, and may additionally consent for the following: whole blood
DNA collection for genetic factors at selected sites.
f. 
Participants should be performed cancer screening tests to exclude participants who meet exclusion criteria #45. The investigator should confirm the results of
cancer screening tests brought by participants if they were performed at any other sites within β years.
g. 
IV administration of study drug at Week 0, IV and SC administration of study drug at Week β4 and all other doses will be SC to be administered at the study site
through Week 7β.
h. 
A 1β-lead ECG will be performed locally. Participants should rest in a supine position for at least 5 minutes before ECG recording and should refrain from talking
or moving arms or legs.
i. 
All assessments for ILD should be kept as close to the specified day as possible. If the investigator identifies new onset or worsening of ILD or observes any
finding which needs to be evaluated by a pulmonologist, the investigator should consider consultation with a pulmonologist and administer rescue treatment as
needed.
j. 
If any findings suggesting worsening or new onset of ILD are obtained, consultation with a pulmonologist is required. See Section 8.β.5.
k. 
Screening Chest x-ray posterior/anterior and lateral views must be taken for both ILD and TB detection.
l. 
Screening HRCT must be read by a radiologist or pulmonologist to evaluate the presence of ILD and TB.
m. TB evaluation includes an assessment of recent exposure or risk of TB including new or chronic cough, fever, night sweats, unintentional weight loss or recent
contact with someone with active TB. If TB is suspected at any time during the study, a chest x-ray, chest HRCT, and T-SPOT.TB test or QFT should be
performed.
n. 
In addition to the urine screening evaluation, a serum pregnancy test may be conducted at any time at the discretion of Investigator or participant. Urine pregnancy
tests may be conducted more frequently (eg, monthly basis). Urine pregnancy tests may not be necessary if a subject is considered a postmenopausal state defined
as no menses for 1β months without an alternative medical cause and a high follicle stimulating hormone (FSH) level (>40 IU/L or mIU/mL) during the study.
o. 
Participants should be monitored for the occurrence of infusion reactions for at least 1 hour after IV infusion and injection-site reactions for at least γ0 minutes
following SC injection.
p. 
See Section 6.5.β for information on glucocorticoid tapering.
q. 
ClinRO portion to be completed by the investigator at all sites.
r. 
It is recommended that MMT-8 be performed by an investigator who does not know the assessment result of participants including laboratory test.


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s. 
Whenever possible, PRO assessments should be conducted before any tests, procedures, or other consultations for that visit to prevent influencing participants’
perceptions. 
t. 
FI-β is recommended to be performed after MMT.
u. 
Assessments must be performed by the central laboratory unless otherwise indicated.
v. 
The same blood draw will be used for the measurement of ustekinumab concentration and detection of antibodies to ustekinumab. For visits with study drug
administration, all blood samples for assessing predose ustekinumab concentration and antibodies to ustekinumab MUST be collected BEFORE the
administration of the study drug. Residual sample may be used to evaluate antibodies to ustekinumab at unspecified visits or other biomarker analysis.
w. 
At Week 0, β separate samples for serum ustekinumab concentrations (indicated by “βX” in the Schedule above) will be collected (1 sample will be collected prior
to IV infusion and the other collected 1 hour after the end of the infusion) for all participants.
x. 
Additional venous blood sample collection for population PK analysis should occur on any day in each of the β designated time periods except on the days of
scheduled study visits. Additionally, this blood sample should be collected at least β4 hours prior to or after the actual time of study drug administration.
y. 
Whole blood will be collected and processed for PBMC isolation and cryopreservation.
z. 
Whole blood for genetic analyses will be collected only from participants who sign a separate informed consent form to participate in the DNA substudy.


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2. 
INTRODUCTION 
Polymyositis (PM) and dermatomyositis (DM) are chronic rheumatic diseases generally
characterized by muscle weakness and low endurance. Most patients present with an insidious
painless proximal symmetrical weakness. Other clinical features include pitting edema, pharyngeal
muscle weakness causing hoarseness, dysphagia, and nasal regurgitation of liquids or aspiration
pneumonia. Gastrointestinal symptoms can also consist of postprandial pain, distension, reflux,
and diarrhea. There can be ventilatory muscle involvement (<5% of patients), which causes
shortness of breath.βγ Skin features pathognomonic of DM are Gottron papules and a heliotrope
rash. Gottron scaly erythematous or violaceous papules appear over bony prominences, mainly the
metacarpophalangeal and proximal and distal interphalangeal joints of the hands. When this occurs
over the extensor aspects of the knees, elbows, and ankles it is known as Gottron sign. The
violaceous heliotrope rash erupts on the upper eyelids.βγ PM/DM often accompany other
extramuscular involvements, such as interstitial lung diseases (ILDs), arthritis, and malignancies
in adult patients. 
Polymyositis and DM have been designated as an intractable disease by Ministry of Health, Labour
and Welfare (MHLW) in Japan. There were β1,8γβ patients with PM/DM in Japan in β016 based
on the intractable disease registration database.
Glucocorticoids are used empirically as the first-line treatment, but have various adverse effects
including glucocorticoid-induced myopathy. In addition, about a half of the patients with
glucocorticoid monotherapy experience the relapse during glucocorticoid tapering.β8
Various studies reported that concomitant treatment with steroid-sparing immunosuppressive
agents, such as methotrexate (MTX), azathioprine (AZA), tacrolimus (TAC), cyclosporine A,
and mycophenolate mofetil (MMF), was effective in idiopathic inflammatory myositis (IIM).
The treatment guideline for PM/DM developed by the research group of Japan College of
Rheumatology, The Japanese Dermatological Association, and Japanese Society of Neurology
supports the use of MTX, AZA, TAC, cyclosporine A, MMF, and cyclophosphamide as
immunosuppressants. Concomitant treatment with these agents reduces the relapse risk during
glucocorticoid tapering.β0 However, effects are often disappointing and many patients are not
able to regain muscle function.4 Health-related quality of life in patients with PM/DM is low
compared with the general population. The majority of commonly used drugs are not approved
for myositis, and only few randomized controlled trials have been performed in this patient
group. Existing therapies for PM/DM are generally either cytotoxic or immunosuppressive and
may have notable safety risks. Thus, there is a large unmet need for new alternative treatments
that can provide significant benefit in this disease without incurring a high safety risk.
The term "sponsor" used throughout this document refers to the entities listed in the ‘Protocol
Supplementary Information’, which will be provided as a separate document.


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2.1. 
Study Rationale 
2.2. 
Background
To date, STELARA (ustekinumab) has received marketing authorization globally, for the
treatment of adult and pediatric patients (age ≥1β to <18 years) with chronic moderate to severe
plaque psoriasis, adult patients with active psoriatic arthritis (PsA), and adult patients with
moderate to severe Crohn’s disease. The cumulative global exposure (through γ1 December β018)
has been estimated as 1,γ75,007 person-years. Based on completed clinical studies alone, 7,164
participants have been exposed to ustekinumab across all indications. In Phase β and Phase γ
clinical studies, participants have been exposed to ustekinumab for 6 months, 1 year, and some
participants have had 5 or more years of exposure to the drug. The overall safety profile of
ustekinumab was similar for patients regardless of indication and the most common adverse
reactions (>5%) in controlled periods of clinical studies were nasopharyngitis and headache. Most
adverse events (AEs) were considered mild and did not necessitate drug discontinuation.
Scientific Rationale for Use of Anti-Interleukin-12/23p40 Therapy in Polymyositis and
Dermatomyositis 
In the pathogenesis of myositis, interleukin (IL)-βγ has attracted attention because some recent
studies in humans and mice support the notion that IL-βγ plays a role in PM/DM. The levels of
IL-βγ are increased in the serum and peripheral blood mononuclear cell (PBMC) of patients with
PM/DM compared with healthy control subjects. By contrast, concentrations of IL-17 in PBMC
from patients with PM/DM were not higher than those from healthy control subjects.ββ A study
has reported detection of immature cluster of differentiation (CD)1a+ dendritic cells (DCs) and
mature DC-LAMP positive and CD8γ+ DCs in association with the proinflammatory cytokines
IL-17 and interferon (IFN)-Ȗ in human muscle tissue of PM/DM.17 In another study, muscle
samples obtained from patients with PM/DM have shown expression of IL-βγ (IL-βγp19)
messenger RNA (mRNA) and IL-17 mRNA though mRNA of these cytokines was not detected in
muscle samples from healthy donors.11 These studies indicate that IL-βγ/Th17 axis could be
associated with pathogenesis of inflammatory myositis. A study of murine model of PM (C
protein-induced myositis, CIM) has reported that serum concentration of IL-βγ was elevated in
myositis mice and that CD68+cells infiltrating into the lesions of myositis expressed IL-βγ.β7
Adoptive transfer of lymph node cells from myositis mice into IL-βγ deficient mice successfully
induced comparable myositis to wild type mice though IL-βγ deficient mice themselves are
resistant to CIM and do not develop myositis. It suggests that autoreactive lymphocytes induced
in myositis mice play an important role in pathogenesis of myositis and that these pathogenetic
lymphocytes are dependent on IL-βγ. In myositis mouse model, anti-IL-βγR antibody ameliorated
myositis therapeutically, which indicates that IL-βγ would be the promising target for treatment of
PM.
Interleukin-1β is known to be an important cytokine for the differentiation of Th1 cells. In addition,
recent studies have shown IL-1β could induce IL-β1 producing T follicular helper (Tfh) cell in a
manner dependent on STAT4.β1 It has been reported that IL-β1 expression is upregulated in
patients with PM/DM in both serum10 and muscle tissue.1β The number of Tfh cells in patients


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with IIM was increased compared to healthy control subjects.6 These findings indicate IL-1β
blockade could reduce the inflammatory response related to Tfh and IL-β1.
Interleukin-1β and IL-βγ secreted by DCs help to polarize Th1 and Th17 cells. The cytokines
secreted by Th1 and Th17 cells such as IFN-Ȗ, play some roles in development of myositis via
upregulation of toll-like receptor γ (TLRγ) pathway.β5,β6
Ustekinumab is a fully human G1 kappa monoclonal antibody that binds with high affinity and
specificity to the shared p40 subunit of human IL-1β and IL-βγ cytokines. The binding of
ustekinumab to the IL-1β/βγp40 subunit blocks the binding of IL-1β or IL-βγ to the IL-1βR1
receptor on the surface of natural killer and CD4+ T cells, inhibiting IL-1β- and IL-βγ-specific
intracellular signaling and subsequent activation and cytokine production. Abnormal regulation of
IL-1β and IL-βγ has been associated with multiple immune-mediated diseases including PM/DM.
Therefore, inhibition of IL-1β and IL-βγ has the potential to be effective in the treatment of
PM/DM.
Though clinical usage of ustekinumab for PM/DM is limited, there is a case report of amyopathic
dermatomyositis (ADM).14 A β0-year-old male had a history of ADM which was refractory to
multiple immunosuppressors. After developing psoriasis, the patient was treated with ustekinumab
and has shown a very good clinical response.
Recent genome-wide association studies revealed considerable genetic overlap among
immune-mediated inflammatory diseases including systemic lupus erythematosus (SLE) and some
rheumatic diseases.5 The findings show that autoantibody-mediated autoimmune diseases cluster
more closely with each other than autoantibody-negative diseases such as psoriasis which form
another genetic cluster. A meta-analysis shows a single nucleotide polymorphism is associated
with susceptibility to several autoimmune diseases including SLE and myositis.γ1 A genome-wide
gene expression analysis has revealed overlap of gene expression signature including interferon
between DM and lupus, which is distinct from other inflammatory skin diseases.γ0 Another
genome-wide association study in DM has confirmed the importance of the major
histocompatibility complex (MHC) complex but also suggested non-MHC genetic features
overlapped with other autoimmune diseases including SLE.1γ These findings indicate the potential
overlap of pathogenesis between SLE and myositis.γ0
A Phase βa trial has shown that administration of ustekinumab in patients with SLE improved
disease activity scores and reduced autoantibody titer. The results from studies in animal models,
human translational and genetic studies also support a role of IL-1β/βγp40 as a therapeutic target
in pathogenesis of PM/DM. 
Taken together, these findings indicate that blockade of IL-1β/IL-βγ would be a promising target
for the treatment of PM/DM.
For the most comprehensive nonclinical and clinical information regarding ustekinumab, refer to
the latest version of the Investigator's Brochure (IB) for ustekinumab.9


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2.3. 
Benefit/Risk Assessment
To date, ustekinumab has received marketing authorization globally for the treatment of adult and
pediatric patients (age ≥1β to <18 years) with chronic moderate to severe plaque psoriasis, adult
patients with active PsA, and adult patients with moderate to severe Crohn’s disease. Japan has
received marketing authorization approval of ustekinumab for the treatment of moderate to severe
psoriasis and PsA in January β011 and for the treatment of Crohn’s disease in March β017.9
The overall safety profile of ustekinumab was similar for patients regardless of indication. Refer
to the latest version of the IB for further details.9
In this Phase γ study, potential risks of treatment with ustekinumab (eg, serious infections
including tuberculosis (TB) and hypersensitivity reactions), as well as the potential risks inherent
in patients with PM/DM (ILD, serious infections, arteriosclerotic diseases, and malignancies), are
being addressed in multiple ways:
 
Inclusion/exclusion criteria (Section 5.1 and 5.β) set limits regarding, for example, history of
unstable or progressive organ-threatening disease, infections or predisposition to infections,
history of reactions to biologic agents, and baseline laboratory abnormalities.
 
Comprehensive medical monitoring of data by the sponsor during the conduct of this study
includes regular assessment of AEs and serious adverse event (SAEs), vital signs, physical
examination, and laboratory results and evaluation for ILD using chest x-ray, high-resolution
computer tomography (HRCT), and pulmonary function test (PFT) (Section 1.γ, Schedule of
Activities) to evaluate individual cases as well as potential emerging safety trends. In addition,
as discussed in Section 9.5.1, an external independent data monitoring committee (IDMC)
will provide oversight and will conduct independent evaluation of the safety data accrued in
this protocol.
 
Certain concomitant medications have been prohibited (Section 6.6) and limitations set on
dose levels of permitted concomitant medications, such as high dose glucocorticoids,
cytotoxic agents, and use of multiple biologics simultaneously, that could introduce safety
risks due to oversuppression of the immune system.
 
The steroid-sparing effects of ustekinumab are being evaluated by implementing a
glucocorticoid taper from Week β to Week 16 and from Week β4 to Week 80. This may add
benefit by reducing the risk of infection and other glucocorticoid-related complications.
However, should a participant experience worsening of disease activity, rescue therapy is
permitted per medical necessity as outlined in Section 6.5.5.
Based on the available safety data from clinical trials and postmarketing experience including other
disease indications, and proposed safety measures, the overall risk/benefit assessment of
ustekinumab in this protocol is acceptable.


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3. 
OBJECTIVES AND ENDPOINTS 
OBJECTIVES
Primary Objective
The primary objective is to evaluate the efficacy of ustekinumab in participants with active
PM/DM despite receiving 1 or more standard-of-care treatments (eg, glucocorticoids and/or
immunomodulators).
Secondary Objectives
The secondary objectives are to evaluate the following in participants with active PM/DM despite
receiving 1 or more standard-of-care treatments (eg, glucocorticoids and/or immunomodulators):
 
Improvement in organ-specific (musculoskeletal, mucocutaneous, etc) measures of PM/DM
disease activity
 
Reduction in PM/DM worsening
Tertiary Objectives
The tertiary objectives are to evaluate:
 
Safety and tolerability
 
Pharmacokinetics (PK) and immunogenicity
 
Pharmacodynamic and response biomarkers of ustekinumab treatment 
 
Effect on health-related quality of life and physical function
ENDPOINTS
Primary Endpoint
The primary endpoint is the proportion of participants who achieve Minimal Improvement in
International Myositis Assessment and Clinical Studies Total Improvement Score (IMACS TIS)
at Week β4.
Secondary Endpoints
The secondary endpoints are: 
 
Mean change from baseline in Functional Index-β (FI-β) at Week β4
 
The proportion of participants who experience disease worsening through Week β4 based on
consensus criteria for worsening
 
Mean change from baseline in Manual Muscle Testing (MMT)-8 at Week β4
 
Mean change from baseline in PhGA at Week β4
 
Mean change from baseline in Extramuscular Assessment (Myositis Disease Activity
Assessment Tool [MDAAT]-Extramuscular Global Assessment) at Week β4


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 
Mean change from baseline in muscle enzymes (creatine kinase [CK], alanine
aminotransferase [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH],
and aldolase) at Week β4
Tertiary Endpoints 
PM/DM Disease Activity
 
The proportion of participants who achieve Minimal Improvement in IMACS TIS over time 
 
The proportion of participants who achieve Moderate Improvement in IMACS TIS over time
 
The proportion of participants who achieve Major Improvement in IMACS TIS over time
 
IMACS TIS score over time
 
Mean change from baseline in PhGA over time
 
The proportion of participants with improvement in PhGA over time
 
Mean change from baseline in MMT-8 over time
 
The proportion of participants with improvement in MMT-8 over time
 
Mean change from baseline in Muscle enzymes (CK, ALT, AST, LDH, and aldolase) over
time
 
The proportion of participants with improvement in Muscle enzymes (CK, ALT, AST, LDH,
and aldolase) over time
 
Mean change from baseline in MDAAT over time 
 
The proportion of participants with improvement in MDAAT over time 
 
Mean change from baseline in FI-β over time
 
The proportion of participants who reduce the use of systemic glucocorticoid from baseline at
Week β4 
 
The proportion of participants who reduce the use of systemic glucocorticoid from baseline
and achieve Minimal Improvement in IMACS ITS at Week β4
 
Time to worsening in participants who experience disease worsening through Week β4 based
on consensus criteria for worsening
Patient-reported Outcomes
 
Mean change from baseline in Patient Global Activity (PtGA) at Week β4
 
The proportion of participants with improvement in PtGA at Week β4
 
Mean change from baseline in Physical Function (Health Assessment Questionnaire
Disability Index [HAQ-DI]) at Week β4
 
The proportion of participants with improvement in Physical Function (HAQ-DI) at Week β4
 
Mean change from baseline in γ6-item short form (SF-γ6) including individual domains and
component summary (PCS, MCS) scores at Week β4


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 
The proportion of participants with improvement in SF-γ6 including individual domains and
component summary (PCS, MCS) scores at Week β4
 
Mean change from baseline in PtGA over time
 
The proportion of participants with improvement in PtGA over time
 
Mean change from baseline in Physical Function (HAQ-DI) over time
 
The proportion of participants with improvement in Physical Function (HAQ-DI) over time
 
Mean change from baseline in SF-γ6 including individual domains and component summary
(PCS, MCS) scores over time
 
The proportion of participants with improvement in SF-γ6 including individual domains and
component summary (PCS, MCS) scores over time
Pharmacokinetics and Immunogenicity
 
Summary of serum ustekinumab concentrations
 
Incidence of anti-ustekinumab antibodies
Biomarkers
 
Biomarkers of ustekinumab treatment response over time
Refer to Section 8, Study Assessments and Procedures for evaluations related to endpoints.
HYPOTHESIS 
Treatment with ustekinumab is superior to placebo in participants with active PM/DM despite
receiving 1 or more standard-of-care treatments as measured by the proportion of participants
achieving IMACS TIS at Week β4.
4. 
STUDY DESIGN 
4.1. 
Overall Design
This is a randomized, double-blind, placebo-controlled, multicenter, interventional study in
participants ≥18 years and ≤75 years of age with active PM/DM despite receiving 1 or more
standard-of-care treatments (eg, glucocorticoids and/or immunomodulators). to evaluate the
efficacy, safety, and tolerability of ustekinumab in addition to standard-of-care background
therapy. 
The total duration of the study is up to 94 weeks, consisting of γ study periods: a ≤6-week screening
period (rescreening is permitted once per participant), a 7β-week study drug administration period,
and a 16-week safety follow-up period.
Approximately 50 participants will be randomly assigned in a 1:1 ratio to receive either
ustekinumab or matching placebo with the following treatment administrations (see Section 6 for
further details of study drug administration): 


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 
Week 0: Body weight-range based intravenous (IV) administration of ustekinumab
(~6 mg/kg) or placebo
 
Week 8 and Week 16: Ustekinumab 90 mg subcutaneous (SC) administration or placebo 
 
Week β4: Placebo group participants crossover to receive body weight-range based IV
administration of ustekinumab (~6 mg/kg) and placebo SC and ustekinumab group
participants receive placebo IV and continue with SC administration of 90 mg ustekinumab
 
Week γβ, Week 40, Week 48, Week 56, Week 64, and Week 7β: SC administration of 90 mg
ustekinumab
A placebo comparator (in addition to standard-of-care background therapy) will be used in this
study through Week β4 to allow for blinded, placebo-controlled evaluation of the efficacy and
safety of ustekinumab in participants with PM/DM. 
Randomization will be stratified by disease subset (PM/DM) and baseline treatment level
(glucocorticoid dose [≥0.5 mg/kg/day or <0.5 mg/kg/day of prednisolone or equivalent]) using
permuted block central randomization.
The primary efficacy analysis will be performed after all participants have completed Week β4
efficacy assessments (or discontinued) with additional secondary endpoints to be analyzed at
Week β4. 
Four database locks (DBLs) will occur at Week β4, Week 5β, Week 7β, and Week 88. In addition
to these 4 DBLs, one DBL will occur for the interim analysis of futility. Investigative study sites
and participants will remain blinded to initial treatment assignment until the DBL at Week 5β.
After the Week β4 DBL, the data will be unblinded to sponsor for analysis while participants are
still participating in the study. Identification of sponsor personnel who will have access to the
unblinded participant data during the period from the Week β4 DBL to the Week 5β DBL will be
documented prior to unblinding to sponsor. After Week β4, participants who are randomized to
placebo group will crossover to receive ustekinumab and all the participants will enter the cross-
over administration phase to allow for evaluation of the long-term efficacy and safety of
ustekinumab. 
Every reasonable effort should be made to keep concomitant medications stable as defined in the
protocol (see Section 6.5.β for information on glucocorticoid tapering). Beginning at the screening
visit, all concomitant therapies and all changes in concomitant therapies should be recorded
throughout the study.
An external IDMC will be commissioned for this study. Refer to Section 9.5.1 for further details.
A futility analysis will be carried out after β0 participants complete Week β4 visit. The analysis
will be performed in an unblinded fashion by the IDMC based primarily on Week β4 efficacy data.
The details of the futility analysis will be included in the interim analysis plan.
A diagram of the study design is provided in Section 1.β, Schema.


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4.2. 
Scientific Rationale for Study Design
Blinding, Control, Study Phase/Periods, Intervention Groups
A placebo control will be used to establish the frequency and magnitude of changes in clinical or
surrogate endpoints that may occur in the absence of active intervention. Randomization will be
used to minimize bias in the assignment of participants to intervention groups, to increase the
likelihood that known and unknown participant attributes (eg, demographic and baseline
characteristics) are evenly balanced across intervention groups, and to enhance the validity of
statistical comparisons across intervention groups. Blinded intervention will be used to reduce
potential bias during data collection and evaluation of clinical and surrogate endpoints.
Biomarker and Pharmacogenomics Collection
It is recognized that genetic variation can be an important contributory factor to interindividual
differences in intervention distribution and response and can also serve as a marker for disease
susceptibility and prognosis. Pharmacogenomic research may help to explain interindividual
variability in clinical outcomes and may help to identify population subgroups that respond
differently to an intervention. The goal of the pharmacogenomic component is to collect
deoxyribonucleic acid (DNA) to allow the identification of genetic factors that may influence the
PK, efficacy, safety, or tolerability of ustekinumab and to identify genetic factors associated with
PM/DM.
Biomarker samples will be collected to evaluate the mechanism of action of ustekinumab or help
to explain interindividual variability in clinical outcomes or may help to identify population
subgroups that respond differently to an intervention. 
A pharmacogenomic blood sample (whole blood DNA) will be collected from participants who
consent separately to this component of the study to allow for pharmacogenomic research, as
necessary. Participant participation in pharmacogenomic research is optional.
Biomarker and DNA samples may be used to help address emerging issues and to enable the
development of safer, more effective, and ultimately individualized therapies.
4.2.1. 
Study-Specific Ethical Design Considerations
Potential participants will be fully informed of the risks and requirements of the study and, during
the study, participants will be given any new information that may affect their decision to continue
participation. They will be told that their consent to participate in the study is voluntary and may be
withdrawn at any time with no reason given and without penalty or loss of benefits to which they
would otherwise be entitled. Only participants who are fully able to understand the risks, benefits,
and potential AEs of the study, and provide their consent voluntarily will be enrolled. Vulnerable
populations (ie, persons in detention) are not eligible for this study.
The total blood volume to be collected is considered to be an acceptable amount of blood to be
collected over this time period from the population in this study based upon the standard of the Japan
Red Cross (400 mL x β~γ times/year of blood for donation).


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Status: Approved, Date:  β9 November β0β1
4.3. 
Justification for Dose
Higher doses and more frequent administration have generally resulted in greater proportions of
patients achieving higher levels of response across disease indications. The planned regimen in
this trial is the highest and most frequent regimen in the approved indication (Crohn’s disease) as
well as ongoing Phase γ studies (ulcerative colitis and SLE). Given the multi-organ systemic
involvement of PM/DM, higher exposures enabled by IV dosing and resultant more rapid onset of
action might be important in maximizing efficacy in PM/DM. In addition, safety data of the
planned regimen (in combination with standard treatment including systemic glucocorticoids and
immunosuppressant agents) were obtained and analyzed in previous clinical trials in participants
with Crohn’s disease, ulcerative colitis, or SLE. The existing safety data from these studies using
the same dosing regimen will provide evidence of the safety of the selected dose in this trial.
Similar clinical features are observed in PM/DM and SLE. Genome-wide association studies
indicate the potential overlap of pathogenesis between myositis and SLE, and biomarker findings
also suggest similarity between DM and SLE. Standard treatments for SLE include systemic
glucocorticoids and immunosuppressants, which are also common treatments for PM/DM. Results
from a Phase β study of ustekinumab in SLE has suggested the effectiveness of ustekinumab in
patients with SLE. PK parameters of ustekinumab have, in general, been similar across multiple
indications, including psoriasis, PsA, Crohn’s disease, and SLE after correcting for body weight-
related PK differences. Study CNTO1β75SLEβ001 has shown that treatment with ustekinumab
administered as an ~6 mg/kg IV dose following by 90 mg SC dose at Week 8 and then every 8
weeks thereafter was efficacious and generally well tolerated in subjects with SLE. The safety
profile of this dose regimen in the CNTO1β75SLEβ001 study was consistent with the well-
established profile observed in several large-scale Phase γ Crohn’s disease studies. Taking the
overlapping features of PM/DM and SLE into account, the planned regimen may be effective in
patients with PM/DM.
4.4. 
End of Study Definition
The end of study is considered as the last follow-up assessment at Week 88 for the last participant
in the study. The final data from the study site will be sent to the sponsor (or designee) after
completion of all Week 88 assessments of the last participant at that study site, in the time frame
specified in the Clinical Trial Agreement. 
5. 
STUDY POPULATION 
Screening for eligible participants will be performed within 6 weeks before administration of the
study drug. Refer to Section 5.4, Screen Failures for conditions under which the repeat of any
screening procedure is allowed.
The inclusion and exclusion criteria for enrolling participants in this study are described below. If
there is a question about these criteria, the investigator must consult with the appropriate sponsor
representative and resolve any issues before enrolling a participant in the study. Waivers are not
allowed. 


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For a discussion of the statistical considerations of participant selection, refer to Section 9.β,
Sample Size Determination.
5.1. 
Inclusion Criteria 
Each potential participant must satisfy all of the following criteria to be enrolled in the study: 
1. 
Be male or female (according to their reproductive organs and functions assigned by
chromosomal complement).
β. 
Must sign an informed consent form (ICF) (or their legally acceptable representative
must sign) indicating that he or she understands the purpose of, and procedures required
for, the study and is willing to participate in the study.
γ. 
Must sign a separate ICF (or their legally acceptable representative must sign) if he or
she agrees to provide an optional DNA sample for research. Refusal to give consent for
the optional DNA research sample does not exclude a participant from participation in
the study
4. 
Be willing and able to adhere to the prohibitions and restrictions specified in this
protocol.
5. 
Be between 18 and 75 years of age, inclusive.
6. 
Must be medically stable on the basis of clinical laboratory tests performed at screening.
If the results of the serum chemistry panel, other specific tests, blood coagulation,
hematology, or urinalysis except for items specified in Inclusion Criteria #β0 and β1 are
outside the normal reference ranges, the participant may be included only if the
investigator judges the abnormalities or deviations from normal to be not clinically
significant or to be appropriate and reasonable for the population under study. This
determination must be recorded in the participant's source documents and initiated by
the investigator.
7. 
Has a diagnosis of PM/DM made or confirmed by a physician (such as a rheumatologist,
neurologist, or dermatologist) experienced in treatment of PM/DM.
8. 
Has a documented medical history that participant met the diagnostic criteria of
probable or definite IIM based on β017 European League Against Rheumatism
(EULAR)/American College of Rheumatology (ACR) classification criteria for adult
and juvenile idiopathic inflammatory myopathies at least 6 weeks prior to first dose of
the study drug. 
If a participant with PM did not have history of muscle biopsy, score of classification
cannot be calculated. If a participant with DM did not have history of muscle biopsy,
score of classification must be calculated based on score without muscle biopsy. In
addition, the diagnosis based on subclassification criteria must be 1 of following;


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 
PM, DM
9. 
Demonstrable muscle weakness at screening and Week 0 measured by the MMT-8 of
≤1γ5 units.
10. 
Demonstrable muscle weakness at screening measured by any β or more of the
followings:
 
PhGA ≥1.5 cm
 
1 or more muscle enzymes (CK and aldolase) ≥1.4×upper limit of normal (ULN)
 
MDAAT-Extramuscular Global Assessment ≥1.5 cm
11. 
Has PM or DM which is considered active despite receiving at least 1 standard-of-care
treatment by the investigator.
1β. 
Criterion modified per Amendment β:
1β.1 Must be receiving 1 or more of the following protocol-permitted, systemic
standard-of-care treatments:
 
If using oral glucocorticoids, must be administered for ≥6 weeks and at a stable
dose for ≥β weeks prior to first dose of the study drug. If not receiving
immunomodulatory drugs and only using oral glucocorticoid as standard treatment,
its daily dose must be between 0.β5 mg/kg and 1.0 mg/kg of prednisolone or
equivalent at first dose of the study drug.
If currently not using oral glucocorticoids, must not have received them for ≥6 weeks
prior to the first dose of the study drug.
 
If using 1 or β of the following immunomodulatory drugs within the range of
maximum dose or concentration, must be receiving all of those for ≥8 weeks and
be on a stable dose for ≥4 weeks prior to first dose of the study drug:
 
MMF ≤γ g/day
 
AZA 1 to β mg/kg/day; up to γ mg/kg/day
 
Oral MTX ≤15 mg/week with concomitant folic acid or calcium folinate
 
Oral TAC targeting trough concentration of 5 to 10 ng/mL
 
Oral cyclosporine A targeting trough concentration of 100 to 150 ng/mL
1γ. 
Criterion modified per Amendment β:
1γ.1 Regular or as needed treatment with topical use of glucocorticoids are permitted
to treat skin lesions on a stable dose for ≥β weeks prior to first dose of the study
drug (see Section 6.5.4. for potency of topical glucocorticoids).


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14. 
Contraceptive (birth control) use by men or women should be consistent with local
regulations regarding the acceptable methods of contraception for those participating in
clinical studies.
Typical use failure rates may differ from those when used consistently and correctly.
Use should be consistent with local regulations regarding the use of contraceptive
methods for participants in clinical studies.
A woman must be (as defined in Section 10.5, Appendix 5: Contraceptive and Barrier
Guidance and Collection of Pregnancy Information),
a. Not of childbearing potential
b. Of childbearing potential and
o 
Practicing a highly effective method of contraception (failure rate of <1%
per year when used consistently and correctly) and agrees to remain on a
highly effective method throughout the study and for at least 16 weeks
after the last dose of the study drug-the end of relevant systemic exposure.
Examples of highly effective methods of contraception are described in
Section 10.5, Appendix 5: Contraceptive and Barrier Guidance and
Collection of Pregnancy Information.
o 
Pregnancy testing (serum or urine) at the end of study intervention.
Note: If childbearing potential changes after start of the study (eg, a woman who is not
heterosexually active becomes active, or a premenarchal woman experiences menarche)
a woman must begin a highly effective method of birth control, as described above.
15. 
A woman of childbearing potential must have a negative highly sensitive serum/urine
(ȕ human chorionic gonadotropin [ȕ-hCG]) obtained during screening and at Week 0
before the first dose of the study drug.
16. 
A woman using oral contraceptives must use an additional contraceptive method (above
that required in Inclusion Criterion #14).
17. 
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the study and for 4 months after receiving the last dose of the study
drug.
18. 
When a man engaging in any activity that allows for passage of ejaculate to another
person and a man has not had a vasectomy, he must agree to use a barrier method of
birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or
partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/suppository. All men must not donate sperm for the purpose of
reproduction during the study and for β0 weeks after receiving the last dose of the study
drug.


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Note: Use should be consistent with local regulations regarding the use of contraceptive
methods for participants.
19. 
Are considered eligible according to the following TB screening criteria:
a. Have no history of latent or active TB prior to screening. An exception is made
for participants who have a history of latent TB and are currently receiving
treatment for latent TB, will initiate treatment for latent TB at least γ weeks
prior to the first administration of the study drug, or have documentation of
having completed appropriate treatment for latent TB within γ years prior to
the first administration of the study drug. It is the responsibility of the
investigator to verify the adequacy of previous antituberculous treatment and
provide appropriate documentation.
b. Have no signs or symptoms suggestive of active TB upon medical history
and/or physical examination.
c. Have had no recent close contact with a person with active TB or, if there has
been such contact, will be referred to a physician specializing in TB to undergo
additional evaluation and, if warranted, receive appropriate treatment for latent
TB at least γ weeks prior to the first administration of the study drug.
d. Within 6 weeks prior to the first administration of the study drug, has a
negative interferon gamma release assays (IGRAs) result, or have a newly
identified positive IGRAs result in which active TB has been ruled out and for
which appropriate treatment for latent TB has been initiated at least γ weeks
prior to the first administration of the study drug. A participant whose first
IGRA result is indeterminate should have the test repeated. In the event that
the second IGRA result is also indeterminate, the participant should be
excluded from the study.
NOTE: IGRA is not required at screening for participants with a history of latent TB
and ongoing treatment for latent TB or documentation of having completed adequate
treatment as described above; Participants with documentation of having completed
adequate treatment as described above are not required to initiate additional treatment
for latent TB.
e. Have a chest radiograph (both posterior-anterior and lateral views) or chest
CT, taken within γ months prior to the first administration of the study drug
and read by a radiologist or pulmonologist, with no evidence of current, active
TB or old, inactive TB.
β0. 
Participants must have laboratory test results within the following parameters at
screening:
 
Hemoglobin ≥8.0 g/dL (International System of Units [SI]: ≥80 g/L)
 
Lymphocytes ≥0.5×10γ/µL (SI: ≥0.5 GI/L)
 
Neutrophils ≥1.5×10γ/µL (SI: ≥1.5 GI/L)


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Status: Approved, Date:  β9 November β0β1
 
Platelets ≥75×10γ/µL (SI: ≥75 GI/L)
 
Serum creatinine ≤1.9β mg/dL (SI: ≤170 µmol/L)
β1. 
The AST and ALT levels must be within γ×ULN range for the laboratory conducting
the test, except that elevation of AST or ALT is considered directly due to disease
activity of myositis by the investigator based on muscle enzyme (CK or aldolase) levels.
ββ. 
A one-time repeat of these screening laboratory tests (ie, hemoglobin, lymphocytes,
neutrophils, platelets, serum creatinine, AST, and ALT) is allowed during the 6-week
screening period and the investigator may consider the participant eligible if the
previously abnormal laboratory test result is within an acceptable range on repeat testing
at the central laboratory. A screening laboratory test analyzed by the central laboratory
may be repeated more than once in the event of suspected error in sample collection or
analysis as long as the result is obtained within the 6-week screening period.
βγ. 
Participants with other marked disease-associated laboratory abnormalities may be
included only if the investigator judges the abnormalities or deviations from normal to
be not clinically significant or to be appropriate and reasonable for the population under
study. This determination must be recorded in the participant’s source documents and
initialed by the investigator. Participants with Common Terminology Criteria for
Adverse Events (CTCAE) Grade γ or Grade 4 laboratory abnormalities must be
discussed with the sponsor to determine eligibility for enrollment.
5.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study: 
1. 
Has myositis other than PM/DM, including but not limited to ADM, clinically
amyopathic DM, juvenile DM, inclusion body myositis (IBM), immune-mediated
necrotizing myopathy diagnosed based on muscle biopsy findings and positive anti-
SRP or anti-HMGCR antibody, drug-induced myositis, PM associated with human
immunodeficiency virus (HIV), muscular dystrophy, congenital myopathy, metabolic
myopathy, and mitochondrial myopathy.
β. 
Has other inflammatory diseases that might confound the evaluations of efficacy,
including but not limited to rheumatoid arthritis (RA), PsA, SLE, psoriasis, or Crohn’s
disease.
γ. 
Has severe or progressive ILD, which was confirmed by the investigator based on
HRCT findings, clinical course consistent with ILD, and consultation with a
pulmonologist. Findings from HRCT at screening should not show clinically significant
worsening compared to past HRCT or comparable CT results taken at least γ months


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Status: Approved, Date:  β9 November β0β1
before screening. The eligibility of ILD may be determined considering the following
but not limited to;
 
Presence of dyspnea on exertion with normal activities of daily living or low grade
exertion (eg, walking), or a recent change in exercise tolerance due to dyspnea
 
Partial pressure of oxygen in arterial blood (PaOβ) of less than 80 mm Hg while
breathing ambient air at rest, not accompanied by abnormal increase of PaCOβ
 
Vital capacity (VC) <80% predicted, or diffusing capacity of the lungs for carbon
monoxide (DLCO) <65% predicted
4. 
Has positive test result of anti-MDA5 antibody (anti-CADM-140 antibody).
5. 
Has severe respiratory muscle weakness confirmed by the investigator based on the
consultation with a pulmonologist and the measures of respiratory muscle strength such
as maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) and/or
maximal voluntary ventilation (MVV) measurements and lung capacity such as forced
vital capacity (FVC). The results need to be within population appropriate normal
limits.
6. 
Has severe muscle damage (Myositis Damage Index-VAS [Muscle Damage] >7 cm),
permanent weakness due to a nonIIM cause, or myositis with cardiac dysfunction.
7. 
Has glucocorticoid-induced myopathy which the investigator considers the primary
cause of muscle weakness.
8. 
Is pregnant, nursing, planning a pregnancy, or planning to father a child while enrolled
in the study or within 4 months after receiving the last administration of the study drug.
9. 
Is an employee of the investigator or study site (ie, personnel to whom the investigator
has delegated a role or responsibility for conducting the study), with direct involvement
in the proposed study or other studies under the direction of that investigator or study
site, as well as family members of the employees or the investigator.
10. 
Lives in an institution on court or authority order, unless permitted by local regulations.
11. 
Any condition for which, in the opinion of the investigator, participation would not be
in the best interest of the participant (eg, compromise the well-being) or that could
prevent, limit, or confound the protocol-specified assessments.
Concomitant or previous medical therapies received:
1β. 
Has received systemic immunomodulatory agents other than those described in
inclusion criteria within 8 weeks or 5 half-lives, whichever is longer, prior to the first
dose of the study drug. Glucocorticoids are not included in this criterion; see
Section 6.5.β regarding glucocorticoid use.


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1γ. 
Has used oral cyclophosphamide within 1β weeks or IV cyclophosphamide within β4
weeks prior to the first dose of the study drug.
14. 
Has ever received ustekinumab.
15. 
Has received prior IV immunoglobulin (Ig) or immunomodulatory biologic therapy not
described in Section 6.6, Prohibited Therapies such as guselkumab, risankizumab,
belimumab, epratuzumab, tocilizumab, alefacept, efalizumab, natalizumab, abatacept,
anakinra, brodalumab, secukinumab, ixekizumab, or agents whose mechanism of action
targets B cell, tumor necrosis factor alpha (TNFα), IL-1, IL-β, IL-6, IL-17, IL-βγ, or
IFN pathways, within 5 half-lives or 1β weeks, whichever is longer, prior to first dose
of the study drug. Has received rituximab within β4 weeks prior to first dose of the
study drug.
16. 
Has received adrenocorticotropic hormone (ACTH) administered by injection within
1 month prior to the first administration of the study drug.
17. 
Has received topical immunomodulatory agents (such as tacrolimus, cyclosporine A)
within 4 weeks prior to the first dose of the study drug.
18. 
Has received an investigational drug that is not previously defined in other exclusion
criteria (including investigational vaccines, branched-chain amino acids, or other
medications specified in Section 6.6) within 5 half-lives or 1β weeks, whichever is
longer, or used an invasive investigational medical device within 1β weeks before the
planned first dose of the study drug, or is currently enrolled in an interventional study.
19. 
Is currently receiving allergen immunotherapy such as cedar pollen.
β0. 
Participants likely to require multiple courses of systemic glucocorticoids for reasons
other than PM/DM (eg, uncontrolled asthma, uncontrolled chronic obstructive
pulmonary disease, etc) should be excluded from study participation.
β1. 
Has received epidural, IV, SC, intramuscular (IM), intra-articular, intrabursal, or
intralesional administration of glucocorticoids within 6 weeks prior to the first
administration of the study drug.
ββ. 
Use of apheresis therapy (including but not limited to plasmapheresis, photopheresis,
leukocytapheresis), or immunoadsorption is prohibited within β4 weeks prior to the first
administration of the study drug.
βγ. 
Has ever received stem cell transplantation (including hematopoietic stem cell
transplantation and mesenchymal stem cell transplantation).


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Infections or predisposition to infections:
β4. 
Has had a Bacille Calmette-Guérin (BCG) vaccination within 1β months of screening.
β5. 
Has received a live virus or live bacterial vaccination within 16 weeks prior to the first
administration of the study drug.
β6. 
Has a history of active granulomatous infection, including histoplasmosis, or
coccidioidomycosis. Refer to Section 5.1 for information regarding eligibility with a
history of latent TB.
β7. 
Has a chest radiograph or chest HRCT within γ months prior to the first administration
of the study drug that shows an abnormality suggestive of a malignancy or current active
infection, including TB. Radiographic findings such as pulmonary nodules should be
evaluated by an experienced radiologist and/or pulmonologist to determine whether the
presentation is suggestive of infection or active malignancy and final assessment
documented by the investigator prior to randomization.
β8. 
Has had a nontuberculous mycobacterial infection or opportunistic infection (eg,
cytomegalovirus, pneumocystosis, aspergillosis).
β9. 
Has a history of, or ongoing, chronic or recurrent infectious disease, including but not
limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), chronic
infectious sinusitis, recurrent urinary tract infection (eg, recurrent pyelonephritis), an
open, draining, or infected skin wound or ulcer.
γ0. 
Has a history of HIV antibody positive, or tests positive for HIV at screening.
γ1. 
Has a hepatitis B infection. Participants must undergo screening for hepatitis B virus
(HBV). At a minimum, this includes testing for HBV surface antigen (HBsAg), HBV
surface antibody (anti-HBs), and HBV core antibody total (anti-HBc total).
γβ. 
Is seropositive for antibodies to hepatitis C virus (HCV), unless has β negative HCV
ribonucleic acid (RNA) test results 6 months apart prior to screening and has a third
negative HCV RNA test result at screening.
γγ. 
Has experienced a recent single dermatomal herpes zoster eruption within the past 4
months or has experienced multiple eruptions of herpes zoster within the past 18 years.
Has ever had multi-dermatomal herpes zoster (defined as appearance of lesion outside
the primary or adjacent dermatome) or central nervous system zoster infection.
γ4. 
Within β months prior to the first administration of the study drug, has had a serious
infection (eg, pneumonia, sepsis, or pyelonephritis), or has been hospitalized for an
infection, or has been treated with IV antibiotics for an infection. Less serious infections


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(eg, acute upper respiratory tract infection, simple urinary tract infection) need not be
considered exclusionary at the discretion of the investigator.
Concurrent medical conditions or past medical history and procedures:
γ5. 
Has a known hypersensitivity to human Ig proteins (eg, IV Ig).
γ6. 
Has known allergies, hypersensitivity, or intolerance to ustekinumab or its excipients
(see Section 6.1and the ustekinumab IB9).
γ7. 
Any major illness/condition or evidence of an unstable clinical condition (eg, renal,
hepatic, significant cardiac, vascular, hematologic, gastrointestinal, endocrine,
pulmonary, neurologic, rheumatologic, immunologic, psychiatric, metabolic
disturbances), disease of any organ system, or active acute or chronic
infection/infectious illness that, in the investigator’s judgment, will substantially
increase the risk to the participant if he or she participates in the study.
γ8. 
Has advanced chronic kidney disease such as end-stage renal disease or receives
hemodialysis.
γ9. 
Has past history of severe ILD flare, severe non-infectious lung inflammation which
required active intervention (systemic glucocorticoid or other immunomodulators), or
multiple relapses of these conditions.
40. 
Has had major surgery, (eg, requiring general anesthesia) within 1 month before
screening, or will not have fully recovered from surgery, or has major surgery (eg,
requiring general anesthesia) planned during the time the participant is expected to
participate in the study or within 1 month after the last dose of the study drug
administration.
Note: Participants with planned minor surgical procedures to be conducted under local
anesthesia may participate after discussion with the sponsor.
41. 
Has a transplanted organ (except for a corneal transplant performed >γ months prior to
the first administration of the study drug).
4β. 
Has or has had a substance abuse (drug or alcohol) problem within the previous γ years.
4γ. 
Is unwilling or unable to undergo multiple venipunctures because of poor tolerability
or lack of easy venous access.
Malignancy or increased potential for malignancy:
44. 
Presence or history of malignancy within 5 years before screening (exceptions are
squamous and basal cell carcinomas of the skin that has been treated with no evidence


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of recurrence for at least γ months before the first study drug administration and
carcinoma in situ of the cervix that has been documented to be surgically cured).
45. 
Has positive cancer screening test dependent on the status of anti-TIF1- Ȗ antibody as
follows;
 
Has negative test result for anti-TIF1- Ȗ antibody and positive cancer screening test
provided by local governments or equivalent test (Section 10.7, Appendix 7:
Cancer Screening Test) including gastric cancer, lung cancer, cervical cancer,
breast cancer, and/or colon cancer within β years before the first study drug
administration if the age and sex of participants are qualified.
 
Has positive test result for anti-TIF1- Ȗ antibody and positive cancer screening test
provided by local governments (Section 10.7, Appendix 7: Cancer Screening Test)
including gastric cancer, lung cancer, cervical cancer, breast cancer, and/or colon
cancer within β years before the first study drug administration irrespective of age
if the sex of participants is qualified.
46. 
Has a known history of lymphoproliferative disease, including lymphoma, or signs and
symptoms 
suggestive 
of 
possible 
lymphoproliferative 
disease, 
such 
as
lymphadenopathy of unusual size or location, clinically significant splenomegaly,
history of splenectomy, or history of monoclonal gammopathy of undetermined
significance.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening.
If a participant's clinical status changes (including any available laboratory results or receipt of
additional medical records) after screening but before the first dose of the study drug is given such
that he or she no longer meets all eligibility criteria, then the participant should be excluded from
participation in the study. Section 5.4, Screen Failures, describes options for retesting. The
required source documentation to support meeting the enrollment criteria are noted in Section 10.β,
Appendix β: Regulatory, Ethical, and Study Oversight Considerations. The sponsor reserves the
right to discontinue the participant for any operational or safety reasons.
5.3. 
Lifestyle Considerations 
Potential participants must be willing and able to adhere to the following lifestyle restrictions
during the course of the study to be eligible for participation:
1. 
Agree to avoid vigorous intensity exercise such as running, contact sports, and weight
training throughout the study.
β. 
Agree to avoid starting exercise therapy throughout the study. In case participants
already receive exercise therapy regularly before screening, they must not change the
intensity and frequency of exercise therapy throughout the study.
γ. 
Agree to use sun protective measures (such as a hat, sunglasses, protective clothing,
sunscreen), limit prolonged exposure to natural sunlight, and avoid artificial sunlight


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(tanning beds or phototherapy) from baseline until the last dose of the study drug for
participants with DM.
4. 
Refer to Section 6.5, Concomitant Therapy for details regarding prohibited and
restricted therapy during the study.
5. 
Agree not to receive a live virus or live bacterial vaccination during the study. Subjects
must also agree not to receive BCG vaccination for 1β months after last dose of study
agent, or any other live vaccine for 16 weeks after receiving the last administration of
study agent.
6. 
Agree to follow all requirements that must be met during the study as noted in the
Inclusion and Exclusion Criteria (eg, contraceptive requirements).
5.4. 
Screen Failures
Participant Identification, Enrollment, and Screening Logs
The investigator agrees to complete a participant identification and enrollment log to permit easy
identification of each participant during and after the study. This document will be reviewed by
the sponsor study site contact for completeness.
The participant identification and enrollment log will be treated as confidential and will be filed
by the investigator in the study file. To ensure participant confidentiality, no copy will be made.
All reports and communications relating to the study will identify participants by participant
identification and age at initial informed consent. In cases where the participant is not randomized
into the study, the date seen and age at initial informed consent will be used.
Rescreening
A one-time repeat of screening laboratory tests (eg, hemoglobin, lymphocytes, neutrophils,
platelets, serum creatinine, AST, and ALT) and screening imaging tests (chest x-ray and HRCT)
is allowed during the 6-week screening period and the investigator may consider the participant
eligible if the previously abnormal laboratory test result or imaging finding is within an acceptable
range on repeat testing at the central laboratory. A screening laboratory tests analyzed by the
central laboratory may be repeated more than once in the event of suspected error in sample
collection or analysis as long as the result is obtained within the 6-week screening period. A
screening imaging test may be repeated once after a period of at least γ0 days.
The goal of the retest procedure is to assess if the participant is eligible for randomization within
the screening window or is a screen failure. Participants who have laboratory values that do not
meet entry criteria following the retest or do not meet disease activity criteria following the repeat
procedure are to be deemed screen failures. Exceptions to this are positive IGRAs, hepatitis C or
B, or HIV tests; unless there is a suspected error in sample collection or analysis performance,
these tests may not be repeated to meet eligibility criteria.


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If a participant is a screen failure, the participant may be rescreened 1 additional time after a period
of at least γ0 days. Participants who are rescreened will be assigned a new participant number,
undergo the informed consent process again, and restart a new screening phase with carrying
screening test results over from previous screening if appropriate.
6. 
STUDY DRUG 
6.1. 
Study Drugs Administered
Intravenous Administration
Ustekinumab supplied for this study is a single-use, sterile solution in γ0 mL vials with 1 dose
strength (ie, 1γ0 mg in β6 mL nominal volume). In addition to ustekinumab, the solution contains
10 mM L-histidine, 8.5% (w/v) sucrose, 0.04% (w/v) polysorbate 80, 0.4 mg/mL L-methionine,
and β0 μg/mL ethylenediaminetetraacetic acid (EDTA) disodium salt dihydrate at pH 6.0. No
preservatives are present.
Placebo administrations will have the same appearance as the respective ustekinumab
administrations. Matching placebo for final vialed product (IV) is supplied as single-use, sterile
solution in γ0 mL vials with a β6 mL nominal volume. The composition of the placebo is 10 mM
L-histidine, 8.5% (w/v) sucrose, 0.04% (w/v) polysorbate 80, 0.4 mg/mL L-methionine, and
β0 µg/mL EDTA disodium salt dihydrate at pH 6.0. No preservatives are present. 
Subcutaneous Administration
Ustekinumab will also be supplied as a single-use prefilled syringe (PFS) in a strength of 90 mg
in 1 mL nominal volume for SC administration. Each 1 mL of ustekinumab solution in the PFS
contains 90 mg ustekinumab with nominal excipient concentrations of 6.7 mM L-histidine, 7.6%
(w/v) sucrose, 0.004% (w/v) polysorbate 80, at pH 6.0. No preservatives are present. The needle
cover on the PFS contains dry natural rubber (a derivative of latex), which may cause allergic
reactions in individuals sensitive to latex.
Placebo administrations will have the same appearance as the respective ustekinumab
administrations. Liquid placebo will also be supplied in a 1 mL PFS, and have a composition
10 mM L-histidine, 8.5% (w/v) sucrose, 0.004% (w/v) polysorbate 80, at pH 6.0. No preservatives
are present. The needle cover on the PFS contains dry natural rubber (a derivative of latex), which
may cause allergic reactions in individuals sensitive to latex. 
The study drug administration must be captured in the source documents and the electronic case
report form (eCRF.) 
Ustekinumab will be manufactured and provided under the responsibility of the sponsor. Refer to
the IB for a list of excipients.9
Dosage Administration
Following randomization at Week 0, participants assigned to the active treatment group will
receive an initial body weight-range based IV dose ~6 mg/kg of ustekinumab (ustekinumab


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β60 mg weight ≤55 kg; ustekinumab γ90 mg weight >55 kg and ≤85 kg; ustekinumab 5β0 mg
weight >85 kg), and participants who were randomized to placebo will receive a single IV dose of
placebo. Starting at Week 8, participants will receive SC dosing with either placebo or
ustekinumab 90 mg q8w through Week β4. At Week β4, participants receiving placebo will
crossover to receive body weight-range based IV administration of ustekinumab. At Week β4, it
is recommended that SC dosing is administrated after completion of IV administration. SC dosing
may be administered before assessment of infusion reactions. However, IV and SC administration
to the same limb should be avoided. Starting at Week γβ, all participants will receive ustekinumab
90 mg SC q8w through Week 7β.
Week 0 up to Week 16
Group 1: Participants will receive body weight-range based IV dosing of ~6 mg/kg of
ustekinumab at Week 0 followed by ustekinumab 90 mg SC administrations at Weeks 8 and 16.
Group 2: Participants will receive IV dosing of placebo at Week 0 followed by placebo SC
administrations at Weeks 8 and 16.
Week 24
Group 1: Participants will receive IV dosing of placebo and ustekinumab 90 mg SC administration.
Group 2: Participants will receive body weight-range based IV dosing of ~6 mg/kg of
ustekinumab and placebo SC administration.
Week 32 up to Week 72
Groups 1 and 2: Participants will receive ustekinumab 90 mg SC q8w administrations through
Week 7β.


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Description of Interventions
Arm Name 
Group 1 
Group 1 
Group 1/β 
Group β 
Group β 
Group β
Intervention Name 
Ustekinumab 
Ustekinumab 
Placebo 
Placebo 
Ustekinumab 
Ustekinumab
Type 
Stud y drug 
Dose Formulation 
 
a single-use, sterile 
solution in γ0 mL 
vials with 1 dose 
strength (ie, 1γ0 mg 
in β6 mL nominal 
volume) 
a single-use PFS  
for SC 
administration 
single-use, sterile 
solution in γ0 mL 
vials with a β6 mL 
nominal volume 
a single-use PFS 
for SC 
administration 
  
a single-use, sterile 
solution in γ0 mL 
vials with 1 dose
strength (ie, 1γ0 mg
in β6 mL nominal
volume)
a single-use PFS
for SC administration
Dosage Level(s) 
 
At Week 0 
Body weight-range 
based IV dosing* 
At Week 8 and q8w 
through Week 7β 
90 mg 
At Week β4(Group1) 
At Week 0(Group β) 
Body weight-range 
based IV dosing*
At Week 8 and 16 
90 mg  
At Week β4 
Body weight-range 
based IV dosing* 
At Week γβ and q8w
through Week 7β
90 mg
Route of 
Administration
IV 
SC 
IV 
SC 
IV 
SC
Use 
 
Treatment 
Treatment 
To maintain the 
blind (Group 1) 
Placebo-comparator
(Group β)
Placebo- 
comparator
Treatment 
Treatment
Sourcing 
Provided centrall y b y the Sponsor
Packaging and 
Labeling 
 
The investigational supplies will be uniquely packaged to assure that they are appropriately managed throughout the supply chain process.
The study drug will be packaged in individual participant kits. Each kit will consist of a single vial or PFS packaged inside a protective outer
carton.
Child Resistant 
or Not
Not in child resistant packaging
*The body weight-range based doses are based on the following:
Body weight ≤55 kg: β60 mg ustekinumab (β vials)
Body weight ˃55 kg and ≤85 kg: γ90 mg ustekinumab (γ vials)
Bod y weight ˃85 kg: 5β0 m  g ustekinumab (4 vials)


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6.2. 
Preparation/Handling/Storage/Accountability
All study drug must be stored at controlled temperatures ranging from γ6°F to 46°F (β°C to 8°C). 
Refer to the pharmacy manual/study site investigational product and procedures manual for
additional guidance on the study drug preparation, handling, and storage.
The investigator is responsible for ensuring that all the study drug received at the site is inventoried
and accounted for throughout the study. The study drug administered to the participant must be
documented on the study drug accountability form. All study drug will be stored and disposed of
according to the sponsor's instructions. Study site personnel must not combine contents of the
study drug containers.
Study drug must be handled in strict accordance with the protocol and the container label, and
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate
environmental conditions. Unused study drug must be available for verification by the sponsor's
study site monitor during on-site monitoring visits. The return to the sponsor of unused study drug,
will be documented on the intervention return form. When the study site is an authorized
destruction unit and study drug supplies are destroyed on-site, this must also be documented on
the intervention return form.
Potentially hazardous materials such as used vials containing hazardous liquids, should be
disposed of immediately in a safe manner and therefore will not be retained for intervention
accountability purposes. 
The study drug should be dispensed under the supervision of the investigator or a qualified member
of the study site personnel, or by a hospital/clinic pharmacist. The study drug will be supplied only
to participants participating in the study. Returned study drug must not be dispensed again, even
to the same participant. The study drug may not be relabeled or reassigned for use by other
participants. The investigator agrees neither to dispense the study drug from, nor store it at, any
site other than the study sites agreed upon with the sponsor.
6.3. 
Measures to Minimize Bias: Randomization and Blinding
Study Drug Allocation
Procedures for Randomization and Stratification
Central randomization will be implemented in this study. Participants will be randomly assigned
to 1 of β intervention groups based on a computer-generated randomization schedule prepared
before the study by or under the supervision of the sponsor. The randomization will be balanced
by using randomly permuted blocks and will be stratified by disease subset (PM/DM) and baseline
treatment level (glucocorticoid dose [≥0.5 mg/kg/day or <0.5 mg/kg/day of prednisolone or
equivalent]). The interactive web response system (IWRS) will assign a unique intervention code,
which will dictate the study drug assignment and matching study drug kit for the participant. The
requestor must use his or her own user identification and personal identification number when


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contacting the IWRS and will then give the relevant participant details to uniquely identify the
participant.
Blinding
The investigator will not be provided with randomization codes. The codes will be maintained
within the IWRS, which has the functionality to allow the investigator to break the blind for an
individual participant.
Data that may potentially unblind the intervention assignment will be handled with special care to
ensure that the integrity of the blind is maintained and the potential for bias is minimized. This can
include making special provisions, such as segregating the data in question from view by the
investigators, clinical team, or others as appropriate until the time of DBL and unblinding.
Under normal circumstances, the blind should not be broken until all participants have completed
the study and the database is finalized. The investigator may in an emergency determine the
identity of the study drug by contacting the IWRS. While the responsibility to break the
intervention code in emergency situations resides solely with the investigator, it is recommended
that the investigator contact the sponsor or its designee if possible to discuss the particular situation,
before breaking the blind. Telephone contact with the sponsor or its designee will be available
β4 hours per day, 7 days per week. In the event the blind is broken, the sponsor must be informed
as soon as possible. The date, time, and reason for the unblinding must be documented by the
IWRS in the appropriate section of the eCRF, and in the source document. The documentation
received from the IWRS indicating the code break must be retained with the participant's source
documents in a secure manner.
In this study, 4 DBLs are planned. These are DBLs at Week β4, Week 5β, Week 7β, and Week 88.
In addition to these 4 DBLs, one DBL will occur for the interim analysis of futility. Investigative
study sites and participants will remain blinded to initial treatment assignment until the DBL at
Week 5β. After the Week β4 DBL, the data will be unblinded to sponsor for analysis while
participants are still participating in the study. Identification of sponsor personnel who will have
access to the unblinded participant data during the period from the Week β4 DBL to the Week 5β
DBL will be documented prior to unblinding to sponsor. After Week β4, participants who are
randomized to placebo group will crossover to receive ustekinumab and all the participants will
enter the cross-over administration phase to allow for evaluation of the long-term efficacy and
safety of ustekinumab.
6.4. 
Study Drug Compliance 
Study site personnel will maintain a log of all the study drug administered. Drug supplies for each
participant will be inventoried and accounted for. The study drug will be administered as an IV
infusion or SC by qualified study site personnel and the details of each administration will be
recorded in the eCRF (including date, start and stop times of the IV infusion, and volume infused).


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Additional details may be provided in a pharmacy manual/study site investigational product and
procedures manual that is provided separately and noted in Study-Specific Materials in Section 8,
Study Assessments and Procedures.
6.5. 
Concomitant Therapy 
All prestudy therapies administered up to 1β weeks before entry into screening must be recorded
at screening. Detailed information of prestudy topical and systemic PM/DM therapies including
dosage and frequency of administration must be recorded. For any therapies that were discontinued,
the reason for discontinuation (eg, no response, loss of response, intolerance, safety concern, etc)
should be documented. Modification of an effective preexisting therapy must not be made for the
explicit purpose of entering a participant into the study.
Concomitant PM/DM therapies and concomitant therapies for indication other than PM/DM must
be recorded throughout the study beginning with start of the first dose of study drug until 8 weeks
after the last dose of study drug. Concomitant therapies should also be recorded beyond 8 weeks
after the last dose of the study drug only in conjunction with new or worsening AEs, SAEs that
meet the criteria outlined in Serious Adverse Events in Section 8.γ.1, Time Period and Frequency
for Collecting Adverse Event and Serious Adverse Event Information.
All therapies (prescription or over-the-counter medications, including polypeptide/amino acid
agent, vaccines, vitamins, herbal supplements; non-pharmacologic therapies such as electrical
stimulation, acupuncture, special diets, exercise regimens) different from the study drug must be
recorded in the eCRF. Recorded information will include a description of the type of therapy,
duration of use, dosing regimen, route of administration, and indication. 
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in
which prohibited therapies are administered.
Every reasonable effort should be made to keep concomitant medications, except for
glucocorticoid (Table 1 and Table β), stable to avoid introducing non-protocol medications for
PM/DM disease activity through Week β4 or as specified in the following sections. Dose
stabilization of all concomitant medications is required prior to randomization (Section 6.5.1,
Prestudy and Concomitant Medications Through Week 80). All medications for the treatment of
PM/DM must meet study protocol guidelines (see Section 6.5.1, Prestudy and Concomitant
Medications Through Week 80). It is recommended that all other concomitant medications be
maintained at stable doses through Week β4 or through the 8-week safety follow-up for those
discontinuing the study prematurely on or before the Week β4 visit. If necessary, a concomitant
medication may be reduced or temporarily discontinued because of abnormal laboratory values,
safety and tolerability issues, concurrent illness, or the performance of a surgical procedure, but
the change and reason for the medication change should be clearly documented in the participant’s
medical record. Adjustments in concomitant therapies (Section 6.5.β, 6.5.γ, and 6.5.4) that do not
comply with the study protocol guidelines should not allowed through Week 80.
During the entire study, investigators should consider whether increases in permitted background
therapy due to increased PM/DM disease activity warrant discontinuation of the study drug. This


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should be discussed with the sponsor. If protocol-prohibited immunosuppressants, biologics (such
as abatacept or rituximab), cytotoxic agents (such as cyclophosphamide), Ig agent (such as
venoglobulin), IV glucocorticoids, apheresis therapy, or high average daily doses of oral
glucocorticoids (≥1 mg/kg/day of prednisolone or equivalent) are initiated for severe, progressive,
or unstable PM/DM disease activity (eg, Progressive ILD), the participant should be discontinued
from the study.
See Section 6.5.β for management of glucocorticoid therapy through Week 80.
6.5.1. 
Prestudy and Concomitant Medications Through Week 80
Limitation of concomitant medications must be followed through Week 80.
6.5.2. 
Glucocorticoid Therapy
Table 1 outlines oral glucocorticoid dose stabilization requirements prior to randomization and
allowable dosing during study period. Changing the kind of glucocorticoid is allowed as long as it
is the same equivalent dose. If participants have glucocorticoid-induced side effects such as
osteoporosis and hyperglycemia, they need to be treated properly in the judgment of the
investigator.
Table 1: 
Prestudy and Concomitant Glucocorticoid Use Through Week 80
Study period 
Allowable dose
Before randomization 
Daily dose must be ≥0.β5 mg/kg of prednisolone or equivalent for
≥6 weeks with stable dosing ≥β weeks prior to the first dose of the
study drug. Daily dose is allowed up to 1 mg/kg of prednisolone or
equivalent at randomization.
Week 0 through Week β 
No adjustments in glucocorticoid dose are permitted.
Week β through Week 16 
Glucocorticoid dose needs to be reduced based on the table of
glucocorticoid tapering schedule (See Table β). Reduction of
glucocorticoid dose should follow study drug administration at the
weeks of study drug administration. If current daily prednisolone or
equivalent dose is ≥50 mg, the dose will be reduced by 10 mg. If
current prednisolone or equivalent dose is <50 mg and ≥β0 mg, the
dose will be reduced by 5 mg. If current prednisolone or equivalent
dose is <β0 mg and ≥1β.5 mg, the dose will be reduced by β.5 mg. If
current prednisolone or equivalent dose is <1β.5 mg and ≥6 mg, the
dose will be reduced by 1 mg. Once the daily prednisolone or
equivalent dose reaches 5 mg, the reduction of glucocorticoid is not
necessary and can be done at the investigator’s discretion. Increase in
glucocorticoid dose up to baseline dose (Week 0) is permitted only
once through Week 16 after discussion with the sponsor. Continuing
the same glucocorticoid dose is permitted only once for less than
consecutive 6 weeks.
Week 16 through Week β4 
No adjustments in glucocorticoid dose are permitted.
Week β4 through Week 80 
Dose adjustment in glucocorticoid is allowed at the investigator’s
discretion as long as the glucocorticoid dose does not exceed the
baseline. Glucocorticoid dose reductions are strongl y encouraged.


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Table 2: 
Glucocorticoid Tapering Schedule (Daily Dose [mg] of Prednisolone or Equivalent)
Week 0 
Week 2 
Week 4 
Week 6 
Week 8 
Week 10 
Week 12 
Week 14 Week 16
60 
50 
40 
γ5 
γ0 
β5 
β0 
15 
1β.5
50 
40 
γ5 
γ0 
β5 
β0 
15 
1β.5 
10
40 
γ5 
γ0 
β5 
β0 
15 
1β.5 
10 
9
γ0 
β5 
β0 
15 
1β.5 
10 
9 
8 
7
β0 
15 
1β.5 
10 
9 
8 
7 
6 
5
15 
1β.5 
10 
9 
8 
7 
6 
5 
5
1β.5 
10 
9 
8 
7 
6 
5 
5 
5
10 
9 
8 
7 
6 
5 
5 
5 
5
6.5.3. 
Non-biologic Immunomodulators
Participants are allowed to use up to β of the following immunomodulatory drugs without any
change in dose from baseline (Week 0) through Week β4. Dose adjustment in immunomodulator
is allowed at the investigator’s discretion after Week β4 as long as the dose does not exceed the
baseline.
 
MMF 
 
AZA 
 
Oral MTX 
 
Oral TAC 
 
Oral cyclosporine A
6.5.4. 
Topical Medications
For the treatment of cutaneous lesion in participants with PM/DM or other concurrent medical
conditions, regular use of topical medications is permitted. However, topical compounds cannot
include a prohibited medication. Topical glucocorticoids must be medium/mild (Group IV) or
weak (Group V) potency glucocorticoids to treat cutaneous lesions of myositis or skin disease of
the same area as cutaneous lesions of myositis. Topical glucocorticoids may be very strong (Group
II) or weaker potency glucocorticoids to treat cutaneous lesions of other concurrent medical
conditions whose area is different from cutaneous lesions of myositis. “As needed” use of topical
glucocorticoids is permitted, but not within 48 hours prior to a study visit for efficacy assessment.
The investigator should notify the sponsor if topical glucocorticoids of very strong (Group II) or
weaker potency are used on skin lesion up to β weeks where there is no preexisting skin eruptions
of myositis in case it is considered due to adverse events other than cutaneous lesions of myositis.
6.5.5. 
Rescue Medication
The following rescue medications may be used if the investigator confirms the worsening of
myositis in such cases of evident elevation of muscle enzymes and the necessity of additional
treatment:


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 
Increase in glucocorticoid dose up to baseline dose is permitted only once after discussion
with the sponsor.
 
Continuing the same glucocorticoid dose is permitted only once for less than consecutive
6 weeks.
The use of rescue medications is allowable at Week β through Week 16 following the
administration of study drug. The date of rescue medication administration as well as the name
and dosage regimen of the rescue medication must be recorded.
6.6. 
Prohibited Therapies
Use of additional immunosuppressants or immunomodulators, other than those explicitly allowed
in the inclusion/exclusion criteria (Sections 5.1 and 5.β), are prohibited until Week 80 visit or
8 weeks safety follow-up including, but not limited to, the following:
 
B-cell targeting agents (anti-CDβ0 eg, rituximab, anti-B-cell activating factor [BAFF], also
known as B lymphocyte stimulator [BLyS], eg, belimumab, or anti-CDββ eg, epratuzumab,
or other B-cell targeting therapies, such as tabalumab, atacicept, daratumumab)
 
Agents targeted at reducing TNF (eg, infliximab, golimumab, certolizumab pegol, etanercept,
CT-P1γ, and adalimumab)
 
Interleukin-1 inhibitors (eg, canakinumab)
 
Interleukin-β inhibitors or exogenous IL-β therapy
 
Interferon inhibitors or exogenous IFN therapy
 
IL-1 receptor antagonist (eg, anakinra)
 
Any biologic targeting IL-6 or IL-6 receptor (eg, tocilizumab)
 
Any janus kinase (JAK) inhibitor (eg, tofacitinib)
 
Abatacept
 
Anti-IL-17 agents (eg, brodalumab, secukinumab, and ixekizumab)
 
Anti-IL-βγ agents (eg, guselkumab and risankizumab)
 
Leflunomide
 
Intravenous or subcutaneous Ig
 
Other immunomodulatory oral or topical preparations (eg, cyclosporine A and TAC) (see
Section 6.5.4)
 
Toll-like receptor inhibitors
 
Thalidomide or lenalidomide
 
Diaphenylsulfone
 
ACTH by injection
 
Epidural, IV, SC, IM, intra-articular, intrabursal, or intralesional administration of
glucocorticoids


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 
Branched-chain amino acids
Cytotoxic drugs that are prohibited during the study include, but are not limited to,
cyclophosphamide, chlorambucil, nitrogen mustard, or other alkylating agents.
The new use of drugs including but not limited to statins and fibrates that are known to cause drug-
induced myopathy is discouraged.
The use of complementary therapies (eg, herbs, ointments, traditional Chinese medicine,
acupuncture) that have the potential to activate or inhibit the immune system is prohibited. In
addition, use of complementary therapies that have the potential to interact with antithrombotic
agents is prohibited in those taking antithrombotic agents.
The use of other complementary therapies is strongly discouraged; in individual cases, use may be
permitted following discussion with the sponsor.
7. 
DISCONTINUATION OF STUDY DRUG AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL
7.1. 
Discontinuation of Study Drug
A participant's study drug must be discontinued if:
 
The investigator and sponsor believe that for safety reasons or tolerability reasons (eg, AE) or
due to severe, unstable, or rapidly progressive PM/DM disease activity it is in the best interest
of the participant to discontinue the study drug.
 
The participant becomes pregnant (Refer to Section 10.5, Appendix 5: Contraceptive and
Barrier Guidance and Collection of Pregnancy Information).
 
The participant experiences an AE temporally associated with the study drug infusion or
injection, resulting in bronchospasm with wheezing and/or dyspnea requiring ventilatory
support, or symptomatic hypotension with a greater than 40 mm Hg decrease in systolic blood
pressure.
 
The participant develops study drug hypersensitivity (eg, anaphylaxis, angioedema) reaction
that is reported as serious or severe.
 
The participant is diagnosed with a malignancy, with the exception of no more than β localized
basal cell skin cancers that are treated with no evidence of recurrence or residual disease.
 
The participant develops new ILD or experiences clinically significant worsening of
preexisting ILD during the study, confirmed by a pulmonologist based on HRCT findings and
the investigator concludes that the study drug needs to be discontinued (See Section 8.β.5).
 
The participant is deemed ineligible according to the following TB criteria:
 
A diagnosis of active TB is made.
 
A participant has symptoms suggestive of active TB based on follow-up assessment
questions and/or physical examination, or has had recent close contact with a person with
active TB, and cannot or will not continue to undergo additional evaluation.


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A participant undergoing evaluation has a chest radiograph with evidence of current
active TB and/or a positive IGRA result, unless active TB can be ruled out and appropriate
treatment for latent TB can be initiated prior to the next administration of the study drug
and continued to completion. Indeterminate IGRA results should be handled as in
Section 5.1. Participants with persistently indeterminate IGRA results may continue
without treatment for latent TB if active TB is ruled out, their chest radiograph shows no
abnormality suggestive of TB (active or old, inactive TB) and the participant has no
additional risk factors for TB as determined by the investigator. This determination must
be promptly reported to the sponsor and recorded in the participant's source documents
and initialed by the investigator.
 
A participant receiving treatment for latent TB discontinues this treatment prematurely
or is noncompliant with the therapy.
 
The participant develops a serious opportunistic infection.
 
The participant requires high dose glucocorticoid (≥1 mg/kg/day of prednisolone or
equivalent) for >β weeks or a prohibited therapy such as a biologic, cyclophosphamide, or IV
glucocorticoid (see Section 6.6). 
If a new immunomodulator or oral glucocorticoid (<1 mg/kg/day of prednisolone or
equivalent) that is permitted per-protocol is initiated, then a participant will be considered a
prohibited change in PM/DM medications but will not need to discontinue the study drug
administrations. Addition of systemic medication for PM/DM activity must be discussed with
the sponsor to determine the suitability of the participant to continue the study drug
administrations.
If a participant discontinues the study drug for any reason on or before the Week 7β assessments
should be obtained and scheduled assessments should be continued.
7.2. 
Participant Discontinuation/Withdrawal From the Study
A participant will not be automatically withdrawn from the study if he or she has to discontinue
the study drug before the end of the study drug regimen.
A participant will be withdrawn from the study for any of the following reasons:
 
Lost to follow-up
 
Withdrawal of consent
 
Death
 
Other
When a participant withdraws before completing the study, the reason for withdrawal is to be
documented in the eCRF and in the source document. The study drug assigned to the withdrawn
participant may not be assigned to another participant. Subjects who withdraw from the study will
not be replaced. If a participant discontinues the study drug and withdraws from the study before
Week 7β, assessments should be obtained at a follow-up visit 8 weeks (EOT) and 16 weeks (EOS)
after the last study drug administration. If the reason for withdrawal from the study is withdrawal
of consent, then no additional assessments are allowed. 


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7.2.1. 
Withdrawal From the Use of Research Samples 
A participant who withdraws from the study will have the following options regarding the optional
research samples:
 
The collected samples will be retained and used in accordance with the participant's original
separate informed consent for optional research samples.
 
The participant may withdraw consent for optional research samples, in which case the
samples will be destroyed and no further testing will take place. To initiate the sample
destruction process, the investigator must notify the sponsor study site contact of withdrawal
of consent for the optional research samples and to request sample destruction. The sponsor
study site contact will, in turn, contact the biomarker representative to execute sample
destruction. If requested, the investigator will receive written confirmation from the sponsor
that the samples have been destroyed.
Withdrawal From the Optional Research Samples While Remaining in the Main Study
The participant may withdraw consent for optional research samples while remaining in the study.
In such a case, the optional research samples will be destroyed. The sample destruction process
will proceed as described above.
Withdrawal From the Use of Samples in Future Research
The participant may withdraw consent for use of samples for research (refer to Long-Term
Retention of Samples for Additional Future Research in Section 10.β, Appendix β: Regulatory,
Ethical, and Study Oversight Considerations). In such a case, samples will be destroyed after they
are no longer needed for the clinical study. Details of the sample retention for research are
presented in the main ICF and in the separate ICF for optional research samples.
7.3. 
Lost to Follow-up
If a participant is lost to follow-up, every reasonable effort must be made by the study site
personnel to contact the participant and determine the reason for discontinuation/withdrawal. Due
diligence should include repeated telephone calls, certified letters, and email requests. Measures
taken to obtain follow-up information must be documented. Refer to Section 7.β, Participant
Discontinuation/Withdrawal From the Study.
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Overview
The Schedule of Activities (Section 1.γ) summarizes the frequency and timing of efficacy, PK,
immunogenicity, biomarker, pharmacogenomic, and safety measurements applicable to this study.
All patient-reported outcome (PRO) assessments, except for FI-β, should be conducted/completed
before any tests, procedures, or other consultations to prevent influencing participant perceptions.
If multiple assessments are scheduled for the same timepoint, it is recommended that procedures
be performed in the following sequence: PRO, electrocardiogram (ECG), vital signs, and blood


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draw. Actual dates and times of assessments will be recorded in the source documentation and
eCRF.
Additional serum or urine pregnancy tests may be performed, as determined necessary by the
investigator or participant or required by local regulation, to establish the absence of pregnancy at
any time during the participation in the study.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the
samples.
The total blood volume to be collected from each participant will be approximately 750 mL.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory
requisition form. 
Refer to the Section 1.γ, Schedule of Activities for the timing and frequency of all sample
collections.
Instructions for the collection, handling, storage, and shipment of samples are found in the
laboratory manual that will be provided. Collection, handling, storage, and shipment of samples
must be under the specified, and where applicable, controlled temperature conditions as indicated
in the laboratory manual.
Study-specific Materials 
The investigator will be provided with the following supplies:
 
IB
 
Pharmacy manual/study site investigational product and procedures manual
 
Laboratory manual and laboratory supplies
 
Certain Clinical Outcome Assessments (COA; includes both PROs and Clinician Reported
Outcomes [ClinROs])
 
COA questionnaires and completion instructions
 
IWRS Manual 
 
eCRF completion guidelines
 
Sample ICF
 
Participant diary 
 
Any other manual or guideline that is deemed necessary for good execution of the study


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8.1. 
Efficacy Assessments 
8.1.1. 
Efficacy Evaluations
Every reasonable effort should be made to have all efficacy evaluations performed by the same
study investigator or subinvestigator to achieve comparable measures over time.
8.1.1.1. 
Physician Global Activity 
PhGA is a partially validated tool to measure the global evaluation by the treating physician of the
overall disease activity of the patient at the time of assessment using a 10 cm VAS.19 Visual
analogue scale should be used for evaluation of IMACS TIS.
8.1.1.2. 
Patient Global Activity 
PtGA is a partially validated tool to measure the global evaluation by the patient of the patient's
overall disease activity at the time of assessment using a 10 cm VAS.19
8.1.1.3. 
Manual Muscle Testing 
MMT is a partially validated tool to assess muscle strength.19 A 0 to 10 point scale is proposed for
use. The MMT-8 is proposed for studies which evaluate 8 muscle groups whose subsets are
selected based on internal/interrater consistency and reliability. The MMT-8, which take less time
and involve less patient effort compared to Total MMT, has results comparable to Total MMT in
terms of responsiveness, content validity, and construct validity.
8.1.1.4. 
Muscle Enzymes
Muscle enzymes are partially validated tool to measure the serum activities of muscle-associated
enzymes including CK, the transaminases (ALT, AST), LDH, and aldolase.19 The values obtained
from central laboratory are used for evaluation. To calculate IMACS TIS, the most abnormal
serum muscle enzyme level at baseline (CK, aldolase, ALT, AST, or LDH) will be used.
8.1.1.5. 
Extramuscular Assessment (Myositis Disease Activity Assessment
Tool)
This validated tool measures the degree of disease activity of extramuscular organ systems and
muscle.19 This is a combined tool that includes the Myositis Disease Activity Assessment VAS
(MYOACT), which is a series of physician's assessments of disease activity of various organ
systems modified from the Vasculitis Activity Index,β9 and the Myositis Intention to Treat Activity
Index (MITAX), which is modified from the British Isles Lupus Activity Group (BILAG)
approach to assess disease activity in lupus. 7 The MITAX is composed of a series of organ-specific
questions relating to the presence or absence of the clinical feature and the degree of treatment
needed for it (intention to treat).
The MDAAT has undergone inter-rater reliability testing in adult myositis patients in workshops.
The MITAX is scored on a 0 to 4 scale, based on worsening or improvement in specific clinical
features and their correlation with the intention to treat. The tool is based on the results of clinical
studies for reliability and validity. The current version is recommended for use in prospective trials


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and clinical studies by IMACS. To calculate IMACS TIS, Extramuscular Global Assessment is
used.
8.1.1.6. 
Physical Function (Health Assessment Questionnaire Disability
Index)
The Stanford HAQ is a brief self-report questionnaire assessing physical function pertaining to
activities of daily living in a variety of domains. Originally developed for use in RA, it has been
successfully applied to a variety of rheumatic conditions, including idiopathic inflammatory
myopathy. For IMACS TIS, the Disability Index is used, which is calculated by dividing the sum
of the worst score of each section by the number of section tested.19
8.1.1.7. 
Functional Index-2 
The FI-β is a functional outcome developed for patients with adult PM or DM to assess muscle
endurance in 7 muscle groups. Each muscle group is scored as the number of correctly performed
repetitions with 60 or 1β0 maximal number of repetitions depending on muscle group. The FI-β is
performed unilaterally, preferably on the participant’s dominant side for muscle groups of shoulder,
hip, and step test. The FI-β has been validated as to content and construct validity and intra- and
interrater reliability.β
8.1.1.8. 
36-item Short Form 
The SF-γ6 is a widely used tool to assess the global medical quality of life, functional health, and
well-being of general and specific populations. It has shown evidence of content, concurrent,
criterion, construct, and predictive validity in many different chronic diseases, and extensive
normative data are available. It is also recommended by IMACS as an important measure to assess
PROs in all forms of adult idiopathic inflammatory myopathy. It has a good construct and content
validity in adult patients with DM, PM, or IBM.19
8.1.2. 
Endpoint Definitions
8.1.2.1. 
IMACS TIS
The IMACS response criteria are standardized clinical response criteria to assess minimal,
moderate and major clinical improvement in patients with adult PM/DM, which was developed by
IMACS.1 These criteria, which have now been accepted by ACR and EULAR, are recommended
for use as primary endpoints in myositis therapeutic trials. The criteria use the 6 IMACS core set
measures, combining the absolute percentage change in each with varying weights to obtain a
Total Improvement Score (TIS) on a scale of 0 to 100.
 
PhGA
 
PtGA
 
MMT-8
 
Muscle Enzymes
 
Extramuscular Assessment (MDAAT)


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 
Physical Function (HAQ-DI)
Different thresholds of improvement have been set for minimal, moderate, and major response.
Minimal improvement is defined as IMACS TIS ≥β0 in participants with PM/DM.
8.1.2.2. 
Disease Worsening
Criteria for disease worsening in a clinical trial were based on international consensus guideline
developed by the IMACS. The worsening of disease is defined as 1 of the following criteria; 
1. Worsening of the PhGA by ≥β cm on a 10-cm VAS and worsening of findings of MMT-8 by
≥β0% from baseline 
β. Worsening of MDAAT-global extramuscular organ disease activity (a composite of
constitutional, cutaneous, skeletal, gastrointestinal, pulmonary, and cardiac activity) by ≥β cm
on a 10-cm VAS from baseline
γ. Worsening of any γ of 6 IMACS core set activity measures by ≥γ0% from baseline
8.2. 
Safety Assessments 
Safety evaluations will include assessment of AEs, concomitant medications, pregnancy testing
(see Section 8.β.6), administration reactions, serum chemistry, hematology and blood coagulation
laboratory tests, vital signs, ECG, general physical examinations, chest x-ray, HRCT, blood gas
analysis, PFT, and TB testing. In addition, HIV, hepatitis B, hepatitis C will be required at
screening (Section 1.γ). 
Details regarding the IDMC is provided in Committees Structure in Section 10.β, Appendix β:
Regulatory, Ethical, and Study Oversight Considerations.
Adverse events will be reported and followed by the investigator as specified in Section 8.γ,
Adverse Events and Serious Adverse Events and Section 10.γ, Appendix γ: Adverse Events:
Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting.
Any clinically relevant changes occurring during the study must be recorded on the Adverse Event
section of the eCRF.
Any clinically significant abnormalities persisting at the end of the study/early withdrawal will be
followed by the investigator until resolution or until a clinically stable condition is reached. 
The study will include the following evaluations of safety and tolerability according to the time
points provided in the Section 1.γ Schedule of Activities:
8.2.1. 
Physical Examination
A physical examination will be performed pretreatment and during the study as shown in
Section 1.γ. A physical examination includes assessment of general appearance, head (including
oral cavity and dentition), eyes, ears, nose, throat, neck, abdomen, lymph nodes, and peripheral


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extremities and the following systems: cardiovascular (including peripheral vascular), respiratory,
neurologic, musculoskeletal, skin, and genitourinary (if clinical history indicates need).
8.2.2. 
Vital Signs
Weight, temperature, pulse/heart rate, respiratory rate, and blood pressure (systolic and diastolic)
will be assessed with a completely automated device. Manual techniques will be used only if an
automated device is not available.
Blood pressure and pulse/heart rate measurements should be preceded by at least 5 minutes of rest
in a quiet setting without distractions (eg, television, cell phones).
8.2.3. 
Electrocardiogram 
A 1β-lead ECG will be performed locally at screening. During the collection of ECGs, participants
should be in a quiet setting without distractions (eg, television, cell phones). Participants should
rest in a supine position for at least 5 minutes before ECG collection and should refrain from
talking or moving arms or legs. If blood sampling or vital sign measurement is scheduled for the
same time point as ECG recording, the procedures should be performed in the following order:
ECG, vital signs, blood draw. If an abnormal result is obtained, the ECG may be repeated.
8.2.4. 
Clinical Safety Laboratory Assessments
Blood samples for serum chemistry, coagulation, and hematology will be collected as shown in
Section 1.γ Schedule of Activities and Section 10.4, Appendix 4: Clinical Laboratory Tests. The
investigator must review the laboratory results, document this review, and record any clinically
relevant changes occurring during the study in the AE section of the eCRF. The laboratory reports
must be filed with the source documents. With prior sponsor approval, local laboratories may be
used in the event of a safety concern or if initiation of treatment is critical and the central laboratory
results are not expected to be available before the need to provide study drug or take action to
ensure participant safety.
8.2.5. 
Interstitial Lung Diseases and Respiratory Muscle
The presence of ILD and respiratory muscle weakness must be evaluated at screening using chest
x-ray, chest HRCT, blood gas analysis (PaOβ and partial pressure of carbon dioxide in arterial
blood [PaCOβ]), and PFT (VC, FVC, DLCO, MIP, MEP, and/or MVV). All participants must be
monitored with SpOβ, chest x-ray, laboratory data (KL-6 and SP-D), chest HRCT, and PFT as
scheduled in Section 1.γ during the study. The investigator may consider additional examination
including C-reactive protein, ferritin, and blood gas analysis as needed. In case of worsening or
new onset of lung lesion, it is recommended to make a differential diagnosis of fungal infection,
cytomegalovirus infection, heart failure and/or other cause using additional laboratory data such
as ȕ-D-glucan, C7-HRP, and/or BNP. If the investigator identifies new onset or worsening of ILD
or observes any finding which needs to be evaluated by a pulmonologist, the investigator should
consider consultation with a pulmonologist and administer rescue treatment as needed. Permanent
discontinuation of the study drug must be considered for participants who experience worsening
of ILD or newly identified severe ILD that is considered serious or severe by the investigator in
cases of the following but not limited to;


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 
Significant worsening of ILD findings based on chest x-ray or HRCT
 
Significant decrease in SpOβ such as SpOβ < 90% or a decrease of SpOβ by 5% or more
The result of consultation with a pulmonologist and the decision by the investigator should be
recorded and discussed with the sponsor.
In addition, IDMC will monitor the safety data including ILD evaluation mentioned above. If
IDMC identify any safety concern, IDMC will recommend the investigator withdrawal of the study
drug as needed.
8.2.6. 
Pregnancy
Female participants of childbearing potential are to be monitored for possible pregnancy using a
urine dipstick test performed at the clinical site as shown in Section 1.γ. Additional serum hCG
testing may also be performed locally or at the central laboratory if desired by the study
investigator.
Pregnancies (of the study participant or if the participant is male, then the participant's partner)
must be followed to determine the outcome (including spontaneous miscarriage, elective
termination, normal birth, or congenital abnormality) and status of mother and child, even if the
participant was discontinued from the study early.
8.2.7. 
Infections
Participants will be counseled on the signs and symptoms of infections and will be instructed to
contact the site between scheduled visits should any signs and symptoms occur. At each site visit,
investigators or other site personnel are required to evaluate participants for any signs or symptoms
of infection and ask about symptoms of infection or other AEs that may have occurred between
site visits. Investigators need to consider additional laboratory examination (such as test for fungal
or viral antigen) based on each participant’s risk of opportunistic infection.
8.2.7.1. 
Tuberculosis
In addition to general evaluation for infection, monitoring for TB will be performed with chest
x-ray or chest HRCT and IGRAs as scheduled in Section 1.γ.
8.2.8. 
Infusion- or Injection-site Reactions
Participants should be monitored for the occurrence of infusion reactions for at least 1 hour after
IV infusion and injection-site reactions for at least γ0 minutes following SC injection.
8.3. 
Adverse Events and Serious Adverse Events
Timely, accurate, and complete reporting and analysis of safety information from clinical studies
are crucial for the protection of participants, investigators, and the sponsor, and are mandated by
regulatory agencies worldwide. The sponsor has established Standard Operating Procedures in
conformity with regulatory requirements worldwide to ensure appropriate reporting of safety
information; all clinical studies conducted by the sponsor or its affiliates will be conducted in
accordance with those procedures.


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Adverse events will be reported by the participant (or, when appropriate, by a caregiver, or
surrogate,) for the duration of the study.
For further details on AEs and SAEs (Definitions and Classifications; Attribution Definitions;
Severity Criteria; Special Reporting Situations; Procedures) as well as product quality complaints,
refer to Section 10.γ, Appendix γ: Adverse Events: Definitions and Procedures for Recording,
Evaluating, Follow-up, and Reporting.
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious
Adverse Event Information
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported from the
time a signed and dated ICF is obtained until completion of the participant's last study-related
procedure, which may include contact for follow-up of safety. Serious AEs, including those
spontaneously reported to the investigator within 16 weeks after the last dose of the study drug or
completion of the participant's last study-related procedure, whichever comes later, must be
reported using the Serious Adverse Event Form. The sponsor will evaluate any safety information
that is spontaneously reported by an investigator beyond the time frame specified in the protocol.
Serious Adverse Events
All SAEs occurring during the study must be reported to the appropriate sponsor contact person
by study site personnel within β4 hours of their knowledge of the event.
Information regarding SAEs will be transmitted to the sponsor using the Serious Adverse Event
Form and Safety Report Form of the eCRF, which must be completed and reviewed by a physician
from the study site, and transmitted to the sponsor within β4 hours. The initial and follow-up
reports of an SAE should be transmitted electronically or by facsimile (fax).
8.3.2. 
Method of Detecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting AEs or SAEs. Open-ended and nonleading
verbal questioning of the participant is the preferred method to inquire about AE occurrence. 
Solicited Adverse Events
Solicited AEs are events which are noted by participants in their participant diary (see Section 8,
Study Assessments and Procedures).
Unsolicited Adverse Events
Unsolicited AEs are all AEs other than solicited AEs as defined above.
8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events
Adverse events, including pregnancy, will be followed by the investigator as specified in
Section 10.γ, Appendix γ: Adverse Events: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting.


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Refer to Section 10.6, Appendix 6: Medical Device Incidents: Definition and Procedures for
Recording, Evaluating, Follow-up, and Reporting for details for which a medical device is
provided for use in the study.
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events
The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities.
The sponsor will also report to the investigator (and the head of the investigational institute where
required) all suspected unexpected serious adverse reactions (SUSARs). For individual SAEs, the
sponsor will make a determination of relatedness in addition to and independent of the
investigator’s assessment. The sponsor will periodically evaluate the accumulating data and, when
there is sufficient evidence and the sponsor has determined there is a reasonable possibility that
the intervention caused a serious event, they will submit a safety report in narrative format to the
investigators (and the head of the institute where required). The investigator (or sponsor where
required) must report SUSARs to the appropriate Independent Ethics Committee/Institutional
Review Board (IEC/IRB) that approved the protocol unless otherwise required and documented
by the IEC/IRB. A SUSAR will be reported to regulatory authorities unblinded. Participating
investigators and IEC/IRB will receive a blinded SUSAR summary, unless otherwise specified. 
8.3.5. 
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants must be
reported to the sponsor by the study site personnel within β4 hours of their knowledge of the event
using the appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg,
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are
considered SAEs and must be reported using the Serious Adverse Event Form. Any participant
who becomes pregnant during the study must discontinue further study drug.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the
infant will be required.
8.3.6. 
Infections
The study drug should not be administered to a participant with a clinically important, active
infection. Treatment with the study drug should be withheld until serious and/or severe infections
are completely resolved. If a participant develops a serious or severe infection, including but not
limited to sepsis or pneumonia, discontinuation of the study drug must be considered. Treatment
must be permanently discontinued for participants who develop a serious opportunistic infection.
This should be discussed with the sponsor. For active varicella zoster infection or a significant
exposure to varicella zoster infection in a participant without history of chickenpox, the participant
should be evaluated for symptoms of infection and if the participant has received appropriate
treatment and/or recovered or has no symptoms of infection, he/she may continue the study drug
after discussion with the sponsor.
8.3.6.1. 
Tuberculosis
Any newly identified case of active TB occurring after the first administration of the study drug in
participants participating in this clinical study must be reported by the investigator according to


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the local procedures. These events are to be considered serious only if they meet the definition of
an SAE. Treatment must be permanently discontinued for participants with active TB.
8.3.7. 
Infusion- or Injection-site Reactions
An infusion reaction is defined as an AE that occurs during or within 1 hour following the infusion
of the study drug, excluding laboratory abnormalities. Permanent discontinuation of the study drug
must be considered for participants who experience an AE of infusion reaction that is considered
serious or severe by the investigator.
8.4. 
Events of Special Interest
Adverse events of special interest: opportunistic infection (ie, infection by an organism that
normally is not pathogenic or does not cause invasive infection in immunocompetent hosts), case
of active TB, ILD, or malignancy occurring after the first administration of study agent in
participants in this clinical study must be reported by the investigator following procedures.
Investigators are also advised that active TB is considered a reportable disease required by local
regulations. These events are to be considered serious only if they meet the definition of an SAE
as shown in Section 10.γ, Appendix γ: Adverse Events: Definitions and Procedures for Recording,
Evaluating, Follow-up, and Reporting. 
8.5. 
Treatment of Overdose
For this study, any dose of ustekinumab greater than set daily dose at Section 6.1 within  β weeks
time period will be considered an overdose. 
In the event of an overdose, the investigator or treating physician should:
 
Contact the sponsor immediately.
 
Closely monitor the participant for AE/SAE, laboratory abnormalities, and any signs or
symptoms until ustekinumab can no longer be detected systemically (at least 16 weeks).
 
Appropriate symptomatic treatment be instituted immediately.
 
Obtain a serum sample for PK analysis if requested by the sponsor (determined on a case-by-
case basis).
 
Document the quantity of the excess dose as well as the duration of the overdosing in the
eCRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in
consultation with the sponsor based on the clinical evaluation of the participant.
8.6. 
Pharmacokinetics and Immunogenicity
Serum samples will be collected for measurement of serum concentrations of ustekinumab and
presence of anti-ustekinumab antibodies. Serum collected for PK may additionally be used to
evaluate safety or efficacy aspects that address concerns arising during or after the study period.
Genetic analyses will not be performed on these serum samples. Participant confidentiality will be
maintained.


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8.6.1. 
Evaluations
The total blood volume to be collected from each participant will be approximately 750 mL.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the
samples.
8.6.2. 
Analytical Procedures 
Pharmacokinetics
Serum samples will be analyzed to determine concentrations of ustekinumab using a validated,
specific, and sensitive immunoassay method by or under the supervision of the sponsor.
Immunogenicity 
The detection and characterization of anti-ustekinumab antibodies will be performed using a
validated assay method by or under the supervision of the sponsor. All samples collected for
detection of anti-ustekinumab antibodies will also be evaluated for ustekinumab serum
concentration to enable interpretation of the antibody data.
8.6.3. 
Pharmacokinetic Parameters and Evaluations
Based on the individual serum concentration-time data, using the actual dose taken and the actual
sampling times, PK parameters and exposure information of ustekinumab may be derived using
population PK modeling. Baseline covariates (eg, body weight, age, sex, CrCL, race) may be
included in the model, if relevant. Details will be given in a population PK analysis plan and the
results of the population PK analysis will be presented in a separate report.
8.6.4. 
Immunogenicity Assessments (Anti-ustekinumab Antibodies) 
Anti-ustekinumab antibodies will be evaluated in serum samples collected from all participants
according to the Time and Events Schedule (See Section 1.γ, Schedule of Activities). Additionally,
serum samples should also be collected at the final visit from participants who are discontinued
from intervention or withdrawn from the study. These samples will be tested by the sponsor or
sponsor's designee. The detection and characterization of anti-ustekinumab antibodies will be
performed using a validated assay method by or under the supervision of the sponsor.
Serum samples will be screened for antibodies binding to ustekinumab and the titer of confirmed
positive samples will be reported. Other analyses may be performed to further characterize the
immunogenicity of ustekinumab. Serum samples that test positive for anti-ustekinumab antibodies
will be further characterized to determine if anti-ustekinumab antibodies could neutralize the
biological effects of ustekinumab in vitro (ie, neutralizing antibodies [NAbs] to ustekinumab). All
samples will be tested by the sponsor or sponsor's designee. 
8.7. 
Genetics
A pharmacogenomic blood sample (whole blood DNA) will be collected from participants who
consent separately to this component of the study to allow for pharmacogenomic research, as
necessary. Participant participation in pharmacogenomic research is optional.


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DNA samples will be analyzed for identification of genetic factors to better understand the
molecular effects of ustekinumab and/or susceptibility to PM/DM, and to evaluate markers that
can predict clinical response. Such analysis may include the human leukocyte antigen (HLA)
alleles and any relevant single nucleotide polymorphisms that are reported to be associated with
ustekinumab and/or the development of PM/DM.
8.8. 
Biomarkers 
Whole blood will be prospectively collected, processed and cryopreserved appropriately for
immune and other biomarker evaluations.
Biomarker assessments may include but not limited to immunophenotyping (by flow cytometry
and/or cytometry by time-of-flight [CyTOF]), gene expression (RNA) as well as disease related
soluble autoantibody profiles, markers of inflammation and other biomarkers associated with
IL1β/ILβγ pathway. Assessments will be performed to identify biomarkers that are relevant to
ustekinumab treatment. 
Serum samples for autoantibody and soluble proteins profiling
Serum samples may be used to detect circulating autoantibodies associated with PM/DM (such as
anti-aminoacyl-tRNA synthetases [Jo-1, PL-7, PL-1β, EJ, OJ, KS], anti-Mi-β, anti-SRP, anti-
TIF1-Ȗ, anti-NXP-β, anti-MDA5, anti-SAE, anti-HMGCR, etc). In addition, soluble levels of Type
I, II and III IFN may be quantitated. Furthermore, biomarkers associated with inflammation, tissue
injury and other soluble proteins may be measured using relevant technological platforms.
Immunoglobulin isotypes may be characterized.
Whole blood and/or PBMC samples for immune profiling
Assessment of immune profiling biomarkers including phenotypic and functional assessments are
anticipated to be performed as outlined below pending availability of samples and validated assays:
Flow cytometry and /or CyTOF assessments including but not limited to T cell, B cell, Dendritic
cell, natural killer cell subsets may be performed.
In vitro functional assays to monitor immune cell responses to relevant stimulations and single cell
analysis of immune populations may be performed.
Whole blood RNA for gene expression analyses
Whole blood collected for RNA may be used in the expression analysis of broader gene transcripts
and/or targeted genes indicated in the IFN or cytotoxic pathway signatures. Technological
platforms may include microarray, RNASeq or relevant targeted gene analysis platforms.
In addition, sequencing of T cell and B cell receptor genes using whole blood RNA may be
conducted to better understand the repertoire composition, clonal diversity and sequence
abundance.


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9. 
STATISTICAL CONSIDERATIONS 
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general
description of the statistical methods to be used to analyze the efficacy and safety data is outlined
below. Specific details will be provided in the Statistical Analysis Plan (SAP).
Descriptive statistics (eg, mean, median, standard deviation [SD], interquartile range, minimum,
maximum) will be used to summarize continuous variables. Numbers and percentages will be used
to summarize categorical variables. Median values will be reported for time-to-event variables. In
addition, graphical data displays (eg, line plots) and participant listings may also be used to
summarize/present the data.
Simple descriptive summary statistics, such as sample size (n), mean, SD, median, interquartile
(IQ) range, minimum, and maximum for continuous variables, and counts and percentages for
discrete variables will be used to summarize data.
Analyses suitable for categorical data (eg, chi-square tests, Cochran-Mantel-Haenszel chi-square
tests, or logistic regression, as appropriate) will be used to compare the proportions of participants
achieving endpoints (eg, IMACS TIS response). In cases of rare events, the Fisher exact test will
be used for treatment comparisons. For continuous efficacy endpoints, treatment comparisons will
be performed using either a mixed-effect model repeated measure (MMRM) model especially with
longitudinal data or an analysis of covariance (ANCOVA) model. If the normality assumption is
in question, an analysis of variance (ANOVA) or ANCOVA on the van der Waerden normal scores
will be used. Time-to-event endpoints will be analyzed using a log-rank test and Kaplan-Meier
plots and adjusting for potential confounders will be performed using a Cox proportional hazards
model. All the models will have treatment group, the adjusting for baseline stratifications as
appropriate, and may include baseline value as covariate.
In general, all statistical tests will be performed at a β-sided significance level of α 0.05. Nominal
p-value will be displayed for all treatment comparisons.
9.1. 
Statistical Hypotheses
This study is designed to show that treatment effect (as measured by the IMACS TIS response at
Week β4) of an ustekinumab as PM/DM treatment is superior to placebo.
If OR is the odds ratio derived from the IMACS TIS response with the placebo and an ustekinumab
groups, then the hypothesis can be written as follows: 
H0:OR 1, H1:OR≠1
Superiority can be concluded if the β-sided p-value adjusted by the stratification factors for the
testing of the hypothesis above is less than 0.05.
9.2. 
Sample Size Determination 
The sample size calculation is based upon the primary endpoint, the proportion of participants who
achieve IMACS TIS response at Week β4. Some published studies designed to assess the efficacy


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of biological therapies in active PM/DM patients using International Myositis Assessment and
Clinical Studies Definition of Improvement (IMACS DOI) indicated a clinically relevant response
following the use of biological therapies in the PM/DM population (Table γ). However, since
ustekinumab is not previously evaluated in any studies for the treatment of patients with active
PM/DM, its effectiveness in this population evaluated by IMACS DOI (IMACS TIS) is not well
understood. To determine the effect size versus placebo used for calculating the sample size, meta-
analyses were conducted for the synthesis of the evidence (Table 4 and Table 5).
By reviewing the literature search results on PubMed and publications listed on the IMACS
academic web site, the following 4 articles were selected to be included in the meta-analyses.
Table 3: 
Overview of IMACS DOI Response Rates at Week 24 in Selected Studies
Reference 
Placebo group 
Active group
The Muscle Stud y Group15 
40.0% (β/5) 
81.8% (9/11)
Oddis et al, β01γ16 
--- 
8β.6% (161/195)a 
Zon  g et al, β014γβ 
--- 
50.0% (5/10)
Tjarnlund et al, β018β4 
11.1% (1/9) 
60.0% (6/10)
Key: IMACS DOI=International Myositis Assessment and Clinical Studies Definition of Improvement
a This response was observed at Week 44
Due to the disproportionately large number of patients and the evaluation timepoint difference in
the study by Oddis et al, β01γ,16 meta-analyses using random-effect, fixed-effect, and Bayesian
models were conducted separately for deletion and inclusion of this study from the pool of the
above 4 studies.
Table 4: 
Meta-analysis Using Random-effect and Fixed-effect Models: Pooled IMACS DOI Response
Rates at Week 24 and Their 95% CIs
Model 
Inclusion/Exclusion of 
Studies
Group 
Mean (95% CI)
Fixed-effectγ 
Excluding Oddis et al, β01γ16 
Placebo 
0.17 (0.00, 0.γ5)
Active 
0.68 (0.5β, 0.84)
Including Oddis et al, β01γ16 
Placebo 
0.17 (0.00, 0.γ5)
Active 
0.81 (0.76, 0.86)
Random-effectγ 
Excluding Oddis et al, β01γ16 
Placebo 
0.19 (0.00, 0.45)
Active 
0.66 (0.47, 0.86)
Including Oddis et al, β01γ16 
Placebo 
0.19 (0.00, 0.45)
Active 
0.74 (0.60, 0.88)
Key: CI=confidence interval; IMACS DOI=International Myositis Assessment and Clinical Studies Definition of
Improvement
 
Table 5: 
Meta-analysis Using Bayesian Model With Non-informative Prior: Posterior Summary of
IMACS DOI Response Rates at Week 24
Inclusion/Exclusion of 
Studies
Group 
2.5 percentile 
Median 
97.5 percentile
Excluding Oddis et al, β01γ16 
Placebo 
0.07 
0.β5 
0.51
Active 
0.47 
0.61 
0.77
Including Oddis et al, β01γ16 
Placebo 
0.07 
0.β5 
0.51
Active 
0.75 
0.80 
0.85
Key: IMACS DOI=International Myositis Assessment and Clinical Studies Definition of Improvement




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 
The safety analysis set will include all randomized participants who receive at least 1 dose
(partial or complete) of ustekinumab and participants will be analyzed based on the treatment
they receive, regardless of the treatment groups to which they are assigned. 
 
The PK analysis set will include all participants who receive at least 1 complete dose of
ustekinumab and have at least 1 postdose sample collection. 
 
The immunogenicity analysis set is defined as all participants who receive at least 1 dose
(partial or complete) of ustekinumab and have at least 1 postdose sample collection.
Participants will be analyzed according to the actual treatment receive. 
 
The pharmacodynamic (PD) analysis set is defined as all participants who receive at least 1
dose (complete or partial) ustekinumab. Participants will be analyzed according to the actual
treatment receive.
For all participants who are randomly assigned to study drug, descriptive statistics (eg, study
completion/withdrawal information, demographic and baseline data) will be provided. 
9.4. 
Statistical Analyses
9.4.1. 
Efficacy Analyses
It is considered that the effectiveness of ustekinumab treatment in adult patients with PM/DM will
be demonstrated if the ustekinumab group is shown to be superior to placebo group for the primary
efficacy analysis in this study.
9.4.1.1. 
Primary Endpoint Analysis
The primary endpoint of this study is the proportion of participants who achieve IMACS TIS
response at Week β4 (Section 8.1.β.1).
9.4.1.1.1. 
Primary Estimand
Primary Trial Objective: To evaluate the efficacy of ustekinumab in participants with active
PM/DM despite receiving 1 or more standard-of-care treatments (eg, glucocorticoids and/or
immunomodulators).
Estimand Scientific Question of Interest: What is the proportion of participants considered to
have benefited from ustekinumab vs placebo for the pre-specified duration (β4 weeks),
administered together with the protocol allowed 1 or more standard-of-care treatments?
The Primary Estimand will be targeted for the primary endpoint.  The Primary Estimand for the
primary endpoint is defined by the following:
 
Study intervention: 
 
Ustekinumab (~6 mg/kg IV at Week 0, and 90 mg SC q8w through Week β4) 
 
Placebo (IV at Week 0 and SC q8w through Week β4)
 
Population: Subjects with active PM/DM despite receiving one or more standard-of-care
treatments.


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 
Variable/endpoint: IMACS TIS binary response variable at Week β4, where a responder is
defined as a participant who achieves IMACS TIS response at Week β4 and does not have a
prohibited change in PM/DM medications. A participant who has a prohibited change in
PM/DM medications or discontinues treatment for any reason including COVID-19 infection
but excluding other COVID-19 reasons is considered a non-responder.
 
Population-level summary: Odds ratio for the proportion of subjects achieving IMACS TIS
response at Week β4 between the ustekinumab and placebo intervention groups.
 
ICEs and their corresponding strategies:
ICEs
Analysis Strategy for
Addressing Intercurrent Events
1. A prohibited change in PM/DM 
medications prior to Week β4  
Composite Strategy: A subject with this intercurrent
event is considered as a non-responder after this
event, the occurrence of this intercurrent event being
captured in the variable definition.
β. Discontinuation 
of 
study
intervention for any reason,
including COVID-19 infection
but excluding other COVID-19
reasons
γ. Discontinuation 
of 
study 
intervention due to COVID-19 
related 
reasons 
(excluding 
COVID-19 infection)
Hypothetical Strategy: This intercurrent event is
addressed with a hypothetical strategy, as if the
intercurrent event would not have occurred.
For subjects experiencing multiple ICEs simultaneously, ICEs in categories 1- β will override ICE
γ. The prohibited changes in PM/DM medications will be defined in the SAP. 
Participants with intercurrent events (ICEs) 1-β before Week β4 will be considered as non-
responders at Week β4. For participants with ICE γ, data collected after this ICE will not be utilized
in the analysis. Participants who don’t experience any ICEs could also have a missing value for
the primary endpoint if missing the IMACS TIS response at Week β4 due to study withdrawal /
missed visits or measurement. How the remaining missing data are treated after accounting for the
ICEs will be specified in the SAP.
In the primary efficacy analysis, data from all randomized participants will be analyzed according
to their assigned treatment group regardless of their actual treatment received. 
Logistic regression adjusting for β stratification factors, disease subset (PM or DM) and baseline
treatment level (glucocorticoid dose [≥0.5 mg/kg/day or <0.5 mg/kg/day of prednisolone or
equivalent]), will be used to analyze the primary endpoint. If the above logistic regression model
does not converge, the binomial test will be conducted without adjusting for the β stratification
factors. The magnitude of the effect will be estimated by the odds ratio in IMACS TIS response
rates between the ustekinumab and placebo groups and the 95% confidence interval (CI) will be
provided.


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9.4.1.1.2. 
Estimands other than the primary estimand
Additional sensitivity/supplemental analyses which vary how intercurrent events (eg,
supplemental estimand) are handled, how observed data are used, and how missing data are treated
will be specified in the SAP to further address the robustness of the primary estimand.
9.4.1.1.3. 
Subgroup Analyses
Subgroup analysis of the primary endpoint based on stratification factors will be performed.
Subgroup analysis of the primary endpoint by other selected baseline characteristics may be also
presented and will be defined in SAP:
 
Disease subset (PM/DM)
 
Baseline treatment level (glucocorticoid dose [≥0.5 mg/kg/day or <0.5 mg/kg/day of
prednisolone or equivalent])
For subgroup analyses, proportion of IMACS TIS response in each treatment group and
corresponding 95% CI will be presented. However, p-values for the comparison across treatment
groups for the subgroups will not be presented.
9.4.1.2. 
Secondary Efficacy Analyses
All endpoints other than the primary endpoint of this study are not prospectively powered. P-values
will be provided without adjusting multiplicity for secondary endpoints analyses.
 
Treatment comparison in time to worsening through Week β4 will be done using a log-rank
test. Kaplan-Meier estimates will be provided for each treatment group. Analysis for time to
worsening will be repeated adjusting for β stratification factors using a proportional hazards
model. In the analyses for time-to-event endpoints, subjects with ICE 1-β will be handled with
Composite Strategy and subjects with ICE γ will be handled with Treatment Policy
Strategy (the observed data will be used regardless of whether or not this ICE had occurred).
 
Analyses comparing the β treatment arms will be performed using a logistic model similar to
primary analysis with the binary outcome related to individual core set measures at Week β4.
The primary estimand approaches dealing with ICEs will be applied to these analyses.
 
All other efficacy endpoints will be summarized over time by treatment group. Treatment
comparisons will be performed using an MMRM model where there are repeated continuous
measurements or a logistic model where there is a dichotomous response variable. The
primary estimand approaches dealing with ICEs will be applied to these analyses also and the
detailed methods of analysis and the data-handling rules will be provided in the SAP.
9.4.2. 
Safety Analyses 
Routine safety evaluations will be performed. Adverse events, SAEs, reasonably related AEs, and
AEs by severity will be summarized by treatment group. More specification of other special
interesting events such as malignancies, serious infections, serious cardiovascular events, and ILD
will be described in the SAP. However, a summary table will not be provided if the number of
events is too few to provide meaningful summary. 


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The laboratory parameters and change from baseline in selected laboratory parameters
(hematology and chemistry), and the number of participants with abnormal laboratory parameters
(hematology and chemistry) based on NCI-CTCAE toxicity grading will be summarized by
treatment group. Listings of SAEs will also be provided. All safety analyses will be based on the
population of participants who receive at least 1 dose of either study drug; participants will be
summarized by the treatment they receive.
Adverse Events
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the
Medical Dictionary for Regulatory Activities (MedDRA). Treatment-emergent AEs are AEs with
onset during the treatment phase or that are a consequence of a preexisting condition that has
worsened since baseline. All reported AEs will be included in the analysis. For each AE, the
percentage of participants who experience at least 1 occurrence of the given event will be
summarized by intervention group. In addition, comparisons between intervention groups will be
provided if appropriate.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those
participants who die, who discontinue intervention due to an AE, or who experience a severe or an
SAE.
AEs of COVID-19, if any occurs, will be summarized separately from other AEs.
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. Reference ranges and markedly
abnormal results (specified in the SAP) will be used in the summary of laboratory data. Descriptive
statistics will be calculated for each laboratory analyte at baseline and for observed values and
changes from baseline at each scheduled time point. Frequency tabulations of the changes from
baseline will be presented in pre- versus postintervention cross-tabulations (with classes for below,
within, and above normal ranges). Frequency tabulations of the abnormalities will be made. A
listing of participants with any laboratory results outside the reference ranges will be provided. A
listing of participants with any markedly abnormal laboratory results will also be provided.
Electrocardiogram 
Clinically relevant abnormalities will be evaluated by frequency tabulations. 
Vital Signs
Descriptive statistics of weight, temperature, pulse/heart rate, respiratory rate, and blood pressure
(systolic and diastolic) values and changes from baseline will be summarized at each scheduled
time point. The percentage of participants with values beyond clinically important limits will be
summarized.


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9.4.3. 
Other Analyses
Pharmacokinetic Analyses 
Serum ustekinumab concentrations will be summarized over time. Descriptive statistics, including
arithmetic mean, SD, median, IQ range, minimum, and maximum will be calculated at each
sampling time point. All concentrations below the lowest quantifiable sample concentration of the
assay (BQL) or missing data will be labeled as such in the concentration data listing or statistical
analysis system (SAS) dataset. The BQL concentrations will be treated as zero in the summary
statistics.
If feasible, population PK analysis of ustekinumab will be performed using nonlinear mixed-
effects modeling. Data may be combined with those of other selected studies to support a relevant
structural model. Details will be given in a population PK analysis plan and the results of the
population PK analysis will be presented in a separate report.
Biomarkers Analyses 
Biomarker analyses performed may include but not limited to serum analysis for levels of IFN as
well as molecular pathway profiling for evidence of IL-1β and IL-βγ pathway modulation. The
biomarkers analyzed may include inflammatory markers, RNA, autoantibodies, T, B, and natural
killer (NK) cell immunophenotyping, and other categories of biomarkers potentially involved in
the development and the progression of PM/DM.
Analytes may include (but are not limited to):
 
Ig isotype profile (IgG, IgM, IgA levels)
 
IL-1β/IL-17/IL-βγ (eg, mRNA, Soluble Protein [Serum])
 
Anti-aminoacyl-tRNA synthetases (Jo-1, PL-7, PL-1β, EJ, OJ, KS)
 
Anti-Mi-β, anti-SRP, anti-TIF1-Ȗ, anti-NXP-β, anti-MDA5, anti-SAE, anti-HMGCR
 
Type I, II, and III IFNs
 
Other inflammation-related molecules and autoantibody profile
 
Participant whole blood gene expression
Biomarker results will be summarized in a separate technical report. Planned biomarker analyses
may be deferred if emerging study data show no likelihood of providing useful scientific
information.
Genetic (DNA) analyses will be conducted only in participants who sign the optional DNA consent
form. These analyses will be summarized in a separate technical report.
Immunogenicity Analyses 
The incidence of anti-ustekinumab antibodies and the impact of antibodies on serum ustekinumab
concentrations will be summarized.


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A listing of participants who are positive for antibodies to ustekinumab will be provided. The
maximum titers of antibodies to ustekinumab will be summarized for participants who are positive
for antibodies to ustekinumab.
The incidence of NAbs to ustekinumab will be summarized for participants who are positive for
antibodies to ustekinumab and have samples evaluable for NAbs to ustekinumab.
Pharmacokinetic/Pharmacodynamic Analyses 
The relationship between serum ustekinumab concentration and efficacy measures for primary and
selected key secondary endpoints will be analyzed graphically. In addition, population PK/PD
modeling may be performed to characterize the relationship between serum ustekinumab exposure
and efficacy measures. Further details will be provided in a population PK/PD analysis plan and
the results will be provided in a separate report.
9.5. 
Interim Analysis 
A futility analysis based on the primary endpoint of IMACS TIS at Week β4 will be conducted
when β0 participants (40% of the originally planned total sample size) have completed the
Week β4 visit. This futility analysis is non-binding. The whole study may be stopped for futility
when the conditional power (ie, the probability of success at the end of the study, given the data at
the interim analysis) is less than a prespecified cutoff. The prespecified cutoff value will be 0.β0.
For the futility analysis, the treatment assignment information will be unblinded to IDMC and
independent statistical support group (SSG) for the β0 participants included in the interim analysis
only (the treatment assignment for the remaining participants will remain blinded at this time). The
details will be stated in interim analysis charter. To protect the integrity of the study, the unblinding
of the treatment assignments and this futility analysis will be handled by an external IDMC and an
independent SSG that are organized outside of the sponsor. The SSG will perform the interim
analysis and the IDMC will form a recommendation on whether or not to stop the trial for futility.
The sponsor decision committee will then review the IDMC’s recommendation and make a final
decision.
The conditional power is estimated by the method proposed by Proschan.18 The simulation study
demonstrates that this futility analysis will result in a slight loss in power (≤0.6%) when the
treatment effect is expected to be 40% assuming the response rate in the placebo group as β5%
and Type I error rate will not inflate (α 0.05, β-sided) for the primary endpoint analysis. Details
about the futility analysis will be specified in the interim analysis plan before the time at which
the futility analysis is performed.
The SAP will describe the planned interim analysis in greater detail.
9.5.1. 
Independent Data Monitoring Committee
An IDMC will be established as noted in Committees Structure in Section 10.β, Appendix β:
Regulatory, Ethical, and Study Oversight Considerations to monitor data on an ongoing basis to
ensure the continuing safety of the participants enrolled in this study and to meet interim analysis
objectives. The committee will meet to review the safety and interim data. After the review, the


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IDMC will make recommendations to the Sponsor Committee who is separate from the study team
regarding the continuation of the study. The details will be provided in a separate IDMC charter.
As needed basis, the IDMC might ask the study team to provide with further information via the
IDMC bureau. The study team make the best effort to collect the further information from each
investigational site for the evaluation by the IDMC. 
The IDMC will consist of β medical experts in the relevant therapeutic area and at least 1
statistician. The IDMC responsibilities, authorities, and procedures will be documented in its
charter.
The study team is defined as a cross-functional team responsible for the planning, initiation,
execution, analysis, and reporting of a trial. This may include but is not limited to: Study
Responsible Physician/Scientist, Global Data Manager, Global Trial Manager, Central Monitoring
Manager, Site Manager, Local Trial Manager, Study Programmer, Study Statistician, Quality
Monitoring & Compliance representative, Clinical Pharmacology representative, and Patient
Reported Outcomes Group Leader. 


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. 
Appendix 1: Abbreviations and Trademarks 
ACR 
American College of Rheumatology
ACTH 
adrenocorticotropic hormone
ADM 
amyopathic dermatomyositis
AE 
adverse event
ALT 
alanine aminotransferase
ANCOVA 
analysis of covariance
anti-HBc total 
HBV core antibod y total
anti-HBs 
HBV surface antibody 
AST 
aspartate aminotransferase
AZA 
azathioprine
BQL 
below the lowest quantifiable sample concentration of the assay 
CD 
cluster of differentiation
CIM 
C protein-induced myositis
CK 
creatine kinase
COA 
clinical outcome assessment (paper or electronic)
CTCAE 
Common Terminology Criteria for Adverse Events
DBL 
database lock 
DC 
dendritic cells
DLCO 
diffusin  g capacit y of the lungs for carbon monoxide
DM 
dermatomyositis
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram
eCRF 
electronic case report forms
eDC 
electronic data capture
EDTA 
ethylenediaminetetraacetic acid 
EULAR 
European League Against Rheumatism
FI-β 
Functional Index-β
FSH 
follicle-stimulatin  g hormone
FVC 
forced vital capacity 
GCP 
Good Clinical Practice
HAQ-DI 
Health Assessment Questionnaire Disabilit y Index
HBsAg 
HBV surface antigen
HBV 
hepatitis B virus
HCV 
hepatitis C virus
HIV 
human immunodeficienc y virus
HRCT 
high-resolution computer tomography 
HRT 
hormonal replacement therapy 
IB 
Investigator's Brochure
IBM 
inclusion bod y myositis
ICF 
informed consent form
ICH 
International Conference on Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use
IDMC 
independent data monitorin  g committee
IEC 
Independent Ethics Committee
IFN 
interferon
Ig 
immunoglobulin
IGRA 
interferon gamma release assay 
IIM 
idiopathic inflammator y myositis
IL 
interleukin
ILD 
interstitial lun  g disease
IM 
intramuscular
IMACS DOI 
International Myositis Assessment and Clinical Studies Definition of Improvement
IMACS TIS 
International Myositis Assessment and Clinical Studies Total Improvement Score
IQ 
interquartile


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IRB 
Institutional Review Board 
IV 
intravenous
IWRS 
interactive web response system
LDH 
lactate dehydrogenase
MDAAT 
Myositis Disease Activit y Assessment Tool
MEP 
maximal expirator y pressure
MHC 
major histocompatibilit y complex
MIP 
maximal inspirator y pressure
MITAX 
Myositis Intention to Treat Activit y Index 
MMF 
mycophenolate mofetil
MMRM 
mixed-effect model repeated measure
MMT 
Manual Muscle Testing 
mRNA 
messenger RNA
MTX 
methotrexate
MVV 
maximal voluntar y ventilation
NAbs 
neutralizin  g antibodies
NCI 
National Cancer Institute
PaCOβ 
partial pressure of carbon dioxide in arterial blood 
PaOβ 
partial pressure of oxygen in arterial blood 
PBMC 
peripheral blood mononuclear cell
PD 
pharmacodynamic
PFS 
prefilled syringe
PFT 
pulmonar y function test
PK 
pharmacokinetic
PM 
polymyositis
PQC 
product qualit y complaint
PRO 
patient-reported outcome
PsA 
psoriatic arthritis
RA 
rheumatoid arthritis
RNA 
ribonucleic acid 
SAE 
serious adverse event
SAP 
statistical analysis plan
SC 
subcutaneous
SD 
standard deviation
SF-γ6 
γ6-item short form 
SI 
International System of Units
SLE 
systemic lupus erythematosus
SSG 
statistical support group
SUSAR 
suspected unexpected serious adverse reactions
TAC 
tacrolimus
TB 
tuberculosis
Tfh 
T follicular helper
TNF 
tumor necrosis factor alpha
tRNA 
transfer RNA
ULN 
upper limit of normal
VAS 
Visual Analogue Scale
VC 
vital capacity 
WBC 
white blood cell
Definitions of Terms 
Clinical outcome 
assessment (COA) 
Includes PROs, Clinician Reported Outcomes (ClinROs), Observer Reported Outcomes
(ObsRO) and Performance Reported Outcomes (PerfRO)
Electronic source 
system 
Contains data traditionally maintained in a hospital or clinic record to document medical
care or data recorded in a CRF as determined by the protocol. Data in this system may be
considered source documentation.


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10.2. 
Appendix 2: Regulatory, Ethical, and Study Oversight Considerations
REGULATORY AND ETHICAL CONSIDERATIONS
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current International Conference on Harmonisation of Technical Requirements for
Registration of Pharmaceuticals for Human Use (ICH) guidelines on Good Clinical Practice (GCP),
and applicable regulatory and country-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing,
conducting, recording, and reporting studies that involve the participation of human participants.
Compliance with this standard provides public assurance that the rights, safety, and well-being of
study participants are protected, consistent with the principles that originated in the Declaration of
Helsinki, and that the study data are credible.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment by
the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by the
investigator. Protocol amendments must not be implemented without prior IEC/IRB approval, or
when the relevant competent authority has raised any grounds for non-acceptance, except when
necessary to eliminate immediate hazards to the participants, in which case the amendment must
be promptly submitted to the IEC/IRB and relevant competent authority. Documentation of
amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the
change(s) involve only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable,
the investigator or other physician in attendance will contact the appropriate sponsor representative
listed in the ‘Protocol Supplementary Information’, which will be provided as a separate document.
Except in emergency situations, this contact should be made before implementing any departure
from the protocol. In all cases, contact with the sponsor must be made as soon as possible to discuss
the situation and agree on an appropriate course of action. The data recorded in the eCRF and
source documents will reflect any departure from the protocol, and the source documents will
describe this departure and the circumstances requiring it.
Regulatory Approval/Notification
This protocol must be submitted to the appropriate regulatory authorities in each respective country,
if applicable. A study may not be initiated until all local regulatory requirements are met.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of the study drug to
the study site:


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 
Protocol signed and dated by the principal investigator
 
A copy of the dated and signed (or sealed, where appropriate per local regulations), written
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if
applicable, participant compensation programs. This approval must clearly identify the
specific protocol by title and number and must be signed (or sealed, where appropriate per
local regulations) by the chairman or authorized designee.
 
Name and address of the IEC/IRB, including a current list of the IEC/IRB members and their
function, with a statement that it is organized and operates according to GCP and the
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, from
the IEC/IRB, a general statement may be substituted for this list. If an investigator or a
member of the study site personnel is a member of the IEC/IRB, documentation must be
obtained to state that this person did not participate in the deliberations or in the vote/opinion
of the study.
 
Regulatory authority approval or notification, if applicable
 
Signed and dated statement of investigator (eg, Form FDA 157β), if applicable
 
Documentation of investigator qualifications (eg, curriculum vitae)
 
Completed investigator financial disclosure form from the principal investigator, where
required
 
Signed and dated clinical trial agreement, which includes the financial agreement
 
Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first
participant:
 
Completed investigator financial disclosure forms from all subinvestigators
 
Documentation of subinvestigator qualifications (eg, curriculum vitae)
 
Name and address of any local laboratory conducting tests for the study, and a dated copy of
current laboratory normal ranges for these tests, if applicable
 
Local laboratory documentation demonstrating competence and test reliability
(eg, accreditation/license), if applicable
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the IEC/IRB
with current and complete copies of the following documents (as required by local regulations):
 
Final protocol and, if applicable, amendments
 
Sponsor-approved ICF (and any other written materials to be provided to the participants)
 
IB (or equivalent information) and amendments/addenda
 
Sponsor-approved participant recruiting materials
 
Information on compensation for study-related injuries or payment to participants for
participation in the study, if applicable


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 
Investigator's curriculum vitae or equivalent information (unless not required, as documented
by the IEC/IRB)
 
Information regarding funding, name of the sponsor, institutional affiliations, other potential
conflicts of interest, and incentives for participants
 
Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final protocol,
amendments (if any, excluding the ones that are purely administrative, with no consequences for
participants, data or study conduct, unless required locally), the ICF, applicable recruiting materials,
and participant compensation programs, and the sponsor has received a copy of this approval. This
approval letter must be dated and must clearly identify the IEC/IRB and the documents being
approved.
Approval for the collection of optional samples for research and for the corresponding ICF must
be obtained from the IEC/IRB. Approval for the protocol can be obtained independent of this
optional research component. 
During the study the investigator (or sponsor where required) will send the following documents
and updates to the IEC/IRB for their review and approval, where appropriate:
 
Protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct)
 
Revision(s) to ICF and any other written materials to be provided to participants
 
If applicable, new or revised participant recruiting materials approved by the sponsor
 
Revisions to compensation for study-related injuries or payment to participants for
participation in the study, if applicable
 
New edition(s) of the IB and amendments/addenda
 
Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at
least annually)
 
Reports of AEs that are serious, unlisted/unexpected, and associated with the study drug
 
New information that may adversely affect the safety of the participants or the conduct of the
study
 
Deviations from or changes to the protocol to eliminate immediate hazards to the participants
 
Report of deaths of participants under the investigator's care
 
Notification if a new investigator is responsible for the study at the site
 
Development Safety Update Report and Line Listings, where applicable
 
Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct), the amendment and applicable ICF revisions


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must be submitted promptly to the IEC/IRB for review and approval before implementation of the
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about
the study completion, the notification will be submitted through the head of investigational
institution.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.β.1.
FINANCIAL DISCLOSURE
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial
information in accordance with local regulations to allow the sponsor to submit complete and
accurate financial certification or disclosure statements to the appropriate regulatory authorities.
investigators are responsible for providing information on financial interests during the course of
the study and for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
INFORMED CONSENT PROCESS 
Each participant must give written consent according to local requirements after the nature of the
study has been fully explained. The ICFs must be signed before performance of any study-related
activity. The ICFs that is/are used must be approved by both the sponsor and by the reviewing
IEC/IRB and be in a language that the participant can read and understand. The informed consent
should be in accordance with principles that originated in the Declaration of Helsinki, current ICH
and GCP guidelines, applicable regulatory requirements, and sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study site personnel
must explain to potential participants the aims, methods, reasonably anticipated benefits, and
potential hazards of the study, and any discomfort participation in the study may entail. Participants
will be informed that their participation is voluntary and that they may withdraw consent to
participate at any time. They will be informed that choosing not to participate will not affect the
care the participant will receive for the treatment of his or her disease. Participants will be told that
alternative treatments are available if they refuse to take part and that such refusal will not
prejudice future treatment. Finally, they will be told that the investigator will maintain a participant
identification register for the purposes of long-term follow up if needed and that their records may
be accessed by health authorities and authorized sponsor personnel without violating the
confidentiality of the participant, to the extent permitted by the applicable law(s) or regulations.
By signing the ICF the participant is authorizing such access, It also denotes that the participant
agrees to allow his or her study physician to recontact the participant for the purpose of obtaining
consent for additional safety evaluations, and subsequent disease-related treatments, if needed. 


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The participant will be given sufficient time to read the ICF and the opportunity to ask questions.
After this explanation and before entry into the study, consent should be appropriately recorded by
means of the participant's personally dated signature. After having obtained the consent, a copy of
the ICF must be given to the participant.
Participants who are rescreened are required to sign a new ICF.
Participants will be asked for consent to provide optional samples for research. After informed
consent for the study is appropriately obtained, the participant will be asked to sign and personally
date a separate ICF indicating agreement to participate in the optional research component. Refusal
to participate in the optional research will not result in ineligibility for the study. A copy of this
signed ICF will be given to the participant.
A separate ICF may be used for the required DNA component of the study.
If the participant is unable to read or write, an impartial witness should be present for the entire
informed consent process (which includes reading and explaining all written information) and
should personally date and sign the ICF after the oral consent of the participant is obtained.
DATA PROTECTION
Privacy of Personal Data
The collection and processing of personal data from participants enrolled in this study will be
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality
and compliance with applicable data privacy protection laws and regulations. Appropriate
technical and organizational measures to protect the personal data against unauthorized disclosures
or access, accidental or unlawful destruction, or accidental loss or alteration must be put in place.
Sponsor personnel whose responsibilities require access to personal data agree to keep the identity
of participants confidential.
The informed consent obtained from the participant includes explicit consent for the processing of
personal data and for the investigator/institution to allow direct access to his or her original medical
records (source data/documents) for study-related monitoring, audit, IEC/IRB review, and
regulatory inspection. This consent also addresses the transfer of the data to other entities and to
other countries.
The participant has the right to request through the investigator access to his or her personal data
and the right to request rectification of any data that are not correct or complete. Reasonable steps
will be taken to respond to such a request, taking into consideration the nature of the request, the
conditions of the study, and the applicable laws and regulations.
Exploratory (DNA, PD, biomarker, PK, and immunogenicity) research is not conducted under
standards appropriate for the return of data to participants. In addition, the sponsor cannot make
decisions as to the significance of any findings resulting from exploratory research. Therefore,


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exploratory research data will not be returned to participants or investigators, unless required by
law or local regulations. Privacy and confidentiality of data generated in the future on stored
samples will be protected by the same standards applicable to all other clinical data.
LONG-TERM RETENTION OF SAMPLES FOR ADDITIONAL FUTURE RESEARCH 
Samples collected in this study may be stored for up to 15 years (or according to local regulations)
for additional research. Samples will only be used to understand ustekinumab, to understand
PM/DM, to understand differential intervention responders, and to develop tests/assays related to
ustekinumab and PM/DM. The research may begin at any time during the study or the poststudy
storage period. 
Stored samples will be coded throughout the sample storage and analysis process and will not be
labeled with personal identifiers. Participants may withdraw their consent for their samples to be
stored for research (refer to Section 7.β.1, Withdrawal From the Use of Research Samples).
COMMITTEES STRUCTURE
Independent Data Monitoring Committee
An IDMC will be established to monitor data on an ongoing basis to ensure the continuing safety
of the participants enrolled in this study and to meet interim analysis objectives. This committee
will consist of β medical experts in the relevant therapeutic area and at least 1 statistician;
committee membership responsibilities, authorities, and procedures will be documented in its
charter. The committee will meet periodically to review the safety and interim data. After the
review, the IDMC will make recommendations regarding the continuation of the study.
PUBLICATION POLICY/DISSEMINATION OF CLINICAL STUDY DATA
All information, including but not limited to information regarding ustekinumab or the sponsor's
operations (eg, patent application, formulas, manufacturing processes, basic scientific data, prior
clinical data, formulation information) supplied by the sponsor to the investigator and not
previously published, and any data, including pharmacogenomic or exploratory biomarker
research data, generated as a result of this study, are considered confidential and remain the sole
property of the sponsor. The investigator agrees to maintain this information in confidence and use
this information only to accomplish this study, and will not use it for other purposes without the
sponsor's prior written consent.
The investigator understands that the information developed in the study will be used by the
sponsor in connection with the continued development of ustekinumab, and thus may be disclosed
as required to other clinical investigators or regulatory agencies. To permit the information derived
from the clinical studies to be used, the investigator is obligated to provide the sponsor with all
data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the sponsor and
will contain data from all study sites that participated in the study as per protocol. Recruitment
performance or specific expertise related to the nature and the key assessment parameters of the


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study will be used to determine a coordinating investigator for the study. Results of
pharmacogenomic or exploratory biomarker analyses performed after the Clinical Study Report
has been issued will be reported in a separate report and will not require a revision of the Clinical
Study Report. 
Study participant identifiers will not be used in publication of results. Any work created in
connection with performance of the study and contained in the data that can benefit from copyright
protection (except any publication by the investigator as provided for below) shall be the property
of the sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal
Editors (ICMJE) guidelines, the sponsor shall have the right to publish such primary (multicenter)
data and information without approval from the investigator. The investigator has the right to
publish study site-specific data after the primary data are published. If an investigator wishes to
publish information from the study, a copy of the manuscript must be provided to the sponsor for
review at least 60 days before submission for publication or presentation. Expedited reviews will
be arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in
writing, the investigator will withhold such publication for up to an additional 60 days to allow for
filing of a patent application. In the event that issues arise regarding scientific integrity or
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will
not mandate modifications to scientific content and does not have the right to suppress information.
For multicenter study designs and substudy approaches, secondary results generally should not be
published before the primary endpoints of a study have been published. Similarly, investigators
will recognize the integrity of a multicenter study by not submitting for publication data derived
from the individual study site until the combined results from the completed study have been
submitted for publication, within 18 months after the study end date, or the sponsor confirms there
will be no multicenter study publication. Authorship of publications resulting from this study will
be based on the guidelines on authorship, such as those described in the ICMJE Recommendations
for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals, which
state that the named authors must have made a significant contribution to the conception or design
of the work; or the acquisition, analysis, or interpretation of the data for the work; and drafted the
work or revised it critically for important intellectual content; and given final approval of the
version to be published; and agreed to be accountable for all aspects of the work in ensuring that
questions related to the accuracy or integrity of any part of the work are appropriately investigated
and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required
by law.


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DATA QUALITY ASSURANCE
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified
investigators and appropriate study sites, review of protocol procedures with the investigator and
study site personnel before the study, and periodic monitoring visits by the sponsor, and direct
transmission of clinical laboratory data from a central laboratory into the sponsor's data base.
Written instructions will be provided for collection, handling, storage, and shipment of samples. 
Guidelines for eCRF completion will be provided and reviewed with study site personnel before
the start of the study. 
The sponsor will review eCRF for accuracy and completeness during on-site monitoring visits and
after transmission to the sponsor; any discrepancies will be resolved with the investigator or
designee, as appropriate. After upload of the data into the study database they will be verified for
accuracy and consistency with the data sources. 
CASE REPORT FORM COMPLETION
Case report forms are prepared and provided by the sponsor for each participant in electronic
format. All data relating to the study must be recorded in eCRF. All eCRF entries, corrections, and
alterations must be made by the investigator or authorized study site personnel. The investigator
must verify that all data entries in the eCRF are accurate and correct.
The study data will be transcribed by study site personnel from the source documents onto an
eCRF, if applicable. Study-specific data will be transmitted in a secure manner to the sponsor.
All participative measurements (eg, pain scale information or other questionnaires) will be
completed by the same individual who made the initial baseline determinations whenever possible.
If necessary, queries will be generated in the electronic data capture (eDC) tool. If corrections to
a eCRF are needed after the initial entry into the eCRF, this can be done in either of the following
ways:
 Investigator and study site personnel can make corrections in the eDC tool at their own
initiative or as a response to an auto query (generated by the eDC tool).
 Sponsor or sponsor delegate can generate a query for resolution by the investigator and study
site personnel.
SOURCE DOCUMENTS
At a minimum, source documents consistent in the type and level of detail with that commonly
recorded at the study site as a basis for standard medical care must be available for the following:
participant identification, eligibility, and study identification; study discussion and date of signed
informed consent; dates of visits; results of safety and efficacy parameters as required by the
protocol; record of all AEs and follow-up of AEs; concomitant medication; intervention
receipt/dispensing/return records; study drug administration information; and date of study


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completion and reason for early discontinuation of the study drug or withdrawal from the study, if
applicable. 
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be
reviewed with the investigator before the study and will be described in the monitoring guidelines
(or other equivalent document).
The following data will be recorded directly into the eCRF and will be considered source data: 
 Race
 Blood pressure and pulse/heart rate 
 Height and weight
 Investigator-completed scales and PRO assessments
The minimum source documentation requirements for Section 5.1, Inclusion Criteria and
Section 5.β, Exclusion Criteria that specify a need for documented medical history are as follows:
 Referral letter from treating physician or
 Complete history of medical notes at the site
 Discharge summaries
Inclusion and exclusion criteria not requiring documented medical history must be verified at a
minimum by participant interview or other protocol required assessment (eg, physical examination,
laboratory assessment) and documented in the source documents.An eSource system may be
utilized, which contains data traditionally maintained in a hospital or clinic record to document
medical care (eg, electronic source documents) as well as the clinical study-specific data fields as
determined by the protocol. This data is electronically extracted for use by the sponsor. If eSource
is utilized, references made to the eCRF in the protocol include the eSource system but information
collected through eSource may not be limited to that found in the eCRF.
MONITORING
The sponsor will use a combination of monitoring techniques central, remote, or on-site monitoring
to monitor this study.
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will
record dates of the visits in a study site visit log that will be kept at the study site. The first
postinitiation visit will be made as soon as possible after enrollment has begun. At these visits, the
monitor will compare the data entered into the eCRF with the source documents
(eg, hospital/clinic/physician’s office medical records). The nature and location of all source
documents will be identified to ensure that all sources of original data required to complete the
eCRF are known to the sponsor and study site personnel and are accessible for verification by the


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sponsor study site contact. If electronic records are maintained at the study site, the method of
verification must be discussed with the study site personnel. 
Direct access to source documents (medical records) must be allowed for the purpose of verifying
that the recorded data are consistent with the original source data. Findings from this review will
be discussed with the study site personnel. The sponsor expects that, during monitoring visits, the
relevant study site personnel will be available, the source documents will be accessible, and a
suitable environment will be provided for review of study-related documents. The monitor will
meet with the investigator on a regular basis during the study to provide feedback on the study
conduct.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during these
remote contacts, study site personnel will be available to provide an update on the progress of the
study at the site. 
Central monitoring will take place for data identified by the sponsor as requiring central review.
ON-SITE AUDITS
Representatives of the sponsor's clinical quality assurance department may visit the study site at
any time during or after completion of the study to conduct an audit of the study in compliance
with regulatory guidelines and company policy. These audits will require access to all study
records, including source documents, for inspection. Participant privacy must, however, be
respected. The investigator and study site personnel are responsible for being present and available
for consultation during routinely scheduled study site audit visits conducted by the sponsor or its
designees. 
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part
of a national GCP compliance program or to review the results of this study in support of a
regulatory submission. The investigator should immediately notify the sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
RECORD RETENTION
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF
and all source documents that support the data collected from each participant, as well as all study
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical
Trial, and all study documents as specified by the applicable regulatory requirement(s). The
investigator/institution will take measures to prevent accidental or premature destruction of these
documents.
Essential documents must be retained until at least β years after the last approval of a marketing
application in an ICH region and until there are no pending or contemplated marketing applications
in an ICH region or until at least β years have elapsed since the formal discontinuation of clinical
development of the investigational product. These documents will be retained for a longer period
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the


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responsibility of the sponsor to inform the investigator/institution as to when these documents no
longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the
responsibility of keeping the study records, custody must be transferred to a person who will accept
the responsibility. The sponsor must be notified in writing of the name and address of the new
custodian. Under no circumstance shall the investigator relocate or dispose of any study documents
before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any
documentation relating to this study, the investigator/institution must permit access to such reports.
STUDY AND SITE CLOSURE
Study Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A
study site is considered closed when all required documents and study supplies have been collected
and a study site closure visit has been performed.
The investigator may initiate study site closure at any time, provided there is reasonable cause and
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are not
limited to:
 Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or
local health authorities, the sponsor's procedures, or GCP guidelines
 Inadequate recruitment of participants by the investigator
 Discontinuation of further study drug development


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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for Recording,
Evaluating, Follow-up, and Reporting
ADVERSE EVENT DEFINITIONS AND CLASSIFICATIONS
Adverse Event
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal
(investigational or non-investigational) product. An AE does not necessarily have a causal
relationship with the intervention. An AE can therefore be any unfavorable and unintended sign
(including an abnormal finding), symptom, or disease temporally associated with the use of a
medicinal (investigational or non-investigational) product, whether or not related to that medicinal
(investigational or non-investigational) product. (Definition per ICH)
This includes any occurrence that is new in onset or aggravated in severity or frequency from the
baseline condition, or abnormal results of diagnostic procedures, including laboratory test
abnormalities.
Note: The sponsor collects AEs starting with the signing of the ICF (refer to All Adverse Events
under Section 8.γ.1, Time Period and Frequency for Collecting Adverse Events and Serious
Adverse Events Information, for time of last AE recording).
Serious Adverse Event
An SAE based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for
Human Use is any untoward medical occurrence that at any dose:
 
Results in death
 
Is life-threatening 
(The participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.)
 
Requires inpatient hospitalization or prolongation of existing hospitalization
 
Results in persistent or significant disability/incapacity
 
Is a congenital anomaly/birth defect
 
Is a suspected transmission of any infectious agent via a medicinal product
 
Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is
also appropriate in other situations, such as important medical events that may not be immediately
life-threatening or result in death or hospitalization but may jeopardize the participant or may
require intervention to prevent 1 of the other outcomes listed in the definition above. These should
usually be considered serious.
If a serious and unexpected AE occurs for which there is evidence suggesting a causal relationship
between the study drug and the event (eg, death from anaphylaxis), the event must be reported as


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a serious and unexpected suspected adverse reaction even if it is a component of the study endpoint
(eg, all-cause mortality). 
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable product
reference safety information. For ustekinumab, the expectedness of an AE will be determined by
whether or not it is listed in the IB.9 For standard-of-care background therapies with a marketing
authorization, the expectedness of an AE will be determined by whether or not it is listed in the
package insert/summary of product characteristics.
Adverse Event Associated With the Use of the Intervention
An AE is considered associated with the use of the intervention if the attribution is possible,
probable, or very likely by the definitions listed below (see Attribution Definitions).
ATTRIBUTION DEFINITIONS
Not Related
An AE that is not related to the use of the intervention.
Doubtful
An AE for which an alternative explanation is more likely, eg, concomitant treatment(s),
concomitant disease(s), or the relationship in time suggests that a causal relationship is unlikely.
Possible
An AE that might be due to the use of the intervention. An alternative explanation, eg, concomitant
treatment(s), concomitant disease(s), is inconclusive. The relationship in time is reasonable;
therefore, the causal relationship cannot be excluded.
Probable
An AE that might be due to the use of the intervention. The relationship in time is suggestive
(eg, confirmed by dechallenge). An alternative explanation is less likely, eg, concomitant
treatment(s), concomitant disease(s).
Very Likely
An AE that is listed as a possible adverse reaction and cannot be reasonably explained by an
alternative explanation, eg, concomitant treatment(s), concomitant disease(s). The relationship in
time is very suggestive (eg, it is confirmed by dechallenge and rechallenge).
SEVERITY CRITERIA 
An assessment of severity grade will be made using the following general categorical descriptors:
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not
interfering with everyday activities.


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Moderate: Sufficient discomfort is present to cause interference with normal activity.
Severe: Extreme distress, causing significant impairment of functioning or incapacitation.
Prevents normal everyday activities.
The investigator should use clinical judgment in assessing the severity of events not directly
experienced by the participant (eg, laboratory abnormalities).
SPECIAL REPORTING SITUATIONS
Safety events of interest on a sponsor study drug in an interventional study that may require
expedited reporting or safety evaluation include, but are not limited to:
 
Overdose of a sponsor study drug
 
Suspected abuse/misuse of a sponsor study drug
 
Accidental or occupational exposure to a sponsor study drug
 
Any failure of expected pharmacologic action (ie, lack of effect) of a sponsor study drug
 
Unexpected therapeutic or clinical benefit from use of a sponsor study drug
 
Medication error involving a sponsor product (with or without participant/patient exposure to
the sponsor study drug, eg, name confusion)
 
Exposure to a sponsor study drug from breastfeeding
Special reporting situations should be recorded in the eCRF. Any special reporting situation that
meets the criteria of an SAE should be recorded on the SAE page of the eCRF.
PROCEDURES
All Adverse Events
All AEs, regardless of seriousness, severity, or presumed relationship to study drug, must be
recorded using medical terminology in the source document and the eCRF. Whenever possible,
diagnoses should be given when signs and symptoms are due to a common etiology (eg, cough,
runny nose, sneezing, sore throat, and head congestion should be reported as "upper respiratory
infection"). investigators must record in the eCRF their opinion concerning the relationship of the
AE to study therapy. All measures required for AE management must be recorded in the source
document and reported according to sponsor instructions.
For all studies with an outpatient phase, including open-label studies, the participant must be
provided with a "wallet (study) card" and instructed to carry this card with them for the duration
of the study indicating the following: 
 
Study number
 
Statement, in the local language(s), that the participant is participating in a clinical study
 
Investigator's name and β4-hour contact telephone number


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 
Local sponsor's name and β4-hour contact telephone number (for medical staff only)
 
Site number
 
Participant number
 
Any other information that is required to do an emergency breaking of the blind
Serious Adverse Events
All SAEs that have not resolved by the end of the study, or that have not resolved upon
discontinuation of the participant's participation in the study, must be followed until any of the
following occurs:
 
The event resolves
 
The event stabilizes
 
The event returns to baseline, if a baseline value/status is available
 
The event can be attributed to agents other than the study drug or to factors unrelated to study
conduct
 
It becomes unlikely that any additional information can be obtained (participant or health care
practitioner refusal to provide additional information, lost to follow-up after demonstration of
due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as an SAE.
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during the
course of a participant's participation in a study must be reported as an SAE, except
hospitalizations for the following:
 
Hospitalizations not intended to treat an acute illness or AE (eg, social reasons such as pending
placement in long-term care facility)
 
Surgery or procedure planned before entry into the study (must be documented in the eCRF).
Note: Hospitalizations that were planned before the signing of the ICF, and where the
underlying condition for which the hospitalization was planned has not worsened, will not be
considered SAEs. Any AE that results in a prolongation of the originally planned
hospitalization is to be reported as a new SAE.
The cause of death of a participant in a study within 16 weeks of the last dose of the study drug,
whether or not the event is expected or associated with the study drug, is considered an SAE.
CONTACTING SPONSOR REGARDING SAFETY
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding safety issues or questions regarding the study are listed in the ‘Protocol Supplementary
Information’, which will be provided as a separate document.
PRODUCT QUALITY COMPLAINT HANDLING
A product quality complaint (PQC) is defined as any suspicion of a product defect related to
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality,


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durability, or reliability of a product, including its labeling or package integrity. A PQC may have
an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting and
analysis of PQC information from studies are crucial for the protection of participants,
investigators, and the sponsor, and are mandated by regulatory agencies worldwide. The sponsor
has established procedures in conformity with regulatory requirements worldwide to ensure
appropriate reporting of PQC information; all studies conducted by the sponsor or its affiliates will
be conducted in accordance with those procedures.
Procedures
All initial PQCs must be reported to the sponsor by the study site personnel within β4 hours after
being made aware of the event.
If the defect is combined with an SAE, the study site personnel must report the PQC to the sponsor
according to the SAE reporting timelines (refer to Section 8.γ.1, Time Period and Frequency for
Collecting Adverse Event and Serious Adverse Event Information). A sample of the suspected
product should be maintained for further investigation if requested by the sponsor.
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding product quality issues are listed in the ‘Protocol Supplementary Information’, which will
be provided as a separate document.






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10.5. 
Appendix 5: Contraceptive and Barrier Guidance and Collection of
Pregnancy Information
Participants must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria.
Pregnancy information will be collected and reported as noted in Section 8.β.6, Pregnancy and
Section 10.γ, Appendix γ: Adverse Events: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting.
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless
permanently sterile (see below).
Woman Not of Childbearing Potential
 
Premenarchal 
A premenarchal state is one in which menarche has not yet occurred.
 
Postmenopausal
A postmenopausal state is defined as no menses for 1β months without an alternative medical
cause. A high follicle stimulating hormone (FSH) level (>40 IU/L or mIU/mL) in the
postmenopausal range may be used to confirm a postmenopausal state in women not using
hormonal contraception or hormonal replacement therapy (HRT), however in the absence of
1β months 
of 
amenorrhea, 
a 
single 
FSH 
measurement 
is 
insufficient.
If there is a question about menopausal status in women on HRT, the woman will be required
to use 1 of the non-estrogen-containing hormonal highly effective contraceptive methods if
she wishes to continue HRT during the study.
 
Permanently sterile
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal
occlusion/ligation procedures, and bilateral oophorectomy.
Note: If the childbearing potential changes after start of the study (eg, a premenarchal woman
experiences menarche) or the risk of pregnancy changes (eg, a woman who is not heterosexually
active becomes active), a woman must begin a highly effective method of contraception, as
described throughout the inclusion criteria.
If reproductive status is questionable, additional evaluation should be considered.
Examples of Contraceptives
EXAMPLES OF CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE:
USER INDEPENDENT
Highly Effective Methods That Are User Independent Failure rate of ≤1% per year when used
consistently and correctly.
 
Implantable progestogen-only hormone contraception associated with inhibition of ovulationb
 
Intrauterine device (IUD)
 
Intrauterine hormone-releasing system (IUS)


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 
Bilateral tubal occlusion
 
Vasectomized partner
(Vasectomized partner is a highly effective contraceptive method provided that the partner is the
sole sexual partner of the woman of childbearing potential and the absence of sperm has been
confirmed. If not, additional highly effective method of contraception should be used.
Spermatogenesis cycle is approximately 74 days.)
USER DEPENDENT
Highly Effective Methods That Are User Dependent Failure rate of <1% per year when used
consistently and correctly.
 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with
inhibition of ovulationb
 
oral
 
intravaginal
 
transdermal
 
injectable
 
Progestogen-only hormone contraception associated with inhibition of ovulationb
 
oral
 
injectable
 
Sexual abstinence
(Sexual abstinence is considered a highly effective method only if defined as refraining from
heterosexual intercourse during the entire period of risk associated with the study drug. The
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and
the preferred and usual lifestyle of the participant.)
NOT ALLOWED AS SOLE METHOD OF CONTRACEPTION DURING THE STUDY (not
considered to be highly effective - failure rate of >1% per year)
 
Progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary
mode of action.
 
Male or female condom with or without spermicidec
 
Cap, diaphragm, or sponge with spermicide
 
A combination of male condom with either cap, diaphragm, or sponge with spermicide (double-
barrier methods)c
 
Periodic abstinence (calendar, symptothermal, postovulation methods)
 
Withdrawal (coitus-interruptus)
 
Spermicides alone
 
Lactational amenorrhea method (LAM)
a) Typical use failure rates may differ from those when used consistently and correctly. Use should be
consistent with local regulations regarding the use of contraceptive methods for participants in
clinical studies.
b) Hormonal contraception may be susceptible to interaction with the study drug, which may reduce
the efficacy of the contraceptive method. In addition, consider if the hormonal contraception may
interact with the study drug.
c) Male condom and female condom should not be used together (due to risk of failure with friction).


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Pregnancy During the Study
See Section 8.γ.5.


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10.6. 
Appendix 6: Medical Device Incidents: Definition and Procedures for
Recording, Evaluating, Follow-up, and Reporting 
The detection and documentation procedures described in this protocol apply to all sponsor
medical devices provided for use in the study (see Section 6.1, Study Interventions Administered
for the list of sponsor medical devices).
Medical Device Incident Definition
 
A medical device incident is any malfunction or deterioration in the characteristics or
performance of a device as well as any inadequacy in the labeling or the instructions for use
which, directly or indirectly, might lead to or might have led to the death of a
participant/user/other person or to a serious deterioration in his/her state of health.
 
Not all incidents lead to death or serious deterioration in health. The nonoccurrence of such a
result might have been due to other fortunate circumstances or to the intervention of health
care personnel.
It is sufficient that:
 
An incident associated with a device happened.
AND
 
The incident was such that, if it occurred again, might lead to death or a serious deterioration
in health.
A serious deterioration in state of health can include any of the following:
 
Life-threatening illness
 
Permanent impairment of body function or permanent damage to body structure
 
Condition necessitating medical or surgical intervention to prevent one of the above
 
Fetal distress, fetal death, or any congenital abnormality or birth defects
Examples of Incidents
 
A participant, user, caregiver, or healthcare professional is injured as a result of a medical
device failure or its misuse.
 
A participant’s study intervention is interrupted or compromised by a medical device failure.
 
A misdiagnosis due to medical device failure leads to inappropriate treatment.
 
A participant’s health deteriorates due to medical device failure.
Documenting Medical Device Incidents
 
Any medical device incident occurring during the study will be documented in the
participant’s medical records, in accordance with the investigator’s normal clinical practice,
and on the appropriate form of the eCRF.
 
For incidents fulfilling the definition of an AE or an SAE, the appropriate Adverse
Event/Serious Adverse Event eCRF page will be completed as described in Section 10.γ,


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Appendix γ: Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting.
 
The eCRF will be completed as thoroughly as possible and signed by the investigator before
transmittal to the sponsor or designee.
 
It is very important that the investigator provides his/her assessment of causality (relationship
to the medical device provided by the sponsor) at the time of the initial AE or SAE report and
describes any corrective or remedial actions taken to prevent recurrence of the incident.
 
A remedial action is any action other than routine maintenance or servicing of a medical
device where such action is necessary to prevent recurrence of an incident. This includes any
amendment to the device design to prevent recurrence.


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10.7. 
Appendix 7: Cancer Screening Test
The following tests will be performed according to the Schedule of Activities:
Protocol-required Cancer Screening Tests 
Cancer 
Assessments for screening* 
Age 
Sex
Gastric cancer  
Medical interview and  
Gastric x-ray or Gastroendoscopy
≥50 
Male and Female
Cervical cancer  
Medical interview, Inspection and 
Cytological diagnosis and
Pelvic examination in the cervix
≥β0 
Female
Lung cancer 
Medical interview, Chest x-ray and 
Sputum cytology**
≥40 
Male and Female
Breast cancer  
Medical interview and Mammography 
≥40 
Female
Colon cancer 
Medical interview and Stool test for 
occult blood 
≥40 
Male and Female
* Assessments can be replaced by alternative tests which have equivalent or better sensitivity and specificity (eg,
colonoscopy for colon cancer).
** This cytology is needed for participants are ≥50 years old and meet smoking index (number of cigarettes smoked
per day x years) is ≥ 600.
Participants should be performed cancer screening tests dependent on the status of anti-TIF1-Ȗ 
antibody as follows;
a. If participants have negative test result for anti-TIF1- Ȗ antibody, these cancer screening
tests should be tested according to the age at informed consent and sex of participants. 
b. If participants have positive test result for anti-TIF1- Ȗ antibody, these cancer screening
tests should be tested irrespective of age according the sex of participants. 
The investigator should confirm the results of cancer screening tests brought by participants if they
were performed at any other sites within β years.




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10.9. 
Appendix 9: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents (TOC).
Amendment 2 (4 Jun 2020)
Overall Rationale for the Amendment: The overall reason for the amendment is to implement
clarifications to the protocol as well feedback from key opinion leaders and study investigators.
Section number 
and Name
Description of Change 
Brief Rationale
1.γ. Schedule of Activities
(SoA)
n. In addition to the urine screening
evaluation, a serum pregnancy test may be
conducted at any time at the discretion of
Investigator or participant. Urine pregnancy
tests may be conducted more frequently (eg,
monthly basis).   Urine pregnancy tests may not
be necessary if a subject is considered a
postmenopausal state defined as no menses for
1β months without an alternative medical cause
and a high follicle stimulating hormone (FSH)
level (>40 IU/L or mIU/mL) during the study.
Text was added to clarify
the condition of participants
who may not be required
urine pregnancy tests.
5.1. Inclusion Criteria 1β. 
Criterion modified per Amendment β:
1β.1 Must be receiving 1 or more of the
following protocol-permitted, systemic
standard-of-care treatments:
 
•If using 1 or β of the following
immunomodulatory drugs within the range of
maximum dose or concentration, must be
receiving all of those for ≥8 weeks and be on a
stable dose for ≥4 weeks prior to first dose of
the study drug:
 
MMF ≤γ g/day
 
AZA 1 to β mg/kg/day; up to
γ mg/kg/day
 
Oral MTX ≤15 mg/week with
concomitant folic acid or calcium
folinate
 
Oral TAC targetingat trough
concentration of 5 to 10 ng/mL
 
Oral cyclosporine A targetingat
trough concentration of 100 to
150 ng/mL
Text was revised to clarify
the inclusion criteria for the
standard of treatment based
on the local guideline and
the package insert.
6.5.γ. Non-biologic
Immunomodulators
Participants are allowed to use up to 1 β of the
following immunomodulatory drugs without
any change in dose from baseline (Week 0)
through Week β4.


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Section number 
and Name
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Brief Rationale
5.1. Inclusion Criteria 1γ. 
Criterion modified per Amendment β: 
1γ.1 Regular or as needed treatment with 
topical use of medium/mild (Group IV) or 
weak (Group V) potency glucocorticoids 
are permitted to treat skin lesions of DM 
on a stable dose for ≥β weeks prior to first 
dose of the study drug. (see Section 6.5.4. 
for potency of topical glucocorticoids)
Text was revised to clarify
the permitted usage of
topical medications as well
as the medical conditions,
for which topical
medications can be
permitted
 
6.5.4. Topical Medications 
For the treatment of cutaneous lesion in
participants with PM/DM or other concurrent
medical conditions, regular use of topical
medications is permitted. However, topical
compounds cannot include a prohibited
medication. Topical glucocorticoids must be
medium/mild (Group IV) or weak (Group V)
potency glucocorticoids to treat cutaneous
lesions of myositis or skin disease of the same
area as cutaneous lesions of myositis. Topical
glucocorticoids may be very strong (Group II)
or weaker potency glucocorticoids to treat
cutaneous lesions of other concurrent medical
conditions whose area is different from
cutaneous lesions of myositis. “As needed” use
of topical medium/mild (Group IV) or weak
(Group V) potency glucocorticoids is
permitted, but not within 48 hours  prior to a
study visit for efficacy assessment. The
investigator should notify the sponsor ifAfter
discussion with the sponsor, topical
glucocorticoids of very strong (Group III) or
weaker potency aremay be used on skin lesion
up to β weeks where there is no preexisting
skin eruptions of myositis DM in case it is
considered due to adverse events other than
cutaneous lesions of myositis DM.
 
5.4. Screen Failures 
Rescreening 
If a participant is a screen failure, the 
participant may be rescreened 1 additional time 
after a period of at least γ0 days. Participants 
who are rescreened will be assigned a new
participant number, undergo the informed
consent process again, and restart a new
screening phase with carrying screening test
results over from previous screening if
appropriate.
Text was added to clarify
the procedure of
rescreening.
6.5.β. Glucocorticoid Therapy 
Glucocorticoid dose needs to be reduced based 
on the table of glucocorticoid tapering schedule 
(See Table β). Reduction of glucocorticoid 
dose should follow study drug administration at
the weeks of study drug administration.
Text was added to clarify
the procedure of reduction
of glucocorticoid dose.
6.6. Prohibited Therapies 
• Intravenous or subcutaneous Ig 
Text was revised to clarify
the details of
immunoglobulin in


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Section number 
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prohibited therapies.
 
7.1. Discontinuation of Study 
Drug  
 
Addition of new therapysystemic medication 
for PM/DM activity must be discussed with the 
sponsor to determine the suitability of the 
participant to continue the study drug
administrations.
Text was revised to clarify
Discontinuation of Study
Drug
10.4. Appendix 4: Clinical 
Laboratory Tests 
 
Laboratory 
Assessments 
Parameters 
Hematology 
platelet count 
Red blood cell count (RBC)
RBC morphology
Hemoglobin
Hematocrit 
 
Note: A WBC evaluation may
include any abnormal cells,
which will then be reported by
the laboratory. A RBC evaluation
may include abnormalities in the
RBC count, RBC parameters, or
RBC morphology, which will
then be reported by the
laboratory. In addition, any other
abnormal cells in a blood smear
will also be reported.
Other 
Screening 
Tests 
• Urine pregnancy testing for
women of childbearing potential
only (performed locally)
• Serum pregnancy test (at the
discretion of the investigator)
• Viral serology (HIV antibody,
HBsAg, anti HBs, anti HBc total,
and HCV antibody)
• IGRA (performed locally)
• anti TIF1 Ȗ(performed locally)
• anti MDA5 (can be performed
locally)
 
Text was revised to clarify
the parameters and note of
Clinical Laboratory Tests.
10.7. Appendix 7: Cancer
Screening Test
10.8.10.7. Appendix 78: Cancer Screening Test
 
Cancer 
Assessments for 
screening*
 
Age 
Sex
Lung 
cancer 
Medical 
interview, Chest 
x ray and 
Sputum
cytology**
≥40 
Male
and
Female
* Assessments can be replaced by alternative
tests which have equivalent or better sensitivity
and specificity (eg, colonoscopy for colon
cancer).
 
** This cytology is needed for participants are
≥50 years old and meet smoking index (number
of cigarettes smoked per day x years) is ≥ 600.
Text was added to clarify
the alternative tests for
cancer screening test based
on medical practice in
Japan.
Throughout the protocol 
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted.


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Amendment 1 (13 August 2019)
Overall Rationale for the Amendment: The overall reason for the amendment is to implement
clarifications to the protocol as well feedback from key opinion leaders and study investigators.
Section number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis
Secondary
Endpoints
Tertiary Endpoints 
 
1.γ.Schedule of
Activities (SoA)
Time and Events
Schedule 
 
γ. OBJECTIVES
AND ENDPOINTS
ENDPOINTS
Secondary
Endpoints
Tertiary Endpoints
 
5.1.Inclusion
Criteria
10.
 
8.1.1.1. Physician
Global Activity
 
8.1.β.1. IMACS TIS
 
8.1.β.β.Disease
Worsening
 
9.4.1.1.β.Treatment
Failure Criteria
Mean change from baseline in Physician Global
Activity (PhGA) Visual Analogue Scale (VAS) at
Week β4
 
Mean change from baseline in Physician Global
Activity PhGA VAS over time
 
The proportion of participants with improvement in
Physician Global Activity PhGA VAS over time
 
Physician Global Activity (PhGA) VAS
 
Physician Global Activity VAS PhGA ≥1.5 cm
 
Physician Global Activity PhGA is a partially
validated tool…
 
Physician Global Activity PhGA VAS
 
Worsening of the Physician Global Activity PhGA
by ≥β cm on a 10-cm VAS and worsening of
findings of MMT-8 by ≥β0% from baseline
 
Physician assessed global PhGA worsening by
≥β cm on a 10-cm VAS and worsening on manual
muscle testing MMT-8 by ≥β0%
Language describing the Physician
Global Activity was revised to
clarify it.
1.1 Synopsis
Tertiary Endpoints 
 
1.γ.Schedule of
Activities (SoA)
Time and Events
Schedule 
 
γ.OBJECTIVES
AND ENDPOINTS
ENDPOINTS
Tertiary Endpoints
 
8.1.1.β. Patient
Global Activity
 
8.1.β.1. IMACS TIS
Mean change from baseline in Patient Global
Activity (PtGA) VAS at Week β4
 
The proportion of participants with improvement in
Patient Global Activity PtGA VAS at Week β4
 
Mean change from baseline in Patient Global
Activity PtGA VAS over time
 
The proportion of participants with improvement in
Patient Global Activity PtGA VAS over time
 
Patient Global Activity (PtGA)  VAS
 
Patient Global Activity PtGA is a partially
validated tool ….
 
Patient Global Activit y PtGA VAS
Language describing the Patient
Global Activity was revised to
clarify it.
1.1 Synopsis
EFFICACY
Measures of global disease activity: Physician
Global Activit y PhGA and Patient Global Activity 
Language describing the Physician
and Patient Global Activit y was


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Section number 
and Name
Description of Change 
Brief Rationale
EVALUATIONS 
PtGA for global evaluation of the patient's overall 
disease activity at the time of assessment using a
10 cm Visual Analogue Scale (VAS).
revised to clarify it.
1.1 Synopsis 
Tertiary Endpoints 
 
γ.OBJECTIVES 
AND ENDPOINTS
ENDPOINTS 
Tertiary Endpoints 
 
8.1.1.6. Physical
Function (Health 
Assessment 
Questionnaire
Disability Index) 
 
8.1.β.1. IMACS TIS 
 
Mean change from baseline in Functional 
Assessment Physical Function (Health Assessment 
Questionnaire Disability Index [HAQ-DI]) at Week
β4
 
The proportion of participants with improvement in
Functional Assessment Physical Function (HAQ-
DI) at Week β4
 
Mean change from baseline in Functional
Assessment Physical Function (HAQ-DI) over time
 
The proportion of participants with improvement in
Functional Assessment Physical Function (HAQ-
DI) over time
 
Functional Assessment Physical Function (Health
Assessment Questionnaire Disability Index)
 
Functional Assessment Physical Function (HAQ-
DI)
Language describing the HAQ-DI
was revised to clarify it.
1.1 Synopsis 
Tertiary Endpoints  
 
γ.OBJECTIVES 
AND ENDPOINTS
ENDPOINTS 
Tertiary Endpoints 
 
Mean change from baseline in γ6-item short form 
(SF-γ6) including individual domains and 
component summary (PCS, MCS) scores survey at
Week β4
 
The proportion of participants with improvement in
SF-γ6 including individual domains and
component summary (PCS, MCS) scores survey at
Week β4
 
Mean change from baseline in SF-γ6 including
individual domains and component summary (PCS,
MCS) scores over time
 
The proportion of participants with improvement in
SF-γ6 including individual domains and
component summar y (PCS, MCS) score s over time
Language describing the SF-γ6 was
revised to clarify it.
1.1 Synopsis 
EFFICACY 
EVALUATIONS 
Patient-reported outcomes (PROs): Health 
Assessment Questionnaire Disability Index (HAQ- 
DI) for physical function functional assessment
and, SF-γ6 survey to assess generic health-related
quality of life (HRQOL) for global medical quality
of life, functional health, well being of the
participants, and FI β.
Language describing the HAQ-DI
and SF-γ6 was revised to clarify it.
1.1 Synopsis 
Secondary Efficacy 
Analysis 
Analyses comparing the β treatment arms will be 
performed using a logistic model similar to primary 
analysis with the binary outcome related to
individual core set measures at Week β4. 
Analyses comparing the β treatment arms with
regard to ≥β0% reduction from baseline for
individual core set measures at Week β4 will be
performed usin  g a logistic model similar to primary 
Text was revised to ensure a
consistent description of the body.


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Section number 
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Brief Rationale
analysis.
1.γ.Schedule of 
Activities (SoA) 
Time and Events 
Schedule  
Footnote b. 
 
It is strongly recommended that participants who 
permanently discontinue study drug, but do not 
withdraw from study participation, be followed at 
all subsequent study visits through Week 80. At a 
minimum, participants who permanently
discontinue study drug, but do not withdraw from
study participation, should return for a follow up
visit 8 weeks after the last study drug
administration to undergo procedures as outlined
for the EO Treatment visit.
Participants, who permanently discontinue study
drug administrations on or before the Week 7β
visit, but do not withdraw from study participation,
must undergo procedures for safety follow-up visits
(postdiscontinuation) as outlined for the end of trial
(EO-Treatment) visit as soon as possible on or
before next scheduled visit.
Participants, who permanently discontinue study
drug administrations on or before the Week 7β
visit, and withdraw from study participation, must
undergo procedures for safety follow-up visits
(postdiscontinuation) as outlined for the end of trial
(EO-Treatment) visit as soon as possible on or
before next scheduled visit, and must return
approximately 8 weeks after last study drug
administration to undergo procedures for safety
follow-up visits (8 weeks postdiscontinuation) as
outlined for the end of trial (EO-Treatment). If the
interval between postdiscontinuation visit and 8
weeks postdiscontinuation visit is less than two
weeks, can skip 8 weeks postdiscontinuation.
Text was revised to clarify the
action in case that participants
permanently discontinue study
drug.
1.γ.Schedule of 
Activities (SoA) 
Time and Events 
Schedule  
Footnote c. 
Participants, who discontinue study drug 
administrations on or before the Week 7β visit, and 
withdraw from study participation, must return 
approximately 16 weeks after last study drug 
administration to undergo procedures for safety
follow-up visits as outlined for the end of trial (EO-
Trial) visit.
Text was revised to clarify the
action in case that participants
permanently discontinue study
drug.
β.β. Background 
The cumulative global exposure (through γ1 
December β0187) has been estimated as 
1,γ75,0071,0γ6,701 person-years.
Text was revised to update the
latest information.
4.γ. Justification for 
Dose 
Results from a Phase β study of ustekinumab in 
SLE has suggested the effectiveness of 
ustekinumab in patients with SLE. PK parameters
of ustekinumab have, in general, been similar
across multiple indications, including psoriasis,
PsA, Crohn’s disease, and SLE after correcting for
body weight-related PK differences. Study
CNTO1β75SLEβ001 has shown that treatment
with ustekinumab administered as an ~6 mg/kg IV
dose following by 90 mg SC dose at Week 8 and
then every 8 weeks thereafter was efficacious and
generally well tolerated in subjects with SLE. The
safety profile of this dose regimen in the
CNTO1β75SLEβ001 stud y was consistent with the
Text was added to clarify the
Justification for Dose.


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Section number 
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Brief Rationale
well-established profile observed in several large-
scale Phase γ Crohn’s disease studies. Taking the
overlapping features of PM/DM and SLE into
account, the planned regimen may be effective in
patients with PM/DM.
5.1.Inclusion 
Criteria 
6. 
Must be medically stable on the basis of clinical 
laboratory tests performed at screening. If the 
results of the serum chemistry panel including liver 
enzymes, other specific tests, blood coagulation,
hematology, or urinalysis except for items
specified in Inclusion Criteria #β0 and β1 are
outside the normal reference ranges, the participant
may be included only if the investigator judges the
abnormalities or deviations from normal to be not
clinically significant or to be appropriate and
reasonable for the population under study. This
determination must be recorded in the participant's
source documents and initiated b y the investigator.
Text was revised to clarify the
inclusion criteria for the clinical
laboratory test.
5.1.Inclusion 
Criteria 
8. 
If a participant with PM did not have history of 
muscle biopsy, score of classification cannot be 
calculated. If a participant with DM did not have 
history of muscle biopsy, score of classification
must be calculated based on score without muscle
biopsy.
Text was revised to clarify the
inclusion criteria for the history of
biopsy at the classification.
5.1.Inclusion 
Criteria 
1β. 
-MMF ≤γ g/day and/or 
-AZA 1 to ≤ β mg/kg/day; up to γ mg/kg/day 
100 mg/day 
Text was revised to clarify the
inclusion criteria for the standard of
treatment based on the package
insert.
5.1.Inclusion 
Criteria 
1γ. 
Regular or as needed treatment with topical use of 
medium/mild (Group IV) or weak low (Group V 
Class VI, VII) potency glucocorticoids (according 
to the World Health Organization classification of
topical glucocorticoids) are permitted to treat skin
lesions of DM on a stable dose for ≥β weeks prior
to first dose of the stud y drug.
The criteria for topical use of
glucocorticoids was revised based
on the medical practice in Japan.
5.1.Inclusion 
Criteria 
19. 
a. Have no history of latent or active TB prior to 
screening. An exception is made for participants 
who have a history of latent TB and are currently 
receiving treatment for latent TB, will initiate
treatment for latent TB at least γ weeks prior to the
first administration of the study drug, or have
documentation of having completed appropriate
treatment for latent TB within γ years prior to the
first administration of the stud y drug. 
The criteria for treatment of latent
TB was revised based on the
medical practice in Japan.
5.β.Exclusion 
Criteria 
1. 
Has myositis other than PM/DM, including but not 
limited to ADM, clinically amyopathic DM, 
juvenile DM, inclusion body myositis (IBM),
immune-mediated necrotizing myopathy diagnosed
based on muscle biopsy findings and positive anti-
SRP or anti-HMGCR antibody, drug-induced
myositis, PM associated with human
immunodeficiency virus (HIV), and muscular
dystrophy, congenital myopathy, metabolic
myopathy, and mitochondrial myopathy.
Text was added to clarify the
exclusion criteria for the myopathy.
5.β.Exclusion 
Has clinical evidence o f severe or progressive ILD, 
Text was revised and added to


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Criteria 
γ. 
which was confirmed by the investigator based on 
HRCT findings, clinical course consistent with 
ILD, and consultation with a pulmonologist.
Findings from HRCT at screening should not show
clinically significant worsening compared to past
HRCT or comparable CT results taken at least γ
months before screening. Other clinical evidence
includes The eligibility of ILD may be determined
considering the following but not limited to;
 
• Presence of dyspnea on exertion with normal
activities of daily living or low grade exertion (eg,
walking), or a recent change in exercise tolerance
due to dyspnea
clarify the exclusion criteria for
severe or progressive ILD.
5.β.Exclusion 
Criteria 
15. 
Has received prior IV immunoglobulin (Ig) or 
immunomodulatory biologic therapy not described 
in Section 6.6, Prohibited Therapies such as 
guselkumab, risankizumab, belimumab, 
epratuzumab, tocilizumab, alefacept, efalizumab,
natalizumab, abatacept, anakinra, brodalumab,
secukinumab, ixekizumab, or agents whose
mechanism of action targets B cell, tumor necrosis
factor alpha (TNFα), IL-1, IL-β, IL-6, IL-17, IL-βγ,
or IFN pathways, within less than 5 half-lives or 1β
weeks γ months, whichever is longer, prior to first
dose of the study drug. Has received rituximab
within β4 weeks 6 months prior to first dose of the
stud y drug.
Corrections were made to indicate
the appropriate time period of
exclusion criteria for concomitant
treatments.
5.β.Exclusion 
Criteria 
18. 
Has received an investigational drug that is not 
previously defined in other exclusion criteria 
(including investigational vaccines, branched-chain 
amino acids, or other medications specified in 
Section 6.6) within 5 half-lives or 1β weeks γ
months, whichever is longer, or used an invasive
investigational medical device within 1β weeks γ
months before the planned first dose of the study
drug, or is currently enrolled in an interventional
study.
Corrections were made to indicate
the appropriate time period of
exclusion criteria for concomitant
treatments.
5.β.Exclusion 
Criteria 
ββ. 
Use of apheresis therapy (including but not limited 
to plasmapheresis, photopheresis, 
leukocytapheresis), or immunoadsorption is 
prohibited within β4 weeks 6 months prior to the 
first administration of the stud y drug.
Corrections were made to indicate
the appropriate time period of
exclusion criteria for concomitant
treatments.
5.γ. Lifestyle 
Considerations 
γ. 
Agree to use sun protective measures (such as a 
hat, sunglasses, protective clothing, sunscreen), 
limit prolonged exposure to natural sunlight, and 
avoid artificial sunlight (tanning beds or
phototherapy) from baseline until the last dose of
the stud y dru  g for participants with DM.
Text was revised to clarify the
Lifestyle Considerations for
participants with DM.
6.1.Study Drugs 
Administered 
At Week β4, participants receiving placebo will 
crossover to receive body weight-range based IV 
administration of ustekinumab. At Week β4, it is 
recommended that SC dosing is administrated after
completion of IV administration. SC dosing may be
administered before assessment of infusion
reactions. However, IV and SC administration to
Text was added to clarify the
procedure of study drug
administration at Week β4.


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the same limb should be avoided. Starting at Week
γβ, all participants will receive ustekinumab 90 mg
SC q8w through Week 7β.
6.5.1.Prestudy and 
Concomitant 
Medications 
Through Week 80 
Limitation of concomitant medications must be 
followed through Week 80. The change of 
administration route is allowed if the equivalent 
dose of the substitution remains the same and the 
substitution is considered as a systemic treatment.
Text was revised to clarify the
change of administration for the
concomitant medications through
Week 80.
6.5.4. Topical 
Medications 
For the treatment of cutaneous lesion in 
participants with DM, regular use of topical 
medications glucocorticoid is permitted. However, 
topical compounds cannot include a prohibited
medication. These Topical glucocorticoids must be
medium/mild (Group IV) or weak (Group V) low
(Class VI, VII) potency glucocorticoids. (according
to the World Health Organization classification of
topical glucocorticoids) “As needed” use of topical
medium/mild (Group IV) or weak (Group V)
potency glucocorticoids is permitted, but not within
with no changes in dose for ≥β weeks prior to first
dose of study drug and during the study. These
topical glucocorticoids should not be used for 48
hours prior to a study visit. After discussion with
the sponsor, topical glucocorticoids of strong
(Group III) or weaker potency may be used on skin
lesion up to β weeks where there is no preexisting
skin eruptions of DM in case it is considered due to
adverse events other than DM.
The criteria for topical use of
glucocorticoids was revised based
on the medical practice in Japan.
6.6. Prohibited 
Therapies 
Epidural, IV, SC, IM, intra-articular, intrabursal, or 
intralesional administration ofIntravenous 
glucocorticoids 
Text was revised to clarify the
details of glucocorticoids in
prohibited therapies.
7.1. Discontinuation 
of Study Drug 
The participant requires high dose glucocorticoid 
(≥1 mg/kg/day of prednisolone or equivalent) for 
>β weeks or a prohibited therapy such as a 
biologic, cyclophosphamide, or IV glucocorticoid 
(see Section 6.6) then the participant must be 
discontinue from the study. 
If a new immunomodulator or oral glucocorticoid
(<1 mg/kg/day of prednisolone or equivalent) that
is permitted per-protocol is initiated, then a
participant will be considered a treatment failure
but will not need to discontinue the study drug
administrations be withdrawn from the study.
Addition of new therapy for PM/DM activity must
be discussed with the sponsor to determine the
suitability of the participant to continue the study
dru  g administrations participatin  g in the study.
Corrections were made to indicate
the appropriate procedure in case
that new immunomodulator, oral or
high dose glucocorticoid are
required.
8. STUDY 
ASSESSMENTS 
AND
PROCEDURES
 
8.6.1. Evaluations
The total blood volume to be collected from each 
participant will be approximately 750 700 mL. 
 
Corrections were made because of
the change of laboratory kit.
8.β.5. Interstitial 
Lun  g Diseases and 
All participants must be monitored with SpOβ, 
chest x-ray, laborator y data (KL-6 and SP-D), chest 
Text was added to clarify the
additional safet y data which IDMC


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Respiratory Muscle 
HRCT, and PFT as scheduled in Section 1.γ during 
the study. The investigator may consider additional
examination including C-reactive protein, ferritin,
and blood gas analysis as needed. In case of
worsening or new onset of lung lesion, it is
recommended to make a differential diagnosis of
fungal infection, cytomegalovirus infection, heart
failure and/or other cause using additional
laboratory data such as ȕ-D-glucan, C7-HRP,
and/or BNP. If the investigator identifies new onset
or worsening of ILD or observes any finding which
needs to be evaluated by a pulmonologist, the
investigator should consider consultation with a
pulmonologist and administer rescue treatment as
needed. Permanent discontinuation of the study
drug must be considered for participants who
experience worsening of ILD or newly identified
severe ILD that is considered serious or severe by
the investigator in cases of the following but not
limited to;
• Significant worsening of ILD findings based on
chest x-ray or HRCT
• Significant decrease in SpOβ such as SpOβ <
90% or a decrease of SpOβ b y 5% or more
members recommended.
8.γ.β. Method of 
Detecting Adverse 
Events and Serious 
Adverse Events 
Solicited Adverse Events 
Solicited AEs are predefined local and systemic 
events for which the participant is specifically 
questioned and which are noted by participants in 
their participant diary (see Section 8, Study
Assessments and Procedures).
 
Unsolicited Adverse Events
Unsolicited AEs are all AEs other than solicited
AEs as defined above for which the participant is
not specificall y questioned in the participant diary.
Corrections were made to indicate
the appropriate these AE definitions
based on the actual participants
diary.
8.γ.4. Regulatory 
Reporting 
Requirements for 
Serious Adverse 
Events
The sponsor assumes responsibility for appropriate 
reporting of anticipated events to the regulatory 
authorities according to requirements in which the 
studies are conducted.
The text was revised to keep a
consistency with Japanese
regulatory requirements.
8.5. Treatment of 
Overdose 
For this study, any dose of ustekinumab greater 
than set daily dose at Section 6.1 within β weeks a 
β4 hour time period will be considered an 
overdose.
The text was revised to keep a
consistency with other ustekinumab
study protocols.
8.7. Genetics  
 
A pharmacogenomic blood sample (whole blood 
DNA) will be collected from participants who 
consent separately to this component of the study
to allow for pharmacogenomic research, as
necessary. Participant participation in
pharmacogenomic research is optional.
DNA samples will be analyzed for identification of
genetic factors to better understand the molecular
effects of ustekinumab and/or susceptibility to
PM/DM, and to evaluate markers that can predict
clinical response. Such analysis may include the
human leukocyte antigen (HLA) alleles and any 
Text was added to clarify the
genetics analysis.


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Section number 
and Name
Description of Change 
Brief Rationale
relevant single nucleotide polymorphisms that are
reported to be associated with ustekinumab and/or
the development of PM/DM.
9.5.1. Independent 
Data Monitoring 
Committee 
After the review, the IDMC will make 
recommendations to the Sponsor Committee who is 
separate from the study team regarding the 
continuation of the study. The details will be 
provided in a separate IDMC charter. As needed 
basis, the IDMC might ask the study team to
provide with further information via the IDMC
bureau. The study team make the best effort to
collect the further information from each
investigational site for the evaluation by the IDMC.
The IDMC will consist of β medical experts in the
relevant therapeutic area and at least 1 statistician.
The IDMC responsibilities, authorities, and
procedures will be documented in its charter.
The study team is defined as a cross-functional
team responsible for the planning, initiation,
execution, analysis, and reporting of a trial. This
may include but is not limited to: Study
Responsible Physician/Scientist, Global Data
Manager, Global Trial Manager, Central
Monitoring Manager, Site Manager, Local Trial
Manager, Study Programmer, Study Statistician,
Quality Monitoring & Compliance representative,
Clinical Pharmacology representative, and Patient
Reported Outcomes Group Leader.
Text was added to clarify the
additional data which IDMC
members recommended,  procedure
to obtain them and a definition of
the study team.
10.8. Appendix 8: 
Cancer Screening 
Test  
Cancer 
Assessments for 
screening 
Age 
Sex 
Lung 
cancer 
Medical interview, 
Chest x ray and 
Sputum cytology* 
≥40 
Male 
and 
Female
 
* This cytology is needed for participants are ≥50
years old and meet smoking index (number of
cigarettes smoked per da y x years) is ≥ 600.
Text was added to clarify the
needed participants for the sputum
cytology based on medical practice
in Japan and study investigator’s
comment.
10.9. Appendix 9: 
Hepatitis B Virus 
Screening 
Added the all contents 
The appendix was added to clarify
the criteria for Hepatitis B Virus
Screening.
Throughout the 
protocol 
Minor grammatical, formatting, or spelling changes 
were made.
Minor errors were noted


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11β
Status: Approved, Date:  β9 November β0β1
11. 
REFERENCES
1. 
Aggarwal R, Rider LG, Ruperto N, et al; International Myositis Assessment and Clinical Studies Group and
the Paediatric Rheumatology International Trials Organisation. β016 American College of
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Response in Adult Dermatomyositis and Polymyositis: An International Myositis Assessment and Clinical
Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Arthritis
Rheumatol. β017 May;69(5):898-910.
β. 
Alexanderson H, Broman L, Tollbäck A, Josefson A, Lundberg IE, Stenström CH. Functional index-β:
Validity and reliability of a disease-specific measure of impairment in patients with polymyositis and
dermatomyositis. Arthritis Rheum.β006 Feb 15;55(1):114-1ββ.
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Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to meta-analysis. Chichester, England:
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Bronner IM, van der Meulen MF, de Visser M, et al. Long-term outcome in polymyositis and dermatomyositis.
Ann Rheum Dis. β006 Nov;65(11):1456-1461.
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David T, Ling SF, Barton A. Genetics of immune-mediated inflammatory diseases. Clin Exp Immunol. β018
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Igarashi A, Kato T, Kato M, Song M, Nakagawa H; Japanese Ustekinumab Study Group. Efficacy and safety
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phase β/γ clinical trial. J Dermatol. β01β. γ9(γ):β4β-β5β.
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Investigator's Brochure: CNTO1β75 (Ustekinumab), Edition 19. Janssen Research & Development (γ1 May
β018).
10. Kageyama T, Suto A, Iwamoto T, et al. IL-β1 exacerbates autoimmune myositis by enhancing the
accumulation of GM-CSF-producing  T cells in the muscle. Immuno Horizons β017;1(8):176-187.
11. Kondo M, Murakawa Y, Harashima N, Kobayashi S, Yamaguchi S, Harada M. Roles of proinflammatory
cytokines and the Fas/Fas ligand interaction in the pathogenesis of inflammatory myopathies. Immunology.
β009 Sep;1β8(1 Suppl):e589-e599.
1β. Liu T, Hou Y, Dai TJ, Yan CZ. Upregulation of Interleukin β1 and Interleukin β1 Receptor in Patients with
Dermatomyositis and Polymyositis. Chin Med J (Engl). β017 Sep 5;1γ0(17):β101-β106.
1γ. Miller FW, Cooper RG, Vencovský J, et al. Myositis Genetics Consortium. Genome-wide association study of
dermatomyositis reveals genetic overlap with other autoimmune disorders. Arthritis Rheum. β01γ
Dec;65(1β):γβγ9-γβ47. 
14. Montoya CL, Gonzalez ML, Ospina FE, Tobón GJ. A Rare Case of Amyopathic Juvenile Dermatomyositis
Associated With Psoriasis Successfully Treated With Ustekinumab. J Clin Rheumatol. β017 Mar;βγ(β):1β9-
1γ0.
15. Muscle Study Group. A randomized, pilot trial of etanercept in dermatomyositis. Ann Neurol. β011. 70(γ):4β7-
4γ6.
16. Oddis CV, Reed AM, Aggarwal R, et al. Rituximab in the treatment of refractory adult and juvenile
dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. β01γ. 65(β):γ14-
γβ4. 
17. Page G, Chevrel G, Miossec P. Anatomic localization of immature and mature dendritic cell subsets in
dermatomyositis and polymyositis: Interaction with chemokines and Th1 cytokine-producing cells. Arthritis
Rheum. β004 Jan;50(1):199-β08.


STELARA® (ustekinumab) 
 
 
Clinical Protocol CNTO1β75DMYγ001 Amendment γ
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
11γ
Status: Approved, Date:  β9 November β0β1
18. Proschan MA, Lan KKG, Wittes JT. Statistical Monitoring of Clinical Trials: A Unified Approach, Springer,
β006.
19. Rider LG, Werth VP, Huber AM, et al. Measures of adult and juvenile dermatomyositis, polymyositis, and
inclusion body myositis: Physician and Patient/Parent Global Activity, Manual Muscle Testing (MMT), Health
Assessment Questionnaire (HAQ)/Childhood Health Assessment Questionnaire (C-HAQ), Childhood Myositis
Assessment Scale (CMAS), Myositis Disease Activity Assessment Tool (MDAAT), Disease Activity Score
(DAS), Short Form γ6 (SF-γ6), Child Health Questionnaire (CHQ), physician global damage, Myositis
Damage Index (MDI), Quantitative Muscle Testing (QMT), Myositis Functional Index-β (FI-β), Myositis
Activities Profile (MAP), Inclusion Body Myositis Functional Rating Scale (IBMFRS), Cutaneous
Dermatomyositis Disease Area and Severity Index (CDASI), Cutaneous Assessment Tool (CAT),
Dermatomyositis Skin Severity Index (DSSI), Skindex, and Dermatology Life Quality Index (DLQI). Arthritis
Care Res (Hoboken). β011 Nov;6γ Suppl 11:S118-157.
β0. Sasaki H, Kohsaka H. Current diagnosis and treatment of polymyositis and dermatomyositis. Mod Rheumatol.
β018 Nov;β8(6):91γ-9β1.
β1. Schmitt N, Morita R, Bourdery L, et al. Human dendritic cells induce the differentiation of interleukin-β1-
producing T follicular helper-like cells through interleukin-1β. Immunity. β009 Jul 17;γ1(1):158-169.
ββ. Shen H, Xia L, Lu J, Xiao W. Interleukin-17 and interleukin-βγ in patients with polymyositis and
dermatomyositis. Scand J Rheumatol. β011 May;40(γ):β17-ββ0.
βγ. Thompson C, Piguet V, Choy E. The pathogenesis of dermatomyositis. Br J Dermatol. β018 Dec;179(6):1β56-
1β6β.
β4. Tjarnlund A, Tang Q, Wich C, et al. Abatacept in the treatment of adult dermatomyositis and polymyositis: a
randomized, phase IIb treatment delayed-start trial. Ann Rheum Dis. β018. 77(1):55-6β.
β5. Tournadre A, Lenief V, Eljaafari A, Miossec P. Immature muscle precursors are a source of interferon-ȕ in
myositis: role of Toll-like receptor γ activation and contribution to HLA class I up-regulation. Arthritis Rheum.
β01β Feb;64(β):5γγ-541.
β6. Tournadre A, Miossec P. A critical role for immature muscle precursors in myositis. Nat Rev Rheumatol. β01γ
Jul;9(7):4γ8-44β.
β7. Umezawa N, Kawahata K, Kimura N, Yoshihashi-Nakazato Y, Kohsaka H. Inhibition of IL-βγ ameliorated
murine model of polymyositis. Modern Rheumatology Abstract Supplement, The 61st annual scientific
Meeting of the Japan College of Rheumatology. β017 S19β.
β8. van de Vlekkert J, Hoogendijk JE, de Haan RJ, et al; Dexa Myositis Trial. Oral dexamethasone pulse therapy
versus daily prednisolone in sub-acute onset myositis, a randomized clinical trial. Neuromuscul Disord. β010
Jun;β0(6):γ8β-γ89.
β9. Whiting-O'Keefe QE, Stone JH, Hellmann DB. Validity of a vasculitis activity index for systemic necrotizing
vasculitis. Arthritis Rheum. 1999 Nov;4β(11):βγ65-βγ71.
γ0. Wong D, Kea B, Pesich R, et al. Interferon and biologic signatures in dermatomyositis skin: specificity and
heterogeneity across diseases. PLoS One. β01β;7(1):eβ9161.
γ1. Zhou Y, Li X, Wang G, Li X. Association of FAM167A-BLK rsβ7γ6γ40 Polymorphism with Susceptibility to
Autoimmune Diseases: A Meta-Analysis. Immunol Invest. β016 May;45(4):γγ6-γ48.
γβ. Zong M, Dorph C, Dastmalchi M, et al. Anakinra treatment in patients with refractory inflammatory
myopathies and possible predictive response biomarkers: a mechanistic study with 1β months follow-up. Ann
Rheum Dis. β014. 7γ(5):91γ-9β0. 


STELARA® (ustekinumab) 
 
 
Clinical Protocol CNTO1β75DMYγ001 Amendment γ
 
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114
Status: Approved, Date:  β9 November β0β1
INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed
regarding the study drug, the conduct of the study, and the obligations of confidentiality.
Coordinating investigator (where required): 
Name (typed or printed): 
Institution and Address: 
Signature: 
 
Date: 
  
 
(Day Month Year)
Principal (Site) investigator: 
Name (typed or printed): 
Institution and Address: 
Telephone Number: 
Signature: 
 
Date: 
  
 
(Day Month Year)
 
Sponsor's Responsible Medical Officer: 
Name (typed or printed): 
Institution: 
Janssen Pharmaceutical K.K.*
Signature: 
electronic signature appended at the end of the protocol 
Date: 
  
 
(Day Month Year)
 
Note: If the address or telephone number of the investigator changes during the course of the study, written
notification will be provided by the investigator to the sponsor, and a protocol amendment will not be required.
PPD


Signature
User 
Date 
Reason
 
 
29-Nov-2021 
06:30:04
(GMT)
Document Approval
PPD


1 
Status: Approved,  Date: 9 Jun 2020 
Janssen Pharmaceutical K.K.* 
Clinical Protocol 
COVID-19 Appendix 
Protocol Title 
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group 
Study of Ustekinumab in Participants With Active Polymyositis and Dermatomyositis Who 
Have Not Adequately Responded to One or More Standard-of-care Treatments  
Protocol CNTO1275DMY3001; Phase 3 
 STELARA®  (ustekinumab)  
*This study is being conducted by Janssen Pharmaceutical K.K. in Japan. The term “sponsor” is used
throughout the protocol to represent Janssen Pharmaceutical K.K. The sponsor is identified on the
Protocol Supplementary Information, which will be provided as a separate document.
Status: 
Approved   
Date: 
9 Jun 2020 
Prepared by: Janssen Pharmaceutical K.K. 
EDMS number: 
EDMS-RIM-78936, 1.0 
THIS APPENDIX APPLIES TO ALL CURRENT APPROVED VERSIONS OF PROTOCOL 
GCP Compliance:  This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements.  
Confidentiality Statement 
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient 
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise. 
NCT03981744


COVID-19 Appendix  
 
STELARA®  (ustekinumab) 
Clinical Protocol CNTO1275DMY3001  
2 
Status: Approved,  Date: 9 Jun 2020 
COVID-19 APPENDIX 
GUIDANCE ON STUDY CONDUCT DURING THE COVID-19 PANDEMIC 
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on 
the conduct of this clinical study due to, for example, self-isolation/quarantine by participants and 
study-site personnel; travel restrictions/limited access to public places, including hospitals; study 
site personnel being reassigned to critical tasks.  
In alignment with recent health authority guidance, the sponsor is providing options for 
study -related participant management in the event of disruption to the conduct of the study. This 
guidance does not supersede any local or government guidelines or requirements or the clinical 
judgement of the investigator to protect the health and well-being of participants and site staff. If 
at any time a participant’s safety is considered to be at unacceptable risk, study intervention will 
be discontinued, and study follow-up will be conducted. 
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent 
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each 
contact, participants will be interviewed to collect safety data. Key efficacy endpoint assessments 
should be performed if required and as feasible. Participants will also be questioned regarding 
general health status to fulfill any physical examination requirement.  
Every effort should be made to adhere to protocol-specified assessments for participants on study 
intervention, including follow up. Modifications to protocol-required assessments may be 
permitted after consultation between the participant and investigator, and with the agreement of 
the sponsor (see below).  
 
The sponsor will continue to monitor the conduct and progress of the clinical study, and any 
changes will be communicated to the sites and to the health authorities according to local guidance.


COVID-19 Appendix  
 
STELARA®  (ustekinumab) 
Clinical Protocol CNTO1275DMY3001  
3 
Status: Approved,  Date: 9 Jun 2020 
 
If a participant has tested positive for COVID-19, the investigator should contact the sponsor’s 
medical officer or designee to discuss plans for study intervention and follow-up.  
ADDITIONAL ELEMENTS, WHERE APPLICABLE:  
 Certain protocol-mandated visits to the study site may not be possible during the COVID-19 
outbreak. Therefore, temporary measures may be implemented if considered appropriate by 
the Sponsor and Investigator to maintain continuity of patient care and study integrity. Certain 
measures, such as those listed below, may be necessary and should be instituted in accordance 
with applicable (including local) laws, regulations, guidelines, and procedures: 
o remote (eg, by phone / telemedicine) or in-person, off-site (eg, in-home) interactions 
between site staff (or designees) and patients for study procedures eg, those related to 
safety monitoring / efficacy evaluation / study drug storage and administration 
(including training where pertinent) 
o procurement of study drug by patients (or designee) or shipment of study drug from the 
study site directly to patients for at home administration (including the potential for 
patient self-administration of study drug) 
o laboratory assessments using a suitably accredited local laboratory; for selected 
measures (eg, urine pregnancy), home testing may be employed 
o other procedures, eg, imaging, may be conducted at an appropriate facility 
 Missed assessments/visits will be captured in the clinical trial management system for 
protocol deviations.  Discontinuations of study interventions and withdrawal from the 
study should be documented with the prefix “COVID-19-related” in the case report form 
(CRF).   
o other relevant study data elements impacted by the pandemic should also be 
documented / labeled as “COVID-19-related” in CRFs and / or other study systems, 
as directed by detailed Sponsor guidance. These may include missed / delayed / 
modified study visits / assessments / dosing, and instances where temporary 
measures such as those above are implemented.   
 The Sponsor will evaluate the totality of impact of COVID-19 on collection of key study 
data and additional data analyses will be outlined in study SAP(s).  
 Exclusion: a potential participant with the following features will be excluded from 
participating in the study protocol: 
o During the 6 weeks prior to baseline, have had ANY of (a) confirmed SARS-CoV-
2 (COVID-19) infection (test positive), OR (b) suspected SARS-CoV-2 infection 


COVID-19 Appendix  
 
STELARA®  (ustekinumab) 
Clinical Protocol CNTO1275DMY3001  
4 
Status: Approved,  Date: 9 Jun 2020 
(clinical features without documented test results), OR (c) close contact with a 
person with known or suspected SARS-CoV-2 infection  
 Exception: may be included with a documented negative result for a 
validated SARS-CoV-2 test 
(i) obtained at least 2 weeks after conditions (a), (b), (c) above (timed from 
resolution of key clinical features if present, eg, fever, cough, dyspnea) 
AND 
(ii) with absence of ALL conditions (a), (b), (c) above during the period 
between the negative test result and the baseline study visit  
 NOTES on COVID-related exclusion: 
1. If a patient is excluded due to recent COVID-19-related features, the reason for screen 
failure should be documented in the case report form under the exclusion criterion of 
having a condition for which participation would not be in the participant’s interest or 
could confound study assessments.  
2. The field of COVID-related testing (for presence of, and immunity to, the SARS-CoV-
2 virus) is rapidly evolving. Additional testing may be performed as part of screening 
and/or during the study if deemed necessary by the investigator and in accordance with 
current regulations / guidance from authorities / standards of care.  
 Precaution: for those who may carry a higher risk for severe COVID-19 illness (eg, those 
aged over 65 years), follow guidance from local health authorities when weighing the 
potential benefits and risks of enrolling in the study, and during participation in the study.  
 
 
 


COVID-19 Appendix  
 
STELARA®  (ustekinumab) 
Clinical Protocol CNTO1275DMY3001  
5 
Status: Approved,  Date: 9 Jun 2020 
INVESTIGATOR AGREEMENT 
I have read this protocol and agree that it contains all necessary details for carrying out this study. 
I will conduct the study as outlined herein and will complete the study within the time designated. 
I will provide copies of the protocol and all pertinent information to all individuals responsible to 
me who assist in the conduct of this study. I will discuss this material with them to ensure that they 
are fully informed regarding the study intervention, the conduct of the study, and the obligations 
of confidentiality. 
Coordinating Investigator (where required): 
 
Name (typed or printed): 
 
Institution and Address: 
 
 
 
 
 
 
 
Signature: 
 
Date: 
 
 
 
 
(Day Month Year) 
 
Principal (Site) Investigator: 
 
Name (typed or printed): 
 
Institution and Address: 
 
 
 
 
 
 
 
Telephone Number: 
 
Signature: 
 
Date: 
 
 
 
 
(Day Month Year) 
 
Sponsor's Responsible Medical Officer: 
 
Name (typed or printed): 
 
Institution: 
Janssen Pharmaceutical K.K.* 
Signature: 
electronic signature appended at the end of the protocol 
Date: 
 
 
 
 
(Day Month Year) 
 
Note: If the address or telephone number of the investigator changes during the course of the study, written 
notification will be provided by the investigator to the sponsor, and a protocol amendment will not be required. 
PPD


Signature
User
Date
Reason
09-Jun-2020
03:27:35
(GMT)
Document Approval
PPD

SAP_001.pdf: 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
1 
Status: Approved,  Date: 17 February 2022 
Janssen Pharmaceutical K.K. * 
Statistical Analysis Plan 
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group 
Study of Ustekinumab in Participants With Active Polymyositis and Dermatomyositis 
Who Have Not Adequately Responded to One or More Standard-of-care Treatments 
Protocol CNTO1275DMY3001; Phase 3 
 STELARA® (ustekinumab) 
* This study is being conducted by Janssen Pharmaceutical K.K. in Japan. The term “sponsor” is used
throughout the protocol to represent Janssen Pharmaceutical K.K. in Japan.
Status: 
Approved  
Date: 
17 February 2022 
Prepared by: 
Janssen Pharmaceutical K.K. 
Document No.: EDMS-ERI-192083060 
Compliance:  The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement 
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient 
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise. 
NCT03981744


STELARA®   (ustekinumab)) 
 
 
 
 Statistical Analysis Plan CNTO1275DMY3001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
2 
Status: Approved,  Date: 17 February 2022 
TABLE OF CONTENTS 
TABLE OF CONTENTS .......................................................................................................................... 2 
AMENDMENT HISTORY......................................................................................................................... 4 
ABBREVIATIONS ................................................................................................................................... 4 
1. 
INTRODUCTION ............................................................................................................................ 5 
1.1. 
Trial Objectives ........................................................................................................................... 5 
1.2. 
Trial Design................................................................................................................................. 6 
1.3. 
Statistical Hypotheses for Trial Objectives ................................................................................... 7 
1.4. 
Sample Size Justification ............................................................................................................ 7 
1.5. 
Randomization and Blinding ........................................................................................................ 7 
1.6. 
Coronavirus 2019 (COVID-19) .................................................................................................... 8 
2. 
GENERAL ANALYSIS DEFINITIONS ............................................................................................ 9 
2.1. 
Visit Windows ............................................................................................................................. 9 
2.2. 
Pooling Algorithm for Analysis Centers ........................................................................................ 9 
2.3. 
Analysis Sets .............................................................................................................................. 9 
2.3.1. 
Enrolled Analysis Set ............................................................................................................... 9 
2.3.2. 
All Randomized Analysis Set ................................................................................................... 9 
2.3.3. 
Safety Analysis Set .................................................................................................................. 9 
2.3.4. 
Pharmacokinetics Analysis Set ................................................................................................ 9 
2.3.5. 
Immunogenicity Analysis Set ................................................................................................. 10 
2.3.6. 
Pharmacodynamics Analysis Set ........................................................................................... 10 
2.3.7. 
Pharmacokinetics/Pharmacodynamics Analysis Set ............................................................... 10 
2.4. 
Analysis Periods and Treatment Groups ................................................................................... 10 
2.5. 
Data cut-off for Week 24, 52 and 72 .......................................................................................... 12 
2.6. 
Definition of Subgroups ............................................................................................................. 12 
2.7. 
Study Day and Relative Day ...................................................................................................... 13 
2.8. 
Baseline .................................................................................................................................... 13 
2.9. 
Imputation Rules for Missing AE Date/Time of Onset/Resolution ............................................... 13 
3. 
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW ..................................... 14 
3.1. 
Interim Analysis......................................................................................................................... 14 
3.2. 
Data Monitoring Committee Review .......................................................................................... 14 
4. 
SUBJECT INFORMATION ........................................................................................................... 15 
4.1. 
Demographics and Baseline Characteristics .............................................................................. 15 
4.2. 
Disposition Information .............................................................................................................. 16 
4.3. 
Treatment Compliance .............................................................................................................. 16 
4.4. 
Extent of Exposure .................................................................................................................... 17 
4.5. 
Protocol Deviations ................................................................................................................... 17 
4.6. 
Prior and Concomitant Medications ........................................................................................... 17 
4.7. 
COVID-19 Related Summaries.................................................................................................. 17 
5. 
EFFICACY ................................................................................................................................... 18 
5.1. 
Analysis Specifications .............................................................................................................. 18 
5.1.1. 
Level of Significance .............................................................................................................. 18 
5.2. 
Primary Efficacy Endpoint ......................................................................................................... 18 
5.2.1. 
Definition ............................................................................................................................... 18 
5.2.1.1.1. 
Physician Global Activity (PhGA) ..................................................................................... 19 
5.2.1.1.2. 
Patient Global Activity (PtGA) .......................................................................................... 19 
5.2.1.1.3. 
Manual Muscle Testing (MMT-8)...................................................................................... 20 
5.2.1.1.4. 
Physical Function (HAQ-DI) ............................................................................................. 20 
5.2.1.1.5. 
Muscle Enzymes ............................................................................................................. 21 


STELARA®   (ustekinumab)) 
 
 
 
 Statistical Analysis Plan CNTO1275DMY3001  
 
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Status: Approved,  Date: 17 February 2022 
5.2.1.1.6. 
Extramuscular Assessment (Myositis Disease Activity Assessment Tool) ......................... 22 
5.2.2. 
Estimands .............................................................................................................................. 26 
5.2.2.1. 
Primary Estimand ............................................................................................................... 26 
5.2.2.2. 
Supplementary Estimands .................................................................................................. 27 
5.2.3. 
Analysis Methods ................................................................................................................... 28 
5.2.3.1. 
Subgroup Analyses ............................................................................................................. 29 
5.2.3.2. 
Sensitivity Analysis ............................................................................................................. 30 
5.2.3.2.1. 
Sensitivity Analysis 1 ....................................................................................................... 30 
5.2.3.2.2. 
Sensitivity Analysis 2 ....................................................................................................... 30 
5.2.3.3. 
Supplementary Analyses .................................................................................................... 30 
5.2.3.3.1. 
Supplementary Analysis 1 (Hypothetical Estimand) .......................................................... 30 
5.2.3.3.2. 
Supplementary Analysis 2 (Treatment Policy Estimand) ................................................... 30 
5.3. 
Secondary Endpoints ................................................................................................................ 31 
5.3.1. 
Definition ............................................................................................................................... 31 
5.3.1.1. 
Functional Index-2 .............................................................................................................. 31 
5.3.1.2. 
Disease Worsening ............................................................................................................. 31 
5.3.1.3. 
Manual Muscle Testing ....................................................................................................... 32 
5.3.2. 
Estimands .............................................................................................................................. 32 
5.3.2.1. 
Main Estimand for Secondary Binary Endpoint .................................................................... 32 
5.3.2.2. 
Main Estimands for Secondary Continuous Endpoints ......................................................... 33 
5.3.3. 
Analysis Methods ................................................................................................................... 34 
5.4. 
Other Efficacy Variable(s) ......................................................................................................... 35 
5.4.1. 
Definition ............................................................................................................................... 36 
5.4.1.1. 
PM/DM Disease Activity Endpoints ..................................................................................... 36 
5.4.1.2. 
Patient-reported Outcomes Endpoints ................................................................................. 37 
5.4.2. 
Analysis Methods ................................................................................................................... 38 
5.4.2.1. 
Analyses from Week 0 through Week 24 ............................................................................. 38 
5.4.2.2. 
Analyses from Week 24 through Week 52/72/88 ................................................................. 39 
6. 
SAFETY ....................................................................................................................................... 39 
6.1. 
Adverse Events ......................................................................................................................... 39 
6.2. 
Clinical Laboratory Tests ........................................................................................................... 40 
6.3. 
Vital Signs and Physical Examination Findings .......................................................................... 41 
6.4. 
Electrocardiogram ..................................................................................................................... 42 
6.5. 
Chest CT Scan and X-Ray ........................................................................................................ 42 
6.6. 
Pulmonary Function Test .......................................................................................................... 42 
6.7. 
COVID-19 Summaries............................................................................................................... 42 
7. 
PHARMACOKINETICS/PHARMACODYNAMICS ........................................................................ 43 
7.1. 
Pharmacokinetics ...................................................................................................................... 43 
7.2. 
Immunogenicity Analyses .......................................................................................................... 45 
7.3. 
Pharmacokinetic/Pharmacodynamic Relationships .................................................................... 46 
8. 
BIOMARKERS ............................................................................................................................. 47 
9. 
REFERENCES ............................................................................................................................. 48 
ATTACHMENTS ................................................................................................................................... 49 
 
 
 
 


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 Statistical Analysis Plan CNTO1275DMY3001  
 
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AMENDMENT HISTORY 
Not Applicable. 
ABBREVIATIONS 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AZA 
azathioprine 
BQL 
below the lowest quantifiable sample concentration of the assay 
CK 
creatine kinase 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
coefficient of variation 
DBL 
database lock 
DLCO 
diffusing capacity of the lungs for carbon monoxide 
DM 
dermatomyositis 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
eCRF 
electronic case report forms 
EDTA 
ethylenediaminetetraacetic acid 
FI-2 
Functional Index-2 
FVC 
forced vital capacity 
GCP 
Good Clinical Practice 
HAQ-DI 
Health Assessment Questionnaire Disability Index 
HRCT 
high-resolution computer tomography 
ICF 
informed consent form 
ILD 
interstitial lung disease 
IMACS TIS 
International Myositis Assessment and Clinical Studies Total Improvement Score 
IQ 
interquartile 
IV 
intravenous 
IWRS 
interactive web response system 
LDH 
lactate dehydrogenase 
MDAAT 
Myositis Disease Activity Assessment Tool 
MEP 
maximal expiratory pressure 
MIP 
maximal inspiratory pressure 
MITAX 
Myositis Intention to Treat Activity Index  
MMF 
mycophenolate mofetil 
MMRM 
mixed-effect model repeated measure 
MMT 
Manual Muscle Testing 
MTX 
methotrexate 
MVV 
maximal voluntary ventilation 
NCI 
National Cancer Institute 
PD 
pharmacodynamic 
PFT 
pulmonary function test 
PK 
pharmacokinetic 
PM 
polymyositis 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SD 
standard deviation 
SF-36 
36-item short form  
TAC 
tacrolimus 
TB 
tuberculosis 
VAS 
Visual Analogue Scale 
VC 
vital capacity 
WBC 
white blood cell 


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 Statistical Analysis Plan CNTO1275DMY3001  
 
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Status: Approved,  Date: 17 February 2022 
1. 
INTRODUCTION 
This Statistical Analysis Plan (SAP) contains definitions of analysis sets, derived variables, and 
statistical methods for the analysis of efficacy, safety, tolerability, pharmacokinetics (PK), 
immunogenicity, pharmacokinetics/pharmacodynamic (PK/PD) and response biomarkers of 
ustekinumab treatment. This document provides analysis plan for all four DBLs of 
CNTO1275DMY3001 study, which will occur at Week 24, Week 52 Week 72 and Week 88.   
1.1. 
Trial Objectives 
Primary Objective 
The primary objective is to evaluate the efficacy of ustekinumab in participants with active 
polymyositis and dermatomyositis (PM/DM) despite receiving 1 or more standard-of-care 
treatments (eg, glucocorticoids and/or immunomodulators). 
Secondary Objectives 
The secondary objectives are to evaluate the following in participants with active PM/DM despite 
receiving 1 or more standard-of-care treatments (eg, glucocorticoids and/or immunomodulators): 
 
Improvement in organ-specific (musculoskeletal, mucocutaneous, etc) measures of PM/DM 
disease activity 
 
Reduction in PM/DM worsening 
Tertiary Objectives 
The tertiary objectives are to evaluate: 
 
Safety and tolerability 
 
Pharmacokinetics (PK) and immunogenicity 
 
Pharmacodynamic and response biomarkers of ustekinumab treatment  
 
Effect on health-related quality of life and physical function 


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1.2. 
Trial Design 
Figure 1 
Schematic overview of the study design 
 
This is a randomized, double-blind, placebo-controlled, multicenter, interventional study in 
participants ≥18 years and ≤75 years of age with active PM/DM despite receiving 1 or more 
standard-of-care treatments (eg, glucocorticoids and/or immunomodulators) to evaluate the 
efficacy, safety, and tolerability of ustekinumab in addition to standard-of-care background 
therapy.  
The total duration of the study is up to 94 weeks, consisting of 3 study periods: a ≤6-week screening 
period (rescreening is permitted once per participant), a 72-week study drug administration period, 
and 16-week follow-up period. 
Key features of study drug administration for each treatment group are outlined below:  
Week 0 through Week 24 (Blinded Treatment Period) 
As depicted in Figure 1, approximately 50 subjects who satisfy all inclusion and exclusion criteria 
will be randomized in a 1:1 ratio to one of two arms: 
 
Group I (n=25): body weight-range based intravenous (IV) administration of ustekinumab 
(~6 mg/kg, ustekinumab 260 mg weight ≤55 kg; ustekinumab 390 mg weight >55 kg and 
≤85 kg; ustekinumab 520 mg weight >85 kg) at Week 0, and ustekinumab 90 mg SC 
administration at Week 8 and 16.  
 
Group II (n=25): IV dosing of placebo at Week 0 followed by placebo SC administration at 
Week 8 and 16.  
Subject will be assigned to 1 of 2 treatment groups using a stratified block randomization method 
in a 1:1 ratio at Week 0. Stratification factors will be disease subset (PM/DM) and baseline 
treatment level (glucocorticoid dose [≥0.5 mg/kg/day or <0.5 mg/kg/day of prednisolone or 
equivalent]).  


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After Week 24 until Week 72 (Cross-over administration Period) 
The observational period will begin from Week 24 and extend until Week 72. All subjects will 
receive active treatment. There will be 16 weeks safety follow-up after Week 72.  
Treatment code will not be revealed to the investigators and subjects until the last subject has 
completed the Week 88 visit. The end of the study is defined as the time the last subject completes 
the Week 88 visit. Database locks will occur at Weeks 24, 52, 72 and 88. Another additional 
database lock will occur when 20 subjects complete 24-week evaluation for the interim analysis 
and analyses for the interim analysis will be detailed in a separate document.  
 
Group I (n=25): placebo IV and ustekinumab 90 mg SC administration at Week 24, and 
ustekinumab 90 mg SC administration thereafter through Week 72.  
 
Group II (n=25): body weight-range based IV administration of ustekinumab (~6 mg/kg) and 
placebo SC at Week 24, and ustekinumab 90 mg SC administration thereafter through Week 
72.  
1.3. 
Statistical Hypotheses for Trial Objectives 
This study is designed to show that treatment effect (as measured by the IMACS TIS response at 
Week 24) of ustekinumab as PM/DM treatment is superior to placebo.  
If OR is the odds ratio derived from the IMACS TIS response with the placebo and an ustekinumab 
groups, then the hypothesis can be written as follows:  
H0:OR=1, H1:OR≠1 
1.4. 
Sample Size Justification 
The sample size calculation is based upon the primary endpoint, the proportion of participants who 
achieve IMACS TIS response at Week 24. To determine the effect size versus placebo used for 
calculating the sample size, meta-analyses were conducted for the synthesis of the evidence. 
Considering the primary endpoint evaluated at Week 24 in Japanese patients, a dropout rate of 5% 
is accommodated for sample size calculation. Particularly focusing on the effect size of 40% which 
is considered a reasonable estimate of effect size, a sample size of 50 participants is projected to 
give 82.2% power to detect a significant difference in response rate compared with placebo 
(assuming 25% and 65% response rates in placebo and ustekinumab, respectively with the 5% 
dropout rate in 24 weeks, which translates to 40% absolute increase over placebo or an odds ratio 
of 5.57) with an alpha level of 0.05 (2-sided).  
1.5. 
Randomization and Blinding 
Randomization  
Central randomization will be implemented in this study. Participants will be randomly assigned 
to 1 of 2 intervention groups based on a computer-generated randomization schedule prepared 
before the study by or under the supervision of the sponsor. The randomization will be balanced 
by using randomly permuted blocks and will be stratified by disease subset (PM/DM) and baseline 


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treatment level (glucocorticoid dose [≥0.5 mg/kg/day or <0.5 mg/kg/day of prednisolone or 
equivalent]). The interactive web response system (IWRS) will assign a unique intervention code, 
which will dictate the study drug assignment and matching study drug kit for the participant. The 
requestor must use his or her own user identification and personal identification number when 
contacting the IWRS and will then give the relevant participant details to uniquely identify the 
participant. 
Blinding 
The investigator will not be provided with randomization codes. The codes will be maintained 
within the IWRS, which has the functionality to allow the investigator to break the blind for an 
individual participant. 
Data that may potentially unblind the intervention assignment will be handled with special care to 
ensure that the integrity of the blind is maintained and the potential for bias is minimized. This can 
include making special provisions, such as segregating the data in question from view by the 
investigators, clinical team, or others as appropriate until the time of DBL and unblinding. 
Under normal circumstances, the blind should not be broken until all participants have completed 
the study and the database is finalized. The investigator may in an emergency determine the 
identity of the study drug by contacting the IWRS. While the responsibility to break the 
intervention code in emergency situations resides solely with the investigator, it is recommended 
that the investigator contact the sponsor or its designee if possible to discuss the particular situation, 
before breaking the blind. Telephone contact with the sponsor or its designee will be available 
24 hours per day, 7 days per week. In the event the blind is broken, the sponsor must be informed 
as soon as possible. The date, time, and reason for the unblinding must be documented by the 
IWRS in the appropriate section of the eCRF, and in the source document. The documentation 
received from the IWRS indicating the code break must be retained with the participant's source 
documents in a secure manner. 
In this study, 4 DBLs are planned. These are DBLs at Week 24, Week 52, Week 72, and Week 88. 
In addition to these 4 DBLs, one DBL will occur for the interim analysis of futility. After Week 
24, participants who are randomized to placebo group will crossover to receive ustekinumab and 
all the participants will enter the cross-over administration phase to allow for evaluation of the 
long-term efficacy and safety of ustekinumab. Investigative study sites and participants will remain 
blinded to initial treatment assignment until after the DBL at Week 52. After the Week 24 DBL, 
the data will be unblinded to sponsor for analysis while investigational sites and participants are 
still participating in the study. Identification of sponsor personnel who will have access to the 
unblinded participant data during the period from the Week 24 DBL to the Week 52 DBL will be 
documented prior to unblinding to sponsor.   
1.6. 
Coronavirus 2019 (COVID-19) 
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on 
the conduct of this clinical study due to, for example, self-isolation/quarantine by subjects and 
study-site personnel; travel restrictions/limited access to public places, including hospitals; study 


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site personnel being reassigned to critical tasks. More details about study operational procedures 
related to COVID-19 are described in the COVID-19 Appendix to the study protocol.  
2. 
GENERAL ANALYSIS DEFINITIONS 
2.1. 
Visit Windows 
Unless otherwise specified, nominal visits will be used for all by visit analyses. The study visits 
scheduled after randomization should occur at the times delineated in the Time and Events 
Schedule of the protocol. If the certain visit occurs greater than 8 weeks of the scheduled visit, or 
cumulative out of visit window weeks until certain visit are greater than 16 weeks of the scheduled 
visits, then all measurements will be treated as missing starting from that visit to Week 24.  
2.2. 
Pooling Algorithm for Analysis Centers 
Unless otherwise specified, data from all investigational centers/sites will be pooled for analyses. 
2.3. 
Analysis Sets 
2.3.1. 
Enrolled Analysis Set 
The enrolled analysis set includes all subjects who signed the ICF. 
2.3.2. 
All Randomized Analysis Set 
The all randomized analysis set includes all subjects who were randomized in the study, namely 
intent-to-treat (ITT). 
In the demographics and disposition analyses, subjects will be analyzed according to their assigned 
treatment group. On the other hand, in the efficacy analyses, subjects will be analyzed according 
to their assigned treatment group regardless of their actual treatment received.  
2.3.3. 
Safety Analysis Set 
The safety analysis set includes all randomized subjects who received at least 1 dose (partial or 
complete, IV or SC) of study agent. 
In the safety analyses, subjects will be analyzed according to the actual treatment received. 
Randomized subjects confirmed not to have taken any study medication will not be included in 
the safety analysis set.  
2.3.4. 
Pharmacokinetics Analysis Set 
The pharmacokinetics (PK) analysis set is defined as subjects who have received at least 1 
complete dose of ustekinumab and have at least one valid blood sample drawn for PK analysis. 
In the PK analyses, subjects will be analyzed according to the actual treatment received. 


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2.3.5. 
Immunogenicity Analysis Set 
The immunogenicity analysis set is defined as all subjects who received at least 1 dose (partial or 
complete, IV or SC) of ustekinumab and have appropriate samples for detection of antibodies to 
ustekinumab (ie, subjects with at least 1 appropriate sample obtained after their first dose of 
ustekinumab). 
In the immunogenicity analyses, subjects will be analyzed according to the actual treatment 
received. 
2.3.6. 
Pharmacodynamics Analysis Set 
The pharmacodynamic analysis set is defined as all subjects who have received at least 1 dose 
(partial or complete) of ustekinumab. 
2.3.7. 
Pharmacokinetics/Pharmacodynamics Analysis Set 
The pharmacokinetics/pharmacodynamics (PK/PD) analysis set is defined as all subjects 
(including participants who received placebo intervention) who have at least 1 paired PK and PD 
data collected at same time point needed for each PK/PD analysis. If participants who receive 
placebo intervention and have no concentration data before Week 24 visit, serum ustekinumab 
concentrations will be imputed as zero and should be included into PK/PD analyses through Week 
24 as well. 
2.4. 
Analysis Periods and Treatment Groups  
Four database locks (DBLs) will occur at Week 24, Week 52, Week 72, and Week 88. Based on 
the study design features, the following analysis periods and treatment groups are defined to 
analyze the data according to the data collection type.  
All the data collected only at Screening and/or Baseline (eg, demographic, medical history), will 
be included in Week 24 DBL report.  
Visit-by-visit data 
Hereinafter in this document, visit-by-visit data is referred as those data which are collected at 
specified visits in the Time and Events Schedule of the protocol, such as, efficacy assessments, 
vital signs, 12-lead ECG, laboratory assessments and PK and Immunogenicity assessments. 
From Week 0 through Week 24 
 
Analyses of efficacy endpoints for placebo comparison through Week 24 will be based 
on the all randomized analysis set and will be summarized by the following treatment 
groups:  
o 
Placebo: Subjects randomized to Placebo group at Week 0 
o 
Ustekinumab: Subjects randomized to Ustekinumab at Week 0 


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 
Analyses of safety endpoints through Week 24 will be based on the safety analysis set 
and will be summarized by the following treatment groups:  
o 
Placebo: Subjects received Placebo at Week 0 
o 
Ustekinumab: Subjects received Ustekinumab at Week 0 
 
Analyses of PK endpoints through Week 24 will be based on the PK analysis set and will 
be summarized by the following treatment groups:  
o 
Placebo: Subjects received Placebo at Week 0 
o 
Ustekinumab: Subjects received Ustekinumab at Week 0 
 
Analyses of immunogenicity endpoints through Week 24 will be based on the 
immunogenicity analysis set and will be summarized by the following treatment groups:  
o 
Placebo: Subjects received Placebo at Week 0 
o 
Ustekinumab: Subjects received Ustekinumab at Week 0 
- 
Analyses of PK/PD endpoints through Week 24 will be based on the PK/PD analysis set 
and will be summarized by the following treatment groups:  
o Placebo: Subjects received Placebo at Week 0 
o Ustekinumab: Subjects received Ustekinumab at Week 0 
From Week 24 through Week 52/72/88 
 
Analyses of efficacy endpoints from Week 24 through Week 52/72/88 will be based on 
the all randomized analysis set and will be summarized by following treatment groups:  
o 
Placebo -> Ustekinumab: Subjects randomized to Placebo group at Week 0 and then 
cross over to receive Ustekinumab at Week 24 
o 
Ustekinumab: Subjects randomized to Ustekinumab at Week 0 and continue 
receiving Ustekinumab throughout the study 
 
Analyses of safety endpoints from Week 24 through Week 52/72/88 will be based on the 
safety analysis set and will be summarized by following treatment groups:  
o 
Placebo -> Ustekinumab: Subjects received Placebo at Week 0 and then cross over 
to receive Ustekinumab at Week 24 
o 
Ustekinumab: Subjects received Ustekinumab at Week 0 and continue receiving 
Ustekinumab throughout the study 
 
Analyses of PK endpoints from Week 24 through Week 52/72/88 will be based on the 
PK analysis set and will be summarized by following treatment groups:  
o 
Placebo -> Ustekinumab: Subjects received Placebo at Week 0 and then cross over 
to receive Ustekinumab at Week 24 
o 
Ustekinumab: Subjects received Ustekinumab at Week 0 and continue receiving 
Ustekinumab throughout the study 


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 
Analyses of immunogenicity endpoints through Week 52/72/88 will be based on the 
immunogenicity analysis set and will be summarized by the following treatment groups:  
o 
Placebo -> Ustekinumab: Subjects received Placebo at Week 0 and then cross over 
to receive Ustekinumab at Week 24 
o 
Ustekinumab: Subjects received Ustekinumab at Week 0 and continue receiving 
Ustekinumab throughout the study 
 
Analyses of PK/PD endpoints from Week 24 through Week 52/72/88 will be based on 
the PK/PD analysis set and will be summarized by following treatment groups:  
o 
Placebo -> Ustekinumab: Subjects received Placebo at Week 0 and then cross over 
to receive Ustekinumab at Week 24 
o 
Ustekinumab: Subjects received Ustekinumab at Week 0 and continue receiving 
Ustekinumab throughout the study 
2.5. 
Data cut-off for Week 24, 52 and 72 
The selections of data to be included in the analysis period through Week 24/52/72 will be done 
by determining a patient specific Week 24/52/72 cut-off date and including all data measured and 
observed up to this cut-off date in the Week 24/52/72 analyses. The patient specific cut-off date is 
defined as: 
Scenarios  
Patient specific cut-off date 
Patients had Week 24/52/72 visit 
Use Week 24/52/72 visit date 
Patients discontinued prior to Week 24/52/72  
No cut-off date and include all their data in 
Week 24/52/72 analyses 
Patients had no Week 24/52/72 visit and did 
not discontinue prior to Week 24/52/72 
Use last visit date up to study day 182/378/523 
relative to the first stud agent administration 
for Week 24/52/72 respectively 
2.6. 
Definition of Subgroups 
Subgroup analysis of the primary endpoint based on the following baseline characteristics may be 
performed: 
Subgroup 
Definition 
Disease subset 
 PM 
 DM 
Baseline treatment level of 
glucocorticoid dose 
 ≥0.5 mg/kg/day of prednisolone or equivalent 
 <0.5 mg/kg/day of prednisolone or equivalent 
Age Group 
 [<65] 
 [≥65] 
BMI 
 [<18.5 kg/m2] 
 [18.5-<25.0 kg/m2] 
 [≥25.0 kg/m2] 
Sex 
 Male 
 Female 
ILD at baseline 
 ILD at baseline 
 No ILD at baseline 


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2.7. 
Study Day and Relative Day 
Study Day 1 or Day 1 refers to the start of the first study agent administration or randomization 
date if subject was never dosed. All efficacy and safety assessments at all visits will be assigned a 
day relative to this date. 
Study day or relative day for a visit is defined as: 
 
Visit date - (date of Study Day 1) +1, if visit date is ≥ date of Day 1 
 
Visit date - date of Day 1, if visit date < date of Day 1 
There is no 'Day 0'. 
2.8. 
Baseline  
Baseline is defined as the last observation prior to the start of the first study agent administration. 
Baseline immunomodulator/glucocorticoid dose is defined as the daily dose on Study day -1 (the 
day before randomization).  
2.9. 
Imputation Rules for Missing AE Date/Time of Onset/Resolution 
Partial AE onset dates will be imputed as follows: 
 
If the onset date of an AE is missing day only, it will be set to: 
 
First day of the month that the AE occurred, if month/year of the onset of AE is different 
than the month/year of the study agent start 
 
The day of study agent start, if the month/year of the onset of AE is the same as 
month/year of the study agent start date and month/year of the AE resolution date is 
different 
 
The day of study agent start or day of AE resolution date, whichever is earliest, if 
month/year of the onset of AE and month/year of the study agent start date and 
month/year of the AE resolution date are same 
 
If the onset date of an AE is missing both day and month, it will be set to the earliest of: 
 
January 1 of the year of onset, as long as this date is on or after the study agent start date 
 
Month and day of the study agent start date, if this date is the same year that the AE 
occurred 
 
Last day of the year if the year of the AE onset is prior to the year of the study agent start 
date, 
 
The AE resolution date. 
 
Completely missing onset dates will not be imputed. 
Partial AE resolution dates not marked as ongoing will be imputed as follows: 


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 
If the resolution date of an AE is missing day only, it will be set to the earliest of the last day 
of the month of occurrence of resolution or the day of the date of death, if the death occurred 
in that month. 
 
If the resolution date of an AE is missing both day and month, it will be set to the earliest of 
December 31 of the year or the day and month of the date of death, if the death occurred in 
that year. 
 
Completely missing resolution dates will not be imputed. 
AE onset/resolution dates with missing times will be imputed as follows: 
 
A missing time of onset of an adverse event will be set to the earlier of: 
 
00:01 as long as the onset date is after the study agent start date 
 
The time of the study agent start if this is the same day the AE occurred. 
 
The missing time of resolution of an adverse event will be set to 23:59. 
If a missing time is associated with a partial or missing date, the date will be imputed first prior to 
imputing the time. 
3. 
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW 
Details of the Data Monitoring Committee (DMC) safety reviews and interim analysis assessments 
are included in a separate DMC Charter and DMC SAP. The DMC SAP contains definitions of 
analysis sets, statistical methods, and data presentation specifications used for safety data review 
and interim analysis.  
The following offers a high-level summary of Interim Analysis and DMC review activities. 
3.1. 
Interim Analysis 
An interim analysis is planned with the objective of stopping the study for futility. It is scheduled 
when approximately 40% of the 50 randomized subjects (20 patients) have completed Week 24 
visit or have ended study participation before Week 24 visit. Data, statistical methods, decision 
rules regarding futility stopping, and mockup tables, listings, and graphs used in the interim 
analysis, are specifically described in DMC SAP.  
3.2. 
Data Monitoring Committee Review 
The independent DMC will monitor data on an ongoing basis to ensure the continuing safety of 
the subjects enrolled in the study. The committee will periodically review interim data. After the 
review, the DMC will make recommendations regarding the continuation of the study. Any safety 
concerns will be communicated to the Sponsor.  
None of the DMC members will be participating in the study; they will be independent of the 
Sponsor. The independent DMC consists of at least 2 medical experts in relevant therapeutic areas 
and 1 statistician and are to be specified before study initiation. The major function of the DMC is 
to monitor the safety of the study agent by reviewing the SAE and unblinded safety data every 2 


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months, and to review unblinded results of interim efficacy analysis in addition to ongoing safety 
review.   
The content of the safety summaries and interim analysis, the DMC roles and responsibilities and 
the general procedures (including communication plan) and their possible recommendations on 
study conduct are defined and documented in the DMC Charter prior to the first DMC review.  
4. 
SUBJECT INFORMATION 
The number of subjects in each analysis set will be summarized and listed by treatment group, and 
overall.  
4.1. 
Demographics and Baseline Characteristics 
Table 1 presents a list of the demographic variables that will be summarized by treatment group, 
and overall for the all randomized analysis set. Prior and concomitant medications used at baseline 
will be listed. 
Table 1: 
Demographic Variables and Disease Characteristics at Baseline 
Continuous Variables: 
Summary Type 
Age (years) 
Descriptive statistics (N, mean, 
standard deviation [SD], median 
and range [minimum and 
maximum]) 
Weight (kg) 
Height (cm) 
Body Mass Index (BMI) (kg/m2) 
Disease duration (years) 
PhGA of disease activity (100 mm) 
PtGA of disease activity (100 mm) 
MMT-8 (0-80) 
Creatine Kinase (CK) (IU/L) 
Alanine Aminotransferase (ALT) (IU/L) 
Aspartate Aminotransferase (AST) (IU/L) 
Lactate Dehydrogenase (LDH) (IU/L) 
Aldolase (IU/L) 
Manual Muscle Testing (MMT)-8 
MDAAT-Extramuscular Global Assessment (100 mm) 
HAQ-DI (1-3) 
SF-36 mental 
SF-36 physical 
Categorical Variables 
 
Age (<65 years and ≥65 years) 
Frequency distribution with the 
number and percentage of subjects 
in each category. 
Sex (male, female) 
Race (Asian) 
BMI (<18.5 kg/m2, 18.5-<25.0 kg/m2, ≥25.0 kg/m2) 
Diagnosis (PM, DM)* 
ILD at baseline (Yes, No) 
Glucocorticoid at baseline (≥0.5 mg/kg/day of prednisolone or equivalent 
, <0.5 mg/kg/day of prednisolone or equivalent) * 
*Diagnosis and Glucocorticoid at baseline will be based on the eCRF page of “PM/DM classification European 
League Against Rheumatism/American College of Rheumatology Classification Criteria” and “Glucocorticoid 
Therapy”. 


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4.2. 
Disposition Information 
Disposition information will be based upon the randomized analysis set. 
The number of subjects in the following disposition categories will be summarized throughout the 
study by treatment group and overall for 4 analysis periods: through Week 24, through Week 52, 
through Week 72, through end of study. 
 
Subjects with informed consent 
 
Subjects with screening failure 
 
Subjects randomized 
 
Subjects receiving study agent 
 
Subjects completing the study 
 
Subjects who discontinued study agent 
 
Reasons for discontinuation of study agent 
 
Subjects who terminated study prematurely 
 
Reasons for termination of study 
Completion status of study agent through Week 24 and through Week 52 is not captured in eCRF 
and will be defined as follows:  
 A patient will be considered a Week 24/52 completer if the patient: 1) has Week 24/52 visit, 
or 2) has no Week 24/52 visit but has not discontinued from the treatment before or on Week 
24/52 cut-off date (ie, no discontinuation is reported or discontinuation is reported on the eCRF 
page of “END OF TREATMENT” but with a Treatment Disposition Date greater than Week 
24/52 cut-off date).  
 A patient will be considered as a Week 24/52 non-completer if the patient has no Week 24/52 
visit and discontinued from the treatment before Week 24/52 cut-off date (ie, discontinuation 
is reported on the eCRF page of “END OF TREATMENT” with a Treatment Disposition Date 
before Week 24/52 cut-off date).  
4.3. 
Treatment Compliance 
The study drug will be administered as an IV infusion or SC by qualified study site personnel and 
the details of each administration will be recorded in the eCRF (including date, start and stop times 
of the IV infusion, and volume infused). Compliance with the treatment assignments will be 
controlled by the study site personnel.  
Study agent compliance will be summarized descriptively. Compliance to randomized treatment 
versus actual treatment through Week 24 will be presented in a summary table. 


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4.4. 
Extent of Exposure 
The number of subjects exposed to study agent, the number of administrations of study agent by 
type of administration (IV and SC), and cumulative dose (IV and SC) of study agent will be 
summarized by treatment group.  
Analysis periods and treatment groups described for summary data in Section 2.4 will also be 
applied to the exposure data.  
4.5. 
Protocol Deviations 
In general, the following list of major protocol deviations may have the potential to impact subjects’ 
rights, safety or well-being, or the integrity and/or result of the clinical study. Subjects with major 
protocol deviations will be identified prior to database lock and the subjects with major protocol 
deviations will be summarized by category. 
 
Developed withdrawal criteria but not withdrawn 
 
Entered but did not satisfy criteria 
 
Received a disallowed concomitant treatment 
 
Received wrong treatment or incorrect dose 
 
Other 
Analysis periods and treatment groups defined in Section 2.4 will be applied for the above analyses.  
4.6. 
Prior and Concomitant Medications 
Background therapy for active PM/DM summarized by treatment group may be provided.  
Prior and Concomitant medications will be coded using the World Health Organization Drug 
Dictionary (WHO-DD). Prior medications are defined as any therapy used before the day of first 
dose (partial or complete) of study agent. Concomitant medications are defined as any therapy 
used on or after the same day as the first dose of study agent, including those that started before 
and continue on after the first dose of study agent. 
Prior medications and concomitant medications will be summarized respectively by treatment 
group and ATC term.   
4.7. 
COVID-19 Related Summaries 
Depending on the COVID-19 impact on this study, the following summarizes may be provided.  
Subject disposition as related to COVID-19 may be summarized by treatment group.  This includes 
the following COVID-19 related disposition events: 
 
Termination of study due to COVID-19 and reason 
 
Discontinuation of study agent due to COVID-19 and reason 
 
Death related to COVID-19 


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Subjects discontinuing treatment or terminating study participation due to COVID-19 and 
reason(s) may be listed. 
Concomitant medications used for COVID-19 may be summarized. Subjects receiving 
concomitant medications related to COVID-19 may be listed. 
Protocol deviations (major and minor) as related to COVID-19 may be summarized and listed. 
5. 
EFFICACY 
5.1. 
Analysis Specifications 
5.1.1. 
Level of Significance 
Unless otherwise stated, the statistical significance is set to 2-sided α-level of 0.05 as per protocol. 
When appropriate, 95% confidence intervals will be provided.  
5.2. 
Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of subjects who achieve IMACS TIS response at 
Week 24.  
5.2.1. 
Definition 
The IMACS TIS (Total Improvement Score) ranges from 0 to 100. This score is the sum of the 6 
IMACS core set measures as follows:  
 
PhGA of disease activity 
 
PtGA of disease activity 
 
MMT-8 
 
Physical Function (HAQ-DI) 
 
Muscle Enzymes  
 
Extramuscular Assessment (MDAAT) 
The absolute percent change is calculated for each core set measure.  
ܣܾݏ݋݈ݑݐ݁ ݌݁ݎܿ݁݊ݐ ܿℎܽ݊݃݁=
ሺ݂݈݅݊ܽ ݒ݈ܽݑ݁ሻ−ሺܾܽݏ݈݁݅݊݁ ݒ݈ܽݑ݁ሻ
ݎܽ݊݃݁
× 100 
The thresholds of improvement and improvement score are summarized in the table for each core 
set (Table 2). The total improvement score is calculated by sum of 6 core set improvement scores. 
The total improvement score is categorized into 3 categories (minimal, moderate and major) 
(Table 3). The IMACS TIS response as the primary endpoint is defined as IMACS TIS ≥20 
(minimal) (Aggarwal 2017).  


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Table 2: 
The Thresholds of Improvement and Improvement Score 
Core Set Measure 
Level of Improvement Based on absolute 
percentage change 
Improvement Score 
PhGA of disease activity 
Worsening to 5% improvement 
0 
>5% to 15% improvement 
7.5 
>15% to 25% improvement 
15 
>25% to 40% improvement 
17.5 
>40% improvement 
20 
PtGA of disease activity 
Worsening to 5% improvement 
0 
>5% to 15% improvement 
2.5 
>15% to 25% improvement 
5 
>25% to 40% improvement 
7.5 
>40% improvement 
10 
Manual Muscle Testing or 
Childhood Myositis 
Assessment Scale 
(MMT-8) 
Worsening to 2% improvement 
0 
>2% to 10% improvement 
10 
>10% to 20% improvement 
20 
>20% to 30% improvement 
27.5 
>30% improvement 
32.5 
(Childhood) Health 
Assessment Questionnaire 
(HAQ-DI) 
Worsening to 5% improvement 
0 
>5% to 15% improvement 
5 
>15% to 25% improvement 
7.5 
>25% to 40% improvement 
7.5 
>40% improvement 
10 
Enzyme (most abnormal)  
(Muscle Enzymes) 
Worsening to 5% improvement 
0 
>5% to 15% improvement 
2.5 
>15% to 25% improvement 
5 
>25% to 40% improvement 
7.5 
>40% improvement 
7.5 
Extramuscular Activity or 
Disease Activity Score 
(MDAAT) 
Worsening to 5% improvement 
0 
>5% to 15% improvement 
7.5 
>15% to 25% improvement 
12.5 
>25% to 40% improvement 
15 
>40% improvement 
20 
 
Table 3: 
Criteria for Minimal, Moderate, and Major Clinical Response 
 
Improvement Category 
Total Improvement Score 
PM/DM thresholds 
Minimal 
≥20 
Moderate 
≥40 
Major 
≥60 
5.2.1.1.1. 
Physician Global Activity (PhGA) 
This is the assessment by the treating physician to measure the global evaluation of the patient’s 
overall disease activity using a 10 cm VAS. Left end of line = no evidence of disease activity, 
midpoint of line = moderate disease activity, and right end of line = extremely active or severe 
disease activity. [range: 10 cm] 
5.2.1.1.2. 
Patient Global Activity (PtGA) 
This is the assessment by the patient to measure the global evaluation of the patient’s overall 
disease activity using a 10 cm VAS. Left end of line = no evidence of disease activity, and right 
end of line = extremely active or severe disease activity. [range: 10 cm] 


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5.2.1.1.3. 
Manual Muscle Testing (MMT-8) 
MMT-8 is a set of 8 designated muscles tested unilaterally, generally on right side (unless cannot 
be tested on right, then use left side) The evaluation is considered as improvement with higher 
score [range: 80].  
The side (right or left) used for calculating the total score at baseline and post-baseline should be 
consistent within each muscle group. Muscle groups with both sides scored at baseline, unless 
there are more missing values on right side scores, then the left side scores should be used.  
MMT-8 total score will be calculated only if at least 4 muscle groups can be scored (ie, 
nonmissing). When at least 4 muscle groups can be scored, missing muscle groups will be imputed 
by the closet previous nonmissing values. If less than 4 muscle groups can be scored, then MMT-
8 total score will be considered as missing.  
5.2.1.1.4. 
Physical Function (HAQ-DI) 
The functional status of the subject is evaluated by HAQ disability index (HAQ-DI) score 
(Fries 1980; Matsuda 2003). The HAQ-DI is composed of eight categories: dressing (C1), arising 
(C2), eating (C3), walking (C4), hygiene (C5), reaching (C6), gripping (C7) and activities of daily 
living (C8). For each of these categories, subjects are asked to record the amount of difficulty they 
may have in performing various activities. The possible answers for the component questions are 
shown in Table 4. 
Table 4: 
The possible answers for the component questions and corresponding scores 
Answer to the component question 
Score 
Without ANY difficulty 
0 
With SOME difficulty 
1 
With MUCH difficulty 
2 
UNABLE To Do 
3 
 
The highest score recorded by the subject for any component question determines the score for 
that category. Subjects are also asked to indicate their use of any AIDS OR DEVICES or if they 
need help from another person for any of these activities. And the component score is adjusted 
based on the subject’s use of any Aid or Device or assistance from any other person for that 
component.  
If Aid or Devices and/or help from another person is checked for a category, the score is set to “2”, 
unless the score is already “3” (i.e., scores of “0” or “1” are increased to “2”).  
The disability index is calculated as the sum of computed component scores (the highest scores in 
each category) divided by the number of categories answered. The disability index is not computed 
if the subject does not have scores for at least 6 categories of the 8 categories.  
HAQ −DI score = ݏݑ݉ ݋݂ ݐℎ݁ ℎ݅݃ℎ݁ݏݐ ݏܿ݋ݎ݁ݏ ݅݊ ݁ܽܿℎ ܿܽݐ݁݃݋ݎݕ
ܶℎ݁ ݊ݑܾ݉݁ݎ ݋݂ ܿܽݐ݁݃݋ݎ݅݁ݏ ܽ݊ݏݓ݁ݎ݁݀
 
The pre-specified devices for the above stated categories are summarized in Table 5. 


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Table 5: 
The pre-specified devices and the corresponding category 
Category 
Name of Category 
Devices 
C1 
Dressing 
Devices used for dressing (button hook, Zipper pull, long-handled 
show horn, etc.) 
C2 
Arising 
Special or built up chair 
C3 
Eating 
Built up or special utensils 
C4 
Walking 
Cane, Walking Frame, Crutches, Wheelchair 
C5 
Hygiene 
Raised toilet seat. Bathtub seat, Bathtub bar, Long-handled 
appliances in the bathroom 
C6 
Reaching 
Long-handled appliances for reach 
C7 
Gripping 
Jar opener (for jars previously opened) 
 
The pre-specified help from another person for the above stated categories are summarized in 
Table 6. 
Table 6: 
The pre-specified help from another person and the corresponding category 
Category 
Name of Category 
Help from another person 
C1 
Dressing 
Dressing and grooming 
C2 
Arising 
Arising 
C3 
Eating 
Eating 
C4 
Walking 
Walking 
C5 
Hygiene 
Hygiene 
C6 
Reaching 
Reach 
C7 
Gripping 
Gripping and opening things 
C8 
Activities 
Errands and chores 
 
The aids or devices other than the ones specified in the table above will be recorded in the “Other 
(Specify)” section. Aids or Devices written in the “Other (Specify)” sections or notes written next 
to any component questions are considered if they could be classified to any of the stated categories.  
5.2.1.1.5. 
Muscle Enzymes 
For muscle enzymes, the most abnormal enzyme at baseline is used. The most abnormal enzyme 
is determined by having the greatest baseline divided by its upper limit of normal. However, if the 
value at Week 24 for the most abnormal enzyme at baseline is missing but the values at Week 24 
for other enzymes are not missing, the other enzyme will be used to calculate the IMACS TIS 
score by the order of degree of abnormality. The values obtained from central laboratory are used 
for evaluation. The enzyme range was calculated based on 90% range of enzymes from natural 
history data (Table 7).  
ܣܾݏ݋݈ݑݐ݁ ݌݁ݎܿ݁݊ݐ ܿℎܽ݊݃݁=
ሺ݂݈݅݊ܽ ݒ݈ܽݑ݁ሻ−ሺܾܽݏ݈݁݅݊݁ ݒ݈ܽݑ݁ሻ
90% ݎܽ݊݃݁
× 100 


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Table 7: 
Muscle enzyme and its range by adults/juveniles 
Adults/Juveniles 
Muscle enzyme 
90% range 
Adults 
CK (creatine kinase) 
15 × ሺݐℎ݁ ݑ݌݌݁ݎ ݈݅݉݅ݐ ݋݂ ݊݋ݎ݈݉ܽሻ 
Aldolase 
6 × ሺݐℎ݁ ݑ݌݌݁ݎ ݈݅݉݅ݐ ݋݂ ݊݋ݎ݈݉ܽሻ 
LDH (lactate dehydrogenase) 
3 × ሺݐℎ݁ ݑ݌݌݁ݎ ݈݅݉݅ݐ ݋݂ ݊݋ݎ݈݉ܽሻ 
AST (aspartate aminotransferase) 
3 × ሺݐℎ݁ ݑ݌݌݁ݎ ݈݅݉݅ݐ ݋݂ ݊݋ݎ݈݉ܽሻ 
ALT (alanine aminotransferase) 
3 × ሺݐℎ݁ ݑ݌݌݁ݎ ݈݅݉݅ݐ ݋݂ ݊݋ݎ݈݉ܽሻ 
Juveniles 
CK (creatine kinase) 
20 × ሺݐℎ݁ ݑ݌݌݁ݎ ݈݅݉݅ݐ ݋݂ ݊݋ݎ݈݉ܽሻ 
Aldolase 
6 × ሺݐℎ݁ ݑ݌݌݁ݎ ݈݅݉݅ݐ ݋݂ ݊݋ݎ݈݉ܽሻ 
LDH (lactate dehydrogenase) 
5 × ሺݐℎ݁ ݑ݌݌݁ݎ ݈݅݉݅ݐ ݋݂ ݊݋ݎ݈݉ܽሻ 
AST (aspartate aminotransferase) 
5 × ሺݐℎ݁ ݑ݌݌݁ݎ ݈݅݉݅ݐ ݋݂ ݊݋ݎ݈݉ܽሻ 
ALT (alanine aminotransferase) 
5 × ሺݐℎ݁ ݑ݌݌݁ݎ ݈݅݉݅ݐ ݋݂ ݊݋ݎ݈݉ܽሻ 
5.2.1.1.6. 
Extramuscular Assessment (Myositis Disease Activity Assessment 
Tool) 
This is the assessment using a 10 cm VAS. Left end of line = no evidence of disease activity, and 
right end of line = extremely active or severe disease activity. The extramuscular assessment VAS 
is used for calculation of IMACS TIS. [range: 10 cm] 
Apart from the extramuscular assessment VAS, MDAAT is measured. The MDAAT is a combined 
tool that includes the Myositis Disease Activity Assessment VAS (MYOACT) and the Myositis 
Intention to Treat Activity Index (MITAX). MYOACT and MITAX score will be calculated only 
if >= 50% of used organ systems can be scored. If < 50% of used organ systems are scored, 
MYOACT and MITAX score will be considered missing. Note that if the MITAX category score 
or VAS for one organ system cannot be assessed, both of them will be considered not assessed. 
Myositis Disease Activity Assessment (MYOACT): The MYOACT is the sum of the 10 cm VAS 
scores for each of the six individual organ systems (Constitutional, Cutaneous, Skeletal, 
Gastrointestinal, Pulmonary, Cardiac) and divided by the total possible score (range = 60). If one 
or more organ systems were not assessed, the resulting score would be divided by the maximum 
possible score from those assessed items (Whiting 1999). For example, if Constitutional VAS = 8, 
Cutaneous VAS = 6, Skeletal VAS = not scored, Gastrointestinal VAS = not scored, Pulmonary 
VAS = 1, Cardiovascular VAS = not scored, then MYOACT score = (8+6+1) / 10*3 = 0.5. 
Myositis Intention to Treat Activity Index (MITAX): 
The MITAX is scored on a 0 to 4 scale, based on worsening or improvement in specific clinical 
features and their correlation with the intention to treat (Hay 1993).  
The MITAX score is the sum of the worst category scores for each of the seven individual organ 
systems (Constitutional, Cutaneous, Skeletal, Gastrointestinal, Pulmonary, Cardiac, Muscle) 
divided by the maximum possible score (range = 1 – 63). If one or more organ systems were not 
assessed, the score would be calculated by dividing the sum by the maximum possible score of the 
assessed organ systems. For example, if Constitutional = category A (9 points), Cutaneous = 
category B (3 points), Skeletal = not scored, Gastrointestinal = not scored, Pulmonary = category 
C (1 point), Cardiovascular = category D (0 point), Muscle = category B (3 points), then MITAX 
score = (9+3+1+0+3) / 9*5 = 0.3556. 


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Score 
Symptoms 
0 
If the feature is not present 
1 
If the feature is improving – clinically significant improvement in the last 4 weeks 
over the previous 4 weeks 
2 
If the feature is the same – manifestations that have been present for the last 4 weeks 
and the previous 4 weeks without significant improvement or deterioration 
3 
If the feature is worse – clinically significant deterioration over the last 4 weeks 
compared to the previous 4 weeks 
4 
If the feature is new – new in the last 4 weeks (compared to the previous 4 weeks) 
NA 
If the feature cannot be assessed 
 
As the table below shows, each organ system of the MITAX is scored by selecting the highest 
category selected for any of the individual items under that organ system (ie, the worse item carries 
the score for the organ system). Whether NA (Not Assessed) or not for each organ system should 
be judged by whether all items used in category A are not NA. If judged to be “Not NA”, the 
system organ will be scored in an order of Category A→B→C→E→D. Only if all Category A, B 
and C are not scored, Category D or E will be scored. Whether Category D or E will be determined 
by the presence of previous activity (Y/N). If all previous scores for this organ system are D or E 
or NA, then this organ system should be scored as E; otherwise scored as D. Screening assessments 
will be used as previous activity for baseline. 
If without ILD, Category A for the pulmonary organ system will be evaluated with item 17a, 17b 
and 19; if with ILD, this score will be evaluated with item 18a, 18b, 18c and 19. Since chest x-ray, 
HRCT and FVC tests are not performed every 4 weeks, the values for these assessments obtained 
within 13 weeks before the visit are allowed to be used for evaluating item 18b and 18c. At baseline, 
because 18c is scored as NA, only 18a and 18b will be used for pulmonary organ system scoring. 
At Week 24 (primary endpoint), all 3 items of 18a, 18b and 18c will be used. 
 


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CATEGORY A 
A = Active 
(9 points) 
CATEGORY B 
B = Beware 
(3 points) 
CATEGORY C 
C = Contentment 
(1 point) 
CATEGORY D 
D = Discount 
(0 points) 
CATEGORY E 
E = No evidence 
(0 points) 
Constitutional 
Disease Activity 
 
Pyrexia (item 1) scoring 2, 3 or 4 
plus two other clinical feature 
scoring > 1: 
-Unintentional weight loss 
(item 2) 
-Fatigue/malaise/lethargy (item 
3) 
Any one clinical feature  
scoring 2, 3 or 4 
 
Any one clinical feature 
scoring 1 
 
No current activity 
but known to have 
been active in the 
past. 
- ie remission 
 
No current or 
previous activity. 
 
 
Cutaneous 
Disease ActIvity 
 
Any one of the following scoring 
2, 3 or 4: 
-Cutaneous ulceration (item 4) 
-Erythroderma (item 5) 
-Erythematous rashes with 
secondary changes eg. 
accompanied by 
vesiculobullous or erosive 
changes or necrosis (item 7a) 
-Panniculitis (item 6) 
 
1) Any Category A clinical feature 
scoring 1 
OR    
2) Any one of the following scoring 
2, 3 or 4: 
-Erythematous rashes without 
secondary changes (item 7b) 
-Heliotrope rash (item 8) 
-Gottron’s papules or sign  (item 
9) 
-Periungual capillary changes  
(item 10) 
-Alopecia: diffuse (item 11a) 
-Mechanic’s hands (item 12) 
1) Any Category B clinical 
feature scoring 1   
OR  
2) Alopecia: focal  (item 11b) 
- scoring   1, 2, 3 or 4 
  
No current activity 
but known to have 
been active in the 
past. 
- ie remission 
 
 
No current or 
previous activity. 
 
Skeletal Disease 
Activity 
Severe inflammatory polyarthritis 
(item 13a) 
scoring 2, 3 or 4 
 
 
1) Severe inflammatory 
polyarthritis scoring 1 (item 13a) 
OR 
 
2) Moderate inflammatory arthritis 
(item 13b) scoring 2, 3 or 4 
 
 
1) Any category B clinical 
feature scoring 1 
OR 
2) Any one of the following 
scoring 1, 2, 3 or 4: 
-Mild arthritis (item 13c) 
-Arthralgia (item 14) 
 
No current activity 
but known to have 
been active in the 
past. 
- ie remission 
 
 
No current or 
previous activity. 
 
Gastrointestinal 
Disease Activity 
Any one of the following scoring 
2, 3 or 4: 
-Moderate to severe dysphagia 
(item 15a) 
-Severe abdominal pain (item 
16a) 
 
1) Any Category A clinical feature 
scoring 1 
OR 
2) Any one of the following scoring  
2, 3 or 4 
-Moderate abdominal pain (item 
16b) 
-Mild dysphagia (item 15b) 
1) Any Category B clinical 
feature scoring 1 
OR 
2) Mild abdominal pain  (item 
16c) scoring 1, 2, 3 or 4 
No current activity 
but known to have 
been active in the 
past. 
- ie remission 
 
 
No current or 
previous activity 


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Pulmonary 
Disease 
 
1)Ventilatory abnormalities due 
to muscle weakness without 
primary lung disease- dyspnea at 
rest scoring 2, 3, or 4 (item 17a) 
 
OR 
 
2)Active ILD scoring 3 (worse) or 
4 (new) in at least two of the 
following: 
a) dyspnea or cough due to 
ILD (item 18a) 
b) parenchymal abnormalities 
on CXR or HRCT and/or 
ground glass-shadowing 
(item 18b) 
c) PFTs  - minimum of 10% 
change in FVC or 15% 
change in DLCO (item 18c) 
1) 17a) scoring 1, OR 
Ventilatory abnormalities due to 
muscle weakness without primary 
lung disease - Dyspnea on 
exertion scoring 2, 3, or 4 (item 
17b) 
 
2) Active ILD scoring 2 (same) in 
at least two of  the following (or 
scoring 1 or 3 in only one category 
with 2 in others) 
a) dyspnea or cough due to 
ILD (item 18a) 
b) parenchymal abnormalities 
on CXR or HRCT and/or 
ground glass-shadowing (item 
18b) 
c) PFTs  - minimum of 10% 
change in FVC or 15% change 
in DLCO (item 18c) 
 
3) Moderate to severe dysphonia 
scoring 2, 3 or 4 (item 19a) 
1) 17 b scoring 1 OR 
Active ILD scoring 1 ( ie 
improvement) in at least two 
of the following: 
a) dyspnea or cough due 
to ILD (item 18a) 
b) parenchymal 
abnormalities on CXR or 
HRCT and/or ground 
glass-shadowing (item 
18b) 
c) PFTs  - minimum of 
10% change in FVC or 
15% change in DLCO 
(item 18c) 
 
2) 
Moderate to severe 
dysphonia scoring 1 (item 
19a) OR Mild dysphonia 
scoring 1, 2, 3 or 4 (item 
19b) 
No current activity 
but known to have 
been active in the 
past 
- ie remission 
 
No current or 
previous activity 
Cardiovascular 
Disease Activity 
Any one of the following scoring 
2, 3 or 4 
 
-Myocarditis (item 
21)/pericarditis (item 20) 
-Severe cardiac arrhythmia 
(item 22a) 
1) Any Category A clinical feature 
scoring 1 
 OR 
2) Any one of the following scoring  
    2, 3 or 4: 
     
 -Mild/moderate cardiac 
arrhythmia (except sinus 
tachycardia) (item 22b) 
 
 1) Any Category B clinical 
feature scoring scoring 1 
OR 
2) Sinus tachycardia scoring    
1, 2, 3 or 4 (item 23) 
No current activity 
but known to have 
been active in the 
past 
- ie remission 
 
No current or 
previous activity 
Muscle Disease 
Activity 
 
Myositis resulting in severe 
muscle inflammation (item 25a) 
scoring 2, 3 or 4  
1) Severe muscle inflammation 
(item 25a) scoring 1,  
OR 
2) Moderate muscle inflammation 
(item 25b) scoring 2, 3, or 4 
1) Myositis resulting in 
moderate inflammation (item 
25b) scoring 1,  
OR 
2) Myositis resulting overall 
in mild inflammation (item 
25c) scoring 1, 2, 3 or 4 
3) Myalgia scoring (item 26) 
scoring 
 1, 2, 3 or 4 
No current activity 
but known to have 
been active in the 
past 
- ie remission 
 
No current or 
previous activity 


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5.2.2. 
Estimands 
5.2.2.1. 
Primary Estimand 
Primary Trial Objective: To evaluate the efficacy of ustekinumab in participants with active 
PM/DM despite receiving 1 or more standard-of-care treatments (eg, glucocorticoids and/or 
immunomodulators). 
Estimand Scientific Question of Interest: What is the proportion of participants considered to 
have benefited from ustekinumab vs placebo for the pre-specified duration (24 weeks), 
administered together with the protocol allowed 1 or more standard-of-care treatments? 
The Primary Estimand will be targeted for the primary endpoint.  The Primary Estimand for the 
primary endpoint is defined by the following: 
 
Study intervention:  
 
Ustekinumab (~6 mg/kg IV at Week 0, and 90 mg SC q8w through Week 24)  
 
Placebo (IV at Week 0 and SC q8w through Week 24) 
 
Population: Subjects with active PM/DM despite receiving one or more standard-of-care 
treatments. 
 
Variable/endpoint: IMACS TIS binary response variable at Week 24, where a responder is 
defined as a participant who achieves IMACS TIS response at Week 24 and does not have a 
prohibited change in PM/DM medications (for details, see Appendix 1). A participant who 
has a prohibited change in PM/DM medications or discontinues treatment for any reason 
including COVID-19 infection but excluding other COVID-19 reasons is considered a non-
responder. 
 
Population-level summary: Odds ratio for the proportion of subjects achieving IMACS TIS 
response at Week 24 between the ustekinumab and placebo intervention groups. 
 
Intercurrent events (ICEs) and their corresponding strategies: 
ICEs 
Analysis Strategy for 
Addressing Intercurrent Events 
1. A prohibited change in PM/DM 
medications prior to Week 24  
Composite Strategy: A subject with this intercurrent 
event is considered as a non-responder after this 
event, the occurrence of this intercurrent event being 
captured in the variable definition. 
 
2. Discontinuation of study 
intervention for any reason, 
including COVID-19 infection but 
excluding other COVID-19 
reasons 
3. Discontinuation of study 
intervention due to COVID-19 
related reasons (excluding 
COVID-19 infection) 
Hypothetical Strategy: This intercurrent event is 
addressed with a hypothetical strategy, as if the 
intercurrent event would not have occurred. 


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For subjects experiencing multiple ICEs simultaneously, ICEs in categories 1- 2 will override 
ICE 3.  
5.2.2.2. 
Supplementary Estimands 
Supplementary Estimand 1 (Hypothetical Estimand) 
Estimand Scientific Question of Interest: If participants are compliant with the investigative 
therapy, what is the proportion of participants considered to have benefited from ustekinumab vs 
placebo for the pre-specified duration (24 weeks), administered together with the protocol allowed 
background standard-of-care medication? 
Hypothetical estimand is defined to support the primary estimand.  
 
Study intervention and Population: Same attributes as primary estimand. 
 
Variable: IMACS TIS binary response variable at Week 24, where a responder is defined as 
a subject who achieves IMACS TIS response at Week 24 
 
Summary Measure (Population-level summary): 
 Odds ratio for the proportion of subjects achieving IMACS TIS response at Week 24 between 
the ustekinumab and placebo treatment groups.  
 
Intercurrent events and their corresponding strategies: 
ICEs 
Analysis Strategy for 
Addressing Intercurrent Events 
1. A prohibited change in PM/DM 
medications prior to Week 24 
Hypothetical Strategy: This intercurrent 
event is addressed with a hypothetical 
strategy, as if the intercurrent event would 
not have occurred.  
2. Discontinuation of study intervention 
for any reason  
Supplementary Estimand 2 (Treatment Policy Estimand): 
Estimand Scientific Question of Interest: What is the proportion of participants considered to 
have benefited from ustekinumab vs placebo for the pre-specified duration (24 weeks), 
administered together with the protocol allowed background standard-of-care medication, 
regardless of initiation/adjustment of concomitant medication or discontinuation of study 
intervention? 
Treatment policy estimand is defined to support the primary estimand.  
 
Study intervention and Population: Same attributes as primary estimand. 
 
Variable: IMACS TIS binary response variable at Week 24, where a responder is defined as 
a subject who achieves IMACS TIS response at Week 24 


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 
Summary Measure (Population-level summary): 
 Odds ratio for the proportion of subjects achieving IMACS TIS response at Week 24 between 
the ustekinumab and placebo treatment groups.  
 
Intercurrent events and their corresponding strategies: 
ICEs 
Analysis Strategy for 
Addressing Intercurrent Events 
1. A prohibited change in PM/DM 
medications prior to Week 24 
Treatment Policy Strategy: Target the 
treatment effect regardless of whether or not 
this intercurrent event had occurred. 
2. Discontinuation of study intervention 
for any reason  
5.2.3. 
Analysis Methods 
In general, the statistical software SAS will be used for all data analysis.  
Data for primary analysis 
Analyses of the primary efficacy endpoint (IMACS TIS response at Week 24) will include subjects 
from all randomized analysis set and be based on their assigned treatment group regardless of the 
actual treatment received. Participants with ICEs 1-2 before Week 24 will be considered as non-
responders at Week 24, as defined in the primary estimand. For participants with ICE 3, data 
collected after this ICE will not be utilized in the analysis. Participants who don’t experience any 
ICEs could also have a missing value for the primary endpoint if missing the IMACS TIS response 
at Week 24 due to study withdrawal / missed visits or measurement.  
Primary analysis method 
To address the primary objective, logistic regression adjusting for 2 stratification factors (as per 
eCRF), disease subset (PM or DM) and baseline treatment level (glucocorticoid dose 
[≥0.5 mg/kg/day or <0.5 mg/kg/day of prednisolone or equivalent]), will be used to analyze the 
primary endpoint. If the above logistic regression model does not converge, the binomial test will 
be conducted without adjusting for the 2 stratification factors. The magnitude of the effect will be 
estimated by the odds ratio in IMACS TIS response rates between the ustekinumab and placebo 
groups, associated 95% confidence interval (CI) and the statistical significance of the difference 
in treatment effect will be provided. The study will be considered positive if the proportion of 
IMACS TIS responders in the ustekinumab group is significantly different from placebo (2-sided 
p-value is less than 0.05).  
The number and proportion of participants who achieve IMACS TIS composite response at Week 
24 will be summarized for each treatment group. In addition, the difference in proportions will 
also be provided.  


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Missing data handling rules for primary estimand 
Missing data of the primary endpoint at Week 24 Missing data handling rules 
Category 1: Data on or after ICE 3 will be assumed 
as missing 
Multiple imputation method under the 
assumption of missing at random, as 
described below. 
Category 2: After accounting for the ICEs, the 
remaining missing data due to operational or 
logistical issues related to COVID-19 
Category 3: After accounting for the ICEs, the 
remaining missing data due to any other reasons, 
except for operational or logistical issues related to 
COVID-19 
Non-responder imputation 
Multiple Imputation Procedure  
 
Step #1: Utilize a Markov Chain Monte Carlo (MCMC) approach to impute intermediate 
(non-monotone) missing data for all subjects.  Perform 500 imputations (seed=127501) to 
create 500 unique datasets now having monotone missing data patterns. As the endpoint is 
binary, if the imputed value is 0.5 or above, the binary value will set to 1 (indicating response) 
and if the imputed value is less than 0.5, the binary value will be set to 0 (indicating non-
response).  
 Step #2: Utilize a monotone logistic multiple imputation method with same covariates as in 
the primary analysis method to impute missing data in the 500 datasets with monotone 
missingness. Perform the imputation (seed=127501) 1 time for each dataset resulting in 500 
unique, imputed datasets (1 imputation on each of the 500 datasets created from the MCMC 
approach). 
 Step #3:  Analyze each of the 500 imputed datasets using the logistic regression model 
described as the primary analysis method. Utilize the SAS® MIANALYZE procedure to 
combine the 500 analysis results. 
5.2.3.1. 
Subgroup Analyses 
Subgroup analysis of the primary endpoint based on stratification factors (as per eCRF) will be 
performed. Subgroup analysis of the primary endpoint by other selected baseline characteristics 
may be presented when the number of subjects in the subset permits (at least 15 subjects for each 
treatment group within a subset):  
 
Disease subset (PM/DM)  
 
Baseline treatment level of glucocorticoid dose (≥0.5 mg/kg/day of prednisolone or equivalent, 
or <0.5 mg/kg/day of prednisolone or equivalent) 
 
Age group (<65 years and ≥65 years) 
 
BMI (<18.5 kg/m2, 18.5-<25.0 kg/m2, ≥25.0 kg/m2) 


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 
Sex (male, female) 
 
ILD at baseline (Yes, No) 
The primary estimand (Section 5.2.2) will be used for these subgroup analyses and the same 
analysis methods defined in this section used for primary estimand will be applied. For subgroup 
analyses, proportion of IMACS TIS response in each treatment group, odds ratio and 
corresponding 95% CI will be presented. However, p-values for the comparison across treatment 
groups for the subgroups will not be presented. In addition, the difference in proportions will also 
be provided. 
5.2.3.2. 
Sensitivity Analysis 
To evaluate the robustness of the primary endpoint analysis, the following sensitivity analyses will 
be performed for primary estimand. 
5.2.3.2.1. 
Sensitivity Analysis 1  
Similar to the primary analysis, however baseline continuous glucocorticoid dose (as per eCRF) 
will be used instead of baseline treatment level (glucocorticoid dose [≥0.5 mg/kg/day or 
<0.5 mg/kg/day of prednisolone or equivalent]) as a covariate in logistic regression model. 
5.2.3.2.2. 
Sensitivity Analysis 2  
Similar to the primary analysis, however baseline glucocorticoid daily dose (mg) as categorized 
by (<=15, >15) will be used instead of baseline treatment level (glucocorticoid dose 
[≥0.5 mg/kg/day or <0.5 mg/kg/day of prednisolone or equivalent]) as a covariate in logistic 
regression model. 
5.2.3.3. 
Supplementary Analyses 
5.2.3.3.1. 
Supplementary Analysis 1 (Hypothetical Estimand) 
This supplementary analysis for the primary endpoint is based on the Supplementary Estimand 1 
(Hypothetical Estimand) defined in Section 5.2.2.2. Data after intercurrent events will not be 
utilized in the analysis, and together with missing data, these data will be imputed using multiple 
imputation methods (eg, multiple imputation utilized to create 500 distinct datasets, logistic 
regression similar to the primary analysis on each of the 500 imputed datasets and results combined 
to make the final inference). The imputation model will include treatment group, disease subset 
(PM or DM) and baseline treatment level (glucocorticoid dose [≥0.5 mg/kg/day or <0.5 mg/kg/day 
of prednisolone or equivalent]) (as per eCRF) as covariates. 
5.2.3.3.2. 
Supplementary Analysis 2 (Treatment Policy Estimand) 
This supplementary analysis for the primary Supplementary Estimand 2 (Treatment Policy 
Estimand) defined in Section 5.2.2.2. For participants who experience intercurrent events through 
Week 24, the treatment policy strategy will be used, and the similar analysis as primary estimand 
will be performed using observed data regardless of intercurrent events without imputation.  


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5.3. 
Secondary Endpoints 
The secondary endpoints are the following:  
1. Mean change from baseline in Functional Index-2 (FI-2) at Week 24 
2. The proportion of participants who experience disease worsening through Week 24 based on 
consensus criteria for worsening 
3. Mean change from baseline in Manual Muscle Testing (MMT)-8 at Week 24 
4. Mean change from baseline in PhGA of disease activity at Week 24 
5. Mean change from baseline in Extramuscular Assessment (Myositis Disease Activity 
Assessment Tool [MDAAT]-Extramuscular Global Assessment) at Week 24 
6. Mean change from baseline in muscle enzymes (creatine kinase [CK], alanine 
aminotransferase [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH], 
and aldolase) at Week 24 
5.3.1. 
Definition 
See Section 5.2.1 for the definitions of Physician Global Activity – Visual Analogue Scale, 
Extramuscular Assessment (MDAAT) and Muscle Enzymes.  
5.3.1.1. 
Functional Index-2 
The FI-2 is a functional outcome developed for patients with adult PM or DM to assess muscle 
endurance in 7 muscle groups. Each muscle group is scored as the number of correctly performed 
repetitions with 60 or 120 maximal number of repetitions depending on muscle group. The FI-2 is 
performed unilaterally, preferably on the participant’s dominant side for muscle groups of shoulder, 
hip, and step test. The FI-2 has been validated as to content and construct validity and intra- and 
interrater reliability. A total score will not be calculated. For those muscle groups which can be 
tested bilaterally, only one side will be tested for each visit. Sides used for post-baseline 
assessments should be consistent with that of baseline. The values at the visits with different side 
from baseline for assessment will be considered as missing.  
Two scales: Repetitions, % / Max Repetitions will be analyzed for each of the following FI-2 item, 
separately: shoulder flexion (0-60), shoulder abduction (0-60), head lift (0-60), hip flexion (0-60), 
step test (0-60), heel lift (0-120), toe lift (0-120). 
5.3.1.2. 
Disease Worsening 
Criteria for disease worsening in a clinical trial were based on international consensus guideline 
developed by the IMACS. The worsening of disease is defined as 1 of the following criteria;  
1. Worsening of the Physician Global Activity by ≥2 cm on a 10-cm VAS and worsening of 
findings of MMT-8 by ≥20% from baseline  
2. Worsening of MDAAT-global extramuscular organ disease activity (a composite of 
constitutional, cutaneous, skeletal, gastrointestinal, pulmonary, and cardiac activity) by 
≥2 cm on a 10-cm VAS from baseline 


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3. Worsening of any 3 of 6 IMACS core set activity measures by ≥30% from baseline 
5.3.1.3. 
Manual Muscle Testing 
Manual Muscle Testing is a partially validated tool to assess muscle strength. A 0 to 10 point scale 
is proposed for use. The MMT-8 is proposed for studies which evaluate 8 muscle groups whose 
subsets are selected based on internal/interrater consistency and reliability. The MMT-8, which 
take less time and involve less patient effort compared to Total MMT, has results comparable to 
Total MMT in terms of responsiveness, content validity, and construct validity. Analysis Methods 
5.3.2. 
Estimands 
5.3.2.1. 
Main Estimand for Secondary Binary Endpoint 
The following describes the attributes of the estimand for the secondary binary endpoint (#2) 
defined in Section 5.3.1. 
 
Study intervention and Population: Same attributes as primary estimand for primary 
endpoint 
 
Variable/endpoint and Population-level summary: 
Estimand 
Variable (Endpoint) 
Population-level summary 
Secondary 
Endpoint #2 
Primary 
Estimand 
Binary variable, Disease worsening 
through Week 24 based on 
consensus criteria for worsening  
Difference in percentage of subjects 
who experienced disease worsening 
through Week 24 based on consensus 
criteria for worsening between 
ustekinumab group and placebo. 
 
Intercurrent events (ICEs) and their corresponding strategies: 
ICEs 
Analysis Strategy for 
Addressing Intercurrent Events 
1. A prohibited change in PM/DM 
medications prior to Week 24 
Composite Strategy: A subject with this intercurrent 
event is considered as experiencing disease 
worsening after this event, the occurrence of this 
intercurrent event being captured in the variable 
definition. 
 
2. Discontinuation of study 
intervention for any reason, 
including COVID-19 infection but 
excluding other COVID-19 
reasons 
3. Discontinuation of study 
intervention due to COVID-19 
related reasons (excluding 
COVID-19 infection) 
Treatment Policy Strategy: Target the treatment 
effect regardless of whether or not this intercurrent 
event had occurred. 
For subjects experiencing multiple ICEs simultaneously, ICEs in categories 1- 2 will override 
ICE 3.  


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5.3.2.2. 
Main Estimands for Secondary Continuous Endpoints 
The following describes the attributes of the estimands for the secondary continues endpoints (#1, 
3, 4, 5, 6) defined in Section 5.3.1. 
 
Study intervention and Population: Same attributes as primary estimand for primary 
endpoint 
 
Variable/endpoint and Population-level summary: 
Estimand 
Variable (Endpoint) 
Population-level summary 
Secondary 
Endpoint #1 
Primary 
Estimand 
Change from baseline in Functional 
Index-2 (FI-2) at Week 24  
Difference in mean change from 
baseline in Functional Index-2 (FI-2) at 
Week 24 between ustekinumab group 
and placebo 
Secondary 
Endpoint #3 
Primary 
Estimand 
Change from baseline in Manual 
Muscle Testing (MMT)-8 at Week 
24 
Difference in mean change from 
baseline in Manual Muscle Testing 
(MMT)-8 at Week 24 
Secondary 
Endpoint #4 
Primary 
Estimand 
Change from baseline in PhGA of 
disease activity at Week 24 
Difference in mean change from 
baseline in PhGA of disease activity at 
Week 24 
Secondary 
Endpoint #5 
Primary 
Estimand 
Change from baseline in 
Extramuscular Assessment 
(Myositis Disease Activity 
Assessment Tool [MDAAT]-
Extramuscular Global Assessment) 
at Week 24 
Difference in mean change from 
baseline in Extramuscular Assessment 
(Myositis Disease Activity Assessment 
Tool [MDAAT]-Extramuscular Global 
Assessment) at Week 24 
Secondary 
Endpoint #6 
Primary 
Estimand 
Change from baseline in muscle 
enzymes (creatine kinase [CK], 
alanine aminotransferase [ALT], 
aspartate aminotransferase [AST], 
lactate dehydrogenase [LDH], and 
aldolase) at Week 24 
Difference in mean change from 
baseline in muscle enzymes (creatine 
kinase [CK], alanine aminotransferase 
[ALT], aspartate aminotransferase 
[AST], lactate dehydrogenase [LDH], 
and aldolase) at Week 24 


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 
Intercurrent events (ICEs) and their corresponding strategies: 
ICEs 
Analysis Strategy for 
Addressing Intercurrent Events 
1. A prohibited change in PM/DM 
medications prior to Week 24 
Composite Strategy: Any value collected after 
experiencing the ICEs will be replaced by the 
baseline observation. 
 
2. Discontinuation of study 
intervention for any reason, 
including COVID-19 infection but 
excluding other COVID-19 
reasons 
3. Discontinuation of study 
intervention due to COVID-19 
related reasons (excluding 
COVID-19 infection) 
Hypothetical Strategy: This intercurrent event is 
addressed with a hypothetical strategy, as if the 
intercurrent event would not have occurred. 
For subjects experiencing multiple ICEs simultaneously, ICEs in categories 1- 2 will override 
ICE 3. 
5.3.3. 
Analysis Methods 
Unless otherwise specified, the analysis population will be the all randomized analysis set defined 
in Section 2.3.2. P-values will be provided without adjusting multiplicity for secondary endpoints 
analyses. 
Binary endpoint 
Binary endpoint (secondary endpoint #2) will be based upon the primary estimand defined in 
Section 5.3.2, and will be analyzed using the same approach as the primary analysis for the primary 
endpoint: Logistic regression adjusting for 2 stratification factors (as per eCRF), disease subset 
(PM or DM) and baseline treatment level (glucocorticoid dose [≥0.5 mg/kg/day or <0.5 mg/kg/day 
of prednisolone or equivalent]) as described in Section 5.2.3 will be used. Participants with ICEs 
1-2 before Week 24 will be considered as experiencing disease worsening from the point of ICE 
forward. For participants with ICE 3, observed data will be used and no imputation will be applied. 
Continuous endpoints 
Continuous endpoints (secondary endpoints #1, 3, 4, 5, 6) will be based upon the primary 
estimands defined in Section 5.3.2 and will be analyzed using a Mixed Model Repeated Measures 
(MMRM) Model to test the difference between a ustekinumab group and placebo group and adjust 
for missing data. The models will include treatment, disease subset (PM or DM), baseline 
treatment level (glucocorticoid dose [≥0.5 mg/kg/day or <0.5 mg/kg/day of prednisolone or 
equivalent]) (as per eCRF), visit, and an interaction of treatment and visit as fixed effects. The 
within-subject covariance between visits will be estimated via an unstructured variance-covariance 
matrix. In case of convergence problems, the compound symmetry structure will be used.  The 
Kenward-Roger method will be used for approximating the denominator degrees of freedom. 


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The model will include all available data from two treatment groups through Week 24. The 
treatment difference between ustekinumab group and placebo group will be estimated by the 
difference in the least squares means (LSmeans). The 95% confidence interval (CI) for the 
differences in LSmeans and p-values will be calculated based on MMRM.  
Residuals from the primary models will be plotted against the predicted values and a QQ plot of 
the residuals versus the expected quantiles of the standard normal distribution will be presented to 
check whether there’s any irregular trend of the residuals.  
For participants who don’t experience any ICEs, missing data will be imputed by baseline 
observation. 
5.4. 
Other Efficacy Variable(s) 
PM/DM Disease Activity 
 
The proportion of participants who achieve Minimal Improvement in IMACS TIS over time  
 
Mean change from baseline in PhGA of disease activity over time 
 
The proportion of participants with improvement in PhGA of disease activity over time 
 
Mean change from baseline in MMT-8 over time 
 
The proportion of participants with improvement in MMT-8 over time 
 
Mean change from baseline in Muscle enzymes (CK, ALT, AST, LDH, and aldolase) over 
time 
 
The proportion of participants with improvement in Muscle enzymes (CK, ALT, AST, LDH, 
and aldolase) over time 
 
Mean change from baseline in MDAAT over time  
 
The proportion of participants with improvement in MDAAT over time  
 
Mean change from baseline in FI-2 over time 
 
The proportion of participants who reduce the use of systemic glucocorticoid from baseline at 
Week 24 
 
The proportion of participants who reduce the use of systemic glucocorticoid from baseline 
and achieve Minimal Improvement in IMACS ITS at Week 24 
 
Time to worsening in participants who experience disease worsening through Week 24 based 
on consensus criteria for worsening 
 
The proportion of participants who achieve Moderate Improvement in IMACS TIS over time 
 
The proportion of participants who achieve Major Improvement in IMACS TIS over time 
 
IMACS TIS score over time 
Patient-reported Outcomes 
 
Mean change from baseline in Patient Global Activity (PtGA) of disease activity at Week 24 


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 
The proportion of participants with improvement in PtGA of disease activity at Week 24 
 
Mean change from baseline in Physical Function (Health Assessment Questionnaire 
Disability Index [HAQ-DI]) at Week 24 
 
The proportion of participants with improvement in Physical Function (HAQ-DI) at Week 24 
 
Mean change from baseline in 36-item short form (SF-36) including individual domains and 
component summary (PCS, MCS) scores at Week 24 
 
The proportion of participants with improvement in SF-36 including individual domains and 
component summary (PCS, MCS) scores at Week 24 
 
Mean change from baseline in PtGA of disease activity over time 
 
The proportion of participants with improvement in PtGA of disease activity over time 
 
Mean change from baseline in Physical Function (HAQ-DI) over time 
 
The proportion of participants with improvement in Physical Function (HAQ-DI) over time 
 
Mean change from baseline in SF-36 including individual domains and component summary 
(PCS, MCS) scores over time 
 
The proportion of participants with improvement in SF-36 including individual domains and 
component summary (PCS, MCS) scores over time 
5.4.1. 
Definition 
5.4.1.1. 
PM/DM Disease Activity Endpoints 
See Section 5.2.1 for the definitions of related endpoints.  
Minimal Improvement in IMACS TIS: Total improvement score of IMACS TIS ≥20 
Improvement in PhGA of disease activity: Improvement score of PhGA of disease activity ≥7.5 
or improvement based on absolute percentage change > 5% 
Improvement in MMT-8: Improvement score of MMT-8≥10 or improvement based on absolute 
percentage change > 2% 
Improvement in Muscle enzymes (CK, ALT, AST, LDH, and aldolase): For most abnormal 
enzyme at baseline, improvement score of enzyme ≥2.5 or improvement based on absolute 
percentage change > 5%. The most abnormal enzyme is determined by having the greatest 
baseline value divided by its upper limit of normal. 
Improvement in MDAAT: Improvement score of Extramuscular Assessment (MDAAT) ≥7.5 or 
improvement based on absolute percentage change > 5% 
Reduction of systemic glucocorticoid from baseline: The subject is considered as successful 
reduction if the latest nonmissing daily glucocorticoid dose before or on Study day 168 can be 
tapered as Table 8: 


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Table 8: 
Glucocorticoid Tapering Schedule (Daily Dose [mg] of Prednisolone or Equivalent) 
Week 0 
Week 2 
Week 4 
Week 6 
Week 8 
Week 10 
Week 12 
Week 14 Week 16 
60 
50 
40 
35 
30 
25 
20 
15 
12.5 
50 
40 
35 
30 
25 
20 
15 
12.5 
10 
40 
35 
30 
25 
20 
15 
12.5 
10 
9 
30 
25 
20 
15 
12.5 
10 
9 
8 
7 
20 
15 
12.5 
10 
9 
8 
7 
6 
5 
15 
12.5 
10 
9 
8 
7 
6 
5 
5 
12.5 
10 
9 
8 
7 
6 
5 
5 
5 
10 
9 
8 
7 
6 
5 
5 
5 
5 
5.4.1.2. 
Patient-reported Outcomes Endpoints 
See Section 5.2.1 for the definitions of Patient Global Activity-VAS and Functional Assessment 
(HAQ-DI). 
Improvement in PtGA of disease activity: Improvement score of PtGA of disease activity ≥2.5 
or improvement based on absolute percentage change > 5% 
Improvement in Physical Function (HAQ-DI): Improvement score of HAQ-DI ≥5  or 
improvement based on absolute percentage change > 5% 
36-item Short Form 
The SF-36 consists of 8 subscales: limitations in physical functioning due to health problems, 
limitations in usual role activities due to physical health problems, bodily pain, general mental 
health (psychological distress and well-being), limitations in usual role activities due to personal 
or emotional problems, limitations in social functioning due to physical or mental health problems, 
vitality (energy and fatigue), and general health perception. These subscales are scored from 0 to 
100 with higher scores indicating better health. Another algorithm yields 2 summary scores, the 
Physical Component Summary (PCS) and the Mental Component Summary (MCS). 
Table 9: 
SF-36 subscales and items 
Subscales 
Items 
Physical functioning 
3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j 
Role limitations due to physical health 
4a, 4b, 4c, 4d 
Role limitations due to emotional problems 
5a, 5b, 5c 
Energy/ fatigue 
9a, 9e, 9g, 9i 
Emotional well being 
9b, 9c, 9d, 9f, 9h 
Social functioning 
6, 10 
Pain 
7, 8 
General health 
1, 11a, 11b, 11c, 11d 
 
Improvement in SF-36: Improvement of 5 points in any of the subscales or 2.5 points of the 
component score 


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5.4.2. 
Analysis Methods 
All other efficacy endpoints will be descriptively summarized by treatment groups. Treatment 
comparisons will be performed at Week 24. Nominal p values and 95% CI for the difference 
between ustekinumab group and placebo group will be provided. No treatment comparison will be 
performed after Week 24.  
5.4.2.1. 
Analyses from Week 0 through Week 24 
Binary Endpoints 
The primary estimand approaches, and the corresponding analysis methods specified for the 
primary endpoint in Section 5.2.2, 5.2.3, will be applied to binary endpoints analysis at Week 24 
as the main estimand. 
For participants who experience intercurrent events before Week 24 as described in Section 5.3.2.1, 
the treatment policy strategy will be applied to binary endpoints that will be summarized over time 
through Week 24. The analysis will be performed based on observed data regardless of intercurrent 
events without imputation. 
Continuous Endpoints 
The primary estimand approaches, and the corresponding analysis methods specified for the 
secondary endpoint in Section 5.3.2.2, 5.3.3, will be applied to continuous endpoints analysis at 
Week 24 as the main estimand. 
For participants who experience intercurrent events before Week 24 as described in Section 5.3.2.2, 
the treatment policy strategy will be applied to continuous endpoints that will be summarized over 
time through Week 24. The analysis will be performed based on observed data regardless of 
intercurrent events without imputation. 
 
Time to Event Endpoint The following describes the attributes of the estimand for time to event 
endpoint.  
 
Study intervention and Population: Same attributes as primary estimand for primary 
endpoint 
 
Variable/endpoint: Time to event through Week 24, where the time to event is defined as 
time to disease worsening based on consensus criteria for worsening or time to any ICE in 
category 1 or 2.  
 
Summary Measure (Population-level summary): Hazard ratio of ustekinumab group and 
placebo 
 
Intercurrent events (ICEs) and their corresponding strategies: 


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ICEs 
Analysis Strategy for 
Addressing Intercurrent Events 
1. A 
prohibited 
change 
in 
PM/DM 
medications prior to Week 24 
Composite Strategy: A participant with 
this intercurrent event is considered to 
experience disease worsening at the time of 
this event. 
2.  Discontinuation of study intervention 
for reasons: adverse event, death, 
prohibited medication or lack of efficacy 
3.  Discontinuation of study intervention 
for remaining reasons 
Treatment Policy Strategy: Target the 
treatment effect regardless of whether or not 
this intercurrent event had occurred. 
For subjects experiencing multiple ICEs simultaneously, ICEs in categories 1- 2 will override ICE 
3. 
For time to event endpoint, treatment comparison in time to worsening through Week 24 will be 
done using a log-rank test to report p-values. The hazard ratio and its associated 95% CI will be 
provided using the Cox proportional hazards model by adjusting for 2 stratification factors. The 
survival curves will be estimated using Kaplan-Meier estimates.   
5.4.2.2. 
Analyses from Week 24 through Week 52/72/88 
No imputation will be performed for missing data (eg, lost to follow up, missed study visit) and 
the values will remain as missing.  
6. 
SAFETY 
All safety analyses will be based on the safety analysis set as described in Section 2.3.3 above 
based on actual treatment received, unless otherwise specified. 
For all continuous safety variables, descriptive statistics will include the N, mean, standard 
deviation, median, minimum, and maximum. Categorical variables will be summarized using 
frequency counts and percentages. 
The general definitions for analysis periods and treatment groups described in Section 2.4 and 
general data cut-off rules for Week 24/52/72 weeks described in Section 2.5 are applicable for 
safety analyses.  
6.1. 
Adverse Events 
The verbatim terms used in the CRF by investigators to identify adverse events will be coded using 
the Medical Dictionary for Regulatory Activities (MedDRA). Any AE occurring at or after the 
initial administration of study agent is considered to be treatment emergent. If the event occurs on 
the day of the initial administration of study agent, and either event time or time of administration 
are missing, then the event will be assumed to be treatment emergent. If the event date is recorded 
as partial or completely missing, then the event will be considered to be treatment emergent unless 


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it is known to be prior to the first administration of study agent based on partial onset date or 
resolution date. All reported treatment-emergent adverse events will be included in the analysis.  
For each adverse event, the number and percentage of subjects who experience at least 
1 occurrence of the given event will be summarized by treatment group. 
Summary tables will be provided for treatment-emergent adverse events by defined analysis 
periods in Section 2.4 (from Week 0 through Week 24, from Week 24 through Week 52/72/88): 
 
TEAEs 
 
Serious TEAEs  
 
TEAEs leading to discontinuation of study agent/termination of study participation 
 
TEAEs by severity (mild, moderate, severe) 
 
TEAEs reasonably related to study agent 
 
Treatment emergent infections  
 
Treatment emergent infusion reactions 
 
Treatment emergent injection-site reactions 
 
Treatment emergent adverse events of special interest 
A reasonably related AE is defined as any event with the relationship to study agent as ‘very likely’, 
‘probable’, or ‘possible’ on the AE eCRF page or if the relationship to study agent is missing.  
Opportunistic infection (ie, infection by an organism that normally is not pathogenic or does not 
cause invasive infection in immunocompetent hosts), case of active TB, ILD, or malignancy are 
considered as adverse events of special interest. 
Summaries for above treatment-emergent adverse events from Week 0 to Week 52/72/88 will also 
be provided using patient-year method.  
In addition to the summary tables, listings will be provided for subjects who: 
 
Had Serious TEAEs 
 
Had TEAEs leading to discontinuation of study agent/termination of study participation 
 
Any deaths 
Since safety should be assessed relative to exposure and follow-up, all AE summary tables will 
summarize the average weeks of follow-up for each treatment group. 
6.2. 
Clinical Laboratory Tests 
Descriptive statistics and graphical displays will be presented for selected chemistry, hematology, 
and urinalysis (pH and specific gravity) laboratory tests at scheduled time points. 
Change from baseline over time will be summarized for selected chemistry, hematology, and 
urinalysis (pH, and specific gravity) tests and displayed by treatment group.  


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 
Hematology: Hemoglobin, Hematocrit, Red blood cell (RBC) count, White blood cell (WBC), 
Platelet count, Lymphocytes, Monocytes, Neutrophils, Eosinophils, Basophils 
 
Chemistry: Albumin, Alkaline phosphatase, Alanine aminotransferase (ALT/SGPT), 
Aspartate aminotransferase (AST/SGOT), Total carbon dioxide (CO2), Total bilirubin, BUN, 
Calcium, Chloride, Creatinine, Glucose, Potassium, Total protein, Sodium, CK, Lactic acid 
dehydrogenase (LDH), Aldolase  
A box plot of change from baseline over time will be provided for CK, LDH, Aldolase, ALT, AST 
The National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE; 
version 4.0) will be used in the summary of laboratory data (Grade 0-4).  The proportion of subjects 
with post-baseline values by maximum toxicity grade for clinical laboratory tests will be 
summarized by treatment group. Shift summaries from baseline laboratory value to the worst on-
treatment grade in chemistry and hematology tests with NCI toxicity grades will be presented. 
Subjects with toxicity grades ≥ 2 will be listed. 
For those labs without NCI toxicity grades, the incidence of markedly abnormal laboratory values 
will be presented by treatment group.  Additionally, the markedly abnormal laboratory values will 
be listed.  Markedly abnormal criteria are defined as Table 10: 
Table 10: 
Markedly abnormal laboratory criteria 
Item 
Criterion of markedly abnormal criteria 
Hematology & Differential panel 
 
Hemoglobin 
≤10݃/݀ܮ 
WBC 
Out of normal range 
Neutrophils 
Out of normal range 
Lymphocytes 
Out of normal range 
Chemistry panel 
 
ALT 
≥3 × ܷܮܰ 
AST 
≥3 × ܷܮܰ 
LDH 
≥3 × ܷܮܰ 
Creatinine 
≥1.5 × ܷܮܰ 
Glucose 
≥300݉݃/݀ܮ 
 
Laboratory results from local lab will be excluded from summary analyses, but only included in 
the listings. 
6.3. 
Vital Signs and Physical Examination Findings 
Continuous vital sign parameters including temperature, respiratory rate, weight, pulse, blood 
pressure (systolic and diastolic) and SpO2 will be summarized at each assessment time point. 
Change from baseline will be summarized by visit and treatment group. Descriptive statistics 
(mean, standard deviation, median, minimum and maximum) will be presented. 
Incidence of clinically important vital signs while on treatment, as defined in Table 11, will be 
summarized for subjects who had a baseline assessment and at least 1 postbaseline assessment for 
that vital sign. A listing of subjects with clinically important vital signs will be presented, along 
with a listing of all vital sign measurements. 


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Table 11: 
Clinically Important Vital Signs 
Vital Sign 
Criteria 
Pulse 
>120 bpm and with >15 bpm increase from baseline 
 
<50 bpm and with >15 bpm decrease from baseline 
Systolic blood pressure 
>180 mm Hg and with >20 mm Hg increase from baseline 
 
<90 mm Hg and with >20 mm Hg decrease from baseline 
Diastolic blood pressure 
>105 mm Hg and with >15 mm Hg increase from baseline 
 
<50 mm Hg and with >15 mm Hg decrease from baseline 
Temperature 
>38oC  
Respiratory rate 
>24 breaths per minute 
Weight 
>10% kg increase from baseline 
 
>10% kg decrease from baseline 
SpO2 
<90% 
 
Vistal sign results from remote visits will be excluded from summary analyses, but only included 
in the listings. 
6.4. 
Electrocardiogram 
The interpretation of the ECGs as determined by a qualified physician (investigator or qualified 
designee) will be displayed by the number and percentage of subjects meeting the normality 
criteria. The interpretation will be summarized over time by treatment group. 
A listing of clinically relevant ECG abnormalities will also be provided. 
6.5. 
Chest CT Scan and X-Ray 
The interpretation of chest high-resolution CT scan and X-Ray will be summarized in number and 
percentage of subjects meeting the normality criteria over time by treatment group. 
Listing of clinically relevant CT and X-Ray abnormalities will also be provided. 
6.6. 
Pulmonary Function Test 
Pulmonary function test (PFT) including vital capacity [VC], forced vital capacity [FVC], 
diffusing capacity of the lungs for carbon monoxide [DLCO], maximal inspiratory pressure [MIP], 
maximal expiratory pressure [MEP], and maximal voluntary ventilation [MVV] will be 
summarized at each assessment time point. Change from baseline will be summarized by visit and 
treatment group. Descriptive statistics (mean, standard deviation, median, minimum and 
maximum) will be presented. A listing of all pulmonary function test will be provided. 
6.7. 
COVID-19 Summaries 
Included in the adverse event summaries discussed in this section will be events related to COVID-
19.  These will be identified and coded using the MedDRA coding guidance for COVID-19.  
Summary tables may be provided for: 
 
COVID-19 related TEAEs 


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 
Selected TEAEs of interest related to COVID-19 
 
Selected serious TEAEs of interest related to COVID-19 
In addition to the summary tables, the following may be listed by subject: 
 
TEAEs related to COVID-19 
 
Serious TEAEs related to COVID-19 
 
Deaths related to COVID-19 
7. 
PHARMACOKINETICS/PHARMACODYNAMICS 
7.1. 
Pharmacokinetics 
Blood samples will be collected to measure for serum ustekinumab concentration at the specified 
visits as shown in the Time and Events Schedule in protocol. PK analyses will be performed on 
the PK analysis set (see Section 2.3.4) and summarized from Week 0 to Week 24/52/72/88 for 
Week 24 DBL, Week 52 DBL, Week 72 DBL and Week 88 DBL respectively.  
Serum ustekinumab concentrations summary will be based on the observed data; therefore, no 
imputation for missing concentration data will be performed. All participants and samples 
excluded from the analysis will be clearly documented (eg, unknown or unreliable drug intake 
information). 
All PK data including actual sampling time will be listed. All serum ustekinumab concentrations 
below the lower limit of quantification (LLOQ) or missing data will be labeled as such in the 
concentration data listing or statistical analysis system dataset. 
Descriptive statistics (N, mean, SD, median, range, CV (%), geometric mean and IQ range) will 
be used to summarize serum ustekinumab concentrations by intervention group (ustekinumab or 
placebo- >ustekinumab) at each sampling time point. 
For descriptive statistics of serum ustekinumab concentrations, the following data handling rules 
will be applied; 
 
Participants will be excluded from the descriptive statistics if their data do not allow for 
accurate assessment of the PK. In particular, all serum concentration data will be excluded, 
from the time of occurrence, data collected for participants who 1) discontinue ustekinumab, 
2) skip an infusion or injection, 3) receive an incomplete infusion or injection, 4) receive an 
incorrect infusion or injection, 5) receive an additional infusion or injection, and/or 6) receive 
commercial ustekinumab. Exclusion data from the descriptive statistics due to such inadequate 
administration will be specified by PK analyst. In addition, PK samples taken outside the 
scheduled visit window (±7 days) will be excluded from the descriptive statistics. 
 
Data of each concentration with no information about the sampling date and time and/or the 
drug administration (time and dosage) will be excluded from descriptive statistics. 
 
Serum ustekinumab concentrations below the LLOQ will be imputed as zero in the summary 
statistics. 


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 
When more than half (>50%) of the serum concentrations of ustekinumab are below 
quantification limit (BQL) at each scheduled time point, mean, median and minimum will be 
shown as ‘BQL’, and SD and %CV will be shown as ‘NC’ (not calculated). IQ range 
[minimum (25% quartile) and maximum (75% quartile)] will be shown as ‘BQL-NC’. 
Maximum observed value will be presented as maximum. 
 
When all serum concentration data are BQL at each scheduled time point, mean and median 
will be reported as ‘BQL’; SD and %CV are reported as ‘NC’ (not calculated); IQ range, 
maximum and minimum will be reported as ‘BQL’. 
 
When the number of serum concentrations data of ustekinumab at each scheduled time point 
is less than or equal to 2, N, mean and median will be calculated, and SD and %CV will be 
shown as ‘NC’. IQ range [minimum (25% quartile) and maximum (75% quartile)] will be 
shown as ‘NC-NC’. Minimum and maximum will be shown as ‘NC’ (number of quantifiable 
data=1) or will be reported as observed including BQL (number of quantifiable data =2). 
 
At the time point where no observation is obtained, ‘NA (not applicable)’ is reported. 
 
Sampling time at Week 0 pre-dose will be substituted with “0”. The data point which means 
of serum ustekinumab concentration is BQL will be treated as LLOQ value (eg, 
0.16880 μg/mL) in graph. 
Analysis period 
See Section 2.4. 
Table 
From Week 0 through Week 24, serum ustekinumab concentration in ustekinumab arm will be 
summarized in table. From Week 24 through each timepoint (Week 52/72/88), serum ustekinumab 
concentration in all participants will be summarized in table by intervention group (ustekinumab 
or placebo- >ustekinumab). In addition, to assess the impact of weight-based IV dosing (~6 mg/kg), 
serum ustekinumab concentrations from Week 0 to Week 8 in ustekinumab group and from Week 
24 to Week 32 in placebo->ustekinumab group will be summarized in a separate table by weight- 
based dose category (See Section 1.2). To assess the impact of body weight on maintenance 
therapy (90 mg SC q8w), serum ustekinumab concentrations from Week 0 through each timepoint 
(Week 24/52/72/88) in ustekinumab group by body weight quartile will summarized. 
Figure 
Serum ustekinumab concentrations data may be displayed graphically, such as median (±inter 
quartile range, IQR) of serum ustekinumab concentrations over time by intervention group by the 
following subgroups: 
 
Median (±IQR) of serum ustekinumab concentration time profiles through Week 24 (in linear 
and semi-log scales) with nominal sampling time will be presented in figure. 
 
Median (±IQR) of serum ustekinumab concentration time profiles through each timepoints 
(Week 52/72/88) (in linear and semi-log scales) with nominal sampling time will be presented 
in figure. 


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Listing 
The elapsed time[day] from last dosing to next PK sampling point will be described in listing. 
Other 
If sufficient data are available, then population PK analysis using serum concentration-time data 
of ustekinumab will be performed using nonlinear mixed-effects modeling. Details will be given 
in a population PK analysis plan and the results of the analysis will be presented in a separate 
report. 
7.2. 
Immunogenicity Analyses 
Blood samples will be collected for the detection of antibodies to ustekinumab at the specified 
visits as shown in the Time and Events Schedule in protocol. Immunogenicity analyses will be 
based on the immunogenicity analysis set (see Section 2.3.5) and summarized from Week 0 to 
Week 24/52/72/88 for Week 24 DBL, Week 52 DBL, Week 72 DBL and Week 88 DBL 
respectively.  
“Sample ADA status” and sample titer as well as the cumulative “subject ADA status” and peak 
titer through the visit will be coded and provided by the bioanalytical group.  
“Subject ADA status” is defined as below. 
 
Participants with treatment-emergent ADA positive to ustekinumab include 
 
Participants with treatment-induced antibodies to ustekinumab  
 
Participants with treatment-boosted antibodies to ustekinumab 
 
Participants with treatment-induced antibodies to ustekinumab have a negative sample prior 
to administration and at least one positive sample after administration 
 
Participants with treatment-boosted antibodies to ustekinumab have a positive sample prior to 
administration and at least one positive sample after administration with increase in titer over 
baseline 
Incidence of antibody status (Subject with baseline positive samples, treatment-emergent ADA 
positive to ustekinumab, treatment-emergent ADA negative to ustekinumab), the maximum titers 
of anti-ustekinumab antibodies and incidence of Neutralizing antibodies (NAb) from Week 0 
through each timepoint (Week 24/52/72/88) will be summarized by intervention groups. 
The summary of following endpoints (ustekinumab concentration, the proportion of participants 
who achieve IMACS TIS minimal improvement at Week 24, and injection site reactions status) 
will be presented by intervention group by treatment-emergent antibodies to ustekinumab status 
(positive or negative).  
1. Descriptive statistics (N, mean, SD, median, range, and IQ range) and incidence (N, %) of 
the relationship between treatment-emergent antibodies to ustekinumab status (positive or 
negative) and ustekinumab concentration from Week 0 through each timepoint (Week 
24/52/72/88) 


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2. Participants in response (N, %) for treatment-emergent antibodies to ustekinumab status 
(positive or negative) and efficacy endpoints (The proportion of participants who achieve 
IMACS TIS minimal improvement at Week 24) 
3. Incidence (N, %) between treatment-emergent antibodies to ustekinumab status (positive or 
negative) and injection site reactions status from Week 0 through each timepoint (Week 
24/52/72/88) 
7.3. 
Pharmacokinetic/Pharmacodynamic Relationships 
If data permit, the relationship between serum ustekinumab concentration (PK data) and efficacy 
measures for primary and selected key secondary endpoints (PD data) may be analyzed tabularly 
or graphically (PK/PD analysis). PK/PD analysis will be performed on the PK/PD analysis set (see 
Section 2.3.7), defined as below: all subjects (including participants who received placebo 
intervention) who have at least 1 paired PK and PD data collected at same time point needed for 
each PK/PD analysis. If participants who receive placebo intervention and have no concentration 
data, serum ustekinumab concentrations will be imputed as zero. 
Following PD data will be used in PK/PD analysis: International Myositis Assessment and Clinical 
Studies Total Improvement Score (IMACS TIS) minimal improvement, IMACS TIS, Manual 
Muscle Testing (MMT)-8, Extramuscular Assessment (Myositis Disease Activity Assessment 
Tool [MDAAT]-Extramuscular Global Assessment), creatinine kinase (CK). 
The data of IMACS TIS response used for PK/PD analysis will be imputed following data handling 
rules for primary estimand of primary efficacy endpoint. Plots for IMACS TIS, MMT-8, MDAAT, 
CK would be based on observed data without imputation. 
IMACS TIS minimal improvement 
Serum ustekinumab concentrations (N, median, range [min-max]) at Week 24 will be tabulated by 
responder status (achieved/not-achieved IMACS TIS minimal improvement). For this analysis the 
subjects randomized to Placebo group at Week 0 will be excluded from PK/PD analysis set. 
In addition, the proportion of participants who are randomized to ustekinumab intervention group 
and achieve IMACS TIS minimal improvement at Week 24 will also be tabulated by ustekinumab 
concentration categories (placebo, <= median or >median). 
IMACS TIS 
Relationship between individual total improvement score in IMACS TIS and serum ustekinumab 
concentrations at Week 24/48 will be summarized using box plot by intervention groups (for Week 
24: ustekinumab and placebo, for Week 48: ustekinumab and placebo -> ustekinumab) and by 
ustekinumab concentration categories (<= median or >median). Individual values will be plotted 
over the box plot on the same figure. 
MMT-8 
Relationship between individual change from baseline in MMT-8 and serum ustekinumab 
concentrations at Week 24/48 will be summarized using box plot by intervention groups 


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(ustekinumab and placebo -> ustekinumab) and by ustekinumab concentration categories (<= 
median or >median). The graph at Week 48 will be shown separately by intervention group 
(ustekinumab or placebo- >ustekinumab). Individual values change from baseline will be plotted 
over the box plot on the same figure. 
MDAAT 
Relationship between individual change from baseline in MDAAT and serum ustekinumab 
concentrations at Week 24/48 will be summarized using box plot by intervention groups 
(ustekinumab and placebo -> ustekinumab) and by ustekinumab concentration categories (<= 
median or >median). The graph at Week 48 will be shown separately by intervention groups 
(ustekinumab or placebo- >ustekinumab). Individual values change from baseline will be plotted 
over the box plot on the same figure. 
CK 
Relationship between individual percentage change from baseline in CK at Week 24/48 and serum 
ustekinumab concentrations at Week 24/48 will be plotted in scatter plot. Data collected from both 
ustekinumab and placebo group will be used and plotted on the same graph with different symbols. 
In addition to the above-mentioned assessments, population PK/PD analysis may also be 
performed using nonlinear mixed-effects modeling. Details will be given in a population PK/PD 
analysis plan and the results of the analysis will be presented in a separate report.  
8. 
BIOMARKERS 
Biomarker results will be summarized in a separate technical report. Planned biomarker analyses 
may be deferred if emerging study data show no likelihood of providing useful scientific 
information. 
Genetic (DNA) analyses will be conducted only in participants who sign the optional DNA consent 
form. These analyses will be summarized in a separate technical report. 


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9. 
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Fries JF., Spitz P., Kraines RG., Holman HR. Measurement of patient outcome in arthritis. Arthritis & Rheumatism. 
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Hay EM., Bacon PA., Gordon C., Isenberg DA., Maddison P., Snaith ML., Symmons DP., Viner N., Zoma A. The 
BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus 
erythematosus. QJM: An international Journal of Medicine. 1993. 86(7): 447-458.  
Matsuda Y., Singh G., Yamanaka H., Tanaka E., Urano W., Taniguchi A., et al. Validation of a Japanese version of 
the Standard Health Assessment Questionnaire in 3,763 patients with rheumatoid arthritis. Arthritis & Rheumatism. 
2003. 49(6): 784-788.  
Whiting-O’Keefe QE., Stone JH., Hellmann DB. Validity of a vasculitis activity index for systemic necrotizing 
vasculitis. Arthritis & Rheumatism. 1999. 42(11): 2365-2371.  
 
 


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Statistical Analysis Plan CNTO1275DMY3001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
49 
Status: Approved,  Date: 17 February 2022 
ATTACHMENTS 
Appendix 1 Prohibited Changes in PM/DM Medications Prior to Week 24 
Only applied during the double-blind portion of the study (from Week 0 through Week 24).  
 
There was addition of a new immunomodulator to the existing treatment regimen  
o Initiation of a new immunomodulator indicated to treat PM/DM to the existing treatment 
(i.e. present at randomization) during the double blind period and this immunomodulator 
does not completely replace the existing immunomodulator of similar mechanism of 
action (i.e. MMF or AZA or Oral MTX or Oral TAC or Oral cyclosporine A) 
 
The dose of an immunomodulator is higher than at baseline 
o Exceeding the 110% of baseline dose of the existing treatment (i.e. present at 
randomization) in daily dose for any week (Week 1 ~ Week 24) during the double-blind 
period. Baseline immunomodulator dose is defined as the daily dose on Study day -1 (the 
day before randomization). The daily dose for Week n (an integer from 1 to 24) is defined 
as the latest non-missing daily dose on Study day 7*n-6 to 7*n. For example, the daily 
dose for Week 2 will be the dose taken on Study day 14, if Study day 14 dose is not 
missing. 
 
For the patients with baseline glucocorticoids dose=0, initiation of sustained treatment with 
oral or IV glucocorticoids for PM/DM-related disease activity, Baseline glucocorticoids dose 
is defined as the daily dose on Study day -1 (the day before randomization). 
o I Initiation of oral glucocorticoids indicated to treat PM/DM and sustained for at least 7 
consecutive days during the double-blind period. 
o  Receiving any IV (including intravenous drip) glucocorticoids indicated to treat PM/DM 
during the double-blind period. 
 
For the patients with baseline glucocorticoids dose > 0, the dose of oral glucocorticoids is 
higher than baseline dose, increased dose below the baseline dose more than once, or remains 
stable dose without glucocorticoid tapering schedule (see Table 2 in section 6.5.2 of the 
protocol) for consecutive 6 weeks or longer during the period from Week 2 through Week 16. 
The switching to glucocorticoid with equivalent potency is not considered a prohibited change. 
Baseline glucocorticoids dose is defined as the daily dose on Study day -1 (the day before 
randomization). 
o Exceeding the 110% baseline dose in daily dose for any 2-weeks (Week 0 ~ Week 2, Week 
2~Week4, …Week 22~Week 24) period during the double period. 
o  Receiving any IV (including intravenous drip) glucocorticoids indicated to treat PM/DM 
during the double-blind period. 
o During the period from Week 2 through Week 16, continue a daily glucocorticoid dose > 
5mg for consecutive >= 3 times i.e., continue a daily glucocorticoid dose > 5mg for >=4 
consecutive 2-weeks. 
o During the period from Week 2 through Week 16, continue a daily glucocorticoid dose > 
5mg for consecutive >= 2 times more than once, i.e., continue a daily glucocorticoid dose 
> 5mg for >=3 consecutive 2-weeks more than once. 


STELARA®   (ustekinumab) 
 
 
 
Statistical Analysis Plan CNTO1275DMY3001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
50 
Status: Approved,  Date: 17 February 2022 
o 2-weeks daily dose exceeds the previous one more than once during the period. 
The daily dose for Week n (a multiple of 2 from 2 to 24) is defined as the latest non-missing 
daily dose on Study day 14*n-13 to 14*n. For example, the daily dose for Week 8 will be the 
dose taken on Study day 56, if Study day 56 dose is not missing; otherwise, it will be the dose 
taken on Study day 55, if Study day 55 dose is not missing. 
Subjects who have a prohibited change in PM/DM medications and reason the change will be 
listed. 
 
 
 


STELARA®   (ustekinumab) 
 
 
 
Statistical Analysis Plan CNTO1275DMY3001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
51 
Status: Approved,  Date: 17 February 2022 
Appendix 2 Unblinding Plan 
Primary endpoint of this study will be evaluated at Week 24. Long-term safety and efficacy of 
ustekinumab will continue being evaluated after Week 24. Investigative study sites and 
participants will remain blinded to treatment assignment until the DBL at Week 52. At the Week 
24 DBL, the data will be unblinded to sponsor for analysis while participants are still participating 
in the study. At Week 24 DBL, a document containing the Week 24 topline results (TLR) will be 
developed and distributed as per sponsor SOP-05501 (Preparation and Communication of Topline 
Results). Furthermore, these topline results will support sponsor’s decision on whether applying 
for orphan designation.  
During the period from Week 24 DBL until Week 52 DBL of this study, in order to maintain the 
blindness of subjects and investigators to protect the trial integrity and minimize the potential 
influence on the behavior of the subjects and investigators who still participate this trial, access to 
the unblinded data a will be protected as defined in this unblinding plan. In principle, the sponsor 
unblinders will be limited to the sponsor personnel who are involved in activities on orphan drug 
application and are notified not to disclose any data to any non-unblinders. In principle, medical 
monitors from sponsor or Contract Research Organization (CRO) will continue to be blinded to 
all data until Week 52 DBL. The sponsor unblinders in each group are as follows: 
1. JCoT (Japan Compound Team) 
JCoT is a sponsor organization that is responsible for developing PM/DM indication for 
ustekinumab in Japan. 
2. TLR-related personnel 
The TLR results will be prepared and communicated as per sponsor SOP-05501. Therefore, all the 
TLR reviewers/approvers and the personnel who are pre-defined in the TLR distribution list will 
be unblinded. 
3. Data management and analysis personnel 
These members will be unblinded to clean/analyze the data.  
4. Other orphan drug application documents writers/reviewers/supporters 
Upon JCoT members’ judgment, sponsor personnel other than JCoT members who need to access 
to the unblinded data to write/review/support orphan drug application documents can also be the 
unblinders. 
 
 
a The unblinded data includes the data unblinded to individual subject treatment assignments, e.g., statistical listings 
and subject narratives and study results by the treatment group without disclosing the individual treatment 
assignments, e.g., statistical tables/figures. 


STELARA®   (ustekinumab) 
 
 
 
Statistical Analysis Plan CNTO1275DMY3001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
52 
Status: Approved,  Date: 17 February 2022 
The sponsor study statistician will keep a running log of personnel who have been unblinded to 
the data and the date of unblinding during the implementation period of this unblinding plan (from 
Week 24 DBL until Week 52 DBL). 
Any sponsor personnel other than the above unblinders will not have access to the unblinded data. 
All the unblinded data will be kept appropriately in a sponsor Sharepoint accessible to unblinders 
only. Before sharing the unblinded data with any new unblinders, it should be clearly noted that 
“it’s an ongoing study and all the study results disclosed are required to be confidential from the 
investigators and subjects of this study.”. When distributing the topline results (TLR), the note of 
“Confidential and forwarding is strictly prohibited.” should be included to avoid further 
dissemination.