Clinical trial NCT05192200
Conditions: Dermatomyositis
Sponsor: Pfizer
Start date: 2021-12-20; Completion date: 2023-11-20
Enrollment: 24 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this research study is to evaluate the long-term safety, and tolerability of PF-06823859 study drug in adult participants with Dermatomyositis (DM) from a qualifying study.

Detailed description:

Arms: arm 1: IV infusion
Interventions: intervention 1: Anti-Beta Interferon (PF-06823859)
Intervention descriptions: intervention 1: IV infusion

Protocol documents:
Prot_000.pdf: 
PF-06823859
Protocol C0251008
Final Protocol, 03 September 2021 
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 March 2021)
Page 1
Title Page
AN OPEN LABEL, LONG-TERM EXTENSION STUDY TO INVESTIGATE THE 
SAFETY OF PF-06823859 ADMINISTERED TO ADULT PARTICIPANTS ≥18 AND 
≤80 WITH ACTIVE DERMATOMYOSITIS.  
Study Intervention Number:
PF-06823859
Study Intervention Name:
N/A
US IND Number:
129230
EudraCT Number:
2021-004787-10 
Protocol Number:
C0251008
Phase:
2b
Brief Title: An Open-Label Extension Study for Participants Who Have Completed the Treatment 
Period of a Qualifying Parent Study.
This document and accompanying materials contain confidential information belonging to Pfizer. Except 
as otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this 
information in confidence and not copy or disclose it to others (except where required by applicable law) 
or use it for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer 
must be promptly notified.
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Protocol C0251008
Final Protocol, 03 September 2021 
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 March 2021)
Page 2
Document History
Document 
Version Date
Original protocol
03 September 2021
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Protocol C0251008
Final Protocol, 03 September 2021 
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 March 2021)
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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................9
1. PROTOCOL SUMMARY...................................................................................................10
1.1. Synopsis ..................................................................................................................10
1.2. Schema ....................................................................................................................13
1.3. Schedule of Activities .............................................................................................14
2. INTRODUCTION ...............................................................................................................22
2.1. Study Rationale .......................................................................................................22
2.2. Background .............................................................................................................22
2.2.1. Clinical Overview.......................................................................................22
2.3. Benefit/Risk Assessment.........................................................................................25
2.3.1. Risk Assessment.........................................................................................26
2.3.2. Benefit Assessment.....................................................................................27
2.3.3. Overall Benefit/Risk Conclusion................................................................27
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS ...........................................................27
4. STUDY DESIGN.................................................................................................................28
4.1. Overall Design.........................................................................................................28
4.2. Scientific Rationale for Study Design.....................................................................29
4.2.1. Diversity of Study Population ....................................................................29
4.2.2. Choice of Contraception/Barrier Requirements .........................................29
4.2.3. Collection of Retained Research Samples..................................................29
4.3. Justification for Dose ..............................................................................................29
4.4. End of Study Definition ..........................................................................................30
5. STUDY POPULATION......................................................................................................30
5.1. Inclusion Criteria.....................................................................................................31
5.2. Exclusion Criteria....................................................................................................31
5.3. Lifestyle Considerations..........................................................................................33
5.3.1. Contraception..............................................................................................33
5.3.2. Surgery........................................................................................................33
5.4. Screen Failures ........................................................................................................33
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY.................................33
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6.1. Study Intervention(s) Administered........................................................................34
6.1.1. Administration............................................................................................34
6.1.1.1. Infusion Discontinuation...........................................................34
6.1.1.2. Pre-Medication Use on the Day of IVIG Administration .........35
6.2. Preparation, Handling, Storage, and Accountability...............................................35
6.2.1. Preparation and Dispensing........................................................................36
6.2.2. Study Intervention Accountability..............................................................36
6.2.2.1. Destruction of Study Intervention Supplies ..............................37
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................37
6.3.1. Allocation to Study Intervention ................................................................37
6.4. Study Intervention Compliance...............................................................................37
6.5. Dose Modification...................................................................................................37
6.6. Continued Access to Study Intervention After the End of the Study......................37
6.7. Treatment of Overdose............................................................................................38
6.8. Concomitant Therapy..............................................................................................38
6.8.1. Prohibited Concomitant Medications .........................................................39
6.8.2. Permitted Concomitant Medications ..........................................................39
6.8.3. Corticosteroids............................................................................................39
6.8.3.1. Guidance for Investigators ........................................................40
6.8.4. Rescue Medicine.........................................................................................40
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................40
7.1. Discontinuation of Study Intervention ....................................................................40
7.2. Participant Discontinuation/Withdrawal From the Study.......................................41
7.2.1. Withdrawal of Consent...............................................................................41
7.3. Lost to Follow-Up ...................................................................................................42
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................42
8.1. Efficacy Assessments..............................................................................................43
8.1.1. CDASI ........................................................................................................43
8.1.2. Total Improvement Score (TIS)..................................................................43
8.1.2.1. Physician Global Assessment (PhGA) Visual Analogue 
Scale (VAS).......................................................................................44
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8.1.2.2. MMT-8......................................................................................44
8.1.2.3. MDAAT ....................................................................................44
8.1.3. Patient Reported Outcomes ........................................................................44
8.1.3.1. The Short Form -36 Version 2, Acute (SF 36 v2 acute) ...........44
8.1.3.2. EuroQoL 5 Dimensions 5 Levels (EQ 5D 5L) and EQ-
VAS ...................................................................................................44
8.1.3.3. Health Assessment Questionnaire – Disability Index 
(HAQ-DI) ..........................................................................................45
8.1.3.4. Patient’s Global Assessment (PtGA) ........................................45
8.1.4. Rater Qualifications....................................................................................45
8.1.4.1. CDASI.......................................................................................46
8.1.4.2. MMT-8......................................................................................46
8.1.4.3. MDAAT ....................................................................................46
8.2. Safety Assessments .................................................................................................46
8.2.1. Medical History ..........................................................................................46
8.2.2. Physical Examinations................................................................................46
8.2.3. Height and Weight......................................................................................47
8.2.4. Vital Signs ..................................................................................................47
8.2.5. Electrocardiograms.....................................................................................48
8.2.6. Infusion Site Reaction Assessment.............................................................49
8.2.7. Photography................................................................................................49
8.2.8. Clinical Safety Laboratory Assessments ....................................................49
8.2.9. Pregnancy Testing ......................................................................................49
8.2.10. Assessment of Suicidal Ideation and Behavior ........................................50
8.2.10.1. Columbia -Suicide Severity Rating Scale (C-SSRS)..............50
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting .................50
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......51
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................51
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................51
8.3.2. Method of Detecting AEs and SAEs ..........................................................52
8.3.3. Follow-Up of AEs and SAEs......................................................................52
8.3.4. Regulatory Reporting Requirements for SAEs...........................................52
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8.3.5. Environmental Exposure, Exposure During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................53
8.3.5.1. Exposure During Pregnancy......................................................53
8.3.5.2. Exposure During Breastfeeding ................................................54
8.3.5.3. Occupational Exposure .............................................................55
8.3.6. Cardiovascular and Death Events...............................................................55
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs..............................................................................55
8.3.8. Adverse Events of Special Interest.............................................................55
8.3.8.1. Lack of Efficacy........................................................................55
8.3.9. Medical Device Deficiencies......................................................................56
8.3.10. Medication Errors.....................................................................................56
8.4. Pharmacokinetics ....................................................................................................56
8.4.1. Serum for Analysis of PF-06823859..........................................................56
8.4.2. Shipment of Pharmacokinetic Samples ......................................................57
8.4.3. IVIG Analysis.............................................................................................58
8.5. Genetics...................................................................................................................58
8.5.1. Specified Genetics ......................................................................................58
8.6. Biomarkers ..............................................................................................................58
8.6.1. PD Biomarkers............................................................................................58
8.6.1.1. Samples for hsCRP Analysis.....................................................58
8.6.1.2. Total IFN.................................................................................59
8.6.1.3. Biospecimen for Blood Muscle Biomarkers .............................59
8.6.2. Retained Research Samples for Biomarkers...............................................59
8.7. Immunogenicity Assessments.................................................................................59
8.7.1. Serum for Analysis of Anti-PF-06823859..................................................59
8.7.1.1. Antibodies (ADA) and Neutralizing Anti-PF-06823859 
Antibodies (NAb) ..............................................................................59
8.7.2. Immunogenicity Analyses ..........................................................................60
8.7.3. Shipment of Immunogenicity (ADA/NAb) Samples .................................60
8.8. Health Economics ...................................................................................................60
9. STATISTICAL CONSIDERATIONS ................................................................................60
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9.1. Statistical Hypotheses .............................................................................................61
9.1.1. Estimands....................................................................................................61
9.1.1.1. Primary Estimands ....................................................................61
9.1.1.2. Secondary Estimands ................................................................61
9.1.2. Multiplicity Adjustment..............................................................................62
9.2. Analysis Sets ...........................................................................................................62
9.3. Statistical Analyses .................................................................................................63
9.3.1. General Considerations...............................................................................63
9.3.2. Primary Endpoint(s) Analysis.....................................................................63
9.3.3. Secondary Endpoint(s)/Estimand(s) Analysis............................................63
9.3.4. Tertiary/Exploratory Endpoint(s) ...............................................................64
9.3.5. Other Safety Analyses ................................................................................64
9.3.5.1. Adverse Events and Suicidality Assessments ...........................64
9.3.5.2. Electrocardiogram Analyses......................................................64
9.3.6. Other Analyse(s).........................................................................................65
9.3.6.1. Pharmacokinetic Analysis.........................................................65
9.4. Interim Analyses .....................................................................................................65
9.5. Sample Size Determination.....................................................................................65
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................66
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............66
10.1.1. Regulatory and Ethical Considerations ....................................................66
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................66
10.1.2. Financial Disclosure .................................................................................67
10.1.3. Informed Consent Process ........................................................................67
10.1.4. Data Protection .........................................................................................68
10.1.5. Committees Structure ...............................................................................68
10.1.5.1. Data Monitoring Committee ...................................................68
10.1.6. Dissemination of Clinical Study Data ......................................................68
10.1.7. Data Quality Assurance ............................................................................70
10.1.8. Source Documents....................................................................................71
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10.1.9. Study and Site Start and Closure ..............................................................71
10.1.10. Publication Policy...................................................................................73
10.1.11. Sponsor’s Qualified Medical Personnel .................................................73
10.2. Appendix 2: Clinical Laboratory Tests .................................................................75
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting .....................................................................76
10.3.1. Definition of AE .......................................................................................76
10.3.2. Definition of an SAE ................................................................................77
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During 
the Active Colletion Period..............................................................................79
10.3.4. Reporting of SAEs....................................................................................82
10.4. Appendix 4: Contraceptive and Barrier Guidance ................................................84
10.4.1. Male Participant Reproductive Inclusion Criteria....................................84
10.4.2. Female Participant Reproductive Inclusion Criteria.................................84
10.4.3. Woman of Childbearing Potential ............................................................85
10.4.4. Contraception Methods.............................................................................86
10.5. Appendix 5: Genetics............................................................................................88
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments .......89
10.7. Appendix 7: ECG Findings of Potential Clinical Concern ...................................91
10.8. Appendix 8: Permitted and Prohibited Concomitant Medications........................93
10.9. Appendix 9: Alternative Measures During Public Emergencies ..........................95
10.9.1. Telehealth Visits (if applicable)................................................................95
10.9.2. Alternative Facilities for Safety Assessments ..........................................95
10.9.2.1. Laboratory Testing (if applicable)...........................................95
10.9.2.2. Electrocardiograms..................................................................96
10.9.3. Home Health Visits...................................................................................96
10.9.4. Adverse Events and Serious Adverse Events...........................................96
10.10. Appendix 10: Guidelines for Participant Safety Monitoring and 
Discontinuation..........................................................................................................98
10.10.1. Monitoring..............................................................................................98
10.10.2. Discontinuation.......................................................................................98
10.11. Appendix 11: Corticosteroid Suggested Taper and Rescue Guidance..............101
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10.11.1. Corticosteroid Suggested Taper............................................................101
10.11.2. Corticosteroid Rescue Guidance...........................................................101
10.11.2.1. Oral or Intramuscular Corticosteroid Rescue 
Recommended Guidance for Dermatomyositis Related 
Reasons............................................................................................101
10.11.2.2. Corticosteroid Rescue Guidance for Non-
Dermatomyositis Reasons ...............................................................102
10.11.2.3. Intra-Articular Corticosteroids ............................................102
10.11.2.4. Immunosuppressives/immunomodulatory Agent 
Rescue Medications.........................................................................103
10.11.2.5. NSAIDs and Analgesics......................................................103
10.12. Appendix 12: Abbreviations .............................................................................104
11. REFERENCES ................................................................................................................108
LIST OF TABLES
Table 1.
DM Participants with Moderate to Severe Skin Disease..........................14
Table 2.
DM Participants with Moderate Muscle Disease .....................................18
Table 3.
Laboratory Tests .......................................................................................75
Table 4.
List of Prohibited and Permitted Concomitant Medications ....................93
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Brief Title: An Open-Label Extension Study for Participants Who Have Completed the 
Treatment Period of a Qualifying Parent Study.
Rationale
The purpose of the study is to evaluate the long-term safety, and tolerability of PF-06823859 
in adult participants with DM from a qualifying study. 
Objectives, Endpoints, and Estimands
Objectives
Endpoints
Estimands
Primary: 
Primary:
Primary: 

To evaluate the long-term 
safety and tolerability of 
PF-06823859.

Incidence of AEs, laboratory 
abnormalities, changes in vital 
signs, and ECG findings.

There are no defined 
estimands for safety and 
tolerability endpoints; these 
will be analyzed using Pfizer 
data standards, as applicable.
Secondary: 
Secondary:
Secondary: 

To evaluate the long-term 
efficacy of PF-06823859 in 
adult participants with 
moderate to severe DM.

Change from baseline in CDASI 
activity score at Week 52.

Absolute values and changes
from baseline of CDASI activity 
and CDASI damage scores at all 
scheduled timepoints.

TIS score at Week 52 and at 
intermediate scheduled 
timepoints for participants who 
entered from Stage 3 of Protocol 
C0251002.

E1: This estimand uses a 
hypothetical estimand 
strategy (ICH E9 addendum) 
estimating the mean effect of 
PF-06823859 in the absence 
of intercurrent events (study 
withdrawal). This is the mean 
change from baseline to 
Week 52 CDASI activity 
score for all randomized and 
dosed participants with 
non-missing baseline score in 
the (a) Skin Analysis Set and 
(b) Muscle Analysis Set (see 
details in Section 9.1.1).

These additional CDASI 
endpoints will be analyzed 
using E1 at all scheduled 
timepoints.

E2: This estimand uses a 
hypothetical estimand 
strategy (ICH E9 addendum) 
estimating the mean effect of 
PF-06823859 in the absence 
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Overall Design
This is a Phase 2b, OLE study to evaluate the long-term safety, and tolerability, of 
PF-06823859 in adult participants with moderate to severe DM who have completed the 
treatment period of a qualifying study (including Protocol C0251002) and have agreement 
from their study doctor to continue active treatment. Eligible participants will not have had 
any significant protocol deviations, (eg, not following the protocol, taking prohibited 
medications, not using appropriate contraception) or have not completed all study treatment 
in a qualifying study. Approximately 30 participants who complete the Week 24 visit during 
the treatment period in Study C0251002 or equivalent in another qualifying study, may be 
enrolled in Protocol C0251008. The treatment duration of OLE study participation will be up 
to 48 weeks (treatment period is up through and including Week 52), with a 16 week 
follow up period.
Eligible participants will be randomized to receive open-label PF-06823859 600 mg IV every 
4 weeks for up to 48 weeks, however the treatment period is up to Week 52. All participants 
will be followed for 16 weeks in the Follow-up Period. Participants who are discontinued 
from study intervention will enter the follow-up period. 
Brief Summary
Based on the mechanism of action of PF-06823859 and preliminary results from the Phase 2 
C0251002 clinical study in adults with DM (see Section 2.2.1.1.4), this OLE study is being 
conducted to provide additional data on the long-term safety and tolerability of IV 
PF-06823859 in adult participants with active DM. 

Change from baseline in the 
CSMs of the TIS including 
PhGA, PtGA, MMT-8, 
HAQ-DI, muscle enzymes, and 
MDAAT at Week 52 and at 
intermediate scheduled 
timepoints.
of intercurrent events (study 
withdrawal). This is the mean 
TIS at Week 52 for all 
randomized and dosed 
participants included with 
non-missing baseline score in 
the Stage 3 Muscle Analysis 
Set (see details in 
Section 9.1.1).

The endpoints for the CSMs
of the TIS will be analyzed 
using E2 at Week 52 and all 
intermediate scheduled 
timepoints.
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Number of Participants
The sample size will be determined by the number of patients who enroll from Protocol 
C0251002 and any other future qualifying studies. It is anticipated that up to approximately 
30 participants from Amended Stage 2 and Stage 3 of Protocol C0251002 will be enrolled to 
receive open-label study intervention. 
Intervention Groups and Duration
This is an open-label study. The site will contact the IRT prior to the start of study 
intervention administration for each participant. The site will record the vial numbers 
assigned on the applicable CRF, if required. 
For this study, the study intervention will be administered intravenously over approximately 
one hour. Study intervention will be administered every 4 weeks, each participant receiving 
up to 13 doses of study intervention. 
Dose modification is not permitted in this study. 
If study intervention is permanently discontinued, the participant will have an End of 
Treatment visit and enter the follow-up period to be evaluated for safety. 
Data Monitoring Committee or Other Independent Oversight Committee: 
Not Applicable.
Statistical Methods
This is an extension study to assess the safety and tolerability of the long-term therapy of 
PF-06823859 in participants with DM. All efficacy endpoints are secondary endpoints. The 
primary analysis population for safety evaluations will be the safety analysis set (See 
Section 9.2). All efficacy evaluations will be completed separately for those originating from 
the skin-predominant DM cohort included in the C0251002 protocol Amended Stage 2 or the 
muscle-predominant DM cohort including Stage 3 of the C0251002 protocol. The respective 
analysis sets for these efficacy evaluations are the Skin Analysis Set and Muscle Analysis 
Set. Baseline will be Day 1 of study C0251008; sensitivity analyses that redefine Baseline as 
Day 1 of the parent study may also be performed and will be defined in the SAP. 
No formal statistical hypothesis testing is planned for this study. 
There are no defined estimands for the incidence of AEs, laboratory abnormalities, changes 
in vital signs, and ECG findings. These endpoints will be analyzed using Pfizer data 
standards as applicable. All participants who receive at least 1 dose of IP will be included in 
the safety analyses. All safety data will be summarized descriptively through appropriate data 
tabulations, descriptive statistics, categorical summaries, and graphical presentations.
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Two estimands are defined for this study. Estimand 1 (E1) will support specified CDASI 
assessments at specified timepoints for participants in the Skin Analysis Set and Muscle 
Analysis Set separately. Estimand 2 (E2) will support TIS and CSM assessments at specified 
timepoints for participants in the Muscle Analysis Set.
1.2. Schema
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1.3. Schedule of Activities
The SoA table provides an overview of the protocol visits and procedures. Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant. 
References to “baseline” in this study correspond to the Week 24 visit of the Phase 2 C0251002 study and Day 1 of this study. All 
study procedures will be completed for Visit 24 in the C0251002 study, and Day 1 in the current study prior to drug administration. 
Table 1.
DM Participants with Moderate to Severe Skin Disease
This SoA focuses on DM participants with moderate skin disease including participants from Amended Stage 2 of the Phase 2 
C0251002 study. The approximate study duration is 68 weeks; 48 weeks of study treatment, (treatment period is up through and 
including Week 52) with a 16 week follow up period. 
Protocol Activity
Treatment Period
Follow-ups
Visit identifier
(Study Visit)
1
Baseline
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
EOS
Participant 
withdrawal 
or Early 
Terminationa
Study Day/Week
Week 24
C0251002
DAY 1
Week 
4
Week 
8
Week 
12
Week 
16
Week 
20
Week 
24
Week 
28 
Week 
32
Week 
36
Week 
40
Week 
44
Week 48 Week 
52
Week 
56
Week 
60
Week
64
Week 
68
N/A
Visit Window
(+) 7 
days*
±3 days
Informed consent
X
Inclusion/exclusion criteriab
X
Medical historyc
X
Demography
X
Clinical Reported Outcomes
C-SSRSd
D
X
X
X
X
X
X
X
PhGA VASe
D
X
X
X
X
X
X
X
X
CDASI
D
X
X
X
X
X
X
X
X
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Protocol Activity
Treatment Period
Follow-ups
Visit identifier
(Study Visit)
1
Baseline
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
EOS
Participant 
withdrawal 
or Early 
Terminationa
Study Day/Week
Week 24
C0251002
DAY 1
Week 
4
Week 
8
Week 
12
Week 
16
Week 
20
Week 
24
Week 
28 
Week 
32
Week 
36
Week 
40
Week 
44
Week 48 Week 
52
Week 
56
Week 
60
Week
64
Week 
68
N/A
Visit Window
(+) 7 
days*
±3 days
Patient Reported Outcomes
SF36 v2 Acutef
D
X
X
X
X
X
X
X
EQ-5D-5L & EQ-VASf
X
X
X
X
X
X
X
X
Medical Assessments
Vital Signs (BP, HR, Pulse, 
and temperature)g
D
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weighth
D
X
X
X
X
Heighth
D
Complete physical 
examinationi
D
X
X
X
X
Targeted physical examinationi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECG 
D
X
X
X
X
X
X
X
Contraception checkj
D
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Safety Assessments
Safety Labs/Urine 
X
X
X
X
X
X
X
X
X
eGFR
X
X
X
X
X
Serum cystatin C
X
X
X
X
X
Urine -hCG
(conducted at site)k
D
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Immunogenicity (ADA, Nab) 
serum
Xl
Xl
Xl
Xl
Xl
X
X
X
Pharmacokinetic (PK)/serumm
X
X
X
X
X
X
X
X
IVIG sample collectionn
X
X
X
X
X
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Protocol C0251008
Final Protocol, 03 September 2021 
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 March 2021)
Page 16
Protocol Activity
Treatment Period
Follow-ups
Visit identifier
(Study Visit)
1
Baseline
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
EOS
Participant 
withdrawal 
or Early 
Terminationa
Study Day/Week
Week 24
C0251002
DAY 1
Week 
4
Week 
8
Week 
12
Week 
16
Week 
20
Week 
24
Week 
28 
Week 
32
Week 
36
Week 
40
Week 
44
Week 48 Week 
52
Week 
56
Week 
60
Week
64
Week 
68
N/A
Visit Window
(+) 7 
days*
±3 days
Retained Research Samples
Prep B1.5 plasma, Prep B2.5 
serum, and Prep R1 whole 
blood
D
X
X
X
X
X
X
Biomarkerso
Blood for muscle biomarkers
D
X
X
X
X
X
X
X
X
Total IFN
X
X
X
X
X
X
X
X
hsCRP
X
X
X
X
X
X
X
X
X
Study Intervention 
Administration
Study Intervention treatment 
administrationq
Xp
X
X
X
X
X
X
X
X
X
X
X
X
Infusion Site Reaction
X
X
X
X
X
X
X
X
X
X
X
X
X
Ongoing Medicationsr
Ongoing Adverse events,c
Concomitant Medications and 
Treatment(s)
D
















X
X
AE monitoring
D
















X
X
Note: D=Done at week 24 visit (C0251002); “X” at week 24 indicates procedure/sample needs to be completed under study C0251008 * (+7 days for baseline): 
Baseline date should be the same date as the last visit from the previous study. In rare circumstances, up to 7 days may occur between the last visit in the feeder 
study and the baseline date of this study. Sponsor approval is required. 
a.
Any participant who prematurely withdraws from the treatment period should undergo the procedures for an early termination visit and return for follow up 
visits. At the time of the early termination visit, blood samples will be collected for PK and PD analysis. As with all PK and PD assessments, the date and 
time of the last dose and time of the sample collection should be captured and reported.
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Protocol C0251008
Final Protocol, 03 September 2021 
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CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 March 2021)
Page 17
b.
Inclusion and exclusion criteria need to be reviewed to ensure participant is eligible for the study. No CRF will be completed, however source 
documentation is required to reflect that participant is eligible for study participation.
c.
Medical History for this study is any ongoing adverse events from the previous study. Please record only ongoing adverse events from the previous study 
onto the medical history page, so that these can be monitored. Any AEs occurring after receiving study drug administration will be considered an AE for this 
study.
d.
The C-SSRS will be used to assess suicidal ideation and behavior during the conduct of the study. At any visits, if there are “yes” answers on items 4, 5 or 
on any suicidal behavior question of the C-SSRS, the participant will be discontinued from treatment and referred to a mental health professional for 
appropriate evaluation and treatment. Please see Section 8.2.10.1.
e.
Physician’s Global Assessment (PhGA, VAS); This assessment should be completed by the same physician completing the CDASI.
f.
Patient reported outcomes (SF-36 v2 acute, and EQ-5D-5L & EQ-VAS) are to be completed at the clinic prior to other clinical assessments. These need to be 
completed in the following order SF-36 v2 acute, EQ-5D-5L & EQ-VAS. 
g.
Vital Signs include blood pressure, heart rate (pulse), and temperature measured after approximately 5 minutes of rest. Participants should be seated in a 
chair, back supported, and arms bared (free of restrictions such as rolled-up sleeves, etc.) and supported at the level of the heart. Measurements should be 
taken on the same arm (preferably the non-dominant arm) at each visit throughout the study after 5-10 minutes of rest and recorded to the nearest mm Hg. 
Participants should refrain from smoking or ingesting caffeine during the 30 minutes prior to the measurements. 
h.
Weight and height will be measured without shoes. 
i.
Complete PE consists of general appearance, skin, HEENT, heart, lungs, breast (optional), abdomen, external genitalia (optional), extremities, neurologic 
function, back, and lymph nodes, please record in source documentation. Targeted PE consists of skin, heart, lungs, abdomen, and examination of body 
systems where there are symptom complaints by the participant. Targeted physical exam should be completed prior to dosing and recorded in source 
documentation.
j.
Contraception check should be completed and documented in source at each and every visit.
k.
Urine pregnancy test must be performed at baseline for all WOCBP prior to dosing with study intervention and at all subsequent visits.
l.
ADA, Nab, and INFβ will be collected prior to investigational drug administration according to the SoA.
m. At dosing visits, PK samples will be collected pre and post dose, preferably after vital signs data and within approximately 30 minutes prior to dosing. PK
will also be collected at the end of the study infusion in the opposite arm of the infusion at all PK collection visits according to the SoA.
n.
Only participants who are on IVIG concomitantly will have a pre-dose blood sample collected. See Section 8.4.3.
o.
Biomarkers will be collected prior to study drug administration according to the SoA. 
p.
All Day 1 and Week 24 from previous study (eg, C0251002) procedures should be completed prior to investigational treatment administration.
q.
Once the infusion has been administered over 60 minutes, all participants will be monitored for an additional 60 minutes to ensure no infusion site reactions. 
r.
All ongoing medications from the previous study should be re-written in the new concomitant medication page for this study.
s.
Participants who experience AEs which are considered attributable to immunogenicity and have ADA may be requested to return for additional follow up for 
up to 5 months after the follow up/EOS visit and will have PK and ADA samples drawn for analysis. This will be recorded as an unscheduled visit.
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Final Protocol, 03 September 2021 
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 March 2021)
Page 18
Table 2.
DM Participants with Moderate Muscle Disease
This SoA focuses on DM participants with moderate muscle disease including participants from Stage 3 of the C0251002 study. The 
approximate study duration is 68 weeks; 48 weeks of study treatment (treatment period is up through and including Week 52) with a 
16 week follow up period. Participants enrolling in the muscle cohort will not be required to provide any skin or muscle biopsies. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant.
References to “baseline” in this study correspond to the Week 24 visit of the Phase 2 C0251002 Study and Day 1 of this study. All 
study procedures will be completed for Visit 24 in the C0251002 study and Day 1 in the current study prior to drug administration.
Protocol Activity
Treatment Period
Follow-ups
Visit identifier (Study 
Visit)
1
Baseline
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
EOS
Participant 
withdrawal 
or Early 
Termination
a
Study Day/Week
Week 24
C0251002
DAY 1
Week 4
Week 
8
Week 
12
Week 
16
Week 
20
Week 
24
Week 
28 
Wee
k 32
Week 
36
Week 
40
Week 
44
Week 
48
Week 
52
Week 56
Week 
60
Week
64
Week 
68
N/A
Visit Window
(+ )7 days*
±3 days
Informed consent
X
Inclusion/exclusion 
criteriab
X
Medical historyc
X
Demography
X
Clinical Reported Outcomes
CDASI Score
D
X
X
X
X
X
X
X
X
C-SSRSd
D
X
X
X
X
X
X
X
PhGA, VASe
D
X
X
X
X
X
X
X
X
MMT-8 Score
D
X
X
X
X
X
X
X
X
MDAAT
D
X
X
X
X
X
X
X
X
Patient Reported Outcomes
PtGAf
D
X
X
X
X
X
X
X
X
HAQ-DIf
D
X
X
X
X
X
X
X
X
SF-36 v2 Acutef
D
X
X
X
X
X
X
X
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Protocol C0251008
Final Protocol, 03 September 2021 
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 March 2021)
Page 19
Protocol Activity
Treatment Period
Follow-ups
Visit identifier (Study 
Visit)
1
Baseline
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
EOS
Participant 
withdrawal 
or Early 
Termination
a
Study Day/Week
Week 24
C0251002
DAY 1
Week 4
Week 
8
Week 
12
Week 
16
Week 
20
Week 
24
Week 
28 
Wee
k 32
Week 
36
Week 
40
Week 
44
Week 
48
Week 
52
Week 56
Week 
60
Week
64
Week 
68
N/A
EQ-5D-5L & 
EQ-VASf
X
X
X
X
X
X
X
X
Medical Assessments
Vital Signs (BP, HR, 
Pulse and 
temperature)g
D
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weighth
D
X
X
X
X
Heighth
D
Complete physical 
examinationi
D
X
X
X
X
Targeted physical 
examinationi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECG
D
X
X
X
X
X
X
X
Contraception checkj
D
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Safety Assessments
Safety Labs/Urine
X
X
X
X
X
X
X
X
X
eGFR
X
X
X
X
X
Serum cystatin C
X
X
X
X
X
Urine -hCG
(conducted at site)k
D
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Immunogenicity 
(ADA, NAb) serum 
Xl
Xl
Xl
Xl
Xl
X
X
X
Pharmacokinetic 
(PK)/serumm
X
X
X
X
X
X
X
X
IVIG sample 
collectionn
X
X
X
X
X
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Protocol C0251008
Final Protocol, 03 September 2021 
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 March 2021)
Page 20
Protocol Activity
Treatment Period
Follow-ups
Visit identifier (Study 
Visit)
1
Baseline
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
EOS
Participant 
withdrawal 
or Early 
Termination
a
Study Day/Week
Week 24
C0251002
DAY 1
Week 4
Week 
8
Week 
12
Week 
16
Week 
20
Week 
24
Week 
28 
Wee
k 32
Week 
36
Week 
40
Week 
44
Week 
48
Week 
52
Week 56
Week 
60
Week
64
Week 
68
N/A
Retained Research Samples
Prep B1.5 plasma, 
B2.5 serum, R1 
whole blood
D
X
X
X
X
X
X
Biomarkerso
Blood for muscle 
biomarkers
D
X
X
X
X
X
X
X
X
Total IFN
X
X
X
X
X
X
X
X
hsCRP
X
X
X
X
X
X
X
X
X
Study Intervention
Study intervention 
administrationq
Xp
X
X
X
X
X
X
X
X
X
X
X
X
Infusion Site 
Reaction
X
X
X
X
X
X
X
X
X
X
X
X
X
Ongoing
Medicationsr
Ongoing AEss,c
Concomitant 
Medications and 
Treatment(s)
D
















X
X
Adverse event 
monitoring
D
















X
X
Note: D=Done in week 24 visit (C0251002); “X” at week 24 indicates procedure/sample needs to be completed under study C0251008 * (+7 days for baseline): 
Baseline date should be the same date as the last visit from the previous study. In rare circumstances, up to 7 days may occur between the last visit in the feeder 
study and the baseline date of this study. Sponsor approval is required. 
a.
Any participant who prematurely withdraws from the treatment period should undergo the procedures for an early termination visit and return for follow up 
visits. At the time of the early termination visit, blood samples will be collected for PK and PD analysis. As with all PK and PD assessments, the date and 
time of the last dose and time of the sample collection should be captured and reported.
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Final Protocol, 03 September 2021 
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 March 2021)
Page 21
b.
Inclusion and exclusion criteria need to be reviewed to ensure participant is eligible for the study. No CRF will be completed, however source 
documentation is required to reflect that participant is eligible for study participation.
c.
Medical History for this study is any ongoing adverse events from the previous study. Please record only ongoing adverse events from the previous study 
onto the medical history page, so that these can be monitored. Any AEs occurring after receiving study drug administration will be considered an AE for this 
study.
d.
The C-SSRS will be used to assess suicidal ideation and behavior during the conduct of the study. At any visits, if there are “yes” answers on items 4, 5 or 
on any suicidal behavior question of the C-SSRS, the participant will be discontinued from treatment and referred to a mental health professional for 
appropriate evaluation and treatment. Please see Section 8.2.10.1.
e.
Physician’s Global Assessment (PhGA, VAS); This assessment should be completed by the same physician completing the CDASI, MMT-8, and the 
MDAAT.
f.
Patient reported outcomes (PtGA, HAQ-DI, SF-36 v2 acute, and EQ-5D-5L & EQ-VAS) are to be completed at the clinic prior to other clinical assessments. 
These need to be completed in the following order, PtGA, HAQ-DI, SF-36 (v2 acute), EQ-5D-5L & EQ-VAS. 
g.
Vital Signs include blood pressure, heart rate (pulse), and temperature measured after approximately 5 minutes of rest. Participants should be seated in a 
chair, back supported, and arms bared (free of restrictions such as rolled-up sleeves, etc.) and supported at the level of the heart. Measurements should be 
taken on the same arm (preferably the non-dominant arm) at each visit throughout the study after 5-10 minutes of rest and recorded to the nearest mm Hg. 
Participants should refrain from smoking or ingesting caffeine during the 30 minutes prior to the measurements. 
h.
Weight and height will be measured without shoes.
i.
Complete PE consists of general appearance, skin, HEENT, heart, lungs, breast (optional), abdomen, external genitalia (optional), extremities, neurologic 
function, back, and lymph nodes, please record in source documentation. Targeted PE consists of skin, heart, lungs, abdomen, and examination of body 
systems where there are symptom complaints by the participant. Targeted physical exam should be completed prior to dosing and recorded in source 
documentation.
j.
Contraception check should be completed and documented in source at each visit.
k.
Urine pregnancy test must be performed at baseline for all WOCBP prior to dosing with study intervention and at all subsequent visits.
l.
ADA, NAb, and INFβ will be collected prior to investigational drug administration according to the SoA.
m. At dosing visits, PK samples will be collected pre and post dose, preferably after vital signs data and within approximately 30 minutes prior to dosing. PK 
will also be collected at the end of the study infusion in the opposite arm of the infusion at all PK collection visits according to the SoA. 
n.
All participants who are on IVIG concomitantly will have a pre-dose blood sample collected. See Section 8.4.3.
o.
Biomarkers will be collected prior to study drug administration according to the SoA. 
p.
All Day 1 and Week 24 from previous study (eg, C0251002) procedures should be completed prior to investigational treatment administration. 
q.
Once the infusion has been administered over 60 minutes, all participants will be monitored for an additional 60 minutes to ensure no infusion site reactions.
r.
All ongoing medications from the previous study should be re-written in the new concomitant medication page for this study. 
s.
Participants who experience AEs which are considered attributable to immunogenicity and have ADA will be requested to return for additional follow up for 
up to 5 months after the follow up/EOS visit and will have PK and ADA samples drawn for analysis. This will be recorded as an unscheduled visit.
090177e1980d3bd4\Approved\Approved On: 13-Sep-2021 10:49 (GMT)


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Protocol C0251008
Final Protocol, 03 September 2021 
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 March 2021)
Page 22
2. INTRODUCTION
DM is an acquired rare inflammatory disease classified as both a neuromuscular disease and 
an autoimmune disease. DM is characterized by a distinctive skin rash and muscle weakness 
or inflamed muscles. Symptoms can come on suddenly or gradually over time. It is thought 
that the inflammation resulting in cell damage is created when the immune system attacks 
healthy muscle tissue and blood vessels under the skin. DM is idiopathic, however some 
individuals may have a genetic predisposition that is triggered by medications, viruses, 
bacteria, trauma, toxins, cancer or other illness. DM symptoms often wax and wane for no 
apparent reason, and females are affected twice as often as males.1,2
2.1. Study Rationale 
The purpose of the study is to evaluate the long-term safety, and tolerability of PF-06823859 
in adult participants with DM who are eligible for enrollment from a qualifying study. 
2.2. Background 
DM has no known cure and there were no previously approved treatments prior to 2021 
when IVIG, Octagam® 10% became the first approved treatment for adults with DM.
However, complications of IVIG therapy have been well documented).3 Patients typically 
use a combination of drugs to seek relief for their inflammatory symptoms. Typically, the 
first line of treatment for the muscle disease is corticosteroids to address the inflammation as 
well as suppress the immune system. Other immunosuppressive drugs, notably azathioprine, 
methotrexate, MMF, and cyclophosphamide are used as subsequent lines of therapies in 
refractory cases or as steroid sparing agents. However, complications of long-term steroid 
and immunosuppressive therapies are also well documented. Other novel approaches have 
emerged as potential treatment, including tacrolimus (broadly immunosuppressive drug 
developed for transplant use), and rituximab, following positive outcomes in some case 
studies. However, additional randomized controlled trials with these treatments are needed to 
guide clinical practice.4 Consequently, DM remains a disease with very high unmet medical 
need, and development of safe and effective therapies is warranted.
PF-06823859 is a potent, selective, humanized IgG1 neutralizing antibody directed against 
the human soluble cytokine IFN, a member of the type I IFN family of cytokines. 
PF-06823859 is a novel compound in development for the treatment of DM with added 
potential for therapeutic benefit in SLE. 
2.2.1. Clinical Overview
2.2.1.1.1. Safety (FIH C0251001)
A FIH study, C0251001, (Phase 1, Randomized, Double Blind, Third Party Open Placebo 
Controlled, Dose Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and 
Pharmacodynamics of Single and Multiple Intravenous and Subcutaneous Doses of 
PF-06823859 in Healthy adult Participants5 completed in August 2017. This study consisted 
of 8 dosing cohorts. There were 5 single dose cohorts 30 mg IV, 100 mg IV, 300 mg IV, 
900 mg IV, and 2000 mg IV. The other 3 cohorts were multiple dose cohorts consisting of 
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Final Protocol, 03 September 2021 
PFIZER CONFIDENTIAL
CT02-GSOP Clinical Protocol Template Phase 1 2 3 4 (01 March 2021)
Page 23
100 mg x 3 SC doses (one dose every 2 weeks), 300 mg x 3 SC doses, (one dose every 
2 weeks). The last cohort evaluated 2 dosing regimens due to a longer than expected half-life 
based on emerging data from the preceding cohorts. This last cohort consisted of 600 mg IV 
x 3 doses (one dose every 2 weeks) and 600 mg IV x 2 doses (one dose every 4 weeks). 
A total of 62 participants completed the study; 48 participants were randomized to receive 
PF-06823859 and 14 participants were randomized to receive placebo. Results from this 
study suggest that PF-06823859 is generally well tolerated and safe when given up to 
2000 mg as single dose and up to 600 mg administered IV every 2 weeks or every 4 weeks.
The most common treatment-related TEAEs were somnolence, upper respiratory tract 
infection and headache. These adverse events were generally mild and resolved without 
further intervention. No serious AE or death occurred during the study.
One participant experienced an ISR after each of the 100 mg SC doses with PF-06823859 
(3 doses) administered every 2 weeks. These were characterized by mild localized erythema 
with induration and tenderness, but no signs or symptoms of a systemic reaction. These local 
reactions resolved without further intervention within a few days. This participant also had 
treatment induced ADA, which had returned to baseline at the time of discharge 
(Section 2.2.1.1.3; Immunogenicity Results).
Overall, there was no apparent difference in the total incidence of adverse events between 
participants treated with the active IP compared to placebo, and no apparent dose relationship 
with the incidence of AEs. However, the rate of mild upper respiratory tract infection 
appeared to be higher in participants treated with PF- 06823859.
There were no clinically significant changes in vital signs or laboratory abnormalities. 
2.2.1.1.2. PK Summary for C0251001
Following single IV infusion dosing of PF-06823859, exposure based on AUCinf and Cmax 
exhibited approximately dose-proportional increase with increasing doses across the dose 
ranges from 30 mg to 2000 mg. Geometric mean CL was slow with values ranging from 
0.006 to 0.007 L/hr across all doses, and small Vss values (geometric mean values ranging 
from 4.8 L to 6.0 L) indicative of distribution primarily in the plasma volume. Mean t½
values were similar across the doses ranging from 23 to 29 days. 
Following multiple SC doses of 100 mg and 300 mg administered Q2W for a total of 3 doses, 
peak serum concentrations were achieved with a median Tmax of 96 hours post dose on 
Day 1, and 48 hours post dose on Day 15 and Day 29. No marked departures from dose 
proportionality were observed for AUCτ and Cmax for the 2 dose regimens. Rac for serum 
AUCτ and Cmax were <2.5 fold and mean t1/2 values ranging from 25 to 35 days. CL/F was 
similar across the 2 dose regimens with geometric mean estimates at 0.016 L/h, while the 
geometric mean Vz/F estimates were approximately similar ranging from 13.9 to 18.9 L. 
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Estimated bioavailability values based on geometric mean AUCτ for the 100 mg and 300 mg 
SC doses on Day 1 were 43% and 44%, respectively, relative to the corresponding IV doses 
in the SAD period. 
Following multiple IV doses of 600 mg administered Q2W for a total of 3 doses; geometric 
mean AUCτ values were slightly higher on Days 15 and 29 compared to that observed on 
Day 1 with similar Cmax values observed across all dosing days. Serum AUCτ for the 
600 mg IV (Q4W) × 2 doses treatment group was slightly higher compared to AUCτ from the 
600 mg IV (Q2W) × 3 doses treatment group on Day 1 and Day 29. Multiple IV dose PK 
results were generally consistent with single dose IV PK data. Rac for serum AUCτ and Cmax
were <1.9 fold and mean t½ of 27 and 28 days was observed following 600 mg IV Q2W and 
600 mg IV Q4W dosing, respectively.
2.2.1.1.3. Immunogenicity Results for C0251001
A tiered approach for screening, characterization and ADA titer assessment of serum samples 
was adopted to characterize immunogenicity.
During the SAD period, there were 3 out of 26 subjects who were confirmed positive for 
treatment induced ADA and none of them were confirmed positive for NAb. During the 
MAD period, there were 2 out of 22 subjects who were confirmed positive for treatment 
induced ADA and 1 of the 2 subjects was confirmed positive for NAb; and 1 out of 
22 subjects was confirmed positive for treatment boosted ADA. 
The low immunogenicity incidence rates, especially for the NAb, did not provide sufficient 
information to adequately determine the impact of ADA/NAb on the PK and safety; there 
were no immunologically related clinical responses of concern observed during the study. 
2.2.1.1.4. Efficacy and Safety (Phase 2 C0251002 Study, Stage 1)
C0251002 is an ongoing multi-center, double blind randomized placebo-controlled Phase 2 
study to evaluate the efficacy, safety, tolerability and PK of PF-06823859 in adult patients 
with active DM. Stage 1 of the study was designed to evaluate the effects of 600 mg 
PF-06823859 and placebo administered IV at baseline, Week 4 and Week 8 in participants 
with skin-predominant DM. The data summarized below are a high level summary based 
upon a snapshot date of 27 February 2020. In that the database of this study is not yet final, 
this should be considered preliminary evidence. 
The primary endpoint of Stage 1 of the study was the change from baseline in the CDASI-A 
score at Week 12. A clinically and statistically significant difference in CDASI-A score over 
time was observed between the active and placebo treatment arms. The least squares mean 
difference estimate of CFB in the CDASI-A in the active treatment versus the placebo group 
(primary endpoint) was -14.82 (90% CI -20.26, -9.37, p=0.0001). 
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A 13-gene Type 1 IFN gene signature was used to assess pharmacodynamic activity in skin 
biopsies. The % change from baseline levels of the gene signature at Week 12 on lesional 
skin was markedly lower (83.6%) for the PF-06823859 group compared to the placebo group 
(11.8%), showing- pharmacodynamic activity (one sided p=0.00016).
PF-06823859 at a dose of 600 mg IV was generally safe and well tolerated, with a 
comparable safety profile between the PF-06823859 and placebo groups. No deaths occurred 
in Stage 1 of the Phase 2 study. There were 3 SAEs and 2 permanent discontinuations due to 
TEAEs, all of which were considered unrelated to treatment by both investigator and 
Sponsor. Most TEAEs were mild or moderate in severity and occurred at a similar frequency 
in the active treatment and placebo groups. Based on the preliminary estimates of effect from 
the Stage 1 data of Study C0251002, PF-06823859 demonstrates a favorable benefit-risk 
profile in the potential treatment of DM.
2.3. Benefit/Risk Assessment
DM is a rare disease with higher prevalence in females than males. Therefore, the trial 
objectives cannot be met without inclusion of WOCBP. Nonclinical data to date has not 
identified any risk to reproductive organs in sexually mature cynomolgus monkeys, the 
pharmacologically relevant species. Given that an ePPND study is ongoing, this protocol that 
allows enrollment of WOCBP has stringent requirements to mitigate unintended exposures 
(pregnancy testing and use of contraceptives). 
Based on non-clinical in vitro data, PF-06832859 did not activate the classical complement 
pathway, induce the release of proinflammatory cytokines or complement-dependent 
cytotoxicity, or suppress a recall immune response to a T-cell-dependent antigens. In 
nonclinical toxicity studies in cynomolgus monkeys, the only pharmacologically relevant 
species, no adverse effects were noted after once weekly IV or SC administration of 
PF-06823859 for up to 6-months in duration to sexually mature or juvenile male and female 
monkeys. PF-06823859 was administered to cynomolgus monkeys by the IV and/or SC 
routes once weekly in the repeat-dose pivotal GLP-compliant toxicity study for a 14-week 
dosing phase followed by an 8-week recovery (dose-free) phase. In that study, the only 
PF-06823859-related effects were non-adverse changes in selected clinical pathology 
parameters which had resolved by the end of the 9-week recovery phase. In the 6-month 
chronic toxicity study, once-weekly IV administration of PF-06823859 at doses of 20, 100, 
and 300 mg/kg/week resulted in likely an immune-mediated hypersensitivity response in 
1 animal at 100 and 1 animal at 300 mg/kg/week, and non-adverse changes in clinical 
chemistry parameters. There were no macroscopic or microscopic effects in male or female 
reproductive organ systems and no hemodynamic effects (ie, ECG or HR) on the 
cardiovascular system were noted. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of PF-06823859 may be found in the current Investigator’s Brochure, which is 
the SRSD for this study. 
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2.3.1. Risk Assessment
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk 
Mitigation Strategy
Study Intervention(s) PF-06823859
Increased susceptibility to viral infections 
There is a potential risk of increased
susceptibility to viral infections with 
IFNβ blockade as with any antagonist of 
Type 1 interferon signaling 
(eg, anti-IFNAR1, anti-IFNα, JAK 
inhibitors). 
Participants may have increased risk of 
SARS-CoV-2 exposure by undergoing a 
study procedure at a study facility.
Serious and non-serious adverse event 
monitoring will occur on an 
ongoing/continuous manner as indicated 
in the Safety Review Plan. 
Alternative measures including use of 
telehealth, home health, etc will be 
utilized in the study in the case of a public 
emergency to minimize potential exposure 
of trial participants to SARS-CoV-2 (see 
Appendix 9; Section 10.9.
Interaction with other medicinal products 
and other forms of interaction
In vitro or in vivo PK drug interaction 
studies have not been conducted with 
PF-06823859. Although several 
cytokines such as IL-6 and TNF-α have 
been shown to modulate expression of 
CYP enzymes and transporters, cytokine 
mediated drug interactions observed in 
the clinic to date have been modest with 
these agents, resulting in a less than 
2-fold change in the exposure of a 
co-administered small molecule drugs. 
Overall, the DDI risk is expected to be
low. 
Participants will abstain from prohibited 
concomitant treatments as described in the 
Appendix 10.8.
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2.3.2. Benefit Assessment
Based on the clinical data from the FIH study (C0251001), the preliminary efficacy and 
safety data from the ongoing Phase 2 study (C0251002) in participants with DM, and the 
available non-clinical data, the risks and potential benefits for PF-06823859 are considered to 
be favorable and support continued clinical development in participants with DM. 
2.3.3. Overall Benefit/Risk Conclusion
Taking into account the measures to minimize risk to study participants, the potential risks 
identified in association with PF-06823859 are justified by the anticipated benefits that may 
be afforded to participants with moderate to severe DM.
3. OBJECTIVES, ENDPOINTS, AND ESTIMANDS
Objectives
Endpoints
Estimands
Primary: 
Primary:
Primary: 

To evaluate the long-term 
safety and tolerability of 
PF-06823859.

Incidence of AEs, laboratory 
abnormalities, changes in vital 
signs, and ECG findings.

There are no defined 
estimands for safety and 
tolerability endpoints; these 
will be analyzed using Pfizer 
data standards, as applicable.
Secondary: 
Secondary:
Secondary: 

To evaluate the long-term 
efficacy of PF-06823859 in 
adult participants with 
moderate to severe DM.

Change from baseline in CDASI 
activity score at Week 52.

Absolute values and change 
from baseline of CDASI activity 
and CDASI damage scores at all 
scheduled timepoints.

TIS score at Week 52 and at 
intermediate scheduled 
timepoints for participants who

E1: This estimand uses a 
hypothetical estimand 
strategy (ICH E9 addendum) 
estimating the mean effect of 
PF-06823859 in the absence 
of intercurrent events (study 
withdrawal). This is the mean 
change from baseline to 
Week 52 CDASI activity 
score for all randomized and 
dosed participants with 
non-missing baseline score in 
the (a) Skin Analysis Set and 
(b) Muscle Analysis Set (see 
details in Section 9.1.1).

These additional CDASI 
endpoints will be analyzed 
using E1 at all scheduled 
timepoints.

E2: This estimand uses a 
hypothetical estimand 
strategy (ICH E9 addendum) 
estimating the mean effect of 
PF-06823859 in the absence 
of intercurrent events (study 
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entered from Stage 3 of Protocol 
C0251002.
Change from baseline in the 
CSMs of the TIS including 
PhGA, PtGA, MMT-8, 
HAQ-DI, muscle enzymes, and 
MDAAT at Week 52 and at 
intermediate scheduled 
timepoints.
withdrawal). This is the mean 
TIS at Week 52 for all 
randomized and dosed 
participants included with 
non-missing baseline score in 
the Muscle Analysis Set (see 
details in Section 9.1.1).

The endpoints for the CSM of 
the TIS will be analyzed 
using E2 at Week 52 and all 
intermediate scheduled 
timepoints.
Tertiary/Exploratory: 
Tertiary/Exploratory:
Tertiary/Exploratory: 

To characterize 
pharmacokinetics (PK) of 
PF-06823859.

To characterize 
pharmacodynamics (PD) 
effects of PF 06823859.

To evaluate immunogenicity of 
PF-06823859.

To evaluate the effect of 
PF‑0682359 on suicidality 
assessment over time in 
participants with active DM.

To evaluate the effect of 
PF-0682359 on SF-36 
(v2 acute) and EQ-5D-5L 
PROs.

Plasma concentrations of 
PF-06823859. 

Absolute values and change 
from baseline in the values of 
selected biomarkers at all 
scheduled time points.

Incidence of ADA and NAb.

Absolute values and change 
from baseline values of 
Columbia‑Suicide Severity 
Rating Scale (C‑SSRS) at all 
scheduled time points.

Absolute values and change 
from baseline in the values of 
PROs including SF-36 (v2 
acute) and EQ-5D-5L at all 
scheduled timepoints. 

Not applicable.
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 2b, OLE study to evaluate the long-term safety and tolerability of 
PF-06823859 in adult participants with moderate to severe DM who completed the treatment 
period of a qualifying study (including Protocol C0251002) and have agreement from their 
study doctor to continue active treatment. Eligible participants will not have had any 
significant protocol deviations (eg, not following the protocol, taking prohibited medications, 
not using appropriate contraception) or have not completed all study treatment in the 
qualifying study. Approximately 30 participants who complete the Week 24 visit during the 
treatment period in Study C0251002 or equivalent in another qualifying study, may be 
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enrolled in Protocol C0251008. The treatment duration of OLE study participation will be up 
to 48 weeks (treatment period is up through and including Week 52), with a 16 week follow 
up period. See Section 1.2 for the study schematic.
Qualified participants will be randomized to receive open-label PF-06823859 600 mg IV 
every 4 weeks for up to 48 weeks, however the treatment period is up to Week 52. All 
participants will be followed for another 16 weeks in the Follow-up Period. Participants who 
are discontinued from study intervention will also enter the follow-up period. 
4.2. Scientific Rationale for Study Design
Based on the mechanism of action of PF-06823859 and preliminary results from the Phase 2 
C0251002 clinical study in adults with DM (see Section 2.2.1.1.4), this OLE study is being 
conducted to provide additional data on the long-term safety and tolerability of IV 
PF-06823859 in adult participants with active DM.
4.2.1. Diversity of Study Population
The diversity of this study population is dependent upon the qualifying studies and those 
participants that become eligible for this OLE study.
4.2.2. Choice of Contraception/Barrier Requirements 
Potential reproductive and/or developmental toxicities are currently not known for 
PF-06823859; therefore, use of a highly effective method of contraception is required. Please 
see Appendix 4 for definitions of highly effective birth control measures and user dependent 
vs. low user dependent examples of contraceptives.
4.2.3. Collection of Retained Research Samples
Retained Research Samples will be collected and stored for further analyses which may, for 
example, provide greater understanding of the study intervention.
4.3. Justification for Dose
A 600 mg IV dose administered Q4W was chosen as a suitable dose for this study based on 
preliminary efficacy and gene suppression data from Stage 1 of Study C0251002 (see 
Section 2.2.1.1.4).
Results from Stage 1 in Study C0251002 showed a difference in CDASI-A over time
between the active and placebo treatment arms that was clinically and statistically significant.
The observed mean CFB in CDASI-A at Week 12 (standard deviation) were -19.62 (9.14) 
and -3.44 (5.27) for the PF-06823859 600 mg IV and placebo groups, respectively. The least 
squares mean difference estimate of CFB in the CDASI-A in the active versus the placebo 
group (primary endpoint) was -14.82 (90% CI -20.26, -9.37), showing statistical significance 
(p=0.0001). Sensitivity analysis using a ANCOVA model for CFB in the CDASI-A at 
Week 12 with baseline CDASI-A and treatment as variables in the model gave an estimated 
mean difference of CFB in the CDASI-A for PF-06823859 600 mg compared to placebo at 
Week 12 of -15.39 (CI -20.24, -10.54), showing similar level of efficacy (p<0.0001) 
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consistent with the primary analysis. The separation of treatment effect for PF-06823859 
compared with placebo, as measured by the CFB in CDASI-A, was observed as early as 
Week 4 and persisted through Week 24 (for available interim data). These results clearly 
suggest that the 600 mg IV dose administered Q4W was highly efficacious in DM 
participants. 
Additionally, the 600 mg IV Q4W was previously tested in healthy participants from Study 
C0251001 as well as DM participants in Study C0251002 and was considered safe. In the 
GLP-compliant 6-month chronic toxicity study in cynomolgus monkeys, there were no test 
article-related adverse effects up to highest dose tested, 300 mg/kg/dose (IV). At the 
proposed clinical dose of 600 mg IV Q4W, exposure margins (ie, safety margins) after the 
third dose relative to the highest dose in the chronic toxicity study are approximately 54x for 
Cav and 40x for Cmax. The proposed dose of 600 mg IV Q4W will maximize the potential for 
efficacy, especially since target engagement of PF-06823859 in skin and muscle is unclear. 
IV was chosen as the route of administration to support the large volume of the dose that will 
be required to obtain the targeted gene signature suppression as well as for participant 
adherence. The frequency of administration was chosen as 4 weeks to achieve targeted gene 
signature suppression but also to reduce study burden on the participant. 
The proposed dose of 600 mg IV Q4W was determined to be suitable in Study C0251008 to 
confirm pharmacology and to test durability of clinical efficacy, with sufficient safety 
margins relative to the toxicology exposure limits. 
Additional information for this compound may be found in the SRSD, which for this study is 
the IB. 
4.4. End of Study Definition
LSLV is defined as the date the investigator reviews the last participant’s final safety data 
and determines that no further evaluation is required for the participant to complete the trial.
A participant is considered to have completed the study if he/she has completed all periods of 
the study, including Visit 18, EOS visit, Week 68 as shown on the SoA.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled. The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate. All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol. 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
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5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex:
1. Participants aged ≥18 and ≤80 with moderate to severe DM, that have completed the 
treatment period of the qualifying study.
Type of Participant and Disease Characteristics:
2. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.
3. Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
Informed Consent: 
4. Capable of giving signed informed consent as described in Appendix 1, which 
includes compliance with the requirements and restrictions listed in the ICD and in 
this protocol.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Other medical or psychiatric condition including recent (within the past year) or 
active suicidal ideation/behavior or laboratory abnormality that may increase the risk 
of study participation or, in the investigator’s judgment, make the participant 
inappropriate for the study.
Prior/Concomitant Therapy:
2. Current use of any prohibited concomitant medication(s) listed in Appendix 8. 
3. Hematologic abnormalities defined as:

ANC ≤1000/mm3;

Platelets ≤25,000/mm3;

Hemoglobin ≤8g/dL.
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4. Hepatic dysfunction defined as:

Total bilirubin ≥2x ULN (≥3x ULN for Gilbert’s disease);

AST ≥2.5 x ULN;

ALT ≥2.5 x ULN;

For Participants with DM who experience elevated AST, ALT, LDH, 
aldolase, and CK, due to muscle involvement the investigator should 
determine whether or not these are related to the existing condition of DM or 
if these lab abnormalities are related to another condition. Information should 
be provided in the source documentation with rationale related to any lab 
abnormalities.
5. Baseline standard 12-lead ECG that demonstrates clinically relevant abnormalities 
that may affect participant safety or interpretation of study results (eg, QTcF interval 
>450 msec, complete LBBB, signs of an acute or indeterminate age myocardial 
infarction, ST-T interval changes suggestive of myocardial ischemia, second or third 
degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline 
uncorrected QT interval is >450 msec, this interval should be rate corrected using the 
Fridericia method and the resulting QTcF should be used for decision making and 
reporting. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be 
repeated 2 more times and the average of the 3 QTcF or QRS values should be used 
to determine the participant’s eligibility. Computer interpreted ECGs should be 
overread by a physician experienced in reading ECGs before excluding a participant.
6. Participants who met discontinuation criteria at any point during the participating 
qualifying studies.
7. Participants with an ongoing safety event in the qualifying studies which, in the 
opinion of the investigator or sponsor, is an ongoing safety concern OR the 
participant has met safety monitoring criteria in the qualifying study that has not 
resolved.
8. Participants with significant protocol deviations (eg, not following the protocol, not 
using appropriate contraception) or have had a serious adverse event related to study 
drug in the previous qualifying studies.
Other Exclusions:
9. Investigator site staff or Pfizer employees directly involved in the conduct of the 
study, site staff otherwise supervised by the investigator, and their respective family 
members. 
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5.3. Lifestyle Considerations
In order to participate in the study, participants must be aware of the life-style guidelines and 
restrictions that apply during and after the study period described in this section.
5.3.1. Contraception 
Studies to evaluate the development toxicity of PF-06823859 have not been 
conducted. Therefore, the use of a highly effective method of contraception is required (see 
Section 10.4).
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant and his or her partner(s) from the permitted list of contraception methods (see 
Appendix 4 Section 10.4.4) and will confirm that the participant has been instructed in its 
consistent and correct use. At time points indicated in the SoA, the investigator or designee 
will inform the participant of the need to use highly effective contraception consistently and 
correctly and document the conversation and the participant’s affirmation in the participant’s 
chart (participants need to affirm their consistent and correct use of at least 2 of the selected 
methods of contraception, preferably 1 highly effective method of low user dependency, or a 
high user dependency method with a barrier method) considering that their risk for 
pregnancy may have changed since the last visit. In addition, the investigator or designee will 
instruct the participant to call immediately if the selected contraception method is 
discontinued or if pregnancy is known or suspected in the participant or partner.
5.3.2. Surgery
During the study, no elective surgery should occur without first consulting with the sponsor. 
Preferably, elective surgery should be delayed until participation in the study is completed. 
The sponsor should be notified if a participant requires surgery (including dental surgery) 
during the study to determine whether the participant should discontinue from the study 
and/or discontinue the study intervention prior to the surgical procedure. In general, planned 
surgical procedures should not be performed unless the study intervention has been 
discontinued for at least 28 days (unless otherwise advised by the sponsor). In addition, the 
sponsor should be notified as soon as possible if a participant undergoes a surgical procedure 
without first informing the study staff.
5.4. Screen Failures 
Since this is an open-label long-term continuation study for participants who have completed 
other qualifying studies, eg, Protocol C0251002, screen failures are not applicable.
6. STUDY INTERVENTION(S) AND CONCOMITANT THERAPY
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, medical device(s), or study procedure(s) intended to be administered to a study 
participant according to the study protocol.
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For the purposes of this protocol, study intervention refers to PF-06823859.
6.1. Study Intervention(s) Administered
For this study, the study intervention will be administered intravenously over approximately 
one hour. Study intervention will be administered every 4 weeks, each participant receiving 
13 doses of study intervention over the duration of the trial. 
Study Interventions(s)
Intervention Name
PF-06823859
ARM Name
(group of patients receiving a specific treatment 
(or no treatment)
PF-06823859
Type
Drug
Dose Formulation
Solution for injection 
Unit Dose Strength(s)
100 mg/mL
Dosage Level(s)
600 mg Q4W
Route of Administration
IV
Use
Experimental
IMP or NIMP
IMP
Sourcing
Provided centrally by the sponsor or locally by the 
trial site, subsidiary, or designee. See IP manual for 
more information.
Packaging and Labeling
Open-label study intervention will be provided in a 
6 mL glass vial sealed with a stopper and aluminum 
flip off cap. Each vial contains 1.35 mL 
PF-06823859. The vials will be packaged into 
cartons containing 6 vials per carton. Each vial and 
carton will be labeled as required per country 
requirement.
6.1.1. Administration
Open-label IV PF-06823859 will be administered at the investigative site or clinic over the 
course of approximately 60 minutes as an IV infusion, using a calibrated infusion pump. 
Once the infusion has completed, all participants will be monitored for an additional 
60 minutes post study intervention administration to ensure no infusion site reactions.
6.1.1.1. Infusion Discontinuation

If a participant experiences symptoms typical of an allergic reaction, the study 
intervention administration should be discontinued immediately and permanently and 
the event should be captured as an AE. 
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
If a participant experiences symptoms typical of infusion reactions 
(eg, lightheadedness, nausea, chills, fever), the study intervention infusion should be 
stopped. At the discretion of the investigator, the infusion can be restarted at a slower 
rate if symptoms are resolved within 1 hour after the stop of infusion. If symptoms 
return, then the study intervention administration should be discontinued immediately 
and permanently. 

In the event that there is an infusion interruption, the entire duration of drug infusion, 
from the initial start of infusion to the completion of infusion, should not exceed 
3 hours. Participants will receive appropriate treatment at the discretion of the 
investigator.
6.1.1.2. Pre-Medication Use on the Day of IVIG Administration
For participants who enroll in the study who are receiving IVIG: On the day of IVIG dose 
administration, pre-medication to prevent hypersensitivity reaction to IVIG is permitted. The 
steroid dose that was previously used for pre-medication will be permitted (on IVIG dosing 
day only). After IVIG dosing day, steroid dosing should remain less than or equal to 15 mg 
or equivalent of prednisone per day for participants in the severe skin disease cohort and 20 
mg or equivalent of prednisone per day for participants in the moderate muscle disease 
cohort as per protocol Section 6.8.3.
There is no need to change the IVIG dosing schedule or adjust the IVIG dosing schedule 
related to study intervention administration.
6.2. Preparation, Handling, Storage, and Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff. At a 
minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request. Data for nonworking days must 
indicate the minimum and maximum temperatures since previously documented for 
all site storage locations upon return to business.
3. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken. The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible. Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 
to use the study intervention. Specific details regarding the definition of an excursion 
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and information the site should report for each excursion will be provided to the site 
in the IP manual.
4. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the label.
5. Study interventions should be stored in their original containers.
6. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records), such as the 
IPAL or sponsor-approved equivalent. All study interventions will be accounted for 
using a study intervention accountability form/record.
7. Further guidance and information for the final disposition of unused study 
interventions are provided in the IP manual. All destruction must be adequately 
documented. If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with 
applicable environmental regulations, institutional policy, and any special instructions 
provided by Pfizer.
Upon identification of a product complaint, notify the sponsor within 1 business day of 
discovery as described in the IP manual.
6.2.1. Preparation and Dispensing
A qualified staff member will dispense the study intervention using the IRT system via 
unique container numbers in the single-use vials provided, in quantities appropriate 
according to the dose assignment. 
See the IP manual for instructions on how to prepare the study intervention for 
administration. Study intervention should be prepared and dispensed by an appropriately 
qualified and experienced member of the study staff (eg, physician, nurse, physician’s 
assistant, nurse practitioner, pharmacy assistant/technician, or pharmacist) as allowed by 
local, state, and institutional guidance. A second staff member will verify the dispensing.
PF-06823859 be prepared by qualified site personnel according to the IP manual. The study 
intervention will be administered in an open-label fashion to the participants.
6.2.2. Study Intervention Accountability
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the study intervention supplies. All study intervention will be accounted 
for using a drug accountability form/record.
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6.2.2.1. Destruction of Study Intervention Supplies
The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site). If destruction is authorized to take place at the investigator site, 
the investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented.
All used glass vials should be maintained at the investigative site for accountability. The 
investigator will maintain the unused supply until destruction is authorized. Pfizer will 
provide instructions as to the disposition of any unused study intervention.
6.3. Measures to Minimize Bias: Randomization and Blinding
6.3.1. Allocation to Study Intervention
Study intervention will be administered at the study visits summarized in the SoA.
This is an open-label study. The site will contact the IRT prior to the start of study 
intervention administration for each participant. The site will record the vial numbers
assigned on the applicable CRF, if required. 
The investigator’s knowledge of the treatment should not influence the decision to enroll a 
particular participant or affect the order in which participants are enrolled.
6.4. Study Intervention Compliance
Participants will receive study intervention directly from the investigator or designee, under 
medical supervision. The date and time of each dose administered in the clinic will be 
recorded in the source documents and recorded in the CRF. The dose of study intervention 
and study participant identification will be confirmed at the time of dosing by a member of 
the study site staff other than the person administering the study intervention. 
The site will complete the required dosage Preparation Record located in the IP manual. The 
use of the Preparation Record is preferred, but it does not preclude the use of an existing 
appropriate clinical site documentation system. The existing clinical site's documentation 
system should capture all pertinent/required information on the preparation and 
administration of the dose. This may be used in place of the Preparation Record after 
approval from the sponsor and/or designee.
6.5. Dose Modification 
Dose modification is not permitted in this study.
6.6. Continued Access to Study Intervention After the End of the Study
No intervention will be provided to study participants at the end of their study participation.
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6.7. Treatment of Overdose
For this study, any dose of PF-06823859 greater than 600 mg within a 24-hour time period 
will be considered an overdose.
There is no experience with overdose of PF-06823859. There is no specific antidote for 
overdose with PF-06823859. Treatment at the discretion of the investigator should be 
symptomatic and supportive. In case of an overdose, it is recommended that the subject be 
monitored for signs and symptoms of adverse reactions. Participants who develop adverse 
reactions should receive appropriate treatment. 
In the event of an overdose, the investigator/treating physician should:
1. Contact the medical monitor within 24 hours.
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities for at 
least 5 half-lives or 28 calendar days after the overdose of PF-06823859 (whichever 
is longer). Closely monitor the participant for any AEs/SAEs.
3. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
4. Overdose is reportable to Pfizer Safety only when associated with an SAE.
5. Obtain a blood sample for PK analysis within 1-2 days from the date of the last dose 
of study intervention if requested by the medical monitor (determined on a 
case-by-case basis).
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
6.8. Concomitant Therapy
Hormonal contraceptives that meet the requirements of this study are allowed to be used in 
participants who are WOCBP (see Appendix 4).
For a list of prohibited and permitted concomitant medications refer to Appendix 8
(Section 10.8).
All ongoing medications from the previous study should be re-written in the new 
concomitant medication page for this study. 
Participants must continue to avoid use of medications that have been washed out prior to 
enrollment in their prior qualifying study (eg, C0251002 Protocol). The indication for use, 
total daily dose, route of administration, and start and stop dates for all ongoing medications 
(including prescription medications and treatments, vaccinations, nonprescription 
medications, nondrug treatments and dietary supplements) will be pulled from the qualifying 
study and documented as prior medications.
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Participants will be asked about all concomitant treatments (including prescription 
medications and treatments, vaccinations, nonprescription medications, nondrug treatments, 
dietary supplements, and herbal preparations) at each study visit. Medications after the first 
dose of study intervention has been administered in this OLE study will be documented as 
concomitant medications. Any new concomitant medications or dose changes to current 
concomitant medications should be evaluated for potential new or worsening AEs.
For the purposes of this protocol, dietary supplements are defined as vitamins, minerals, 
purified food substances, and herbals with pharmaceutical properties. Vitamins, minerals, 
purified food substances, and herbals with pharmaceutical properties are allowed in amounts 
not known to be associated with adverse effects (such as hypervitaminosis). 
6.8.1. Prohibited Concomitant Medications
Please see Appendix 8, Section 10.8.
6.8.2. Permitted Concomitant Medications
NSAIDs and aspirin are allowed; however, they may potentially affect efficacy parameters 
(eg, the skeletal disease activity VAS, arthritis assessment and gastrointestinal disease 
activity VAS for the MDAAT and thus should be used judiciously. Participants taking 
NSAIDS/analgesics should not take a dose of these medications within 12 hours prior to such 
assessments at those visits. 
Acetaminophen is primarily an analgesic and lacks the anti-inflammatory properties of 
NSAIDS. The use of acetaminophen is recommended when possible to treat non-DM related 
conditions, in the absence of a pre-existing hepatic function deficiency. 
6.8.3. Corticosteroids
Please refer to Appendix 11, Section 10.11.
The decision for increasing or tapering steroids is entirely up to the study investigator, and 
any change in the steroid dose should be recorded on the concomitant medication page. 
All concomitant treatments including corticosteroids or equivalent taken during the study 
must be recorded in study records with indication for use, total daily dose, and start and stop 
dates of administration. 
Oral corticosteroids taken by the participants during the study will be captured on a separate 
CRF. The CRF page will capture the name of the corticosteroid taken, indication for use, 
total daily dose, route of administration, and start date and stop dates of administration.
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6.8.3.1. Guidance for Investigators
During the course of the study, those participants who experience a severe flare requiring 
new or increased doses of immunosuppressants (including new or increased doses of 
corticosteroids beyond what is permitted), will be discontinued from the treatment period of 
the study and placed in the follow up period, and therefore, will receive no further study 
intervention. Rescue therapy may be administered as clinically necessary. 
See Appendix 11 (Section 10.11) for further guidelines for corticosteroid use.
6.8.4. Rescue Medicine 
If the participant requires the addition of higher DMARD doses or an additional DMARD for 
a flare or persistent increase in dermatomyositis activity, then the participant should be 
discontinued from the treatment period but complete the follow-up visits. High dose oral 
corticosteroids (>100 mg/day prednisone, or equivalent) or pulse IV doses, or any IV or IM 
steroid injection would exclude the participant for further treatment in the study.
See Appendix 11 (Section 10.11) for further guidelines for rescue medication.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
It may be necessary for a participant to permanently discontinue study intervention. Reasons 
for permanent discontinuation of study intervention include the following:

Serious infections defined as any infection;

Other serious or severe AEs;

Laboratory abnormalities deemed clinically significant by the investigator that can 
adversely affect the participant;

Use of prohibited medications.
Full details for reasons for permanent discontinuation of study intervention as well as 
monitoring criteria are included in Section 10.10 (Appendix 10).
Note that discontinuation of study intervention does not represent withdrawal from the study. 
If study intervention is permanently discontinued, the participant will remain in the study to
be evaluated for safety. See the SoA for data to be collected at the time of discontinuation of 
study intervention and follow-up for any further evaluations that need to be completed.
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In the event of discontinuation of study intervention, it must be documented on the 
appropriate CRF/in the medical records whether the participant is discontinuing further 
receipt of study intervention or also from study procedures, posttreatment study follow-up, 
and/or future collection of additional information.
7.2. Participant Discontinuation/Withdrawal From the Study 
A participant may withdraw from the study at any time at his/her own request. Reasons for 
discontinuation from the study include the following:

Refused further study procedures;

Lost to follow-up;

Death;

Study terminated by sponsor;

Consent: Withdrawal of consent (see Section 7.2.1).
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
The participant will be permanently discontinued from the study intervention and the study at 
that time.
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples taken and not tested, and the investigator must document any such requests in the 
site study records and notify the sponsor accordingly.
If the participant withdraws from the study and also withdraws consent (see Section 7.2.1 for 
disclosure of future information, no further evaluations should be performed and no 
additional data should be collected. The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
7.2.1. Withdrawal of Consent 
Participants who request to discontinue receipt of study intervention will remain in the study 
and must continue to be followed for protocol-specified follow-up procedures. The only 
exception to this is when a participant specifically withdraws consent for any further contact 
with him or her or persons previously authorized by the participant to provide this 
information. Participants should notify the investigator in writing of the decision to withdraw 
consent from future follow-up, whenever possible. The withdrawal of consent should be 
explained in detail in the medical records by the investigator, as to whether the withdrawal is 
only from further receipt of study intervention or also from study procedures and/or 
posttreatment study follow-up, and entered on the appropriate CRF page. In the event that 
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vital status (whether the participant is alive or dead) is being measured, publicly available 
information should be used to determine vital status only as appropriately directed in 
accordance with local law.
7.3. Lost to Follow-Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to attend a required study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible. Counsel the participant on the importance of maintaining the 
assigned visit schedule, and ascertain whether the participant wishes to and/or should 
continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures. 
Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Safety issues should be discussed with the sponsor immediately upon occurrence or 
awareness to determine whether the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All baseline evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.
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Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of the ICD may be utilized for baseline purposes provided 
the procedures met the protocol-specified criteria and were performed within the time frame 
defined in the SoA.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test. In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant. When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible. The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The actual collection times of blood sampling may change. Additional blood samples may be 
taken for safety assessments at times specified by Pfizer or at the discretion of the 
investigator, provided the total volume taken during the study does not exceed 550 mL 
during any period of 56 consecutive days.
8.1. Efficacy Assessments
8.1.1. CDASI
The secondary endpoints for this study assess changes in the modified CDASI6 activity score 
as well as the individual components. 
8.1.2. Total Improvement Score (TIS)
There are 6 core set measures that comprise the total improvement score. These components 
are:

PhGA, VAS (see Section 8.1.2.1);

PtGA (see Section 8.1.3.4);

MMT-8 score (see Section 8.1.2.2);

HAQ- DI score (see Section 8.1.3.3);

MDAAT Global Extramuscular Disease Activity (Section 8.1.2.3 and 

The participant’s most elevated muscle enzymes. 
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The total improvement score is the sum of all 6 improvement scores associated with the 
change in each core set measure.
8.1.2.1. Physician Global Assessment (PhGA) Visual Analogue Scale (VAS)
The PhGA, VAS is an assessment of the participant’s general health status rather than the 
disease activity in a specific organ. The investigator will be asked to make a mark on a visual 
analog scale answering the question “The patient’s DM at this time is”. The scale uses a 
100 mm VAS which has verbal anchors at 0 (very good) and 100 (very poor). The 
investigator is asked to evaluate the participant’s overall disease activity and response to 
treatment at the time of the clinic visit. 
This assessment should be completed by the same physician completing the clinical medical 
assessments.
8.1.2.2. MMT-8 
This partially validated tool assesses muscle strength using MMT. A 0 – 10-point scale is 
proposed for use. An abbreviated group of 8 proximal, distal, and axial muscles performs 
similarly to a total of 24 muscle groups, and is also proposed for use for research studies.
8.1.2.3. MDAAT
Global extramuscular disease activity is measured by the MDAAT, a tool with a 
comprehensive approach that assesses constitutional, cutaneous, skeletal, gastrointestinal, 
pulmonary, and cardiovascular activity. 
8.1.3. Patient Reported Outcomes
When the participant reports to the clinic for a visit, the order in which the patient reported 
outcomes are completed is important, and these assessments should be completed at every 
visit in the same consistent order. Please find the following descriptions of all PROs used in 
this study. 
8.1.3.1. The Short Form -36 Version 2, Acute (SF 36 v2 acute)
The SF-36 v2 acute is a 36 item generic health status measure.5,7,8 It measures 8 health 
domains: physical function, role physical, bodily pain, general health, vitality, social 
functioning, role emotional, and mental health. These domains can be summarized as PCS 
and MCS. The SF-36 acute version uses a one-week recall and is suitable for use when the 
measure is administered repeatedly on a weekly basis. The SF-36 will be collected as 
indicated in the Schedule of Activities. (Section 1.3).
8.1.3.2. EuroQoL 5 Dimensions 5 Levels (EQ 5D 5L) and EQ-VAS 
The EQ 5D 5L is a validated, standardized, generic instrument that is the most widely used 
preference based HRQoL questionnaire in cost effectiveness and HTA.9,10,11 It is a well 
established instrument to measure health states and utilities in various disease areas. The 
EQ-5D 5L contains 5 items that cover mobility, self-care, usual activities, pain/discomfort, 
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and anxiety/depression, with five response levels of severity ranging from no problems to 
unable to/extreme problems. The measure also includes a VAS, which records the 
respondent’s overall current health. The vertical EQ VAS, labelled with ‘The best health you 
can imagine’ and ‘The worst health you can imagine’, provides a quantitative measure of the 
patient’s perception of their overall health. The EQ-5D-5L and EQ-VAS will be collected as 
indicated in the Schedule of Activities (Section 1.3). 
8.1.3.3. Health Assessment Questionnaire – Disability Index (HAQ-DI) 
Participants will complete the HAQ-DI that assesses the degree of difficulty a patient has 
experienced during the past week in 8 domains of daily living activities: dressing and 
grooming, arising, eating, walking, hygiene, reach, grip, and other activities.12
For each of these eight domains, the patient reports the amount of difficulty they have in 
performing specific activities. For each question, the level of difficulty is scored from 0 to 3 
with 0 representing “without any difficulty,” and 3 as “unable to do.” Participants should 
complete the section on activities that require them to use aids and/or devices or if they need 
help from another person. These sections may be left blank if no aids or devices are required 
or no help from another person is needed. The HAQ-DI will be collected as indicated in the 
Schedule of Activities (Section 1.3).
8.1.3.4. Patient’s Global Assessment (PtGA) 
The PtGA is a single item question to measure the global evaluation as reported by the 
patient. The PtGA question assesses the patient’s overall activity at the time of assessment 
using a 10 cm VAS by asking the patient to answer: “Your myositis is the result of the 
combined effects of many disease processes. One of these is disease activity, which is active 
inflammation in your muscles, skin, joints, intestines, heart, lungs or other parts of your 
body, which can improve when treated with medicines. Considering all the ways that 
myositis affects you, please rate the overall activity of your disease today by placing a mark 
on the line below.” Higher scores indicate extremely active or severe disease activity.13,14
The PtGA will be collected as indicated in the Schedule of Activities (Section 1.3).  
8.1.4. Rater Qualifications
For specific rating assessments, only qualified raters will be allowed to evaluate and/or rate 
participants in this study. The minimum qualifications a rater must meet for each study rating 
assessment will be outlined in the training materials provided to each participating site. The 
level of experience with the target population (or equivalent), specific scale experience (or 
equivalent), and certification required (if applicable) will be listed and used to determine 
whether a rater is approved for a given assessment. The rater must become certified to 
perform selected study assessments before he or she can participate in the conduct of the 
study. For specifically defined assessments, rater training and standardization exercises may 
be conducted, and written documentation will be provided by the site for each rater’s 
certification. In return, each site will be provided written documentation outlining each 
rater’s certification for specific study assessments. Recertification may be required at 
periodic intervals during the study. The raters who administer specific study assessments will 
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be documented in a centralized location and all site staff who administer ratings will be 
verified in the site study documentation during the conduct of the study.
8.1.4.1. CDASI 
To ensure uniform conduct of the CDASI in participants with DM, investigators or other 
qualified site personnel will be required to go through training session(s) led by a qualified 
individual. Personnel responsible for conducting the CDASI will be permitted to complete 
CDASI assessments once training is completed and proper documentation of training is 
issued. It is highly recommended that the same individual conduct the CDASI assessment 
from visit to visit to decrease variability. It is also highly recommended that the same 
physician complete the PhGA, VAS for consistency.
8.1.4.2. MMT-8 
To ensure uniform conduct of the MMT-8 in participants with DM, investigators or other 
qualified site personnel will be required to go through training session(s) led by a qualified 
individual, or video training. Personnel responsible for conducting the MMT-8 will be 
permitted to complete MMT-8 assessments once training is completed and proper 
documentation of training is issued. It is highly recommended that the same individual 
conduct the CDASI assessment from visit to visit to decrease variability. 
8.1.4.3. MDAAT 
To ensure uniform conduct of the MDAAT in participants with DM, investigators or other 
qualified site personnel will be required to go through training session(s) led by a qualified
individual, or video training.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA. Unscheduled clinical 
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety issues.
8.2.1. Medical History
A participant’s complete medical history will be transferred from the qualifying study 
(eg, C0251002). In addition, all ongoing adverse events from the previous qualifying study 
will be recorded on the medical history page in the new study and monitored until resolved. 
Any new adverse events will be recorded after the administration of study intervention.
8.2.2. Physical Examinations
Complete PE consists of assessments of general appearance, skin, HEENT, heart, lungs, 
breasts (optional), abdomen, external genitalia (optional), extremities, neurologic function, 
back, and lymph nodes. Complete PE must be performed by the investigator, sub-investigator 
or a qualified health professional per local guidelines. 
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Targeted PE consists of assessments of skin, heart, lungs, abdomen, and examination of body 
systems where there are symptom complaints by the participant. Target physical exam should 
be completed prior to dosing. Targeted PE must be performed by the investigator, 
sub-investigator or a qualified health professional per local guidelines. 
Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
Complete and targeted physical examinations are performed at various time points, see 
Schedules of Activities (Section 1.3).
Physical examination findings collected during the study will be considered source data and 
will not be required to be reported, unless otherwise noted. Any untoward physical 
examination findings that are identified during the active collection period and meet the 
definition of an AE or SAE (Appendix 3) must be reported according to the processes in 
Sections 8.3.1 to 8.3.3.
8.2.3. Height and Weight
Height and weight will be measured without the participant wearing shoes. Height (inches or 
centimeters) and weight (pounds or kilograms) will be measured up to one decimal place and 
recorded in the source document at the baseline visit.
Height (inches or centimeters) will be measured at baseline only. Weight will continue to be 
assessed and recorded at various time points, see Schedules of Activities (Section 1.3).
8.2.4. Vital Signs
Vital signs (blood pressure, heart rate [pulse], and temperature) will be measured after 
approximately 5 minutes of rest as indicated in the Schedules of Activities (Section 1.3). BP 
will be measured using a standard calibrated blood pressure measuring device. A BP device 
that uses multiple cuff sizes for the participant based on the arm circumference is required. 
The arm circumference at the midpoint of the length of the upper arm should be measured to 
determine the appropriate cuff size in accordance with the specifications of the BP measuring 
device. The same properly sized and calibrated blood pressure cuff will be used to measure 
blood pressure each time. The use of automated devices for measuring BP and heart rate 
(pulse) are acceptable, although, when done manually, heart rate will be measured in the 
brachial/radial artery for at least 30 seconds.
Participants should be seated in a chair, back supported, and arms bared (free of restrictions 
such as rolled-up sleeves, etc.) and supported at the level of the heart. Measurements should 
be taken on the same arm (preferably the non-dominant arm) at each visit throughout the 
study after 5-10 minutes of rest and recorded to the nearest mm Hg. Participants should 
refrain from smoking or ingesting caffeine during the 30 minutes prior to the measurements.
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Heart rate should be measured at approximately the same time as BP for a minimum of 
30 seconds. When the timing of BP and heart rate measurements coincides with a blood 
collection or other study procedure, BP and heart rate should be obtained first.
It is preferred that body temperature be collected using the tympanic or oral methods and that 
the same method be used consistently throughout the study.
8.2.5. Electrocardiograms
Standard 12-leads utilizing limb leads (with a 10 second rhythm strip) should be collected at 
times specified in the SoA section of this protocol using an ECG machine that automatically 
calculates the heart rate and measures PR, QT, and QTc intervals and QRS complex. 
Alternative lead placement methodology using torso leads (eg, Mason-Likar) should not be 
used given the potential risk of discrepancies with ECGs acquired using standard limb lead 
placement. All scheduled ECGs should be performed after the participant has rested quietly 
for at least 5 minutes in a supine position. 
The Day 1 pre-dose ECG values will serve as each participant’s baseline values. To ensure 
safety of the participants, a qualified individual (investigator or sub-investigator) at the 
investigator site will make comparisons to baseline measurements. A paper or digital copy of 
the ECG should be filed in the participant’s chart and must be available to the sponsor upon 
request. Any clinically significant changes will be recorded as AEs and evaluated further, as 
clinically warranted. In some cases, it may be appropriate to repeat abnormal ECGs to rule 
out improper lead placement as contributing to the ECG abnormality.
If a postdose QTcF interval remains ≥60 msec from the baseline and is >450 msec; or b) an 
absolute QT value is ≥500 msec for any scheduled ECG for greater than 4 hours (or sooner, 
at the discretion of the investigator); or c) QTcF intervals get progressively longer, the 
participant should undergo continuous ECG monitoring. A cardiologist should be consulted 
if QTcF intervals do not return to less than the criteria listed above after 8 hours of 
monitoring (or sooner, at the discretion of the investigator). 
ECG data will be read locally. The final ECG report should be maintained in the participant’s 
source documentation and be the final interpretation of the ECG recording. Any clinically 
significant changes from the baseline/Day 1 ECG may potentially be AEs (Appendix 7) and 
should be evaluated further, as clinically warranted. 
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings. If a machine-read QTc 
value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTcF values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 7.
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8.2.6. Infusion Site Reaction Assessment
Infusion site reactions will be assessed according to the Schedules of Activities (Section 1.3). 
Infusion site reactions may include but are not limited to erythema, induration, ecchymosis, 
pain, and pruritus. 
Any signs or symptoms related to an infusion site reaction should be treated according to the 
investigator’s standard of care and reported as adverse events.
8.2.7. Photography
During the study, photographic images may be taken of the participant’s skin. The 
photographs taken for this study are for source documentation purposes only and will not be 
evaluated, nor included in the clinical study report.
8.2.8. Clinical Safety Laboratory Assessments 
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency. All protocol-required laboratory assessments, as defined in 
Appendix 2, must be conducted in accordance with the laboratory manual and the SoA. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety issues. 
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 5 terminal half-lives after the last dose of study 
intervention should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator or medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified, and the sponsor notified.
See Appendix 6 for suggested actions and follow-up assessments in the event of potential 
drug-induced liver injury.
8.2.9. Pregnancy Testing 
Pregnancy tests will be urine tests, but must have a sensitivity of at least 25 mIU/mL. 
Pregnancy tests will be performed in WOCBP at the times listed in the SoA. Following a 
negative pregnancy test result at screening, appropriate contraception must be commenced,
and a second negative pregnancy test result will be required at the baseline visit prior the 
participant’s receiving the study intervention. Pregnancy tests will also be done whenever 
1 menstrual cycle is missed during the active treatment period (or when potential pregnancy 
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is otherwise suspected) and at the end of the study. Pregnancy tests may also be repeated if 
requested by IRBs/ECs or if required by local regulations. If a urine test cannot be confirmed 
as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the 
participant must be excluded if the serum pregnancy result is positive.
8.2.10. Assessment of Suicidal Ideation and Behavior
8.2.10.1. Columbia -Suicide Severity Rating Scale (C-SSRS)
Due to the increased rate of depression in the participants diagnosed with DM, the C-SSRS 
will be used to assess suicidal ideation and behavior during the conduct of the study. The 
C-SSRS is a patient-reported questionnaire administered by the investigator or site staff that 
have been trained to administer the test. The C-SSRS is a validated tool to evaluate suicidal 
ideation and behavior.15
At any visit, if the participant answers “yes” on items 4, 5 or on any suicidal behavior 
question of the C-SSRS, the participant will be discontinued from treatment and referred to 
a mental health professional for appropriate evaluation and treatment. If the participant 
cannot be seen by a mental health professional within 24 hours, the participant should be 
sent to a local emergency room for psychiatric assessment.
8.3. Adverse Events, Serious Adverse Events, and Other Safety Reporting
The definitions of an AE and an SAE can be found in Appendix 3.
AEs may arise from symptoms or other complaints reported to the investigator by the 
participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally 
authorized representative), or they may arise from clinical findings of the Investigator or
other healthcare providers (clinical signs, test results, etc.).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether the 
event meets the criteria for classification as an SAE or caused the participant to discontinue 
the study intervention (see Section 7.1). 
During the active collection period as described in Section 8.3.1, each participant will be 
questioned about the occurrence of AEs in a nonleading manner.
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
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8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving study intervention), through and including a 
minimum of 5 months after the last administration of the study intervention. 
Since this is an extension study, once the ICD is signed, any newly developed adverse events
recorded prior to study drug dosing should be recorded in the participant’s medical history. 
Once the participant receives study drug, all and any adverse events will be reviewed and 
recorded on the adverse event page.
Follow-up by the investigator continues throughout and after the active collection period and 
until the AE or SAE or its sequelae resolve or stabilize at a level acceptable to the 
investigator.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
If the participant withdraws from the study and also withdraws consent for the collection of 
future information, the active collection period ends when consent is withdrawn.
If a participant permanently discontinues or temporarily discontinues study intervention 
because of an AE or SAE, the AE or SAE must be recorded on the CRF and the SAE 
reported using the CT SAE Report Form.
Investigators are not obligated to actively seek information on AEs or SAEs after the 
participant has concluded study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has completed the study, and he/she 
considers the event to be reasonably related to the study intervention, the investigator must 
promptly report the SAE to Pfizer using the CT SAE Report Form.
8.3.1.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period as described in 
Section 8.3.1 are reported to Pfizer Safety on the CT SAE Report Form immediately upon 
awareness and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 3. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
All nonserious AEs and SAEs occurring in a participant during the active collection period, 
which begins after obtaining informed consent as described in Section 8.3.1, will be recorded 
on the AE section of the CRF.
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The investigator is to record on the CRF all directly observed and all spontaneously reported 
AEs and SAEs reported by the participant.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-Up of AEs and SAEs
After the initial AE or SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality. Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided. In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 3.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/ECs, and investigators.
Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.
An investigator who receives SUSARs or other specific safety information (eg, summary or 
listing of SAEs) from the sponsor will review and then file it along with the SRSD(s) for the 
study and will notify the IRB/EC, if appropriate according to local requirements.
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8.3.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and 
Occupational Exposure
Environmental exposure occurs when a person not enrolled in the study as a participant 
receives unplanned direct contact with or exposure to the study intervention. Such exposure 
may or may not lead to the occurrence of an AE or SAE. Persons at risk for environmental 
exposure include healthcare providers, family members, and others who may be exposed. An 
environmental exposure may include exposure during pregnancy, exposure during 
breastfeeding, and occupational exposure.
Any such exposure to the study intervention under study are reportable to Pfizer Safety 
within 24 hours of investigator awareness.
8.3.5.1. Exposure During Pregnancy
An EDP occurs if: 

A female participant is found to be pregnant while receiving or after discontinuing 
study intervention.

A male participant who is receiving or has discontinued study intervention exposes a 
female partner prior to or around the time of conception.

A female is found to be pregnant while being exposed or having been exposed to 
study intervention due to environmental exposure. Below are examples of 
environmental EDP: 

A female family member or healthcare provider reports that she is pregnant after 
having been exposed to the study intervention by accidental needle stick during 
drug preparation.

A male family member or healthcare provider who has been exposed to the study 
intervention by accidental needle stick during drug preparation then exposes his 
female partner prior to or around the time of conception.
The investigator must report EDP to Pfizer Safety within 24 hours of the investigator’s 
awareness, irrespective of whether an SAE has occurred. The initial information submitted 
should include the anticipated date of delivery (see below for information related to 
termination of pregnancy). 

If EDP occurs in a participant or a participant’s partner, the investigator must report 
this information to Pfizer Safety on the CT SAE Report Form and an EDP 
Supplemental Form, regardless of whether an SAE has occurred. Details of the 
pregnancy will be collected after the start of study intervention and until at least 
5 terminal half-lives after the last dose. This time would be approximately 20 weeks 
or 5 months after the last dose of study intervention. 
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
If EDP occurs in the setting of environmental exposure, the investigator must report 
information to Pfizer Safety using the CT SAE Report Form and EDP Supplemental 
Form. Since the exposure information does not pertain to the participant enrolled in 
the study, the information is not recorded on a CRF; however, a copy of the 
completed CT SAE Report Form is maintained in the investigator site file.
Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP Supplemental Form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
Abnormal pregnancy outcomes are considered SAEs. If the outcome of the pregnancy meets 
the criteria for an SAE (ie, ectopic pregnancy, spontaneous abortion, intrauterine fetal 
demise, neonatal death, or congenital anomaly in a live-born baby, a terminated fetus, an 
intrauterine fetal demise, or a neonatal death), the investigator should follow the procedures 
for reporting SAEs. Additional information about pregnancy outcomes that are reported to 
Pfizer Safety as SAEs follows: 

Spontaneous abortion including miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs. In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the study intervention. 
Additional information regarding the EDP may be requested by the sponsor. Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the participant with the Pregnant Partner Release of Information 
Form to deliver to his partner. The investigator must document in the source documents that 
the participant was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.3.5.2. Exposure During Breastfeeding
An exposure during breastfeeding occurs if: 

A female participant is found to be breastfeeding while receiving or after 
discontinuing study intervention.
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
A female is found to be breastfeeding while being exposed or having been exposed to 
study intervention (ie, environmental exposure). An example of environmental 
exposure during breastfeeding is a female family member or healthcare provider who 
reports that she is breastfeeding after having been exposed to the study intervention 
by accidental needle stick during drug preparation.
The investigator must report exposure during breastfeeding to Pfizer Safety within 24 hours 
of the investigator’s awareness, irrespective of whether an SAE has occurred. The 
information must be reported using the CT SAE Report Form. When exposure during 
breastfeeding occurs in the setting of environmental exposure, the exposure information does 
not pertain to the participant enrolled in the study, so the information is not recorded on a 
CRF. However, a copy of the completed CT SAE Report Form is maintained in the 
investigator site file.
An exposure during breastfeeding report is not created when a Pfizer drug specifically 
approved for use in breastfeeding women (eg, vitamins) is administered in accord with 
authorized use. However, if the infant experiences an SAE associated with such a drug, the 
SAE is reported together with the exposure during breastfeeding.
8.3.5.3. Occupational Exposure
The investigator must report any instance of occupational exposure to Pfizer Safety within 
24 hours of the investigator’s awareness using the CT SAE Report Form, regardless of 
whether there is an associated SAE. Since the information about the occupational exposure 
does not pertain to a participant enrolled in the study, the information is not recorded on a 
CRF; however, a copy of the completed CT SAE Report Form must be maintained in the 
investigator site file.
8.3.6. Cardiovascular and Death Events
All CV and death events should be reported according to the instructions in Section 8.3.1 to 
Section 8.3.3. 
8.3.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs 
or SAEs 
Not Applicable.
8.3.8. Adverse Events of Special Interest 
Not Applicable.
8.3.8.1. Lack of Efficacy
The investigator must report signs, symptoms, and/or clinical sequelae resulting from lack of 
efficacy. Lack of efficacy or failure of expected pharmacological action is reportable to 
Pfizer Safety only if associated with an SAE. 
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8.3.9. Medical Device Deficiencies 
Not Applicable.
8.3.10. Medication Errors
Medication errors may result from the administration or consumption of the study 
intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the study intervention under study may occur in clinical trial settings, such as 
medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the study intervention;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified within 24 hours.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and nonserious, are recorded on the AE page of the 
CRF. 
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.
8.4. Pharmacokinetics 
8.4.1. Serum for Analysis of PF-06823859
Blood samples will be collected for measurement of serum concentrations of PF-06823859
at times specified in the Schedule of Activities. Instructions for the collection and handling 
of biological samples will be provided in the laboratory manual or by the sponsor. The 
actual date and time (24 hour clock time) of each sample will be recorded. PK should be 
taken from the opposite arm that the drug was administered. If a participant is suspected to 
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be experiencing an immune-related event, the unscheduled blood samples should be 
collected for concentration of PF-06823859 within 3 days of the event and sampling time 
and date should be documented. A PK collection will also be collected at the early 
withdrawal visit if necessary.
The actual times may change, but the number of samples will remain the same. All efforts 
will be made to obtain the samples at the exact nominal time relative to dosing. 
Samples will be used to evaluate the PK of PF-06823859. Each serum sample will be 
prepared as described in the lab manual. Samples collected for analyses of PF-06823859 
serum concentration may also be used to evaluate safety or efficacy aspects related to 
concerns arising during or after the study, for metabolite identification and/or evaluation of 
the bioanalytical method, or for other internal exploratory purposes and not reported in the 
CSR.
Genetic analyses will not be performed on these serum samples unless consent for this was 
included in the informed consent. Participant confidentiality will be maintained.
Samples collected for measurement of serum concentrations of study intervention will be 
analyzed using a validated analytical method in compliance with applicable SOPs.
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity. Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor. 
On a case-by-case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised. Any changes in the timing or addition of time points for any 
planned study assessments must be documented and approved by the relevant study team 
member and then archived in the sponsor and site study files, but will not constitute a 
protocol deviation. The IRB/EC will be informed of any safety issues that require alteration 
of the safety monitoring scheme or amendment of the ICD.
As part of understanding the pharmacokinetics of the study intervention, samples may be 
used for metabolite identification and/or evaluation of the bioanalytical method. These data 
will be used for internal exploratory purposes and will not be included in the clinical study
report.
8.4.2. Shipment of Pharmacokinetic Samples
The shipment address and contact information will be provided to the investigator site prior 
to the initiation of the study. The central laboratory will provide collection materials and 
directions for packaging and shipment of samples and will forward samples to the contract 
analytical laboratory. The contract analytical laboratory will be provided with randomization 
codes so that only samples in the PF-06823859 treatment groups are assayed. Refer to the 
central laboratory manual for further information.
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8.4.3. IVIG Analysis
In this study, IVIG is permitted as a concomitant treatment and participants enrolled who are 
treated with IVIG concomitantly will have blood samples collected prior to study 
intervention administration. These samples will be collected to measure IVIG concentrations
in the event that there are changes in the participant’s pharmacokinetic profile. These 
samples may be analyzed and reported separately. 
If unscheduled labs are determined to be necessary, participants who are continuing to 
receive IVIG will also need an IVIG sample collection and a corresponding PK specimen 
(see Section 8.4.3).
8.5. Genetics
8.5.1. Specified Genetics
Genetics (specified analyses) are not evaluated in this study.
8.6. Biomarkers
8.6.1. PD Biomarkers
The PD samples must be processed and shipped as indicated to maintain sample integrity. 
Any deviations from the PD processing steps, including any actions taken, must be 
documented and reported to the sponsor. On a case-by-case basis, the sponsor may make a 
determination as to whether sample integrity has been compromised. 
All efforts will be made to obtain the PD samples at the exact nominal time relative to 
dosing. Please consult the laboratory manual(s) for final instructions on sample collection, 
storage, and shipping requirements. These laboratory manual(s) supersede the instructions 
listed in the applicable protocol sections. Samples that are handled according to the 
respective manual guidance are considered “per protocol”.
Samples will be analyzed using fit for purpose or validated analytical methods in compliance 
with Pfizer standard operating procedures.
As part of understanding the pharmacodynamics of the study intervention and the disease 
under study, samples may be used for evaluation of the bioanalytical method. These data will 
be used for internal (ie, Pfizer) exploratory purposes and may not be included in the clinical 
study report. 
8.6.1.1. Samples for hsCRP Analysis
Blood samples to provide serum for the analysis of hsCRP will be collected into 
appropriately labeled tubes according to the times outlined in the Schedule of Activities
(Section 1.3).
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8.6.1.2. Total IFN
Blood samples to provide serum for the analysis of total IFNwill be collected into 
appropriately labeled tubes according to the times outlined in the Scheduled of Activities
(Section 1.3).
8.6.1.3. Biospecimen for Blood Muscle Biomarkers
Blood samples to provide serum for the analysis of muscle biomarkers will be collected into 
appropriately labeled tubes according to the times outlined in the Schedule of Activities
(Section 1.3).
8.6.2. Retained Research Samples for Biomarkers
These Retained Research Samples will be collected in this study:

6 mL whole blood (Prep B1.5 plasma);

6 mL whole blood (Prep B2.5 serum);

2.5 mL whole blood (Prep R1 optimized for RNA).
Retained Research Samples will be collected as local regulations and IRB/ECs allow 
according to the SoA. 
Retained Research Samples may be used for research related to the study intervention(s): and 
DM. Genes and other analytes (eg, proteins, RNA, nondrug metabolites) may be studied 
using the retained samples. 
See Appendix 5 (Section 10.5) for information regarding genetic research. Details on 
processes for collection and shipment of these samples can be found in the lab manual. 
8.7. Immunogenicity Assessments
8.7.1. Serum for Analysis of Anti-PF-06823859
8.7.1.1. Antibodies (ADA) and Neutralizing Anti-PF-06823859 Antibodies (NAb)
Blood samples for the detection of ADA and NAb will be collected at the times specified in 
Schedule of Activities. Instructions for the collection and handling of biological samples will 
be provided in the laboratory manual or by the sponsor. The actual date and time (24-hour 
clock time) of each sample will be recorded.
Any changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
sponsor and site study files, but will not constitute a protocol deviation. The IRB/EC will be 
informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICD.
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Further details regarding the collection, processing, storage and shipping of the blood 
samples will be provided in the lab manual.
8.7.2. Immunogenicity Analyses
The immunogenicity samples must be processed and shipped as indicated to maintain sample 
integrity. Any deviations from the immunogenicity processing steps, including any actions 
taken, must be documented and reported to the sponsor. On a case by case basis, the sponsor 
may make a determination as to whether sample integrity has been compromised. Any 
sample deemed outside of established stability, or of questionable integrity, will be 
considered a protocol deviation.
Samples will be analyzed using validated analytical methods in compliance with Pfizer 
standard operating procedures. Samples tested as ADA positive, (not just confirmed positive, 
but also with a titer positive result) will be further tested for NAb using validated NAb 
assays. Participants with positive results at the conclusion of the study may be requested to 
return for additional follow-up for up to approximately 5 months after the last scheduled 
follow-up visit. An additional PK and ADA sample will be collected, and the information 
recorded as an unscheduled visit.
Samples collected for determination of ADA and NAb may also be used for additional 
characterization of the immune response and/or evaluation of the bioanalytical method, or for 
other internal exploratory purposes. These data will be used for internal exploratory purposes 
and not reported in the CSR.
Samples collected for detecting ADA and NAb will be retained in accordance to local 
regulations and if not used within this timeframe, will be destroyed. Additional exploratory 
testing of samples may be performed to further characterize the ADA response and /or 
evaluation of the bioanalytical method. These data will be used for internal exploratory 
purposes and will not be included in the clinical report. 
8.7.3. Shipment of Immunogenicity (ADA/NAb) Samples
The shipment address and assay lab contact information will be provided to the investigator 
site prior to initiation of the study.
8.8. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a SAP, which will be maintained by the sponsor. The 
SAP may modify what is outlined in the protocol where appropriate; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
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9.1. Statistical Hypotheses
No statistical hypothesis testing is planned for this study.
9.1.1. Estimands
9.1.1.1. Primary Estimands
There are no defined estimands for the incidence of AEs, laboratory abnormalities, changes 
in vital signs, and ECG findings. These endpoints will be analyzed using Pfizer data 
standards as applicable. All participants who receive at least 1 dose of IP will be included in 
the safety analyses. All safety data will be summarized descriptively through appropriate data 
tabulations, descriptive statistics, categorical summaries, and graphical presentations. 
9.1.1.2. Secondary Estimands
Two estimands are defined for this study. Estimand 1 (E1) will support specified CDASI 
assessments at specified timepoints for participants in the Skin Analysis Set and Muscle
Analysis Set separately (Section 9.2). Estimand 2 (E2) will support TIS and CSM 
assessments at specified timepoints for participants in the Muscle Analysis Set.
E1 will be the population average effect of PF-06823859 on CFB in CDASI activity score at 
Week 52 for all randomized and dosed participants with non-missing baseline in a specified 
analysis set (Skin or Muscle Analysis Set) in the absence of dropout. Measurements taken 
after a participant withdraws from treatment will be censored and treated as missing data. 
The population‑based estimate for the effect of PF-06823859 will be the mean CFB in 
CDASI-activity score at Week 52.
E1 will also be applied to each combination of the following endpoints, timepoints, and 
analysis sets:

Endpoints: Change from baseline and absolute values of CDASI activity score and 
CDASI damage score;

Timepoints: Week 52 and all scheduled intermediate timepoints;

Analysis sets: Skin Analysis Set and Muscle Analysis Set.
E2 will be the population average estimate for the effect of PF-06823859 on TIS at Week 52
for all randomized and dosed participants with non-missing baseline in the Stage 3 Muscle 
Analysis Set in the absence of dropouts. Measurements taken after a participant withdraws 
from treatment will be censored and treated as missing data. The population‑based estimate
for the effect of PF-06823859 will be the mean TIS at Week 52. 
E2 will also be applied to each combination of the following endpoints and timepoints in the 
Stage 3 Analysis Set:

Endpoints: TIS and change from baseline in each of the CSM of the TIS.
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
Timepoints: Week 52 and all scheduled intermediate timepoints.
9.1.2. Multiplicity Adjustment
Multiplicity adjustment is not applicable. No formal hypothesis testing is planned in this 
study. 
9.2. Analysis Sets
For purposes of analysis, the following analysis sets are defined:
Participant Analysis Set
Description
Randomized 
"Randomized" means a participant's, agreement to participate 
in a clinical study following completion of the informed 
consent process. A participant will be considered enrolled if 
the informed consent is not withdrawn prior to participating in 
any study activity.
Full Analysis Set (FAS) 
All participants enrolled who take at least 1 dose of study 
intervention.
Safety Analysis Set
All participants enrolled who take at least 1 dose of study 
intervention. This includes all such participants regardless of 
which parent study or stage the participant entered from.
Skin Safety Analysis Set
All participants with skin predominant DM who take at least 
1 dose of study intervention including participants entering 
from Amended Stage 2 of the C0251002 protocol.
Muscle Safety Analysis 
Set
Al participants with muscle predominant DM who take at least 
1 dose of study intervention including participants entering 
from Stage 3 of the C0251002 protocol. 
Defined Analysis Set 
(Efficacy)
Description
Skin Analysis Set
All participants with skin predominant DM in the FAS 
including participants who were enrolled in Amended Stage 2 
of the C0251002 study.
Muscle Analysis Set
All participants with muscle predominant DM in the FAS 
including participants who were enrolled in Stage 3 of the 
C0251002 study.
Pooled Skin Analysis Set
All participants in the FAS with a CDASI activity score of 14 
or greater at baseline of study C0251002. This analysis set 
includes all subjects from Amended Stage 2 of the C0251002 
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study and potentially some subjects from Stage 3 of the 
C0251002 study who also have skin disease.
9.3. Statistical Analyses
The SAP will be developed and finalized before any analyses are performed and will 
describe the analyses and procedures for accounting for missing, unused, and spurious data. 
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints.
9.3.1. General Considerations
This is an extension study to assess the safety and tolerability of the long-term therapy of 
PF-06823859 in participants with DM. All efficacy endpoints are secondary endpoints. The 
primary analysis population for safety evaluations will be the safety analysis set (see 
Section 9.2). All efficacy evaluations will be completed separately for those originating from 
the skin-predominant DM cohort including the C0251002 protocol second stage (Amended 
Stage 2) or the muscle-predominant DM cohort including the C0251002 third stage (Stage 3) 
of the C0251002 protocol. The respective analysis sets for these efficacy evaluations are the 
Skin Analysis Set and Muscle Analysis Set. Baseline will be Day 1 of the C0251008 study; 
sensitivity analyses that redefine Baseline as Day 1 of the parent study may also be 
performed and will be defined in the SAP.
9.3.2. Primary Endpoint(s) Analysis
The primary objective is to assess the long-term safety and tolerability of PF-06823859 in 
participants with DM. All safety endpoints will be listed and summarized in accordance with 
Pfizer Data Standards. Categorical outcomes (eg, AEs) will be summarized by participant 
counts and percentage. Continuous outcome (eg, BP, heart rate) will be summarized using N, 
mean, median, standard deviation. Change from baseline in laboratory data and vital signs 
will also be summarized according to sponsor Data Standards. 
9.3.3. Secondary Endpoint(s)/Estimand(s) Analysis
All efficacy endpoints are continuous variables and will be summarized with descriptive 
statistics at each time point (n, proportion, mean, standard deviation, median, etc.). For each 
efficacy endpoint, the estimates for the effect of PF-06823859 will be obtained by fitting a 
LANCOVA model from baseline to Week 52. Each LANCOVA model will include week as 
a fixed effect and baseline value as a covariate, as appropriate. An unstructured 
variance-covariance matrix will be allowed. Estimates and 90% CI will be reported. No 
p-values will be computed for the analysis. See Section 9.1.1.2 for a description of the 
secondary estimands.
In the longitudinal modeling (LANCOVA) of repeated measures of continuous outcomes 
(both efficacy measures and covariates) it is assumed that missing data are generated by the 
“missing at random” mechanism and, therefore imputation of the missing data is not 
necessary.
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A sensitivity analysis will be based on the ANCOVA. The ANCOVA-based estimation of the 
effect of PF-06823859 will use the observations collected at baseline and Week 52 visits only 
and will eliminate the complexity of modeling the covariance between the repeated measures 
of outcome observed at different visits. The resulting estimate may be slightly less precise 
than the LANCOVA-based estimate. 
Another sensitivity analysis for E1 will be performed that uses the pooled skin disease 
analysis set for assessment of the CDASI activity score. Other sensitivity analyses may be 
performed and will be described in the SAP.
Additional longitudinal efficacy and safety analyses that define baseline as Day 1 of the 
parent study may be performed and will be described in the SAP.
9.3.4. Tertiary/Exploratory Endpoint(s) 
The values of PROs at each visit will be summarized by descriptive statistics. 
Additional exploratory endpoints will be described in the SAP.
9.3.5. Other Safety Analyses
9.3.5.1. Adverse Events and Suicidality Assessments
The safety analyses will be carried out in the safety population and detailed analyses will be 
described in the SAP. 
Data relevant to the assessment of suicidality will be mapped to the C-CASA codes. Baseline 
and post baseline C-SSRS data (mapped to C-CASA scores) will be summarized 
descriptively by treatment group at baseline and each post baseline visit. The safety analyses 
will be carried out in the safety population, detailed analyses will be described in the SAP.
9.3.5.2. Electrocardiogram Analyses
Changes from baseline for the ECG parameters QT interval, heart rate, QTc interval, PR 
interval, and QRS complex will be summarized by treatment and time. The Day 1 pre-dose 
ECG measurements will be used as a participant’s baseline. 
The number (%) of participants with maximum postdose QTc values and maximum increases 
from baseline in the following categories will be tabulated by treatment: 
Safety QTc Assessment
Degree of Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450-480
>480-500
>500
Increase from baseline
30-60
>60
In addition, the number of participants with absolute QTc values ≥500 msec will be listed.
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9.3.6. Other Analyse(s) 
9.3.6.1. Pharmacokinetic Analysis
The PK concentration population for PF-06823859 is defined as all enrolled participants who 
received at least one dose of PF-06823859 and in whom at least one concentration value is 
reported.
PK concentrations will be summarized and presented with summary statistics and, if 
appropriate, noncompartmental PK parameter estimates may be provided. 
A population PK/PD model may be developed to characterize the PK and PD following 
PF-06823859 administration as well as to understand the covariates that describe inter-
subject variability in PK and PD. Any population PKPD model developed will not be part of 
the CSR and may be reported separately.
Data permitting, the relationship between exposure and clinical responses (efficacy and 
safety) in DM participants may be explored. Exposure-response analyses conducted will not 
be part of the CSR and may be reported separately. 
Pharmacogenomic or biomarker data from Retained Research Samples may be collected 
during or after the trial and retained for future analyses; the results of such analyses are not 
planned to be included in the CSR. 
9.4. Interim Analyses
No formal interim analysis will be conducted for this study. As this is an open-label study,
the sponsor may conduct unblinded reviews of the data during the course of the study for the 
purpose of safety assessments, facilitating PK/PD modeling, and/or supporting clinical 
development. 
9.5. Sample Size Determination
The sample size will be determined by the number of patients who enroll from Protocol 
C0251002 and any other future qualifying studies. It is anticipated that up to approximately 
30 participants from Amended Stage 2 and Stage 3 of Protocol C0251002 will be enrolled to 
receive open-label study intervention.
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines, including the 
Declaration of Helsinki and CIOMS International Ethical Guidelines;

Applicable ICH GCP guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, SRSD(s), and other relevant documents 
(eg, advertisements) must be reviewed and approved by the sponsor, submitted to an IRB/EC 
by the investigator, and reviewed and approved by the IRB/EC before the study is initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
Protocols and any substantial amendments to the protocol will require health authority 
approval prior to initiation except for changes necessary to eliminate an immediate hazard to 
study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH GCP guidelines, the IRB/EC, European regulation 
536/2014 for clinical studies (if applicable), European Medical Device Regulation 
2017/745 for clinical device research (if applicable), and all other applicable local 
regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
intervention, Pfizer should be informed immediately. 
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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of the ICH GCP guidelines that the investigator 
becomes aware of.
10.1.2. Financial Disclosure
Investigators and sub investigators will provide the sponsor with sufficient, accurate financial
information as requested 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.
10.1.3. Informed Consent Process 
The investigator or his/her representative will explain the nature of the study, including the 
risks and benefits, to the participant and answer all questions regarding the study. The 
participant should be given sufficient time and opportunity to ask questions and to decide 
whether or not to participate in the trial.
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, privacy and data protection requirements, where 
applicable, and the IRB/EC or study center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date on which the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICD.
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Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the participant.
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic form and 
will be password-protected to ensure that only authorized study staff have access. The study 
site will implement appropriate technical and organizational measures to ensure that the 
personal data can be recovered in the event of disaster. In the event of a potential personal 
data breach, the study site will be responsible for determining whether a personal data breach
has in fact occurred and, if so, providing breach notifications as required by law.
To protect the rights and freedoms of participants with regard to the processing of personal 
data, participants will be assigned a single, participant-specific numerical code. Any 
participant records or data sets that are transferred to the sponsor will contain the numerical 
code; participant names will not be transferred. All other identifiable data transferred to the 
sponsor will be identified by this single, participant-specific code. The study site will 
maintain a confidential list of participants who participated in the study, linking each 
participant’s numerical code to his or her actual identity and medical record ID. In case of 
data transfer, the sponsor will protect the confidentiality of participants’ personal data 
consistent with the clinical study agreement and applicable privacy laws.
10.1.5. Committees Structure
10.1.5.1. Data Monitoring Committee
This study will not use a DMC.
10.1.6. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the EudraCT, and/or 
www.pfizer.com, and other public registries in accordance with applicable local 
laws/regulations. In addition, Pfizer reports study results outside of the requirements of local 
laws/regulations pursuant to its SOPs.
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
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www.clinicaltrials.gov
Pfizer posts clinical trial results on www.clinicaltrials.gov for Pfizer-sponsored interventional 
studies (conducted in patients) that evaluate the safety and/or efficacy of a product, 
regardless of the geographical location in which the study is conducted. These results are 
submitted for posting in accordance with the format and timelines set forth by US law.
EudraCT
Pfizer posts clinical trial results on EudraCT for Pfizer-sponsored interventional studies in 
accordance with the format and timelines set forth by EU requirements.
www.pfizer.com
Pfizer posts public disclosure synopses (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the corresponding study results are 
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the EMA website. Clinical data, under Phase 1 of this policy, includes clinical 
overviews, clinical summaries, CSRs, and appendices containing the protocol and protocol 
amendments, sample CRFs, and statistical methods. Clinical data, under Phase 2 of this 
policy, includes the publishing of individual participant data. Policy 0070 applies to new 
marketing authorization applications submitted via the centralized procedure since 
01 January 2015 and applications for line extensions and for new indications submitted via 
the centralized procedure since 01 July 2015.
Data sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contributes to the scientific understanding of the 
disease, target, or compound class. Pfizer will make data from these trials available 
24 months after study completion. Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations. CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
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10.1.7. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
Guidance on completion of CRFs will be provided in the CRF Completion Requirements 
document.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic form and are password protected to prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents. This 
verification may also occur after study completion. It is important that the investigator(s) and 
their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques 
(central, virtual, or on-site monitoring), are provided in the data management plan and 
monitoring plan maintained and utilized by the sponsor or designee. 
The sponsor or designee is responsible for the data management of this study, including 
quality checking of the data.
Records and documents, including signed ICDs, pertaining to the conduct of this study must 
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such 
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory retain 
notification in relation to the study. Furthermore, the investigator will cooperate with the 
sponsor or its agents to prepare the investigator site for the inspection and will allow the 
sponsor or its agent, whenever feasible, to be present during the inspection. The investigator 
site and investigator will promptly resolve any discrepancies that are identified between the 
study data and the participant's medical records. The investigator will promptly provide 
copies of the inspection findings to the sponsor or its agent. Before response submission to 
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the regulatory authorities, the investigator will provide the sponsor or its agents with an 
opportunity to review and comment on responses to any such findings.
10.1.8. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site.
Data reported on the CRF or entered in the eCRF that are from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available.
In this study, the CRF will serve as the source document. A document must be available at 
the investigative site that identifies those data that will be recorded on the CRF and for which 
the CRF will be the source document.
Definition of what constitutes source data and its origin can be found in the clinical 
monitoring plan, which is maintained by the sponsor.
Description of the use of the computerized system is documented in the Data Management 
Plan, which is maintained by the sponsor.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP guidelines, and all applicable regulatory requirements.
10.1.9. Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the date of the first participant’s first visit and will be the study 
start date.
The sponsor designee 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.
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The investigator may initiate study-site closure at any time upon notification to the sponsor if 
requested to do so by the responsible IRB/EC or if such termination is required to protect the 
health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or the ICH GCP 
guidelines;

Inadequate recruitment of participants by the investigator; 

Discontinuation of further study intervention development.
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the ECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of 
the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up.
If the sponsor decides to terminate the study for a reason unrelated to the safety of
PF-06823859, participants may continue to receive PF-06823859(s) per the investigator’s 
judgement and protocol-specified safety assessments will continue to be performed for these 
participants until the end of study as defined in Section 4.4. The following non-safety-related 
study procedures and assessments may be stopped upon written notification from the 
sponsor:

CDASI;

TIS;

MMT-8;

MDAAT Global extramuscular disease activity;

PROs (SF-36 v2 acute, EQ-5D-5L, HAQ-DI, and PtGA);

PhGA,VAS.
Study termination is also provided for in the clinical study agreement. If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
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10.1.10. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after the end of the study 
(or study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications, 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission. This allows the sponsor to protect proprietary information and to 
provide comments, and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
intervention-related information necessary for the appropriate scientific presentation or 
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites. In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data. In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
this section will not apply.
10.1.11. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the supporting study portal.
To facilitate access to appropriately qualified medical personnel for study-related medical
questions or problems, participants are provided with an Emergency Contact Card (ECC) at 
the time of informed consent. The ECC contains, at a minimum, (a) protocol and study 
intervention identifiers, (b) participant’s study identification number, (c) site emergency 
phone number active 24 hours/day, 7 days per week, and (d) Pfizer Call Center number.
The ECC is intended to augment, not replace, the established communication pathways 
between the investigator, site staff, and study team. The ECC is to be used by healthcare 
professionals not involved in the research study only, as a means of reaching the investigator 
or site staff related to the care of a participant. The Pfizer Call Center number should only be 
used when the investigator and site staff cannot be reached. The Pfizer Call Center number is 
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not intended for use by the participant directly; if a participant calls that number directly, he 
or she will be directed back to the investigator site.
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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol. Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory, or as derived 
from calculated values. These additional tests would not require additional collection of 
blood. Unscheduled clinical laboratory measurements may be obtained at any time during the 
study to assess any perceived safety issues.
Any unscheduled visits or unscheduled labs may be performed at the Investigator’s discretion 
if a participant experiences a flare or an adverse event. For participants receiving 
concomitant IVIG, see Section 8.4.3 for unscheduled specified analyses.
Table 3.
Laboratory Tests
Hematology
Chemistry
Urinalysis
Other
Hemoglobin 
Hematocrit 
RBC count 
Platelet count
WBC count with differential 
Total neutrophils (%, Abs) 
Eosinophils (%, Abs) 
Basophils (%, Abs) 
Lymphocytes (%, Abs) 
Monocytes (%, Abs) PT/PTT
hsCRP
BUN and Creatinine 
Serum cystatin C
CK Glucose (fasting & non 
fasting) 
Sodium
Potassium 
Chloride 
Calcium
Total CO2 (Bicarbonate) 
AST, ALT
LDH
Aldolase
CK-MB (Only if CK is 
elevated)
Total Indirect and Direct 
Bilirubin
Alkaline phosphatase 
Uric acid
Albumin Total protein
pH
Glucose (qual) Protein 
(qual) 
Blood (qual) 
Ketones 
Nitrites
Leukocyte esterase 
Microscopya
Spot Urine (Upr:Ucr) 
eGFRb
-hcG c
Retained Research Sample
Prep R1
Retained Research Sample
Prep B1.5
Retained Research Sample
B2.5
PK collections
IVIG collections for 
participants taking IVIG 
concomitantly.
Immunogenicity, 
ADA.NAb,
total IFN,
Blood for muscle 
biomarkers
a.
Only if urine dipstick at the central  lab is positive for blood or protein.
b.
eGFR Serum cystatin C and urinalysis will be collected every 6 months. See the SoA.
c.
Urine pregnancy tests must be performed for all WOCBP as defined in the SoA.
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF.  
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF.  
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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting
10.3.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or not 
considered related to the study intervention.

Note: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator. Any abnormal laboratory test 
results that meet any of the conditions below must be recorded as an AE:

Is associated with accompanying symptoms.

Requires additional diagnostic testing or medical/surgical intervention.

Leads to a change in study dosing (outside of any protocol-specified dose 
adjustments) or discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy.

Exacerbation of a chronic or intermittent preexisting condition, including either an 
increase in frequency and/or intensity of the condition.

New condition detected or diagnosed after study intervention administration, even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE or SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of 
sequelae.
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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.
10.3.2. Definition of an SAE
An SAE is defined as any untoward medical occurrence that, at any dose, meets one 
or more of the criteria listed below:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which 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.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been admitted (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AEs. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious.
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Hospitalization for elective treatment of a preexisting condition that did not worsen 
from baseline is not considered an AE.
d. Results in persistent or significant disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance, such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle), that may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Is a suspected transmission via a Pfizer product of an infectious agent, pathogenic 
or non-pathogenic, is considered serious. 
The event may be suspected from clinical symptoms or laboratory findings indicating 
an infection in a participant exposed to a Pfizer product. The terms “suspected 
transmission” and “transmission” are considered synonymous. These cases are 
considered unexpected and handled as serious expedited cases by pharmacovigilance 
personnel. Such cases are also considered for reporting as product defects, if 
appropriate.
g. Other situations:

Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations, such as significant 
medical events that may jeopardize the participant or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse.
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10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During the Active 
Colletion Period 
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording AEs on the CRF and for 
reporting SAEs on the CT SAE Report Form to Pfizer Safety throughout the active 
collection period. These requirements are delineated for 3 types of events: (1) SAEs; 
(2) nonserious AEs; and (3) exposure to the study intervention under study during 
pregnancy or breastfeeding, and occupational exposure. 
It should be noted that the CT SAE Report Form for reporting of SAE information is not 
the same as the AE page of the CRF. When the same data are collected, the forms must be 
completed in a consistent manner. AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE 
Report Form for reporting of SAE information.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours 
of Awareness
SAE
All
All
Nonserious AE
All
None
Exposure to the study 
intervention under study 
during pregnancy or 
breastfeeding.
All AEs or SAEs 
associated with exposure 
during pregnancy or 
breastfeeding
Note: Instances of EDP or 
not associated with an AE 
or SAE are not captured in 
the CRF.
All instances of EDP are 
reported (whether or not 
there is an associated 
SAE)*
All instances of EDB are 
reported (whether or not 
there is an associated 
SAE).**
Environmental or 
occupational exposure to 
the product under study to 
a non-participant (not 
involving EDP or EDB).
None. Exposure to a study 
non-participant is not 
collected on the CRF.
The exposure (whether or 
not there is an associated 
AE or SAE) must be 
reported.***
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*
EDP (with or without an associated AE or SAE): any pregnancy information is reported to Pfizer 
Safety using CT SAE Report Form and EDP Supplemental Form; if the EDP is associated with an 
SAE, then the SAE is reported to Pfizer Safety using the CT SAE Report Form. 
** EDB is reported to Pfizer Safety using the CT SAE Report Form which would also include details 
of any SAE that might be associated with the EDB. 
*** Environmental or Occupational exposure: AEs or SAEs associated with occupational exposure are 
reported to Pfizer Safety using the CT SAE Report Form. 

When an AE or SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.

The investigator will then record all relevant AE or SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE or SAE CRF page.

There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE or SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 

Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.

Moderate: Minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental ADL. Instrumental ADL refers to preparing meals, 
shopping for groceries or clothes, using the telephone, managing money, etc. 

Severe: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling, limiting self 
care ADL. Self care ADL refers to bathing, dressing and undressing, feeding self, 
using the toilet, taking medications, and not bedridden. 
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An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE or SAE. The investigator will use clinical 
judgment to determine the relationship.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration, will be considered and investigated.

The investigator will also consult the IB and/or product information, for marketed 
products, in his/her assessment.

For each AE or SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE or SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the study intervention caused the 
event, then the event will be handled as “related to study intervention” for reporting 
purposes, as defined by the sponsor. In addition, if the investigator determines that 
an SAE is associated with study procedures, the investigator must record this causal 
relationship in the source documents and CRF, and report such an assessment in the 
dedicated section of the CT SAE Report Form and in accordance with the SAE 
reporting requirements.
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Follow-Up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations, as medically indicated or as requested by the 
sponsor, to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare providers.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings, including histopathology.

New or updated information will be recorded in the originally submitted 
documents.

The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.
10.3.4. Reporting of SAEs 
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE to Pfizer Safety will be the electronic 
data collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as the data 
become available.

After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to Pfizer Safety by telephone.
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SAE Reporting to Pfizer Safety via CT SAE Report Form

Facsimile transmission of the CT SAE Report Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the CT SAE Report Form sent by overnight mail or 
courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the CT SAE Report Form pages within the designated reporting 
time frames.
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10.4. Appendix 4: Contraceptive and Barrier Guidance 
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 5 terminal half-lives after the last dose of study 
intervention, (approximately 150 days) which corresponds to the time needed to eliminate 
reproductive safety risk of the study intervention(s):

Refrain from donating sperm.
PLUS either:

Be abstinent from heterosexual intercourse with a female of childbearing potential as 
their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and 
agree to remain abstinent. 
OR

Must agree to use contraception/barrier as detailed below:

Agree to use a male condom and should also be advised of the benefit for a 
female partner to use a highly effective method of contraception as a condom may 
break or leak when having sexual intercourse with a woman of childbearing 
potential who is not currently pregnant.

In addition to male condom use, a highly effective method of contraception may be 
considered in WOCBP partners of male participants (refer to the list of highly 
effective methods below in Section 10.4.4).
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 10.4.3).
OR

Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), preferably with low user dependency, as described below 
during the intervention period and for at least 150 days after the last dose of study 
intervention, which corresponds to the time needed to eliminate any reproductive 
safety risk of the study intervention(s). The investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose of study 
intervention.
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
Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), with high user dependency, as described below during the 
intervention period and for at least 150 days after the last dose of study intervention,
which corresponds to the time needed to eliminate any reproductive safety risk of the 
study intervention(s). In addition, a second effective method of contraception, as 
described below, must be used. The investigator should evaluate the effectiveness of 
the contraceptive method in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy. 
10.4.3. Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following: 

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation for any of the above categories can come from the site personnel’s 
review of the participant’s medical records, medical examination, or medical history 
interview. The method of documentation should be recorded in the participant’s medical 
record for the study.
2. Postmenopausal female:

A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. In addition:
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
A high FSH level in the postmenopausal range must be used to confirm a 
postmenopausal state in women under 60 years of age and not using hormonal 
contraception or HRT. 

A female on HRT and whose menopausal status is in doubt will be required to 
use one of the nonestrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment.
10.4.4. Contraception Methods
Contraceptive use by men or women should be consistent with local availability/regulations 
regarding the use of contraceptive methods for those participating in clinical trials.
Highly Effective Methods That Have Low User Dependency 
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device.
3. Intrauterine hormone-releasing system.
4. Bilateral tubal occlusion (eg, bilateral tubal ligation).
5. Vasectomized partner.

A vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the WOCBP and the absence of sperm has 
been confirmed. If not, an additional highly effective method of contraception 
should be used. The spermatogenesis cycle is approximately 90 days.
Highly Effective Methods That Are User Dependent 
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:

Oral;

Intravaginal;

Transdermal.
7. Progestogen-only hormone contraception associated with inhibition of ovulation:

Oral;
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
Injectable.
8. 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 intervention. 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.
One of the following effective barrier methods must be used in addition to the highly 
effective methods listed above that are user dependent:

Male or female condom with or without spermicide;

Cervical cap, diaphragm, or sponge with spermicide;

A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods).
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10.5. Appendix 5: Genetics
Use/Analysis of DNA

Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and severity and progression of disease. Therefore, where local 
regulations and IRBs/ECs allow, a blood sample will be collected for DNA analysis.

The scope of the genetic research may be narrow (eg, 1 or more candidate genes) or 
broad (eg, the entire genome), as appropriate to the scientific question under 
investigation.

The samples may be analyzed as part of a multistudy assessment of genetic factors 
involved in the response to PF-06823859 or study interventions of this class to 
understand treatments for the disease(s) under study or the disease(s) themselves.

The results of genetic analyses may be reported in CSR or in a separate study 
summary, or may be used for internal decision making without being included in a 
study report.

The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 

The samples will be retained as indicated:

Retained samples will be stored indefinitely or for another period as per local 
requirements.

Participants may withdraw their consent for the storage and/or use of their Retained
Research Samples at any time by making a request to the investigator; in this case, 
any remaining material will be destroyed. Data already generated from the samples 
will be retained to protect the integrity of existing analyses.

Samples for genetic research will be labeled with a code. The key between the code 
and the participant’s personally identifying information (eg, name, address) will be 
held securely at the study site.
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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury but adapt 
are termed “adaptors.” In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome. These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as DILI. 
Participants who experience a transaminase elevation above 3 × ULN should be monitored 
more frequently to determine if they are “adaptors” or are “susceptible.”
In the majority of DILI cases, elevations in AST and/or ALT precede TBili elevations 
(>2 × ULN) by several days or weeks. The increase in TBili typically occurs while AST/ALT 
is/are still elevated above 3 × ULN (ie, AST/ALT and TBili values will be elevated within 
the same laboratory sample). In rare instances, by the time TBili elevations are detected, 
AST/ALT values might have decreased. This occurrence is still regarded as a potential DILI. 
Therefore, abnormal elevations in either AST OR ALT in addition to TBili that meet the 
criteria outlined below are considered potential DILI (assessed per Hy’s law criteria) cases 
and should always be considered important medical events, even before all other possible 
causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions. Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value 
<2 × ULN or not available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).
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Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor. 
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history, and physical assessment. 
In addition to repeating measurements of AST and ALT and TBili for suspected Hy’s law 
cases, additional laboratory tests should include albumin, CK, direct and indirect bilirubin, 
GGT, PT/INR, total bile acids, and alkaline phosphatase. Consideration should also be given 
to drawing a separate tube of clotted blood and an anticoagulated tube of blood for further 
testing, as needed, for further contemporaneous analyses at the time of the recognized initial 
abnormalities to determine etiology. A detailed history, including relevant information, such 
as review of ethanol, acetaminophen/paracetamol (either by itself or as a coformulated 
product in prescription or over-the-counter medications), recreational drug, or supplement 
(herbal) use and consumption, family history, sexual history, travel history, history of contact 
with a jaundiced person, surgery, blood transfusion, history of liver or allergic disease, and 
potential occupational exposure to chemicals, should be collected. Further testing for acute 
hepatitis A, B, C, D, and E infection, liver imaging (eg, biliary tract), and collection of serum 
samples for acetaminophen/paracetamol drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the LFT abnormalities has yet been found. Such potential DILI (Hy’s law) 
cases are to be reported as SAEs, irrespective of availability of all the results of the 
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of 
reasonable investigations have been received and have excluded an alternative etiology.
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10.7. Appendix 7: ECG Findings of Potential Clinical Concern
ECG Findings That May Qualify as AEs

Marked sinus bradycardia (rate <40 bpm) lasting minutes.

New PR interval prolongation >280 msec.

New prolongation of QTcF to >480 msec (absolute) or by ≥60 msec from baseline.

New-onset atrial flutter or fibrillation, with controlled ventricular response rate:
ie, rate <120 bpm.

New-onset type I second-degree (Wenckebach) AV block of >30 seconds’ 
duration.

Frequent PVCs, triplets, or short intervals (<30 seconds) of consecutive ventricular 
complexes.
ECG Findings That May Qualify as SAEs

QTcF prolongation >500 msec.

New ST-T changes suggestive of myocardial ischemia.

New-onset left bundle branch block (QRS >120 msec).

New-onset right bundle branch block (QRS >120 msec).

Symptomatic bradycardia. 

Asystole:

In awake, symptom-free patients in sinus rhythm, with documented periods of 
asystole ≥3.0 seconds or any escape rate <40 bpm, or with an escape rhythm 
that is below the AV node; 

In awake, symptom-free patients with atrial fibrillation and bradycardia with 
1 or more pauses of at least 5 seconds or longer; 

Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.

Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short 
duration with relevant symptoms or lasting >1 minute).
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
Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm (heart 
rate <40 bpm), accelerated idioventricular rhythm (HR 40 bpm to <100 bpm), and 
monomorphic/polymorphic ventricular tachycardia (HR >100 bpm (such as 
torsades de pointes)).

Type II second-degree (Mobitz II) AV block.

Complete (third-degree) heart block.
ECG Findings That Qualify as SAEs

Change in pattern suggestive of new myocardial infarction. 

Sustained ventricular tachyarrhythmias (>30 seconds’ duration).

Second- or third-degree AV block requiring pacemaker placement.

Asystolic pauses requiring pacemaker placement.

Atrial flutter or fibrillation with rapid ventricular response requiring cardioversion.

Ventricular fibrillation/flutter.

At the discretion of the investigator, any arrhythmia classified as an adverse 
experience.
The enumerated list of major events of potential clinical concern are recommended as “alerts” or 
notifications from the core ECG laboratory to the investigator and Pfizer study team, and not to be 
considered as all inclusive of what to be reported as AEs/SAEs.
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10.8. Appendix 8: Permitted and Prohibited Concomitant Medications 
The prohibited concomitant medications listed below (Table 4) should not be taken during 
the C0251008 study. 
The Pfizer study team is to be notified of any prohibited medications taken during the study. 
After consulting with the sponsor, the investigator will make a judgement on the ongoing 
participation of any participant with prohibited medication use during the study.
This list of drugs prohibited for potential DDI concerns with the IMP may be revised during 
the course of the study with written notification from the sponsor, to include or exclude 
specific drugs or drug categories for various reasons (eg, emerging DDI results for the IMP, 
availability of new information in literature on the DDI potential of other drugs). 
This is not an all-inclusive list. Site staff should consult with the sponsor or designee with 
any questions regarding potential DDI.
Table 4.
List of Prohibited and Permitted Concomitant Medications
Medications
C0251008
Treatment Period Day 1-Week 52
C0251008
Follow-up Period
Corticosteroids
Parenteral injections 
(intra-articular) IA, 
IM, or IV)
Prohibited
Permitted
Oral (prednisone or 
equivalent)
Permitted (Stage 2)

Prednisone ≤15 mg/day or equivalent 
provided dose is stable for at least 
30 days prior to Day 1. 
Permitted (Stage 3)

Prednisone ≤20 mg/day or equivalent 
provided dose is stable for at least 
30 days prior to Day 1.

Tapering of steroids is permitted after 
Week 52, in Amended Stage 2 and 
Stage 3.
Permitted
Immunosuppressive or immunomodulatory 
agents including methotrexate (MTX), 
azathioprine (AZA), leflunomide, 
mycophenolate (including mycophenolate 
mofetil, mycophenolate mofetil 
hydrochloride, and mycophenolate sodium), 
or 6-mercaptopurine (6-MP).
Permitted

Provided pre-existing dose is stable for at 
least 60 days prior to Day 1.

No new immunosuppressives or increase 
in dose is allowed during the treatment 
period.

Participants can be on 1 of the 
following cytotoxic agents: MTX, 
AZA, leflunomide, mycophenolate, or 
6-MP, but not on any combination of 
these cytotoxic agents.
Permitted
Antimalarials (eg, hydroxychloroquine, 
chloroquine, quinacrine)
Permitted

Provided pre-existing dose is stable 
for at least 60 days prior to Day 1.
Permitted
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Medications
C0251008
Treatment Period Day 1-Week 52
C0251008
Follow-up Period

No new antimalarial drugs or increase 
in dose is allowed during the 
treatment period.
Thalidomide, tacrolimus, calcineurin 
inhibitor or mizoribine
Prohibited

Any form of tacrolimus or topical 
calcineurin inhibitors are not allowed
during the treatment period.
Permitted 
Immunosuppressive topical 
Permitted 

Immunosuppressive topical for the 
scalp. 
Permitted 
Immunosuppressive eye drops
Permitted
Permitted
Investigational or marketed biologics (eg, 
abatacept, tocilizumab, TNF inhibitors)
Prohibited
Prohibited
Cyclophosphamide or chlorambucil
Prohibited
Permitted
Cyclosporine
permitted
Permitted
Other investigational drugs or 
investigational combinations
Prohibited
Prohibited
B-cell depleting therapy (eg, rituximab, 
belimumab, epratuzumab)
Prohibited
Prohibited
Any live (live attenuated) vaccines
Prohibited
Prohibited
Inactivated vaccine and boosters
Permitted
Permitted
Kinase inhibitors (eg, tofacitinib, 
ruxolitinib)
Prohibited
Permitted
IVIG 
Permitted
Permitted
Pre- Medication with corticosteroids for 
IVIG administration: On the day of the 
IVIG dose administration, pre-medication to 
prevent hypersensitivity reaction to IVIG is 
permitted. Steroid dose that was previously 
used for pre- medication will be permitted 
(on IVIG dosing day only). After IVIG 
dosing day, steroid dosing should remain 
less than or equal to the permitted steroid 
dosing in the protocol for skin and muscle 
cohorts.
Permitted
Permitted
Investigators should consult the relevant product label for any other medication used during 
the study for information regarding medication that is prohibited for concomitant use. 
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10.9. Appendix 9: Alternative Measures During Public Emergencies
The alternative study measures described in this section are to be followed during public 
emergencies, including the COVID-19 pandemic. This appendix applies for the duration of 
the COVID-19 pandemic globally and will become effective for other public emergencies 
only upon written notification from Pfizer. 
Use of these alternative study measures are expected to cease upon the return of business as 
usual circumstances (including the lifting of any quarantines and travel bans/advisories). 
10.9.1. Telehealth Visits (if applicable)
In the event that in-clinic study visits cannot be conducted, every effort should be made to 
follow up on the safety of study participants at scheduled visits per the Schedule of Activities
or unscheduled visits. Telehealth visits may be used to continue to assess participant safety 
and collect data points. Telehealth includes the exchange of healthcare information and 
services via telecommunication technologies (eg, audio, video, video-conferencing software) 
remotely, allowing the participant and the investigator to communicate on aspects of clinical 
care, including medical advice, reminders, education, and safety monitoring. The following 
assessments must be performed during a telehealth visit:

Review and record any AEs and SAEs since the last contact. Refer to Section 8.3.

Review and record any new concomitant medications or changes in concomitant 
medications since the last contact.

Review and record contraceptive method and results of pregnancy testing. Confirm 
that the participant is adhering to the contraception method(s) required in the 
protocol. Refer to Appendix 4 and Section 1.3 of this appendix regarding pregnancy 
tests.
Study participants must be reminded to promptly notify site staff about any change in their 
health status.
10.9.2. Alternative Facilities for Safety Assessments 
10.9.2.1. Laboratory Testing (if applicable)
If a study participant is unable to visit the site for protocol-specified safety laboratory 
evaluations, testing may be conducted at a local laboratory if permitted by local regulations.
The local laboratory may be a standalone institution or within a hospital. The following 
safety laboratory evaluations may be performed at a local laboratory: 
Please refer to Table 3 of the protocol; not all laboratory collections may be possible.

Hematology;

Chemistry;
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
Urinalysis;

Pregnancy testing (if applicable);

PK (if applicable).
If a local laboratory is used, qualified study site personnel must order, receive, and review 
results. Site staff must collect the local laboratory reference ranges and certifications/
accreditations for filing at the site. Laboratory test results are to be provided to the site staff 
as soon as possible. The local laboratory reports should be filed in the participant’s source 
documents/medical records. Relevant data from the local laboratory report should 
be recorded on the CRF.
If a participant requiring pregnancy testing cannot visit a local laboratory for pregnancy 
testing, a home urine pregnancy testing kit with a sensitivity of at least 25 mIU/mL may be 
used by the participant to perform the test at home, if compliant with local regulatory 
requirements. The pregnancy test outcome should be documented in the participant’s source 
documents/medical records and relevant data recorded on the CRF. Confirm that the 
participant is adhering to the contraception method(s) required in the protocol.
10.9.2.2. Electrocardiograms
If the participant is unable to visit the study site for ECGs, the participant may visit an 
alternative facility to have the ECGs performed. Qualified study site personnel must order, 
receive, and review results. 
10.9.3. Home Health Visits
A home health care service may be utilized to facilitate scheduled visits per the Schedule of 
Activities. Home health visits include a healthcare provider conducting an in-person study 
visit at the participant’s location, rather than an in-person study visit at the site. The 
following may be performed during a home health visit:

Lab collection;

Physical assessment;

Vital signs. 
10.9.4. Adverse Events and Serious Adverse Events
If a participant has COVID-19 during the study, this should be reported as an AE or serious 
SAE and appropriate medical intervention provided. There is a potential risk of increased 
susceptibility to viral infections with IFNblockade as with any antagonist of Type 1 
interferon signaling (eg, anti-IFNAR1, anti-IFN, JAK inhibitors). Viral monitoring will be 
conducted as a precautionary measure to ensure participant safety. Details can be found in 
the trial protocol as well as the investigators brochure. Temporary discontinuation of the 
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study intervention may be medically appropriate until the participant has recovered from 
COVID-19. 
It is recommended that the investigator discuss temporary or permanent discontinuation of 
study intervention with the study medical monitor. 
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10.10. Appendix 10: Guidelines for Participant Safety Monitoring and Discontinuation
These guidelines for participant safety monitoring and discontinuation are to be applied to all 
participants in Study C0251008. 
Additional individual participant monitoring is at the discretion of the investigator and 
dependent on any perceived safety concerns. Unscheduled clinical labs may be obtained at 
any time during the study to assess such concerns, and a participant may be withdrawn at any 
time at the discretion of the investigator. For participants on permitted concomitant IVIG, see 
Section 8.4.3 for specified analyses to be performed at unscheduled visits.
10.10.1. Monitoring
Please Note: For Participants with DM who experience elevated AST, ALT, LDH, Aldolase, 
and CK, due to muscle involvement the investigator should determine whether or not these 
are related to the existing condition of DM or if these lab abnormalities are related to another 
condition. If related to DM, GGT should be <1.5 ULN. Information should be provided in 
the source documentation with rationale related to any lab abnormalities. 
The following laboratory abnormalities require re-testing within 1 week:

Any single AST and/or ALT elevation ≥3 times the upper limit of normal (repeat 
laboratory testing should include albumin, creatine kinase, total bilirubin, direct and 
indirect bilirubin, GGT, PT with INR, and alkaline phosphatase), regardless of the 
total bilirubin. Please note that 3 times the upper limit of normal increases in ALT, 
AST need confirmation on separate blood draw before undertaking thorough 
evaluation for liver injury (See Appendix 6 for suggested actions and follow-up 
assessments in the event of potential drug-induced liver injury);

For women of child-bearing potential with any positive urine -hCG test, the 
participant will have study intervention interrupted and a serum sample submitted to 
the central laboratory for -hCG testing.
10.10.2. Discontinuation
Investigators are encouraged to discuss with the sponsor’s clinical team as soon as possible, 
and participants are to be discontinued from treatment if any of the following occur during 
the study:

Potential Cases of Decreased eGFR

If an individual participant demonstrates CONCOMITANT SCr-based AND 
serum Cystatin C-based eGFR decline of ≥30% compared to the participant’s 
baseline eGFR, then the participant should not be further dosed and adequate, 
immediate, supportive measures including immediate evaluation by a 
nephrologist (preferably within 24 hours) with appropriate management and 
treatment as clinically indicated. Results should be repeated as indicated by the 
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nephrologist or weekly at a minimum until the eGFR returns to baseline ±15%, or 
the renal parameters are deemed to be stable by the nephrologist and/or the 
investigator. 

If the participant cannot be seen by a nephrologist within 24 hours (as described 
above), then the participant should be sent to a local emergency room for 
evaluation and treatment as clinically indicated. 

Follow-up evaluations should include laboratory tests, detailed history, and 
physical assessment. In addition to repeating SCr and serum cystatin C, laboratory 
tests should also include: serum BUN, serum CK, serum electrolytes (including at 
a minimum potassium, sodium, phosphate/phosphorus, calcium), in addition to 
urine dipstick, urine microscopic examination, and urinary indices. All cases 
confirmed on repeat testing as meeting the laboratory criteria for acute kidney 
injury, with no other cause(s) of laboratory abnormalities identified should be 
considered as potential cases of drug-induced kidney injury irrespective of 
availability of all the results of the investigations performed to determine etiology 
of the abnormal SCr. 

All relevant test results will be forwarded to Sponsor Medical Monitor for review 
immediately upon receipt by the PI.

Serious infections defined as any infection (viral, bacterial, and fungal) requiring 
parenteral antimicrobial therapy, hospitalization for treatment, or meeting other 
criteria that require the infection to be classified as serious adverse event;

Other serious or severe AEs, at the discretion of the investigator or sponsor;

If there are “yes” answers on items 4, 5, or on any behavior question of the 
C-SSRS, the participant will be discontinued from treatment and referred to a 
mental health professional for appropriate evaluation and treatment (if the 
participant cannot be seen by a mental health professional within 24 hours, then
the participant should be sent to a local emergency room for psychiatric 
assessment);

All of the following laboratory abnormalities require discontinuation if they are 
confirmed (confirmation through re-testing is expected to occur within 1 week):

Two sequential AST or ALT elevation ≥3 times the upper limit of normal with at
least one total bilirubin value ≥2 times the upper limit of normal;a

Two sequential AST or ALT elevation ≥3 times the upper limit of normal
accompanied by signs or symptoms consistent with hepatic injury; a

Two sequential AST or ALT elevation ≥5 times the upper limit of normal,
regardless of total bilirubin or accompanying signs or symptoms;a
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
Female participants found to be pregnant during the study;

Other serious or severe AEs, after consultation with the Pfizer medical monitor or 
designee.
a. In each case, there is a need for additional investigations, such as review of ethanol, 
recreational drug and dietary supplement consumption; testing for acute hepatitis A, B or C 
infection and biliary tract imaging should be promptly discussed with the Pfizer medical 
monitor or designee.

Use of prohibited medications require participant discontinuation as reflected in 
Section 6.8.1 and Appendix 8 (Section 10.8) for prohibited medication listing.

A participant who meets either bulleted criterion based on repeat ECG readings 
will be withdrawn from the study intervention. 

QTcF >500 msec.

Change from baseline: QTcF >60 msec and QTcF >450 msec.
If a clinically significant finding is identified (including, but not limited to, 
changes from baseline in QTcF after enrollment), the investigator or qualified 
designee will determine if the participant can continue in the study and if any 
change in participant management is needed. This review of the ECG printed 
at the time of collection must be documented. Any new clinically relevant 
finding should be reported as an AE. See Appendix 7 (Section 10.7) for 
further details regarding ECG findings of potential clinical concern.

Lack of efficacy will be the discretion of the investigator (see rescue medication 
guidance, Section 6.8.4).
Any participant meeting discontinuation criteria must enter follow-up with their first 
follow-up visit occurring 1 week after their last dose whenever possible, until the event has 
returned to normal or baseline levels or is deemed clinically stable. The procedures scheduled 
for the early withdrawal visit will be performed on the last day the participant takes the study 
intervention or as soon as possible thereafter. The only exception to this is when a participant 
specifically withdraws consent for any further contact with him/her or persons previously 
authorized by the participant to provide this information.
Participants will be followed post drug discontinuation for 5 terminal half-lives. Additional 
follow-up visits may occur as needed until any clinically relevant abnormalities or adverse 
events have resolved, returned to a baseline state, or are deemed clinically stable.
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10.11. Appendix 11: Corticosteroid Suggested Taper and Rescue Guidance
10.11.1. Corticosteroid Suggested Taper
The following protocol recommended corticosteroid taper is provided as a guide only. 
Corticosteroid tapering is ultimately based upon investigator discretion. 
The protocol recommended corticosteroid taper is suggested to be started after Week 4 of the 
C0251008 study. It is also suggested that no corticosteroid tapering occurs between Week 44
and Week 52 due to final assessments being completed. All doses are in prednisone 
equivalent.
Recommended Oral Prednisone Taper (all doses are approximate as these are examples 
only):

Prednisone dose of 15-20 mg:

Decrease by 2.5 mg every 4 weeks. If starting dose is 19 or 18 mg, then first 
decrease will be to 17.5 mg a day. If starting dose is 16 or 17 mg, then first 
decrease will be to 15 mg a day.

Prednisone dose of 10-15 mg

Decrease by 2.5 mg every 4 weeks. If starting dose is 13 or 14 mg, then first 
decrease will be to 12.5 mg. if starting dose is 11 or 12 mg, then first decrease 
will be to 10 mg. 

Prednisone dose of 5-10 mg:

Decrease by 1 mg every 2 weeks. If starting dose is 7.5 mg, then first decrease 
will be to 7 mg.

Prednisone dose of 5 mg or less:

No taper is recommended, but prednisone dose can be tapered as per the 
investigator.
10.11.2. Corticosteroid Rescue Guidance
10.11.2.1. Oral or Intramuscular Corticosteroid Rescue Recommended Guidance for 
Dermatomyositis Related Reasons
Systemic corticosteroids may be increased as clinically required; however, are suggested to 
remain within the following stipulations as a guidance.
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Recommended Oral or Intramuscular corticosteroid rescue therapy:

Two of the following options, or the same option used twice are allowed at any time, 
except between Week 44 and Week 52 due to final assessments being completed. 

Each event of corticosteroid rescue is recommended to be recorded on the 
concomitant medication pages (All doses are approximate as these are examples 
only):
1. Increase in oral corticosteroid dose up to the participant’s baseline dose (dose at 
Day 1). Consideration can then be given to following the protocol driven 
corticosteroid recommended taper.
2. Increase in oral corticosteroid dose up to 20 mg of prednisone equivalent per day. 
Consideration can then be given to following the protocol driven corticosteroid 
recommended taper.
3. Oral corticosteroid taper of 20 mg prednisone equivalent per day of over 1 month 
can be given on top of the baseline corticosteroid dose.
Recommended taper on top of the baseline dose as follows: 20 mg prednisone 
equivalent per day for 1 week, then 15 mg per day for 1 week, then 10 mg per day 
for 1 week, then 5 mg per day for 1 week, then back to baseline corticosteroid 
dose. Consideration can then be given to following the protocol driven 
corticosteroid recommended taper. 
4. An intramuscular injection of approximately 40 mg Depo-Medrol 
(methylprednisolone acetate suspension [50 mg prednisone equivalent]) as an 
example. Consideration can then be given to following the protocol driven 
corticosteroid recommended taper. 
10.11.2.2. Corticosteroid Rescue Guidance for Non-Dermatomyositis Reasons
Non-DM reasons may include, for example, poison ivy, or asthma exacerbation.
For example, prednisone equivalent dose of 60 mg or less for 10 days or less. However, this 
is recommended to be avoided between Week 44 and Week 52 due to final assessments 
being completed. If corticosteroids for non-dermatomyositis reasons are needed within 
4 weeks of the final trial visit, then efficacy assessments will be conducted at the first 
follow-up visit, such that it is as approximate to 4 weeks after the corticosteroid rescue.
10.11.2.3. Intra-Articular Corticosteroids
A participant who receives an intra-articular steroid injection will be allowed to continue in 
the treatment period of the trial. However, it is preferable to have an intra-articular 
corticosteroid injection >30 days before the clinical efficacy assessment visit.
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A participant who receives an intra-articular corticosteroid injection within 30 days of when 
efficacy assessments are performed will need to complete the efficacy assessments.
10.11.2.4. Immunosuppressives/immunomodulatory Agent Rescue Medications.
A participant who requires an increase or additional non-steroid 
immunosuppressive/immunomodulatory agent, including prohibited medications, will be 
withdrawn from the treatment period and enter the follow-up period of the trial. 
However, if there is a requirement for a decrease in a non-steroid 
immunosuppressive/immunomodulatory agent for a safety or a tolerability issue, then this 
may be allowed after a discussion with the medical monitor and should be documented.
10.11.2.5. NSAIDs and Analgesics
The dose and the frequency of NSAIDs, acetaminophen, aspirin and other analgesic or 
pruritis medication is recommended to remain stable throughout the clinical trial. 
Addition of a new or an increase in the dose of NSAIDs, aspirin or pruritis medications are 
allowed, but their use is recommended to be minimized as much as possible and documented, 
because they may potentially affect efficacy parameters (eg, the skeletal disease activity 
VAS, arthritis assessment and gastrointestinal disease activity VAS for the MDAAT and thus 
is recommended to be used judiciously.
Participants taking additional frequency/dose of NSAIDS/analgesics, including topical 
NSAIDS (that were not being used at screening/baseline), are recommended to not take the 
additional dose of these medications within 24 hours prior to clinical assessment visits.
Acetaminophen is primarily an analgesic and lacks the anti-inflammatory properties of other 
NSAIDS. The use of acetaminophen is recommended, when possible, to treat non-
dermatomyositis related conditions, in the absence of a pre-existing hepatic function 
deficiency.
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10.12. Appendix 12: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
ADA
anti-drug antibody
ADL
activities of daily living
AE
adverse event
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
anti-IFNAR1
interferon-alpha/beta receptor alpha
anti-IFN
anti-interferon alpha
AST
aspartate aminotransferase
AUC
area under the curve
AV
atriaventricular
AZA
Azathioprine

beta
-hCG
beta-human chorionic gonadotropin
BP
blood pressure
BUN
Blood Urea Nitrogen
C-CASA
Columbia Classification Algorithm of Suicide Assessment
Cmax
maximum (or peak) serum concentration
CDASI
Cutaneous Dermatomyositis Disease Area and Severity Index
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
Creatinine Kinase
CL
Chloride
CL/F
Clearance of drug from plasma
CK-MB
Creatinine Kinase MB enzyme
COVID-19
Corona Virus Disease 2019
CRF
case report form
CRO
Clinical Research Organization
CSM
core set measure
CSR
clinical study report
C-SSRS
Columbia-Suicide Severity Rating Scale
CT
clinical trial
CV
cardiovascular
CYP
cytochrome P450 enzymes
DDI
drug-drug interaction
DILI
drug-induced liver injury
DLQI
Dermatology and Life Quality Index
DM
dermatomyositis
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Abbreviation
Term
DMARDs
disease-modifying antirheumatic drugs
DMC
Data monitoring committee
DNA
deoxyribonucleic acid
EC
ethics committee
ECC
Emergency contact card
ECG
electrocardiogram
EDB
Exposure during breastfeeding
EDP
exposure during pregnancy
eGFR
Estimated glomerular filtration rate
EMA
European medicines agency
EOS
end of study
ePPND
enhanced pre and postnatal development
EQ-5D-5L & EQ-VAS
European Quality of Life, 5 Dimension, 5 Level Scale and Visual 
Analogue Scale
EU
European Union
ET
early termination
EudraCT
European Union Drug Regulating Authorities Clinical Trials 
Database
FAS
Full analysis set
FDA
Food and Drug Administration
FIH
first in human
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GLP
good laboratory practice
HAQ-DI
Health Assessment Questionnaire and Disease Index
HEENT
head, eyes, ears, nose and throat
HR
heart rate
HRT
Hormone replacement therapy
hsCRP
high-sensitivity C-reactive protein
HTA
Health technology assessment
IA
Interim Analyses
IB
Investigator’s Brochure
ICD
informed consent document
ICH
International Conference on Harmonisation
ID
identification
IFN 
interferon beta
IFNAR 
interferon-/receptor 
Ig
immunoglobulin
IgG1
immunoglobulin G1
IL-6
interleukin 6
IM
intramuscular
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Abbreviation
Term
IMACS
International Myositis Assessment & Clinical Studies
IMP
investigational medicinal product
IND
investigational new drug application
INF
interferon
INR
international normalized ratio
IP
investigational product
IPAL
Investigational product accountability log
IRB
institutional review board
IRT
interactive response technology
ISR
injection site reaction
IV
intravenous
IVIG
intravenous immunoglobulin
JAK
Janus kinase 
LANCOVA
longitudinal analysis of covariance
LDH
lactate dehydrogenase
LFT
liver function test
LSLV
last subject last visit
MAD
multiple ascending dose
MCS
multiple chemical sensitivity
MDAAT
Myositis Disease Activity Assessment Tool
MDI
Muscle Disease Index
MMF
Mycophenolate mofetil
MMT-8
Manual Muscle Testing-8 designated muscle groups
6-MP
Mercaptopurine
MTX
Methotrexate
N/A
not applicable
NAb
neutralizing anti-body
NIMP
Non investigational medicinal products
NSAID
Non-steroidal anti-inflammatory drugs
PCS
physical component scores
PD
Pharmacodynamics
PE
physical examination
PhGA
physician global assessment
PI
principal investigator
PK
pharmacokinetics
PR interval
period, in milliseconds, that extends from beginning of P wave 
until beginning of QRS complex
PRO
patient reported outcome
PT
prothrombin time
PtGA
Patient global assessment
PTT
partial thromboplastin time
PVC
Premature ventricular contractions
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Abbreviation
Term
QoL
quality of life
QRS complex
combination of the Q wave, R wave and S wave
QT interval
measure between Q wave and T wave
QTcF
QT interval calculated by Fridericia's formula
Q4W
every 4 weeks
Rac
Accumulation ratio
RBC
Red blood cell
RNA
ribonucleic acid
SAD
single ascending dose
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SC
subcutaneous
SCr
Serum Creatinine
SF-36
The Short Form (36) Health Survey
SoA
schedule of assessments
SLE
systemic lupus erythematous
SOC
system organ class
SOP
standard operating procedure
SRSD
single reference safety document
SUSARs
Suspected Unexpected Serious Adverse Reaction
Tmax
time drug is present at maximum concentration in serum
TBili
total bilirubin
TEAE
treatment-emergent adverse event
TIS
Total Improvement Score
TNF
tumor necrosis factor
T1/2
half-life
ULN
upper limit of normal
Upr:Ucr
Urine protein: Urine creatinine
US
United States
VAS
visual analog scale
Vss
volume at steady state
Vz/F
volume of distribution at pseudo-distribution equilibrium/fraction 
absorbed
WBC
white blood cell
WOCBP
women of child bearing potential
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11. REFERENCES
1.
National Organization of Rare Disorders, NORD 2015. Available from: 
http://rarediseases.org/rare-diseases/dermatomyositis/.
2.
Myositis Support and Understanding Association Inc. 2010-2017. Available from: 
https://understandingmyositis.org/types-of-myositis/dermatomyositis/?gclid=CIXP-
fLSns8CFYM9gQodSZIDlA.
3.
Guo Yi, Tian X, Wang X, et al. Adverse effects of immunoglobulin therapy. Frontiers 
in Immunology. 2018;9(1299):1-13.
4.
Fasano S, Alves SC, Isenberg DA. Current pharmacological treatment of idiopathic 
inflammatory myopathies. Expert Rev Clin Pharmacol. 2015;(Dec):1-31.
5.
Neelakantan S, Oemar B, Johnson K, et al. Safety, tolerability, and pharmacokinetics of 
PF-06823859, an anti-interferon monoclonal antibody: a randomized, phase I, 
single- and multiple-ascending-dose study. Clinical Pharmacology in Drug 
Development. 2020;10(3):307-16. Accessed: 03 Sep 2021.
6.
Anyanwu CO, Fiorentino DF, Chung L, et al. Validation of the cutaneous 
dermatomyositis disease area and severity index: characterizing disease severity and 
assessing responsiveness to clinical change. Br J Dermatol. 2015; 173:969-74.
7.
McHorney CA, Ware JE, Lu JFR, et al.  The MOS 36 Item Short Form Health Survey 
(SF 36®): III. tests of data quality, scaling assumptions and reliability across diverse 
patient groups. Med Care. 1994;32(1):40-66.
8.
Ware JE, Snow KK, Kosinski M, et al. SF-36® health survey. Manual and interpretation 
guide. Boston, MA: New England Medical Center, The Health Institute, 1993.
9.
The EuroQol Group. EuroQol-a new facility for the measurement of health-related 
quality of life. Health Policy. 1990;16(3):199–208.
10.
Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new 
five-level version of EQ-5D (EQ 5D 5L). Qual Life Res. 2011;20(10):1727–36.
11.
Janssen MF, Pickard AS, Golicki D, et al. Measurement properties of the EQ-5D-5L 
compared to the EQ-5D-3L across eight patient groups: a multi-country study. Qual 
Life Res. 2013;22(7):1717–27.
12.
Fries JF, Spitz PW, Young DY. The dimensions of health outcomes: the health 
assessment questionnaire, disability and pain scales. J Rheumatol. 1982;9(5):789-93.
13.
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 
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(HAQ)/Childhood Health Assessment Questionnaire (C-HAQ), Childhood Myositis 
Assessment Scale (CMAS), Myositis Disease Activity Assessment Tool (MDAAT), 
Disease Activity Score (DAS), Short Form 36 (SF-36), Child Health Questionnaire 
(CHQ), Physician Global Damage, Myositis Damage Index (MDI), Quantitative Muscle 
Testing (QMT), Myositis Functional Index-2 (FI-2), 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. 2011;63(11):S118-57.
14.
International Myositis Assessment & Clinical Studies Group (IMACS). Disease 
Activity Core Set Measures.  Available from: 
https://www.niehs.nih.gov/research/resources/imacs/diseaseactivity/index.cfm.
15.
Posner K, Oquendo MA, Gould M, et al. Columbia-classification algorithm of suicide 
assessment (C-CASA): classification of suicidal events in the FDA’s pediatric suicidal 
risk analysis of antidepressants.  Am J Psychiatry. 2007;164(7):1035-43.
090177e1980d3bd4\Approved\Approved On: 13-Sep-2021 10:49 (GMT)

SAP_001.pdf: 
        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 1
Pr ot oc ol C 0 2 5 1 0 0 8
A N O P E N L A B E L, L O N G -T E R M E X T E N SI O N S T U D Y T O I N V E S TI G A T E T H E 
S A F E T Y O F P F -0 6 8 2 3 8 5 9 A D MI NI S T E R E D T O A D U L T P A R TI CI P A N T S ≥1 8 A N D 
≤8 0 WI T H A C TI V E D E R M A T O M Y O SI TI S  
St atistic al A n al ysis Pl a n 
( S A P)
Versi o n:
1   
D ate:
3 0 N o v 2 0 2 1 
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 2
T A B L E O F C O N T E N T S
LI S T O F T A B L E S .....................................................................................................................4
LI S T O F FI G U R E S ...................................................................................................................4
1. V E R SI O N HI S T O R Y ............................................................................................................5
2. I N T R O D U C TI O N .................................................................................................................5
2. 1. St u d y  O bjecti ves, E n d p oi nts, a n d Esti ma n ds............................................................5
2. 1. 1. Pri mar y  Esti ma n d(s).....................................................................................7
2. 1. 2. Sec o n dar y  Esti ma n d(s).................................................................................7
2. 2. S t u d y Desi g n.............................................................................................................8
3. E N D P OI N T S A N D B A S E L I NE V A RI A B L E S: D E F I NI TI O N S A N D 
C O N V E N TI O N S ..................................................................................................................9
3. 1. Pri mar y  E n d p oi nt(s)..................................................................................................9
3. 1. 1. I nci de nce of A d verse E ve nts ( A Es) ..............................................................9
3. 1. 2. L a b orat or y A b n or malities.............................................................................9
3. 1. 3. C ha n ges i n Vital Si g ns ................................................................................1 0
3. 1. 4. E C G Fi n di n gs .............................................................................................1 0
3. 2. Sec o n dar y  E n d p oi nt(s)............................................................................................1 0
3. 2. 1. C D A SI  Acti vit y a n d Da ma ge Sc ores .........................................................1 0
3. 2. 2. TI S ..............................................................................................................1 0
3. 2. 2. 1. P h G A .........................................................................................1 0
3. 2. 2. 2. Pt G A ..........................................................................................1 0
3. 2. 2. 3. M M T - 8 ......................................................................................1 1
3. 2. 2. 4. H A Q -DI .....................................................................................1 1
3. 2. 2. 5. Gl o bal E x tra m usc ular Disease Acti vity Assess me nt fr o m 
t he M D A A T.......................................................................................1 1
3. 2. 2. 6. M uscle E nz y mes .......................................................................1 1
3. 3. Ot her E n d p oi nt(s) ....................................................................................................1 1
3. 3. 1. P K a n d P D E n d p oi nts .................................................................................1 1
3. 3. 2. I m m u n o ge nicit y ..........................................................................................1 1
3. 3. 3. C ol u m bia -S uici de Se verit y  Rati n g Scale ( C-S S R S) ...................................1 2
3. 3. 4. P R Os ...........................................................................................................1 2
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 3
3. 4. Baseli ne Varia bles................................................................................................... 1 2
3. 5. Safet y E n d p oi nts .....................................................................................................1 2
4. A N A L Y SI S S E T S ( P O P U L A T I O N S F O R A N A L Y SI S)...................................................1 2
5. G E N E R A L M E T H O D O L O G Y A N D C O N V E N TI O N S ....................................................1 4
5. 1. H y p ot heses a n d Decisi o n R ules ..............................................................................1 4
5. 2. Ge neral Met h o ds .....................................................................................................1 4
5. 2. 1. A nal y ses f or C o nti n u o us E n d p oi nts ...........................................................1 4
5. 3. Met h o ds t o Ma na ge Missi n g Data ..........................................................................1 4
6. A N A L Y S E S A N D S U M M A RI E S ......................................................................................1 5
6. 1. Pri mar y  E n d p oi nt(s)................................................................................................1 5
6. 1. 1. I nci de nce of A Es, La b orat or y  A b n or malities, C ha n ges i n Vital Si g ns, 
a n d E C G Fi n di n gs ............................................................................................1 5
6. 1. 1. 1. Se nsiti vit y / S u p ple me ntar y A nal yses .........................................1 5
6. 2. Sec o n dar y  E n d p oi nt(s)............................................................................................1 5
6. 2. 1. C D A SI  Acti vit y a n d Da ma ge Sc ores .........................................................1 5
6. 2. 1. 1. Mai n A nal ys is ...........................................................................1 5
6. 2. 1. 2. Se nsiti vit y  a n d S u p p orti ve A nalys es .........................................1 6
6. 2. 2. TI S ..............................................................................................................1 6
6. 2. 2. 1. Mai n A nal ys is ...........................................................................1 6
6. 2. 2. 2. Se nsiti vit y  a n d S u p p orti ve A nalys es .........................................1 7
6. 2. 3. C S Ms ..........................................................................................................1 7
6. 2. 3. 1. Mai n A nal ys is ...........................................................................1 7
6. 2. 3. 2. Se nsiti vit y  a n d S u p p orti ve A nalys es .........................................1 7
6. 3. Ot her E n d p oi nt(s) ....................................................................................................1 7
6. 3. 1. P K E n d p oi nts ..............................................................................................1 7
6. 3. 2. P D E n d p oi nts, i ncl u di n g Selecte d Bi o mar kers ( hs C R P, t otal IF N ) .........1 8
6. 3. 3. I m m u n o ge nicit y ..........................................................................................1 9
6. 3. 4. C -S S R S .......................................................................................................2 0
6. 3. 5. P R Os ( E Q -5 D -5 L , S F-3 6 v 2 ac ute) ............................................................2 0
6. 4. S u bset A nal y ses.......................................................................................................2 0
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 4
6. 5. Baseli ne a n d Ot her S u m maries a n d A nal ys es .........................................................2 1
6. 5. 1. Baseli ne S u m maries ....................................................................................2 1
6. 5. 2. St u d y  C o n d uct a n d Partici pa nt Dis p ositi o n................................................2 1
6. 5. 3. St u d y  Treat me nt E x p os ure .........................................................................2 1
6. 5. 4. C o nc o mita nt Me dicati o ns a n d N o n dr u g Treat me nts ..................................2 1
6. 6. Safet y S u m maries a n d A nal yses .............................................................................2 1
6. 6. 1. A d verse E ve nts ...........................................................................................2 1
6. 6. 2. L a b orat or y Data..........................................................................................2 1
6. 6. 3. Vital Si g ns ..................................................................................................2 2
6. 6. 4. Electr ocar di o gra ms .....................................................................................2 2
6. 6. 5. P h y sical E xa mi nati o n .................................................................................2 2
7. I N T E RI M A N A L Y S E S .......................................................................................................2 2
8. R E F E R E N C E S ....................................................................................................................2 3
9. A P P E N DI C E S .....................................................................................................................2 4
9. 1. Defi niti o n a n d Use of Visit Wi n d o ws i n Re p orti n g ................................................2 4
9. 2. C D A SI .....................................................................................................................2 5
9. 2. 1. T he Acti vit y  Sc ore ( A S).............................................................................2 6
9. 2. 2. Da ma ge Sc ore .............................................................................................2 6
9. 3. TI S usi n g C S M i n D M ............................................................................................2 7
9. 4. Cate g ories f or E C G a n d Vital Si g n O utc o mes........................................................ 2 9
9. 5. L ist of A b bre viati o ns...............................................................................................2 9
LI S T O F T A B L E S
Ta ble 1.
S u m mar y  of C ha n ges..................................................................................5
Ta ble 2.
List of St u d y  O bjecti ves, Esti ma n ds, a n d E n d p oi nts..................................5
LI S T O F FI G U R E S
Fi g ure 1.
St u d y  Sc he ma .............................................................................................8
Fi g ure 2.
Prese nts t he C D A SI Scale ........................................................................2 5
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 5
1. V E R SI O N HI S T O R Y
T a ble 1.
S u m m ar y of C h a n ges
Versi o n /
D ate
Ass oci ate d
Pr ot oc ol 
A m e n d me nt
R ati o n ale
S pecific C h a n ges
1
3 0 N o v 2 0 2 1
Ori gi nal 
3 Se pt 2 0 2 1
N/ A  
N/ A
N O T E: It alicize d te xt wit hi n t his d oc u me nt has bee n ta ke n ver bati m fr o m t he Pr ot oc ol.
2. I N T R O D U C TI O N
T his statistical a nal ysis pla n ( S A P) pr o vi des t he detaile d met h o d ol o g y  f or s u m mar y a n d 
statistical a nal yses of t he data c ollecte d i n S t u d y C 0 2 5 1 0 0 8 .  T his d oc u me nt ma y m o dif y t he 
pla ns o utli ne d i n t he pr ot oc ol; h o we ver, a n y maj or m o dificati o ns of t he pri mar y e n d p oi nt 
defi niti o n or its a nal y sis will als o be reflecte d i n a pr ot oc ol a me n d me nt.
2. 1. St u d y O bjecti ves , E n d p oi nts, a n d Esti m a n ds
T a ble 2.
List of St u d y O bjecti ves, Esti m a n ds, a n d E n d p oi nts
O bjectives
E n d p oi nts
Esti m a n ds
Pri m ary: 
Pri m ary:
Pri m ary: 

T o ev al u ate t he l o n g -ter m 
s afety a n d t oler a bility of 
P F -0 6 8 2 3 8 5 9.

I nci de nce of A Es, l a b or at ory 
a b n or m alities, c h a n ges i n vit al 
si g ns, a n d E C G fi n di n gs.

T here are n o defi ne d 
esti m a n ds f or s afety a n d 
t oler a bility e n d p oi nts; t hese 
will be a n alyze d usi n g Pfizer 
d at a st a n d ar ds, as a p plic a ble.
Sec o n d ary: 
Sec o n d ary:
Sec o n d ary: 

T o ev al u ate t he l o n g -ter m 
effic acy of P F -0 6 8 2 3 8 5 9 i n 
a d ult p artici p a nts wit h 
m o der ate t o severe D M.

C h a n ge fr o m b aseli ne i n C D A SI 
activity sc ore at Week 5 2.

E 1: T his esti m a n d uses a 
hy p ot hetic al esti m a n d 
str ate gy (I C H E 9 a d de n d u m) 
esti m ati n g t he me a n effect of 
P F -0 6 8 2 3 8 5 9 i n t he a bse nce 
of i nterc urre nt eve nts (st u dy 
wit h dr a w al). T his is t he me a n 
c h a n ge fr o m b aseli ne t o 
Week 5 2 C D A SI activity sc ore 
f or all r a n d o mize d a n d d ose d 
p artici p a nts wit h n o n -missi n g 
b aseli ne sc ore i n t he ( a) Ski n 
A n alysis Set a n d ( b) M uscle 
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 6

A bs ol ute v al ues a n d c h a n ge 
fr o m b aseli ne of C D A SI activity 
a n d C D A SI d a m a ge sc ores at 
all sc he d ule d ti me p oi nts.

TI S sc ore at Week 5 2 a n d at 
i nter me di ate sc he d ule d 
ti me p oi nts f or p artici p a nts w h o 
e ntere d fr o m St a ge 3 of 
Pr ot oc ol C 0 2 5 1 0 0 2.

C h a n ge fr o m b aseli ne i n t he 
C S Ms of t he TI S i ncl u di n g 
P h G A, Pt G A, M M T -8, H A Q -DI, 
m uscle e nzy mes, a n d M D A A T
at Week 5 2 a n d at i nter me di ate 
sc he d ule d ti me p oi nts.
A n alysis Set (see det ails i n
Secti o n 4 ).

T hese a d diti o n al C D A SI 
e n d p oi nts will be a n alyze d 
usi n g E 1 at all sc he d ule d 
ti me p oi nts.

E 2: T his esti m a n d uses a 
hy p ot hetic al esti m a n d 
str ate gy (I C H E 9 a d de n d u m) 
esti m ati n g t he me a n effect of 
P F -0 6 8 2 3 8 5 9 i n t he a bse nce 
of i nterc urre nt eve nts (st u dy 
wit h dr a w al). T his is t he me a n 
TI S at Week 5 2 f or all 
r a n d o mize d a n d d ose d 
p artici p a nts i ncl u de d wit h 
n o n -missi n g b aseli ne sc ore i n 
t he M uscle A n alysis Set (see 
det ails i n Secti o n 4 ).

T he e n d p oi nts f or t he C S M of 
t he TI S will be a n alyze d usi n g 
E 2 at Week 5 2 a n d all 
i nter me di ate sc he d ule d 
ti me p oi nts.
Terti ary/ E x pl or at ory: 
Terti ary/ E x pl or at ory:
Terti ary/ E x pl or at ory: 

T o c h ar acterize 
p h ar m ac oki netics ( P K) of 
P F -0 6 8 2 3 8 5 9.

T o c h ar acterize 
p h ar m ac o dy n a mics ( P D) 
effects of P F -0 6 8 2 3 8 5 9.

T o ev al u ate i m m u n o ge nicity of 
P F -0 6 8 2 3 8 5 9. 

T o ev al u ate t he effect of 
P F ‑ 0 6 8 2 38 5 9 o n s uici d ality 
assess me nt over ti me i n 
p artici p a nts wit h active D M.

T o ev al u ate t he effect of 
P F -0 6 8 2 3 8 5 9 o n S F -3 6 

Pl as m a c o nce ntr ati o ns of 
P F -0 6 8 2 3 8 5 9. 

A bs ol ute v al ues a n d c h a n ge 
fr o m b aseli ne i n t he v al ues of 
selecte d bi o m arkers at all 
sc he d ule d ti me p oi nts.

I nci de nce of A D A a n d N A b.

A bs ol ute v al ues a n d c h a n ge 
fr o m b aseli ne v al ues of 
C ol u m bi a ‑ S uici de Severity 

N ot a p plic a ble.
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 7
(v 2 ac ute) a n d E Q -5 D -5 L 
P R Os.
R ati n g Sc ale ( C ‑ S S R S) at all 
sc he d ule d ti me p oi nts.

A bs ol ute v al ues a n d c h a n ge 
fr o m b aseli ne i n t he v al ues of 
P R Os i ncl u di n g S F -3 6 
(v 2 ac ute) a n d E Q -5 D -5 L at all 
sc he d ule d ti me p oi nts. 
2. 1. 1. Pri m ar y Esti m a n d (s)
T here are n o defi ne d esti m a n ds f or t he i nci de nce of A Es, l a b or at ory a b n or m alities, c h a n ges 
i n vit al si g ns, a n d E C G fi n di n gs. T hese e n d p oi nts will be a n alyze d usi n g Pfizer d at a 
st a n d ar ds as a p plic a ble. All p artici p a nts w h o receive at le ast 1 d ose of I P will be i ncl u de d i n 
t he s afety an alyses. All s afety d at a will be s u m m arize d descri ptively t hr o u g h a p pr o pri ate 
d at a t a b ul ati o ns, descri ptive st atistics, c ate g oric al s u m m aries, a n d gr a p hic al prese nt ati o ns. 
2. 1. 2. Sec o n d ar y Esti m a n d (s)
T w o esti m a n ds are defi ne d f or t his st u dy. Esti m a n d 1 ( E 1) will s u p p ort s pecifie d C D A SI 
assess me nts at s pecifie d ti me p oi nts f or p artici p a nts i n t he Ski n A n alysis Set a n d M uscle 
A n alysis Set se p ar ately. Esti m a n d 2 ( E 2) will s u p p ort TI S a n d C S M assess me nts at s pecifie d 
ti me p oi nts f or p artici p a nts i n t he M uscle A n alysis Set.
E 1 will be t he p o p ul ati o n aver a ge effect of P F -0 6 8 2 3 8 5 9 o n C F B i n C D A SI activity sc ore at 
Week 5 2 f or all r a n d o mize d a n d d ose d p artici p a nts wit h n o n -missi n g b aseli ne i n a s pecifie d 
a n alysis set ( Ski n or M uscle A n alysis Set) i n t he a bse nce of dr o p o u t. Me as ure me nts t ake n 
after a p artici p a nt wit h dr a ws fr o m tre at me nt will be ce ns ore d a n d tre ate d as missi n g d at a. 
T he p o p ul ati o n ‑ b ase d esti m ate f or t he effect of P F-0 6 8 2 3 8 5 9 will be t he me a n C F B i n 
C D A SI -activity sc ore at Week 5 2.
E 1 will als o be a p plie d t o e ac h c o m bi n ati o n of t he f oll o wi n g e n d p oi nts, ti me p oi nts, a n d 
a n alysis sets:

E n d p oi nts: C h a n ge fr o m b aseli ne a n d a bs ol ute v al ues of C D A SI activity sc ore a n d 
C D A SI d a m a ge sc ore;

Ti me p oi nts: Week 5 2 a n d all sc he d ule d i nter me di ate ti me p oi nts;

A n alysis sets: Ski n A n alysis Set a n d M uscle A n alysis Set.
E 2 will be t he p o p ul ati o n aver a ge esti m ate f or t he effect of P F -0 6 8 2 3 8 5 9 o n TI S at W eek 5 2 
f or all r a n d o mize d a n d d ose d p artici p a nts wit h n o n-missi n g b aseli ne i n t he St a ge 3 M uscle 
A n alysis Set i n t he a bse nce of dr o p o uts. Me as ure me nts t ake n after a p artici p a nt wit h dr a ws 
fr o m tre at me nt will be ce ns ore d a n d tre ate d as missi n g d at a. T he p o p ul ati o n ‑ b ase d esti m ate 
f or t he effect of P F-0 6 8 2 3 8 5 9 will be t he me a n TI S at W eek 5 2. 
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 8
E 2 will als o be a p plie d t o e ac h c o m bi n at i o n of t he f oll o wi n g e n d p oi nts a n d ti me p oi nts i n t he 
St a ge 3 A n alysis Set:

E n d p oi nts: TI S a n d c h a n ge fr o m b aseli ne i n e ac h of t he C S M of t he TI S.

Ti me p oi nts: Week 5 2 a n d all sc he d ule d i nter me di ate ti me p oi nts.
2. 2. St u d y Desi g n
T his is a P h ase 2 b, O L E st u dy t o ev al u ate t he l o n g -ter m s afety a n d t oler a bility of 
P F -0 6 8 2 3 8 5 9 i n a d ult p artici p a nts wit h m o der ate t o severe D M w h o c o m plete d t he tre at me nt 
peri o d of a q u alifyi n g st u dy (i ncl u di n g Pr ot oc ol C 0 2 5 1 0 0 2) a n d h ave a gree me nt fr o m t heir 
st u dy d oct or t o c o nti n ue active tre at me nt. Eli gi ble p artici p a nts will n ot h ave h a d a ny 
si g nific a nt pr ot oc ol devi ati o ns (e g , n ot f oll o wi n g t he pr ot oc ol, t aki n g pr o hi bite d me dic ati o ns, 
n ot usi n g a p pr o pri ate c o ntr ace pti o n) or h ave n ot c o m plete d all st u dy tre at me nt i n t he 
q u alifyi n g st u dy. A p pr oxi m ately 3 0 p artici p a nts w h o c o m plete t he Week 2 4 visit d uri n g t he 
tre at me nt peri o d i n St u dy C 0 2 5 1 0 0 2 or e q uiv ale nt i n a n ot her q u alifyi n g st u dy, m ay be 
e nr olle d i n Pr ot oc ol C 0 2 5 1 0 0 8. T he tre at me nt d ur ati o n of O L E st u dy p artici p ati o n will be 
u p t o 4 8 weeks (tre at me nt peri o d is u p t hr o u g h a n d i ncl u di n g W eek 5 2), wit h a 1 6 week 
f oll o w u p peri o d. See Fi g ure 1 f or t he st u dy s c he matic.
Q u alifie d p artici p a nts will be r a n d o mize d t o receive o pe n -l a bel P F-0 6 8 2 3 8 5 9 6 0 0 m g I V 
every 4 weeks f or u p t o 4 8 weeks, h o wev er t he tre at me nt peri o d is u p t o Week 5 2. All 
p artici p a nts will be f oll o we d f or a n ot her 1 6 weeks i n t he F oll o w -u p Peri o d. P artici p a nts 
w h o are disc o nti n ue d fr o m st u dy i nterve nti o n will als o e nter t he f oll o w -u p peri o d. 
Fi g ure 1.
St u d y Sc he m a
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 9
3. E N D P OI N T S A N D B A S E LI N E V A RI A B L E S: D E FI NI TI O N S A N D 
C O N V E N TI O N S
F or t he s ki n c o h ort (ie, partici pa nts e nteri n g C 0 2 5 1 0 0 8 fr o m A me n de d Sta ge 2 of 
C 0 2 5 1 0 0 2), t he maj or efficac y  a nalys es assess c ha n ges i n t he m o difie d C D A SI  activity a n d 
d a m a ge sc ores. T he details of t he calc ulati o n of t hese sc ores are prese nte d i n Secti o n 9. 2 .
F or t he m uscle c o h ort (ie, partici pa nts e nteri n g C 0 2 5 1 0 0 8 fr o m Sta ge 3 of C 0 2 5 1 0 0 2), t he 
maj or efficac y a nal ys es assess c ha n ges i n t he m o difie d C D A SI  acti vit y a n d da ma ge sc ores 
a n d c ha n ges i n t he TI S a n d t he C S M. T he details of t he calc ulati o n of t he TI S are prese nte d 
i n Secti o n 9. 3 .  
Safet y  assess me nts f or t he pri mar y e n d p oi nt will be re p orte d f or all partici pa nts a n d b y 
c o h ort. Efficac y  assess me nts will ge nerally be re p orte d b y c o h ort.
U nless s pecificall y  state d ot her wise, t he baseli ne val ue f or all assess me nts is defi ne d as t he 
last n o n-missi n g meas ure me nt c ollecte d pri or t o t he first a d mi nistrati o n of st u d y  dr u g at 
D a y 1. C ha n ge fr o m baseli ne is defi ne d as t he val ue at a s pecific visit mi n us t he val ue fr o m 
baseli ne.
3. 1. Pri m ar y E n d p oi nt(s)
3. 1. 1. I nci de nce of A d verse E ve nts ( A Es)
Re p orti n g f or A Es is descri be d i n Secti o n 6. 6. 1 . A p pe n di x 3 of t he C 0 2 5 1 0 0 8 St u d y  Pr ot oc ol 
pr o vi des defi niti o ns f or a n A E a n d S A E. A n A E i s c o nsi dere d treat me nt e mer ge nt relati ve t o 
a gi ve n treat me nt if:

t he e ve nt occ urs f or t he first ti me d uri n g t he effecti ve d urati o n of treat me nt a n d was 
n ot see n pri or t o t he start of treat me nt (f or e xa m ple, d uri n g t he baseli ne or r u n -i n 
peri o d), or

t he e ve nt was see n pri or t o t he start of treat me nt b ut i ncrease d i n se verity d uri n g 
treat me nt.
3. 1. 2. L a b or at or y A b n or m alities
Re p orti n g f or la b orat or y data is d escri be d i n Secti o n 6. 6. 2 . T o deter mi ne if t here are a n y 
cli nicall y si g nifica nt la b orat or y a b n or malities, t he safety la b orat or y tests will be assesse d 
a gai nst t he criteria s pecifie d i n t he C 0 2 5 1 0 0 8 St u d y Pr ot oc ol . Baseli ne of safet y la b orat or y 
tests will be t he last pre-d ose meas ure me nt.
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 1 0
3. 1. 3. C h a n ges i n Vit al Si g ns
Vital si g ns (i ncl u di n g bl o o d press ure, p ulse, res pirat or y rates a n d te m perat ure) will be 
meas ure d after 5 mi n utes of rest as i n dicate d i n t he Sc he d ule of Acti vities.
Baseli ne will be 
t he last meas ure me nt pri or t o recei vi n g st u d y treat me nt . Re p orti n g f or c ha n ges i n vital si g ns 
is descri be d i n Secti o n 6. 6. 3 .
3. 1. 4. E C G F i n di n gs
Re p orti n g f or E C G fi n di n gs is descri be d i n Secti o n 6. 6. 4 . Baseli ne will be t he last 
meas ure me nt pri or t o recei vi n g st u d y treat me nt .
3. 2. Sec o n d ar y E n d p oi nt(s)
3. 2. 1. C D A SI A cti vit y a n d D a m a ge S c ores
T he C D A SI acti vit y  a n d da ma ge sc ores are c o nti n u o us meas ures wit h ra n ges of 0- 1 0 0 a n d 
0 -3 2 res pecti vel y , w here hi g her sc ores i n dicate hi g her le vels of disa bility. B ot h C D A SI 
sc ores are c o m p ute d as t he s u m of c o m p o ne nt sc ores as descri be d i n A p pe n di x 9. 2 . T he
a bs ol ute val ue a n d c ha n ge fr o m baseli ne ( C F B ) val ues of t he C D A SI acti vit y a n d da ma ge 
sc ores will be assesse d.
3. 2. 2. T I S
T he TI S is a c o nti n u o us meas ure ra n gi n g fr o m 0 t o 1 0 0 t hat assesses disease acti vit y  relati ve 
t o baseli ne. B y defi niti o n, all partici pa nts ha ve a TI S of 0 at baseli ne. A T IS ≥2 0 re pres e nts 
mi ni mal i m pr o ve me nt , TI S ≥4 0 re prese nts m o derate i m pr o ve me nt , a n d TI S ≥6 0 re prese nts 
maj or i m pr o ve me nt .
Si x C S Ms c o ntri b ute t o t he TI S, i ncl u di n g t he P h G A, Pt G A, M M T -8, H A Q -DI , gl o bal 
e xtra m usc ular disease acti vit y assess me nt fr o m t he M D A A T, a n d m uscle e nz ymes.
T he TI S 
is t he s u m of all 6 i m pr o ve me nt sc ores ass ociate d wit h t he c ha n ge i n eac h C S M. 
A p pe n di x 9. 3 pr o vi des f ull details o n t he c o m p utati o n of t he TI S a n d eac h C S M . T he 
a bs ol ute val ues a n d C F B i n eac h C S M will be assesse d.
3. 2. 2. 1. P h G A
P h y sicia n Gl o bal Assess me nt Sc ore ( P h G A) is defi ne d as a val ue wit hi n ( 0-1 0 0 m m or 
0- 1 0 c m) o n a v is ual a nal o g scale. F or c o m p utati o n of t he TI S, t he P h G A is dra w n fr o m t he 
M D A A T. 
Hi g her sc ores i n dicate a hi g her le vel of disa bilit y.
3. 2. 2. 2. Pt G A
Patie nt Gl o bal Assess me nt Sc ore ( PtG A) is defi ne d as a val ue wit hi n ( 0-1 0 0 m m or 0 -1 0 c m) 
o n a vis ual a nal o g scale. Hi g her sc ores i n dicate a hi g her le vel of disa bilit y .
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 1 1
3. 2. 2. 3. M M T - 8
M M T -8 is a t o ol t hat assesses m uscle stre n gt h usi n g ma n ual m uscle testi n g. Ei g ht
desi g nate d m uscles are teste d u nilateriall y wit h a t otal p ote ntial s u m me d sc ore of 0-8 0. 
L o wer sc ores i n dicate a hi g her le vel of disa bilit y .
3. 2. 2. 4. H A Q -DI
T he H A Q -DI  c o ntai ns ei g ht secti o ns (i ncl u di n g dressi n g & gr o o mi n g, arisi n g, eati n g, 
wal ki n g, h y g ie ne, gri p, reac h, a n d acti vities) wit h ite ms t hat ca n be sc ore d fr o m 0 t o 3. 
Hi g her sc ores i n dicate hi g her le vel of disa bilit y. T he H A Q -DI  sc ore use d i n t he C S M 
calc ulati o n f or t he TI S is t he a vera ge of t hese sc ores.  
3. 2. 2. 5. Gl o b al E xtr a m usc ul ar D ise ase A cti vit y A ssess me nt fr o m t he M D A A T
T he gl o bal e xtra m usc ular disease acti vit y  assess me nt fr o m t he M D A A T is o ne of t he C S Ms 
use d i n t he c o m p utati o n of t he TI S . T he gl o bal e x tra m usc ular disease acti vit y is defi ne d as a 
val ue wit hi n 0 -1 0 c m o n a vis ual a nal o g scale. Hi g her sc ores i n dicate hi g her le vel of 
disa bilit y . 
3. 2. 2. 6. M uscle E nz y mes
Fi ve m uscle e nz y m es are assesse d f or t he TI S, i ncl u di n g al d olase, ala ni ne a mi n otra nsferase, 
as partate a mi n otra nsferase, lactate de h y d r o ge nase, a n d creati ne ki nase. T he m ost a b n or mal 
ser u m m uscle e nz yme a m o n g t hese is use d i n t he c o m p utati o n of t he m uscle e nz y me C S M of 
t he TIS.
3. 3. Ot her E n d p oi nt (s)
3. 3. 1. P K a n d P D E n d p oi nts
T he P K/ P D e n d p oi nts i ncl u de:

Pl as ma P F-0 6 8 2 3 8 5 9 c o nce ntrati o ns .

P D bi o mar kers: t otal I F N , hs C R P, m uscle bi o mar kers descri be d i n Secti o n 3. 2. 2. 6 .
T he a bs ol ute val ue a n d C F B will be assesse d f or eac h bi o mar ker.
3. 3. 2. I m m u n o ge nicit y
I m m u n o ge nicity will be assesse d t hr o u g h re p orti n g t he i nci de nce of a nti-dr u g a nti b o dies 
( A D As) a n d ne utralizi n g a nti b o dies ( N A bs ).
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 1 2
3. 3. 3. C ol u m bi a -S uici de Se verit y R ati n g Sc ale ( C- S S R S )
T he C -S S R S is use d t o assess s uici dal i deati o n a n d be ha vi or d uri n g t he c o n d uct of t he st u d y.
T he C -S S R S is a patie nt -re p orte d q uesti o n naire a d mi nistere d b y t he i n vesti gat or or site staff 
t hat ha ve bee n trai ne d t o a d mi nister t he test. T he a bs ol ute val ue a n d C F B i n t he C-S S R S will 
be assesse d.
3. 3. 4. P R Os

E ur o pea n Q ualit y  of Li fe – 5 Di me nsi o ns -5 Le vel ( E Q -5 D -5 L ) Q uesti o n naire 
assesses i m pact o n healt h -relate d q ualit y of life i n 5 d o mai ns: m o bilit y, self-care, 
us ual acti vities, pai n/ disc o mf ort, a n d a n xiet y / de pressi o n. A d diti o nall y , sc ores fr o m 
t he 5 d o mai ns ma y  be use d t o calc ulate a si n gle i n de x val ue, als o k n o w n as a utilit y 
sc ore. Hi g her sc ores i n dicate hi g her le vel of disa bilit y. T he a bs ol ute val ue a n d C F B 
i n t he E Q-5 D -5 L  will be assesse d.

T he S F -3 6 v. 2 ( Ac ute vers i o n) is a 3 6-ite m ge neric healt h stat us meas ure. It meas ures
8 ge neral healt h c o nce pts or d o mai ns: p h y sical f u ncti o ni n g ( P F), r ole p h ys ical ( R P), 
b o dil y pai n ( B P), ge neral healt h ( G H), vitalit y ( V T), s ocial f u ncti o ni n g ( S F), r ole
e m oti o nal ( R E) a n d me ntal healt h ( M H). T hese d o mai ns are als o s u m marize d as
p h y sical a n d me ntal c o m p o ne nt sc ores ( P C S a n d M C S). Hi g her sc ores i n dicate l o wer 
le vel of disa bilit y. T he a bs ol ute val ue a n d C F B i n t he S F -3 6 v. 2 sc ores will be 
assesse d.
3. 4. B aseli ne V ari a bles
U nless s pecif icall y state d ot her wise, t he baseli ne val ue f or all assess me nts is defi ne d as t he 
last n o n-missi n g meas ure me nt c ollecte d pri or t o t he first a d mi nistrati o n of st u d y  dr u g at 
D a y 1. Refere nces t o “ b aseli ne ” i n t his st u dy c orres p o n d t o t he Week 2 4 visit of t h e P h ase 2 
C 0 2 5 1 0 0 2 st u dy a n d D ay 1 of t his st u dy.
3. 5. S afet y E n d p oi nts
Safet y  e n d p oi nts are descri be d i n Secti o n 3. 1 .
4. A N A L Y SI S S E T S ( P O P U L A TI O N S F O R A N A L Y SI S )
D ata f or all partici pa nts will be assesse d t o deter mi ne if partici pa nts meet t he criteria f or 
i ncl usi o n i n eac h a nalys is p o p ulati o n pri or t o releasi ng t he data base a n d classificati o ns will 
be d oc u me nte d per sta n dar d o perati n g pr oce d ures.
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 1 3
P artici p a nt A n al ysis Set
Descri pti o n
R a n d o mize d 
" R a n d o mize d" me a ns a p artici p a nt's a gree me nt t o p artici p ate 
i n a cli nic al st u dy f oll o wi n g c o m pleti o n of t he i nf or me d 
c o nse nt pr ocess. A p artici p a nt will be c o nsi dere d e nr olle d if 
t he i nf or me d c o nse nt is n ot wit h dr a w n pri or t o p artici p ati n g i n 
a ny st u dy activity.
F ull A n alysis Set ( F A S) 
All p artici p a nts e nr olle d w h o t ake at le ast 1 d ose of st u dy 
i nterve nti o n.
S afety A n alysis Set
All p artici p a nts e nr olle d w h o t ake at le ast 1 d ose of st u dy 
i nterve nti o n. T his i ncl u des all s uc h p artici p a nts re g ar dless of 
w hic h p are nt st u dy or st a ge t he p artici p a nt e ntere d fr o m.
Ski n S afety A n alysis Set
All p artici p a nts wit h ski n pre d o mi n a nt D M w h o t ake at le ast 
1 d ose of st u dy i nterve nti o n i ncl u di n g p artici p a nts e nteri n g 
fr o m A me n de d St a ge 2 of t he C 0 2 5 1 0 0 2 pr ot oc ol.
M uscle S afety A n alysis 
Set
Al p artici p a nts wit h m uscle pre d o mi n a nt D M w h o t ake at le ast 
1 d ose of st u dy i nterve nti o n i ncl u di n g p artici p a nts e nteri n g 
fr o m St a ge 3 of t he C 0 2 5 1 0 0 2 pr ot oc ol. 
P K C o nce ntrati o n Set
All partici pa nts assi g ne d t o i n vesti gati o nal st u d y  treat me nt a n d 
w h o ta ke at least 1 d ose of i n vesti gati o nal pr o d uct a n d ha ve at 
least 1 meas ura ble c o nce ntrati o n.
P D Data Set
All partici pa nts assi g ne d t o i n vesti gati o nal st u d y  treat me nt a n d 
w h o ta ke at least 1 d ose of i n vesti gati o nal pr o d uct a n d ha ve at 
least 1 of t he P D para meters of i nterest. 
I m m u n o ge nicity 
assess me nt p o p ulati o n
All e nr olle d s u bjects w h o recei ve d at least o ne d ose of 
P F -0 6 8 2 3 8 5 9 wit h at least o ne p ost -treat me nt 
a nti-P F -0 6 8 2 3 8 5 9 a nti b o d y  deter mi nati o n.
Defi ne d A n al ysis Set 
( Effic ac y)
Descri pti o n
Ski n A n alysis Set
All p artici p a nts wit h ski n pre d o mi n a nt D M i n t he F A S 
i ncl u di n g p artici p a nts w h o were e nr olle d i n A me n de d St a ge 2 
of t he C 0 2 5 1 0 0 2 st u dy.
M uscle A n alysis Set
All p artici p a nts wit h m uscle pre d o mi n a nt D M i n t he F A S 
i ncl u di n g p artici p a nts w h o were e nr olle d i n St a ge 3 of t he 
C 0 2 5 1 0 0 2 st u dy.
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 1 4
P o ole d Ski n A n alysis Set
All p artici p a nts i n t he F A S wit h a C D A SI activity sc ore of 
1 4 or gre ater at b aseli ne of st u dy C 0 2 5 1 0 0 2. T his a n alysis set 
i ncl u des all s u bjects fr o m A me n de d St a ge 2 of t he C 0 2 5 1 0 0 2 
st u dy a n d p ote ntially s o me s u bjects fr o m St a ge 3 of t he 
C 0 2 5 1 0 0 2 st u dy w h o als o h ave ski n dise ase.
5. G E N E R A L M E T H O D O L O G Y A N D C O N V E N TI O N S
Fi nal a nal y ses will occ ur after data base l oc k after Last Partici pa nt Last Visit ( LP L V).
5. 1. H y p ot heses a n d Decisi o n R ules
N o statistical h y p ot hesis testi n g is pla n ne d f or t his st u d y .
5. 2. Ge ner al Met h o ds
A nal y ses will ge nerall y be re p orte d b y c o h ort (s ki n or m uscle). Se nsiti vit y a nal ys es will be 
perf or me d f or t he C D A SI acti vit y sc ore, C D A SI da ma ge sc ore, a n d T I S. S u p p orti ve 
a nal ys es f or t he C D A SI acti vit y  a n d da ma ge sc ores will use t he p o ole d s ki n a nalys is set, 
w hic h i ncl u des all partici pa nts fr o m A me n de d Sta ge 2 of st u d y C 0 2 5 1 0 0 2 a n d partici pa nts 
fr o m Sta ge 3 of st u d y C 0 2 5 1 0 0 2 wit h s ufficie nt s ki n disease (see Secti o n 4 ). 
5. 2. 1. A n al yses f or C o nti n u o us E n d p oi nts
F or E 1 a n d E 2, t he L o n git u di nal A N C O V A M o del ( L A N C O V A, use d f or sec o n dar y
a nal ys es) a n d c o n ve nti o nal a nal ys is of c o varia nce ( A N C O V A, use d f or se nsiti vit y a nal ys es) 
met h o ds will be use d .
T he L A N C O V A a nal ys is will use eit her t he c ha n ge fr o m baseli ne val ue ( C D A SI acti vit y or 
C D A SI  da ma ge) or t he direct val ue ( TI S) as t he c o nti n u o us varia ble i n t he o utc o me i n t he 
m o del , w hic h will be fit fr o m baseli ne t o Wee k 5 2 . F or t he C F B C D A SI acti vit y  a n d da ma ge 
e n d p oi nts, t he LA N C O V A m o dels will i ncl u de wee k as a fi xe d effect a n d baseli ne val ue as a 
c o variate. F or t he TI S, t he L A N C O V A m o del will i ncl u de wee k as a fi xe d effect. I n all 
m o dels, a n u nstr uct ure d varia nce -c o varia nce matri x will be use d . Esti mates a n d 9 0 % CI will 
be re p orte d. N o p -val ues will be c o m p ute d f or t he a nal ys is. 
5. 3. Met h o ds t o M a n a ge Missi n g D at a

I n t he l o n git u di nal m o deli n g ( L A N C O V A) of re peate d meas ures of c o nt i n u o us 
o utc o mes ( b ot h efficac y meas ures a n d c o variates) it is ass u me d t hat missi n g data are 
ge nerate d b y t he “ missi n g at ra n d o m” mec ha nis m a n d, t heref ore i m p utati o n of t he 
missi n g data is n ot necessar y .

I n all data prese ntati o ns of P K o utc o me (e xce pt listin gs), c o nce ntrati o ns bel o w t he 
li mit of q ua ntificati o n ( B L Q) will be set t o zer o. (I n listi n gs B L Q val ues will be 
re p orte d as “ < L L Q”, w here L L Q will be re place d wit h t he val ue f or t he l o wer li mit of 
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 1 5
q ua ntificati o n ). I n s u m mar y ta bles a n d pl ots of me dia n pr ofiles, statistics will be 
calc ulate d ha vi n g set c o nce ntrati o ns t o missi n g if c o nce ntrati o n meas ure me nt was n or 
d o ne or sa m ple was n ot c ollecte d.

T he P K s u m mar y statistics will n ot be prese nte d at a partic ular ti me p oi nt if m ore 
t ha n 5 0 % of t he P K data are missi n g.

I m m u n o ge nicity assa y  titers will be use d t o deter mi ne i nci de nce f or A D A a n d N A b. 
If a titer val ue is missi n g data i m p utati o n will n ot occ ur a n d missi n g val ues will be 
re prese nte d by N C (ie, n ot -calc ulate d). 

F or ot her e n d p oi nts, statistical a nal ys es will be base d o n a vaila ble data. Missi n g data 
will n ot be i m p ute d. 
6. A N A L Y S E S A N D S U M M A RI E S
6. 1. Pri m ar y E n d p oi nt (s)
6. 1. 1. I nci de nce of A Es, L a b or at or y A b n or m alities, C h a n ges i n V it al Si g ns, a n d E C G 
F i n di n gs

Esti ma n d strate g y: N ot a p plica ble f or safet y e n d p oi nts.

A nal y sis sets: Safet y  A nal ysis Set, S ki n Safety A nal ysis Set, M uscle Safet y A nal ysis 
Set .

A nal y sis met h o d ol o g y: Descri pti ve statistics .

I nterc urre nt e ve nts a n d missi n g data: Data after st u d y wit h dra wal will be e xcl u de d; 
i nter me diate missi n g val ues will n ot be i m p ute d.

Cate g orical o utc o mes (e g, A Es) will be s u m marize d b y  partici pa nt c o u nts a n d 
perce nta ge. C o nti n u o us o utc o me (e g, B P, heart rate) will be s u m marize d usi n g N, 
mea n, me dia n, sta n dar d de viati o n , mi ni m u m, ma xi m u m. C ha n ge fr o m baseli ne i n 
la b orat or y data a n d vital si g ns will als o be s u m marize d acc or di n g t o s p o ns or Data 
Sta n dar ds.
6. 1. 1. 1. Se nsiti vit y /S u p ple me nt ar y A n al yse s
6. 2. Sec o n d ar y E n d p oi nt(s)
6. 2. 1. C D A SI A cti vit y a n d D a m a ge S c ores
6. 2. 1. 1. M ai n A n al ysis

Esti ma n d stra te g y: E 1.
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 1 6

A nal y sis sets: S ki n A nal ysis Set a n d M uscle A nal ysis Set.

A nal y sis met h o d ol o g y: Eac h C D A SI e n d p oi nt (i ncl u di n g C F B C D A SI acti vit y sc ore, 
C F B C D A SI da ma ge sc ore, a bs ol ute val ue of C D A SI  acti vit y sc ore, a n d a bs ol ute 
val ue of C D A SI da ma ge sc ore) will be a nal yz e d usi n g L A N C O V A i ncl u di n g data 
fr o m baseli ne t o Wee k 5 2 wit h w ee k as a fi xe d effect a n d baseli ne sc ore as a 
c o variate a n d a n u nstr ucte d c o varia nce matri x ( Secti o n 5. 2. 1 ).  

I nterc urre nt e ve nts a n d missi n g data: Data after st u d y dr u g disc o nti n uati o n will be 
e xcl u de d; i nter me diate missi n g val ues will n ot be i m p ute d.

T he sa m ple size, mea n, sta n dar d de viati o n, me dia n, mi ni m u m, a n d ma xi m u m at t he 
baseli ne a n d p ost baseli ne visits f or o bser ve d C D A SI  sc ores a n d c ha n ge fr o m baseli ne 
C D A SI  sc ores will be prese nte d f or eac h c o h ort f or eac h C D A SI e n d p oi nt.

F or eac h C D A SI e n d p oi nt, t he least -s q uares ( LS) mea ns a n d t he 9 0 % c o nfi de nce 
i nter val f or t he L S mea ns will be prese nte d a n d pl otte d f or all p ost baseli ne visits. 
6. 2. 1. 2. Se nsiti vit y a n d S u p p orti ve A n al ys es

S u p p ortive : F or eac h C D A SI e n d p oi nt, t he a nal ys is of Secti o n 6. 2. 1. 1 will be re peate d 
usi n g t he P o ole d S ki n A nal y sis Set.
6. 2. 2. TI S
6. 2. 2. 1. M ai n A n al ysis

Esti ma n d strate g y : E2.

A nal y sis sets: M uscle A nal ysis Set.

A nal y sis met h o d ol o g y: T he TI S will be a nal yz e d usi n g L A N C O V A i ncl u di n g data 
fr o m baseli ne t o Wee k 5 2 wit h wee k as a fi xe d effect a n d a n u nstr ucte d c o varia nce 
matri x ( Secti o n 5. 2. 1 ).  

I nterc urre nt e ve nts a n d missi n g data: Data after st u d y dr u g disc o nti n uati o n will be 
e xcl u de d; i nter me diate missi n g val ues will n ot be i m p ute d.

T he sa m ple size, mea n, sta n dar d de viati o n, me dia n, mi ni m u m, a n d ma xi m u m at t he 
baseli ne a n d p ost baseli ne visits f or t he TIS will be prese nte d .

T he L S mea ns a n d t he 9 0 % c o nfi de nce i nter val f or t he L S mea ns will be prese nte d 
a n d pl otte d f or all p ost baseli ne visits. 
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 1 7
6. 2. 2. 2. Se nsiti vit y a n d S u p p orti ve A n al yses

S u p p ortive : t he fre q ue nc y a n d pr o p orti o ns of patie nts ac hie vi n g mi ni mal 
i m pr o ve me nt ( TI S≥2 0 ), m o derate i m pr o ve me nt ( TIS ≥4 0 ) a n d maj or i m pr o ve me nt
( TIS ≥6 0 ) will als o be re p orte d f or eac h p ost baseli ne visit. 9 0 % CI s will als o be 
pr o vi de d usi n g C ha n a n d Z ha n g’s e xact CI met h o d.
6. 2. 3. C S Ms
6. 2. 3. 1. M ai n A n al ysis

Esti ma n d strate g y : E2.

A nal y sis sets: M uscle A nal ysis Set.

A nal y sis met h o d ol o g y: T he C F B i n eac h C S M (i ncl u di n g P h G A, Pt G A, M M T -8, 
H A Q -DI , gl o bal e xtra m usc ular disease acti vity assess me nt fr o m t he M D A A T, a n d 
m ost a b n or mal m uscle e nz y m e ) will be a nal y ze d usi n g L A N C O V A i ncl u di n g d ata 
fr o m baseli ne t o Wee k 5 2 wit h wee k as a fi xe d effect a n d baseli ne sc ore as a 
c o variate a n d a n u nstr ucte d c o varia nce matri x ( Secti o n 5. 2. 1 ).  

I nterc urre nt e ve nts a n d missi n g data: Data after st u d y dr u g disc o nti n uati o n will be 
e xcl u de d; i nter me diate missi n g val ues will n ot be i m p ute d.

T he sa m ple size, mea n, sta n dar d de viati o n, me dia n, mi ni m u m, a n d ma xi m u m at t he 
baseli ne a n d p ost ba seli ne visits f or t he TIS will be prese nte d .

T he L S mea ns a n d t he 9 0 % c o nfi de nce i nter val f or t he L S mea ns will be prese nte d 
a n d pl otte d f or all p ost baseli ne visits. 
6. 2. 3. 2. Se nsiti vit y a n d S u p p orti ve A n al yses

S u p p ortive : F or eac h C S M at Wee k
5 2, t he fre q ue nc y  a n d pr o p orti o n of partici pa nts 
i n eac h i m pr o ve me nt cate g or y (as defi ne d i n Secti o n 9. 3 ) will be re p orte d.

S u p p ortiv e: S u m mar y statistics f or t he a bs ol ute val ue of eac h C S M, i ncl u di n g the 
sa m ple size, mea n, sta n dar d de viati o n , me dia n, mi ni m u m, a n d ma xi m u m at t he 
baseli ne a n d p ost baseli ne visits will als o be prese nte d.
6. 3. Ot her E n d p oi nt(s)
6. 3. 1. P K E n d p oi nts

A nal y sis p o p ulati o ns: P K c o nce ntrati o n p o p ulati o n .

A nal y sis ti me p oi nts: all ti mes wit h P K sa m ples ta ke n. 
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 1 8

A nal y sis met h o d ol o g y: s u m mar y statistics will be pr o vi de d f or ser u m c o nce ntrati o ns. 

Re p orti n g res ults: Prese ntati o ns f or P F -0 6 8 2 3 8 5 9 c o nce ntrati o ns will i ncl u de: 

a listi n g of all c o nce ntrati o ns s orte d b y partici pa nt I D, c o h ort, a n d n o mi nal ti me 
p ost -d ose.  T he c o nce ntrati o n listi n g will als o i ncl u de t he act ual ti mes. De viati o ns 
fr o m t he n o mi nal ti me will be gi ve n i n a se parate listi n g. 

a s u m mar y of c o nce ntrati o ns b y n omi nal ti me p ost -d ose, w here t he set of 
statistics will i ncl u de n, mea n, me dia n, sta n dar d de viati o n, c oefficie nt of variati o n 
( C V), mi ni m u m, ma xi m u m, a n d t he n u m ber ( perce nta ge) of c o nce ntrati o ns a b o ve 
t he l o wer li mit of q ua ntificati o n ( L L Q). 

m e dia n c o nce n trati o ns ti me pl ots (se mi-l o g scale) a gai nst n o mi nal ti me p ost-d ose .

m ea n c o nce ntrati o ns ti me pl ots (se mi -l o g scale) a gai nst n o mi nal ti me p ost-d ose .

in di vi d ual c o nce ntrati o n ti me pl ots b y  partici pa nt ( o n se mi-l o g scale) a gai nst 
act ual ti me p ost -d ose (t he re will be se parate pl ots f or eac h partici pa nt per scale). 
T he le n gt h of ti me use d f or t he x -a xes of t hese pl ots will be deci de d o n re vie w of t he data, 
a n d will de pe n d o n h o w l o n g t he res pecti ve P K c o nce ntrati o n is q ua ntifia ble i n t he matri x.
F or s u m mar y statistics, me dia n a n d mea n pl ots b y sa m pli n g ti me, t he n o mi nal P K sa m pli n g 
ti me will be use d, f or i n di vi d ual partici pa nt pl ots b y  ti me, t he act ual P K sa m pli n g ti me will 
be use d.
If data per mits , n o n-c o m part me ntal P K para meters ma y  be deri ve d fr o m t he P F-0 6 8 2 3 8 5 9
ser u m c o nce ntrati o ns.
P o p ulati o n P K m o deli n g ma y  be perf or me d wit h t he c o nce ntrati o n data fr o m t his st u d y al o ne 
or c o m bi ne d wit h data fr o m ot her st u dies. I n a d diti o n, a relati o ns hi p bet wee n e x p os ures a n d 
efficac y/safety e n d p oi nts ma y be e val uate d usi n g p o p ulati o n P K/ P D a p pr oac h. A n y 
p o p ulati o n a nal y ses c o n d ucte d will n ot be part of t he cli nical st u d y re p ort ( C S R) a n d ma y be 
re p orte d se parately.
6. 3. 2. P D E n d p oi n ts, i ncl u di n g S electe d B i o m ar kers ( hs C R P, t ot al I F N)

A nal y sis p o p ulati o n: bi o mar ker a nalys is p o p ulati o n.

A nal y sis ti me p oi nts: all visits wit h sa m ples ta ke n.

A nal y sis met h o d ol o g y: s u m mar y statistics. T he c ha n ge fr o m baseli ne ma y als o be 
i n vesti gate d by a p pl yi n g t he LA N C O V A m o del (as descri be d i n Secti o n 5. 2. 1 ).  T he 
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 1 9
l o g-tra nsf or mati o n of t he o utc o mes ma y be a p plie d t o t he ori gi nal o bser vati o ns after 
a nal ys is of t he distri b uti o n of o bser ve d data.

Descri pti ve statistics f or a bs ol ute val ues, c ha n ge fr o m baseli ne, perce nt c ha n ge fr o m 
baseli ne will i ncl u de sa m ple size, mea n, sta n dar d de viati o n, me dia n, mi ni m u m a n d 
ma xi m u m b y  visit.

Pres e ntati o ns f or bi o mar ker c o nce ntrati o ns will als o i ncl u de: 

A listi n g of all c o nce ntrati o ns s orte d b y partici pa nt I D, c o h ort, a n d n o mi nal ti me 
p ost -d ose.   T he c o nce ntrati o n listi n g will als o i ncl u de t he act ual ti mes.   
De viati o ns fr o m t he n o mi nal ti me will be gi ve n i n a se parate listi n g. 

A s u m mar y of c o nce ntrati o ns b y n o mi nal ti me p ost-d ose, w here t he set of 
statistics will i ncl u de n, mea n, me dia n, sta n dar d de viati o n, C V, mi ni m u m, 
ma xi m u m a n d t he n u m ber of c o nce ntrati o n s a b o ve t he l o wer li mit of 
q ua ntificati o n. 

M e dia n c o nce ntrati o ns ti me pl ots (se mi -l o g scale) a gai nst n o mi nal ti me p ost -d ose .

M ea n c o nce ntrati o ns ti me pl ots (se mi -l o g scale) a gai nst n o mi nal ti me p ost-d ose .

In di vi d ual c o nce ntrati o n ti me pl ots b y  partici pa nt (se mi-l o g scales) a gai nst act ual 
ti me p ost-d ose will be prese nte d.
A d diti o nal bi o mar kers ma y  be re p orte d a n a d diti o nal e x pl orat or y a nalys is re p ort.
6. 3. 3. I m m u n o ge nicit y
I m m u n o ge nicity will be assesse d t hr o u g h a nal ys is of A D As a n d N A bs. 

A nal y sis p o p ulati o n: im m u n o ge nicit y assess me nt p o p ulati o n.

A nal y sis ti me p oi nts: all visits wit h sa m ples ta ke n.

A nal y sis met h o d ol o g y: s u m mar y statistics.

Re p orti n g res ults: T he i nci de nce of de vel o p me nt of A D A N A b a gai nst P F -0 6 8 2 3 8 5 9
will be prese nte d.  Prese ntati o ns f or i m m u n o ge nicit y  will i ncl u de: 

S u m mar y  of A D A a n d Na b a nalys is b y sa m ple a n d partici pa nt;

S u m mar y  of c u m ulati ve i nci de nce of A D A a n d N A b o ver ti me;

S u m mar y  of A D A a n d N A b i nci de nce a n d titers o ver ti me ;
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 2 0

S u m mar y  of ti me t o first A D A a n d N A b occ urre nce;

I m pact of A D A a n d N A b stat us of P F-0 6 8 2 3 8 5 9  c o nce ntrati o ns ( data 
per mitti n g);

I m pact of A D A a n d N A b stat us o n bi o mar kers ( data per mitti n g);

I m pact of A D A a n d N A b stat us o n C D A SI  ( data per mitti n g);

C o m bi ne d pl ot of P K, P D (t otal I F N), A D A a n d N A b res p o nse o ver ti me ( data 
per mitti n g) . 
6. 3. 4. C- S S R S
F or eac h of t he o bser vati o n ti mes t he descri pti ve statistics will s h o w n u m ber of partici pa nts
i n t he data set a n d pr o p orti o n of partici pa nts w h o c o m plete d s uci de, atte m pte d s uici de ha d 
pre parat or y  acts t o war ds i m mi ne nt s uici de be ha vi or, s uici deal i deati o n or self-i nj uri o us 
be ha vi or wit h o ut s uici dal atte m pt i n b ot h c o h orts.
6. 3. 5. P R Os ( E Q-5 D -5 L, S F -3 6 v 2 ac ute)

A nal y sis p o p ulati o n: S ki n a nal ys is set a n d m uscle a nalys is set.

A nal y sis ti me p oi nts: all visits wit h res p o nses assesse d.

A nal y sis met h o d ol o g y: s u m mar y statistics. F or t he S F-3 6 o bser vati o ns , t w o 
s u m mar y c o m p o ne nt sc ores ( P C S a n d M C S) a n d 8 scale s u bsc ores ( P F, R P, B P, G H,
V T, S F, R E, a n d M H) will be s u m marize d. 
C F B will als o be re p orte d f or t he P C S 
a n d M C S sc ores. F or t he E Q -5 D -5 L , t he s u m me d n u m ber of c hec ke d b o xes u n der 
eac h of t he fi ve secti o ns will be re p orte d .

Re p orti n g res ults: 

C ha n ge fr o m baseli ne: T he sa m ple size, mea n, sta n dar d de viati o n, me dia n, 
mi ni m u m a n d ma xi m u m b y  visit.

A bs ol ute val ues: T he sa m ple size, mea n, sta n dar d de viati o n, me dia n, mi ni m u m 
a n d ma xi m u m b y visit.
A d -h oc a nal y ses f or P R Os wit h mi ni m u m cli nicall y i m p orta nt differe nces ma y be perf or me d.
6. 4. S u bset A n al yses
N o s u bset a nal ys es are pla n ne d.
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 2 1
6. 5. B aseli ne a n d Ot her S u m m aries a n d A n al yses
6. 5. 1. B aseli ne S u m m aries
A brea k d o w n of all partici pa nts will be pr o vi de d b y  de m o gra p hic c haracteristics (a ge, race, 
wei g ht, b o d y mass i n de x, a n d hei g ht), e xte nt of disease a n d pri or use of c o n ve nti o nal t hera p y 
i n acc or da nce wit h Pfizer data sta n dar ds.   Mea n ster oi d use a n d d urati o n of disease will als o 
be prese nte d b y c o h ort .  Baseli ne C D A SI  (acti vit y a n d da ma ge) will be s u m mariz e d 
descri pti vel y.
6. 5. 2. St u d y C o n d uct a n d P artici p a nt Dis p ositi o n
Partici pa nt e val uati o n gr o u ps will s h o w e n d of st u d y  partici pa nt dis p ositi o n a n d will s h o w 
w hic h partici pa nts were a nal yz e d i n t he f ull a nal ysis set , s ki n a nal ysis set, a n d m uscle 
a nal ys is set, a n d as well as f or safety, P K a n d P D.   Fre q ue nc y  c o u nts will be s u p plie d f or 
partici pa nt disc o nti n uati o ns b y  treat me nt.  Dis p ositi o n will als o be s u m marize d se paratel y f or 
partici pa nts w h o disc o nti n ue.
Data will be re p orte d i n acc or da nce wit h re p orti n g sta n dar ds.
6. 5. 3. St u d y Tre at me nt E x p os ure
T he n u m ber of t he d oses of acti ve treat me nt will be rec or de d a n d s u m marize d b y  c o h ort.
6. 5. 4. C o nc o mit a nt Me dic ati o ns a n d N o n d r u g T re at me nts
All c o nc o mita nt me dicati o n(s) as well as n o n -dr u g treat me nt(s) will be pr o vi de d i n t he
listi n gs. T hese will be liste d f or eac h c o h ort a n d c o h ort will be i n dicate d.  A se parate listi n g 
ma y  be pr o vi de d f or D M-relate d pri or a n d c o nc o mita nt me dicati o ns.
6. 6. S afet y S u m m aries a n d A n al yses
T he safet y will be m o nit ore d o ver t he st u d y peri o d t hat i ncl u des treat me nt a n d f oll o w -u p 
peri o ds i n all c o h ort s.
6. 6. 1. A d verse E ve nts
O verall sta n dar d A E e n d p oi nts f or t his st u d y are inci de nce of T E A E , i nci de nce of S A Es, a n d 
inci de nce of A Es lea di n g t o disc o nti n uati o n . Se parate A E ta bles will s h o w t he A E data f or 
eac h c o h ort.
6. 6. 2. L a b or at or y D at a
La b orat or y  data will be liste d a n d s u m marize d b y treat me nt i n acc or da nce wit h t he s p o ns or
re p orti n g sta n dar ds. T he la b orat or y  data listi n g will i n dicate c o h ort.
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 2 2
6. 6. 3. Vit al Si g ns
S y st olic bl o o d press ure, diast olic bl o o d press ure a n d p ulse rate will be liste d a n d ta b ulate d by 
wee k wit h descri pti ve statistics ( N, mea n, sta n dar d de viati o n, me dia n, mi ni m u m a n d 
ma xi m u m).  C ha n ge fr o m baseli ne ( defi ne d as mea n pre -d ose val ue c ollecte d at baseli ne will 
als o be s u m marize d usi n g t he sa me descri pti ve statistics b y  wee k.
6. 6. 4. Electr oc ar di o gr a m s
Si n gle 1 2- lea d E C Gs s h o ul d be c ollecte d at ti mes s pecifie d i n t he Sc he d ule of Acti vities.
T he f oll o wi n g E C G data will be liste d: Q T, Q Tc ( Fri dericia’s), he art rate, Q R S d urati o n, P R 
i nter val. Q Tc base d o n Fri dericia’s c orrecti o n will be deri ve d.
Baseli ne a n d c ha n ge fr o m baseli ne f or Q T, Q Tc F, heart rate, Q R S, P R will be s u m marize d 
usi n g descri pti ve statistics b y  st u d y wee k i n eac h c o h ort .  F or Q Tc F a classif icati o n of 
a bs ol ute val ues a n d i ncrease fr o m baseli ne will be use d.
T he n u m bers of s u bjects wit h E C G o utc o mes wit hi n t he s pecifie d cate g ories (see 
Secti o n 9. 4 ) a n d n u m ber of partici pa nts wit h u nc orrecte d Q T val ues ≥5 0 0 ms will be 
s u m marize d b y treat me nt a n d st u d y wee k.
6. 6. 5. P h ysic al E x a mi n ati o n
All p h y sical e xa m data will be pr o vi de d i n t he listi n gs.
7. I N T E RI M A N A L Y S E S
N o f or m al i nteri m a n alysis will be c o n d ucte d f or t his st u dy. As t his is a n o pe n -l a bel st u dy, t he 
s p o ns or m ay c o n d uct u n bli n de d revie ws of t he d at a d uri n g t he c o urse of t he st u dy f or t he 
p ur p ose of s afety assess me nts, f acilit ati n g P K/ P D m o deli n g, a n d/ or s u p p orti n g cli nic al 
d evel o p me nt. 
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 2 3
8. R E F E R E N C E S
1.
A g gar wal R, Ri der L G, R u pert o N, et al. 2 0 1 6 A merica n c olle ge of 
r he u mat ol o g y/ E ur o pea n lea g ue a gai nst r he u matis m criteria f or mi ni mal, m o derate, a n d 
maj or cli nical res p o nse i n a d ult der mat o m y ositis a n d p ol y m y ositis: a n i nter nati o nal
m y ositis assess me nt a n d cli nical st u dies gr o u p/ pae diatric r he u mat ol o g y  i nter nati o nal 
trials or ga nisati o n c olla b orati ve i nitiati ve. Art hritis & R he u mat ol o g y . 
2 0 1 7; 6 9( 5): 8 9 8 -9 1 0.
2.
Pfizer G ui da nce f or E val uati o n of Q T/ Q Tc I nter val Pr ol o n gati o n a n d Pr oarr h yt h mic 
P ote ntial f or N o n-a ntiarr h yt h mic Dr u gs; Me m bers of t he Car di o vasc ular Safet y & 
A d vis or y C o u ncil ( C V S A C) ; Ja n uar y 2 6, 2 0 1 8 .
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 2 4
9. A P P E N DI C E S
9. 1. Defi niti o n a n d Use of Visit Wi n d o ws i n Re p orti n g
T he c urre ntl y  ass u me d assi g n me nt of t he o bser vati o ns t o visits is base d o n t he partici pa nt’ s 
arri val da y.  It ass u mes t hat t he arri val ti mes f or p ost baseli ne visits occ ur wit hi n t he (- 3, 3) 
da y s ti me wi n d o w ce ntere d ar o u n d t he tar get da y as s pecifie d i n t he sc he d ule of acti vities.  
We will c hec k t he vali dit y of t he ass u m pti o n b y  t he a nalys is of distri b uti o ns of act ually 
o bser ve d arri val da y s at t he e n d of t he st u dy a n d ma y u p date t he assi g n me nt r ules sli g htl y. 
Visit L a bel
T ar gete d D a y
A n al ysis wi n d o w
Baseli ne *
D a y 1
(refere nce da y)
D a y  1
(refere nce da y)
Wee k 4
Da y 2 9
D a y s 26- 3 2
Wee k 8
Da y 5 7
D a y s 54- 6 0
Wee k 1 2
Da y 8 5
D a y s 8 2 -8 8
Wee k 1 6
Da y 1 1 3
D a y s 11 0 - 11 6
Wee k 2 0
Da y 1 4 1
D a y s 1 38- 1 4 4
Wee k 2 4
Da y 1 6 9
D a y s 1 66- 1 7 2
Wee k 2 8
Da y 1 9 7
D a y s 1 94- 2 0 0
Wee k 3 2
Da y 2 2 5
D a y s 2 2 2 - 22 8
Wee k 3 6
Da y 2 5 3
D a y s 2 5 0 - 25 6
Wee k 4 0
Da y 2 8 1
D a y s 2 7 8 - 28 4
Wee k 4 4
Da y 3 0 9
D a y s 3 0 6 -3 1 2
Wee k 4 8
Da y 3 3 7
D a y s 3 3 4 -3 4 0
Wee k 5 2
Da y 3 6 5
D a y s 3 6 2 -3 6 8
Wee k 5 6
Da y 3 9 3
D a y s 3 9 0 -3 9 6
Wee k 6 0
Da y 4 2 1
D a y s 4 1 8 -4 2 4
Wee k 6 4
Da y 4 4 9
D a y s 4 4 6 -4 5 2
Wee k 6 8
Da y 4 7 7
D a y s 4 7 4 -4 8 0
* B aseli ne occ urs wit hi n 7 da ys of Wee k 2 4 C 0 2 5 1 0 0 2 Da y 1.
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 2 5
If m ore t ha n o ne o bser vati o n fr o m t he sa me partici pa nt falls i nt o t he sa me wi n d o w t he n t he 
ass ociati o n of t he o bser vati o n wit h t he visit will be d o ne after t he c o ns ultati o n wit h t he st u d y  
cli nicia n a n d lea d statisticia n. 
9. 2. C D A SI
Fi g ure 2.
Prese nts t he C D A SI Sc ale
T he mai n o utc o mes of i nterest are t he acti vit y  sc ore a n d da ma ge sc ore.
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)
C O P Y RI G H T E D M A T E RI A L


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 2 6
9. 2. 1. T he Acti vit y Sc ore ( A S)
T he Acti vit y  Sc ore ( A S) is calc ulate d as a s u m of t he c o ntri b uti o n fr o m t he e xte nt sc ore ( E S), 
G ott or n ha n ds sc ore ( G H S), peri n g ual sc ore ( P S) a n d all o pecia sc ore ( A S).
A S = E S + G H S + P S + A S 
T he t otal e xte nt sc ore ( E S)  is o btai ne d b y  s u m mi n g u p sc ores f or t he t otal er yt he ma ( E R, 
q ua ntifies re d ness of t he s ki n or m uc o us me m bra nes), t otal scali n g ( S C, q ua ntifies peeli n g of 
t he s ki n) a n d t otal er osi o n/ ulcerati o n ( E U, q ua ntifies prese nce of t he dee per w o u n d).
E S = E R + S C + E U
T ot al er yt he ma ( E R), scali n g ( S C) a n d er osi o n/ ulcerati o n ( E U) sc ores are calc ulate d as a s u m 
of t he c o ntri b uti o ns fr o m 1 5 i n di vi d ual areas of t he b o d y .  T he ra n ge of t he t otal er yt her ma 
sc ore is 0-4 5, t he ra n ge of t he t otal scali n g sc ore is 0 -3 0 a n d t he ra n ge of t otal 
er osi o n/ ulcerati o n is 0 -1 5.  T he res ulti n g ra n ge of t he e xte nt sc ore is 0 -9 0.
G ott or n ha n ds sc ore ( G H S) c haracterizes pa p ules (s welli n gs) o n ha n d a n d is a s u m of t he 
pa p ule’s c haracterizati o n sc ore (ra n ge 0 -6) a n d ulcerati o n sc ore (ra n ge = 0 -1). 
Peri n g ual sc ore ( P S) c haracterizes a b n or malities ar o u n d nails a n d its ra n ge is 0 -2.  T he 
al o pecia sc ore ( A S) c haracterizes hair l oss a n d has t he ra n ge 0 -1.
T he res ulti n g ra n ge of t he acti vit y  sc ore is 0-1 0 0.
9. 2. 2. D a m a ge Sc ore
T he Da ma ge Sc ore ( D S) is calc ulate d as a s u m of t he t otal p oil kil o d er ma sc ore ( P O L S), t otal 
calci n osis sc ore ( C A LS) a n d G ot or n’s ha n ds da ma ge sc ore ( G H D S).
D S = P O L S + C A L S + G D H S
T he p oli ki ol der ma sc ore c haracterizes s pecific dis pi g me ntati o n i n t he partic ulal area a n d 
calci n osis sc ore c harac terizes calcificati o n of t he s ki n i n t he partic ular area.  T he t otal 
p oli ki ol der ma sc ore ( P O L S) a n d t he t otal calci n osis sc ore ( C A L S) are s u m me d u p o ver 
1 5 i n di vi d ual areas i n t he b o d y a n d eac h of t he m has ra n ge 0-1 5.  T he G ot or n’s ha n ds 
da ma ge sc ore ( G H D S ) has t he ra n ge 0-2 s o t hat t he da ma ge sc ore ( D S) has t he ra n ge 0 -3 2.
I n o ur a nalys is we will l o o k at t he acti vit y sc ore ( A S), da ma ge sc ore ( D S). 
F or t he acti vit y  sc ore we will a nal yze t he f oll o wi n g s u bsc ores: t otal e xte nt sc ore ( E S), t otal 
er yt he ma sc ore ( E R), t otal scali n g ( S C) a n d t otal er osi o n/ ulcerati o n sc ores ( E U), G ott or n 
ha n ds sc ore ( G H S), peri n g ual sc ore ( P S), a n d al o pecia sc ore ( A S).
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 2 7
F or t he da ma ge sc ore we will a nal y ze t he f oll o wi n g s u bsc ores: t otal p oil kil o d er ma sc ore 
( P O LS), t otal calci n osis s c ore ( C A L S) a n d G ot or n’s ha n ds da ma ge sc ore ( G H D S).
9. 3. TI S usi n g C S M i n D M
T he t otal i m pr o ve me nt sc ore is t he s u m of all 6 i m pr o ve me nt sc ores ass ociate d wit h t he 
c ha n ge i n eac h c ore set meas ure.  A t otal i m pr o ve me nt sc ore of ≥2 0 re prese nts mi ni mal 
i m pr o ve me nt, a sc ore of ≥4 0 re prese nts m o derate i m pr o ve me nt, a n d a sc ore of 
≥6 0 re prese nts maj or i m pr o ve me nt.1
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 2 8
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)
C O P Y RI G H T E D M A T E RI A L


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 2 9
9. 4. C ate g ories f or E C G a n d Vit al Si g n O utc o mes
T he f oll o wi n g Pfizer’s sta n dard will be use d. F or t he sitti n g meas ure me nts of p ulse rate t he 
cate g ories f or t he s u pi ne p ulse rate ( mi n < 4 0 b p m a n d ma x > 1 2 0 b p m) will be use d .
9. 5. List of A b bre vi ati o ns
A b bre vi ati o n
Ter m
A bs
a bs ol ute
A D A
a nti-dr u g a nti b o d y
A E
a d verse e ve nt
A N C O V A
a nal ys is of c o varia nce
A N O V A
a nal ys is of varia nce
A T C
A nat o mic T hera pe utic C he mical
A U C
area u n der t he c ur ve
B A
bi oa vaila bilit y
B E
bi oe q ui vale nce
B L Q
bel o w t he li mit of q ua ntitati o n
B O C F
baseli ne o bser vati o n carrie d f or war d
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 3 0
A b bre vi ati o n
Ter m
B P
bl o o d press ure
C D A R S
Cli nical Data A nal ys is a n d Re p orti n g Sys te m ( of U S F o o d a n d Dr u g 
A d mi nistrati o n)
C D A SI
c uta ne o us der mat o m yositis disease area a n d se verit y  i n de x
CI
c o nfi de nce i nter val
C ma x
ma xi m u m o bser ve d c o nce ntrati o n
C M H
C oc hra n -Ma ntel -Hae nszel
C R F
case re p ort f or m
C S M
c ore set meas ure
C S R
cli nical st u d y re p ort
C -S S R S
C ol u m bia s uici de se verit y rati n g scale
D M C
data m o nit ori n g c o m mittee
E A C
e ve nt a dj u dicati o n c o m mittee
E C G
electr ocar di o gra m
E -D M C
e xter nal data m o nit ori n g c o m mittee 
E Q -5 D -5 L
E ur o Q o L 5 di me nsi o ns 5 le vels
F A S
f ull a nal ysis set
F D A
F o o d a n d Dr u g A d mi nistrati o n ( U nite d States)
G C P
G o o d Cli nical Practice
G LI M MI X
ge neralize d li near mi xe d -effects m o del wit h re peate d meas ures
G M C
ge o metric mea n c o nce ntrati o n
G M F R
ge o metric mea n f ol d rise
G M R
ge o metric mea n rati o
G M T
ge o metric mea n titer
H A Q -DI
healt h assess me nt q uesti o n naire disa bilit y  i n de x
I C D
i nf or me d c o nse nt d oc u me nt
I C H
I nter nati o nal C o u ncil f or Har m o nisati o n
I R C
i nter nal re vie w c o m mittee
I S T
i n de pe n de nt statistical tea m
I T T
i nte nt-t o-treat
L L O Q
l o wer li mit of q ua ntitati o n
L O C F
last o bser vati o n carrie d f or war d
L O D
li mit of detecti o n
L S
least-s q uares
L S M
least-s q uares mea n
M A R
missi n g at ra n d o m
M D A A T
m y ositis disease acti vit y  assess me nt t o ol
Me d D R A
Me dical Dicti o nar y  f or Re g ulat or y Acti vities
mI T T
m o difie d i nte nt -t o-treat
M M R M
mi xe d -effects m o del wit h re peate d meas ures
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)


        Pr ot oc ol C 0 2 5 1 0 0 8 (P F -0 6 8 2 3 8 5 9 ) Statistical A nal ysis Pla n
P FI Z E R G E N E R A L B U SI N E S S 
T M F D oc I D: 9 8. 0 3
T he official versi o n of t his f or m is l ocate d i n t he electr o nic d oc u me nt ma na ge me nt s yste m.
D M B 0 2 -G S O P -R F 0 2 6. 0 St atistic al A n alysis Pl a n Te m pl ate 0 1 -J ul-2 0 2 1
Pa ge 3 1
A b bre vi ati o n
Ter m
M M T
ma n ual m uscle testi n g
M N A R
missi n g n ot at ra n d o m
N/ A
n ot a p plica ble
N A b
ne utralizi n g a nti b o d y
N N B
n u m ber nee de d t o be nefit
N N H
n u m ber nee de d t o har m
N N T
n u m ber nee de d t o treat
N O A E L
n o -o bser ve d -a d verse-effect le vel
P D
p har mac o d y n a mic(s)
P h G A
p h y sicia n gl o bal assesse me nt
P K
p har mac o ki netic(s)
P P
per -pr ot oc ol
P P A S
per -pr ot oc ol a nal ys is set
P R O
patie nt -re p orte d o utc o me
P T
preferre d ter m
Pt G A
patie nt gl o bal assess me nt
Q Tc
c orrecte d Q T
Q Tc F
c orrecte d Q T ( Fri dericia met h o d)
q ual
q ualitati ve
R C D C
re verse c u m ulati ve distri b uti o n c ur ve
R R
relati ve ris k
S A E
seri o us a d verse e ve nt
S A P
statistical a nal ysis pla n
S D
sta n dar d de viati o n
S F
s h ort f or m
S G S
Statistical G ui da nce Sta n dar ds
S O P
sta n dar d o perati n g pr oce d ure
S U S A R
s us pecte d u ne x pecte d seri o us a d verse reacti o n
T A
t hera pe utic area
TI S
t otal i m pr o ve me nt sc ore 
U L N
u p per li mit of n or mal
W H O 
W orl d Healt h Or ga nizati o n
W H O D D
W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y
0 9 0 1 7 7 e 1 9 8 b a 2 1 0 6\ A p pr o v e d\ A p pr o v e d O n: 3 0- N o v- 2 0 2 1 1 5: 1 1 ( G M T)