Clinical trial NCT03181893
Conditions: Dermatomyositis
Sponsor: Pfizer
Start date: 2018-01-23; Completion date: 2022-11-28
Enrollment: 75 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
A Study looking at Investigational drug and Placebo administered to adult Patients with moderate to severe Dermatomyositis

Detailed description:

Arms: arm 1: None arm 2: None arm 3: None
Interventions: intervention 1: PF-06823859 low intervention 2: Placebo Arm intervention 3: PF-06823859 high
Intervention descriptions: intervention 1: A humanized immunoglobulin neutralizing antibody intervention 2: Placebo contains histidine, sucrose, PS80, ethylene diamine, and triacetic acid intervention 3: A humanized immunoglobulin neutralizing antibody

Protocol documents:
Prot_000.pdf: 
PF-06823859
C0251002
Final Protocol Amendment 6, 20 September 2021 
PFIZER CONFIDENTIAL
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A PHASE 2 DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY 
TO EVALUATE THE EFFICACY, SAFETY, AND TOLERABILITY OF 
PF-06823859 IN ADULT SUBJECTS WITH DERMATOMYOSITIS
Investigational Product Number:
PF-06823859
Investigational Product Name:
Not Applicable (N/A)
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trials Database 
(EudraCT) Number: 
2020-004228-41
Protocol Number:
C0251002
Phase:
2
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
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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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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 6
20 September 2021
The overall rationale for the amendment is to 
permit participants actively enrolled in the 
C0251002 study to have the option to continue 
active treatment into a long term open label 
extension study, known as protocol C0251008. 
This study is An Open Label, Extension Study 
for Study Participants who have completed the 
full treatment period in one of the qualifying 
parent studies (eg, protocol C0251002) utilizing 
the PF-06823859 compound in adult participants 
with Dermatomyositis. Participants will be 
enrolled per investigator discretion and 
eligibility. If participants do not continue in the 
open label extension study due to any reason, 
they will continue into the follow up portion of 
the C0251002 study. 
Added throughout protocol: All participants who 
complete the treatment period in this study up 
through and including (Visit 9, Week 24), will 
have the opportunity to continue treatment in the 
open label extension C0251008 protocol.  
Participants who have completed the treatment 
period and have not had any significant protocol 
deviations, or safety events will be eligible. 
SOA: Footnote added to Visit 9, Week 24 on the 
amended stage 2 and stage 3.  This footnote was 
added to note that if patients are eligible and if 
per the investigator discretion, they may enter 
into the long term open lable extension study.
SOA: Amended Stage 2, added hsCRP to the 
early withdraw visit.  
Rationale: To make consistent between 
Stage 3 and Amended Stage 2.
SOA: For amended Stage 2 and Stage 3, 
collection of height was added at Week 24, 
Visit 9, so that these assessments are completed 
for anyone moving into the open label extension 


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study.  All participants will have height assessed 
at Week 24.  Also removed height from the early 
termination visits as not needed and to make both 
muscle and skin assessments consistent.
Rationale: Allow participants the opportunity 
to enroll into the open label extension study.  
All pariticipants will have height recorded at 
Week 24.  This will allow the participants 
moving into the open label extension a 
complete baseline.
Section 3.1: Study Design: 
Added rationale for Amendment 5 and 
Amendment 6; Added that current participants 
upon completing Visit 9, Week 24 will have the 
opportunity to enroll into an open label extension 
study. 
New Figures added to reflect OLE
Section 4.1, 4.2, 4.3, 4.4, 4.5 and 4.6: Inclusion 
and exclusion criteria associated with use of 
contraception has been updated.  
Section 4.2 and 4.6: exclusion criteria have been 
updated.

Clarified that oral tacrolimus within 
30 days of the Day 1 visit is an exclusion.

Clarified that topical calcicneurin 
inhibitors within 14 days of the Day 1 
visit is an exclusion.
Section 4.8.2: Contraception section was updated 
with the bullets above.
Section 5.8.5: Corticosteroids: Added under 
amended stage 2 and stage 3 steroid taper should 
not be started if the participant is continuing into 
the open label extension study.  


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Rationale: Participants going into the open 
label extension study require a stable 
corticosteroid dose at baseline. 
Section 5.8.5: Removed oral corticosteroids will 
be recorded on a separate CRF.  
Rationale: Corticosteroids will be recorded on 
the concomitant medication page.
Appendix 15 and 16: Clarification made that oral 
tacrolimus requires a 30 day washout period, 
topical calcineurin inhibitors require a 14 day 
washout period, and topical calcineurin inhibitors 
are prohibited throughout the treatment period.
Rationale: Clarification.
Added Appendix 25 Contraceptive and Barrier 
use.  

Clarified that due to the half life of the 
study drug, males should not donate 
sperm during the study. 

Provided the definition of user dependent 
vs. non user dependent birth control.

Defined highly effective contraception.
Rationale: Updated to most current protocol 
template.  
Section 7.5.6: Height and Weight; updated height 
to be completed at times in the SOA.
Rationale: Height will be collected at 
Week 24 with weight for a robust baseline in 
the extension study.
Section 7.10: Laboratory tests; upated anc 
corrected footnotes in Table 1.
Amendment 5
04 May 2021
Country Specific Amendment Germany:
Rationale: The purpose of the amendment is 
to address changes requested from German 


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Health Authority and is only applicable to 
sites participating in Germany.
Section 4.8.2: Contraception section was updated 
for clarification and for participants from 
Germany to see Appendix 24, CTFG guidelines, 
for permitted contraceptive methods.
Section 5.2: Breaking the Blind section was 
further clarified that blinding codes can be 
broken by the investigator at any time. 
Rationale: In Section 5.2 investigators are 
encouraged to discuss with the sponsor’s 
medical monitor if they believe unblinding is 
necessary, however, under no circumstances 
should unblinding be delayed in an 
emergency situation.
Appendix 14: Guidelines for Participant Safety 
Monitoring and Discontinuation were, further 
clarified by adding “Please see Appendix 16, 
prohibited medications”.  
Rationale: Discontinuation criteria in 
Appendix 14 did not specify if a prohibited 
medication was taken during the treatment 
period, the participant should be discontinued
from treatment and proceed to the follow-up 
period.
Added contraception guidelines from Clinical 
Trials Facilitation and Coordination Group, 
CTFG version 1.1 in Appendix 24. 
Rationale: Contraception language was 
updated throughout the protocol to 
“Participants from Germany please see 
Appendix 24”.
Administrative changes to Amended stage 2 and 
stage 3 schedule of activities which apply to sites 
in all countries.
Rationale: Two Protocol administration 
letters, one dated 03 February 2021 and 
another dated 01 March 2021 were sent out 


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to all investigative sites with updates to the 
Schedule of Activities for amended stage 2 
and stage 3 regarding assessments that were 
omitted during the formatting of the protocol.
The additions corrections are:
Feb 2, 2021: In the Schedule of Activities (SOA) 
for amended Stage 2 of the study, vital signs are 
collected at every visit. In the previous version 
of the protocol, an, X” for collection of vital 
signs on days 10, 12 and 13 was missing “. This 
error was corrected.
In the SOA for Stage 3, lab assessments for,Viral 
Surveillance (CMV, VZV, EBV, HHV6, 
HSV-1/2) should be collected at Visit 11 and not 
Visit 10. Correction: Please note: An “X” was 
added at Visit 11, and removed from Visit 10.
In the SOA for Stage 3, the C-SSRS assessment 
should be collected at the early termination visit. 
Correction: An “X” was added at the Early 
termination visit for CSSR-S. 
In the SOA for amended study Stage 2 and 
Stage 3, an “X” was removed from the SOA at 
visit 3 for infusion site reaction, as no infusion 
site reaction is collected at this visit.  Moved 
footnotes “u, v, w” to corresponding visits
associated with biomarker collection, Day 1 drug 
administration and monitoring time after drug 
administration.
01 March 2021: (Stage 3 SOA)
Please note: An “X” should be marked at 
Screening for the PtGA, as this assessment is 
required at Screening to derive inclusion 
criteria #3, (Section 4.5).
Amendment 4 
20 Nov 2020
The C0251002 protocol was amended to add  a 
moderate muscle disease cohort of approximately
8-16 participants, known as Stage 3.  This cohort 
was added to further investigate PF-06823859 
and placebo in DM participants with moderate 
muscle disease. The Stage 2, skin disease cohort, 


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was amended to allow placebo participants the 
opportunity to receive active study drug, which 
extended the study duration for 12 weeks. 
The following sections have been updated:
Cover Page: Added (Eudra CT Number).
Rationale: Study will be conducted in 
Europe.
Added SOA for Amended Stage 2, and Stage 3.
Rationale: Study extended for Amended 
Stage 2 and Stage 3. All participants will 
receive 12 weeks active study drug. This 
will allow placebo participants to receive 
active treatment during the study.  Stage 3 
SoA: Added a cohort of 8-16 
Dermatomyositis participants with moderate 
muscle disease.
Section 1.6 Dose Selection Rationale.
Updated to add additional dosing information for 
Amended Stage 2 and Stage 3 participants. 
Rationale: The published clinical type I 
interferon gene signature model for the 
IFNAR1 inhibitor, anifrolumab, was adapted 
to project a gene signature suppression by 
PF-06823859 in DM participants. 
Specifically, the published model was 
modified to include IFN-and a biologically 
relevant mechanism for gene signature 
production and incorporated the PK data 
from C0251001. The modified model 
provided the rationale for doses to be 
considered in treatment of DM participants
with clinical manifestations of skin disease 
and muscle disease. The efficacious dose 
was defined as the dose required to suppress 
gene signature by ≥80% in participants at 
trough for a duration of 4 weeks after the 
third dose in Study C0251002 (with IV doses 
once every 4 weeks for a total of 3 doses).  
Using this approach, the predicted efficacious 


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dose of PF-06823859 in DM participants
with skin and muscle was estimated to be 
600 mg.
Since this is the first evaluation of 
PF-06823859 in adult DM participants with 
muscle disease, the highest 600 mg Q4W 
dose with estimated gene suppression ≥80% 
at trough will be investigated.
Section 2. Study Objectives and Endpoints:
Section 2.3 and 2.4 added, Amended Stage 2 and 
Stage 3 Objectives and Endpoints.
Rationale: Stage 2 was amended to provide 
all participants 3 consecutive doses of active 
study drug and 3 doses of placebo during the 
study. Objectives and endpoints were added
for the Stage 3 participants enrolling into the 
muscle disease cohort.
Section 3, Study Design:
Updated the duration of the study to 69 months 
from FSFV to LSLV.  Also increased the number 
of investigative sites to approximately 35 to 40.
Rationale: Changes reflect the increased 
duration of the study and the need to utilize 
additional investigative sites. 
Section 3.1 Study Design updates updated to 
include details on the study design for Amended 
Stage 2 and Stage 3).
Study Schematic Figures 3 and 4 added under 
Study Design.
Rationale: To support Amended Stage 2 and 
Stage 3 study designs.
Section 4.0 Participant Eligibility:


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Updated eligibility for Amended Stage 2 and 
Stage 3. Inclusion and exclusion criteria added 
for Amended Stage 2 and stage 3.
Rationale: Due to the study being extended 
for 12 weeks, added additional assessments 
under Amended Stage 2 and new assessments 
for Stage 3.
Exclusion criterion #7; lab values lowered for 
Hgb and Creatine Clearance for Amended 
Stage 2 and Stage 3. 
Rationale: DM can cause an anemia of 
chronic disease in which a Hgb of <9.0 g/dL 
is acceptable.
Creatinine clearance decreases with age.  
Study inclusion age limit is 80 years in which 
a creatine clearance of 50 ml/minute is 
acceptable. 
Section 5.8.5.: Updated permitted doses of 
corticosteroids for Stage 3 vs. Stage 2 and 
Amended Stage 2.
Rationale: Muscle disease may require a 
higher permitted dose of steroids. 
Added tapering of steroids may occur after 
Week 12 for Stage 2. Amended Stage 2 and 
Stage 3 tapering can occur after Week 24.  
Tapering is per the investigator’s discretion. 
Rationale: Tapering steroids per the 
investigator’s discretion is common practice.
Section 6. Added Treatment Period assessments 
for Amended Stage 2, and Stage 3.
Rationale: Clarification.
Section 6. Added Follow-up Visits for Amended 
Stage 2, and Stage 3.
Rationale: Added 3 additional visits during 
the treatment period for placebo participants 


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to receive active study drug, therefore 
additional follow up visits required.
Section 7.5.10 Biopsies.
Added that all participants in Amended Stage 2 
will have 2 additional punch biopsies due to the 
study being extended so that all participants 
receive active study drug. 
Added types of analysis on the biopsy tissue.
Rationale: To ensure all participants receive 
active study drug, two additional biopsies 
will be collected at week 24 when the 
treatment period is over.
Section 7.6: Rater Qualifications:
Added MMT-8 and the MDAAT.
Rationale: Training is required in order to 
complete these assessments.
Section 7.7: Patient Reported Outcomes, added 
HAQ-DI, PtGA, EQ-5D-5L, 
 
, FACIT-F and then added the order for 
completion for Amended Stage 2 and Stage 3.
Rationale: Added several different patient 
reported outcomes and listed them in the 
order that is required for the different 
cohorts. These assessments were added for 
additional collection of information.
Section 7.9: Added Total Improvement Score 
description and definition. 
Rationale: This tool is required for the 
Stage 3 cohort as the TIS is the secondary 
endpoint being measured in Stage 3.
Section 9.0: Added Stage 1 data, (preliminary 
draft) may be shared externally and internally at a 
high level. 
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Section 9.1.3: Added Sample Size Determination 
for Stage 3.
Rationale: Clarification on sample size.
Section 9.2.2.2: Added supportive analysis for 
CDASI data in Stage 2. This includes data from 
Day 1 through Week 12 and supportive data from 
Week 12 through Week 24.
Section 9.2.1.3, 9.2.2.3, 9.2.3.3: Added 
description of analyses for primary, secondary, 
and 
 for Stage 3.
Rationale: Overview of the major analyses 
and summaries to be performed.
Section 9.3: Added Pharmacokinetic Analysis for 
Amended Stage 2, and Stage 3.
Rationale: Clarification.
Section 9.5: Added that an additional interim 
analysis for the Stage 3 “may be conducted”
depending on the enrollment rate.
Rationale: Related to internal decision 
making. 
Section 16: Added references related to the 
newly added patient reported outcomes and 
additional information related to muscle disease 
and measurement over time.
Rationale: Clarification.
Appendix 1: Added abbreviations
Rationale: Clarification.
Added the following Appendices:
Appendix 10, EQ-5D-5L, Appendix 11, FACIT-
F Scale, Appendix 12, HAQ-DI scale, Appendix 
13, PtGA, Appendix 18, 
, 
Appendix 19 Muscle Enzymes Measurement, 
Appendix 20, MDAAT, Appendix 21, MMT-8, 
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Appendix 22, TIS using core set measures in 
DM.
Rationale: To provide clarification and 
additional information related to the Stage 3. 
Appendix 16: Updated corticosteroid doses for 
Stage 3, and that tapering of steroids is permitted 
after week 12 for stage 2 per investigator 
discretion.  For Amended Stage 2 and Stage 3, 
tapering of steroids may occur after Week 24.
Rationale: Decreasing steroids or equivalent 
if not needed is a health benefit. 
Administrative spelling errors corrected 
throughout the protocol. 
Amendment 3
01 July 2020
The C0251002 protocol was amended after an 
interim analysis of the data was conducted on 
32 participants.  An internal review committee, 
separate from the blinded study team, determined
to continue the study and enroll approximately 
20 additional participants to evaluate an 
additional lower dose of PF-06823859, (150 mg) 
in addition to the 600 mg and placebo dose.  This 
dose was added to explore the exposure response 
relationship. 
The primary objective, To evaluate the efficacy 
of PF-06823859 dose in adult participants with 
moderate to severe DM was changed to “doses” 
due to adding 1 additional dose.
The terminology “Subjects” replaced with 
participants throughout the protocol.  Updated to 
support the latest template language.
Section 1.6 Dose Selection Rationale updated to 
include justification for the addition of the 
150 mg Q4W IV dose to characterize 
exposure-response. 
Section 2.2 added under objectives and 
endopoints.  Study was split into 2 Stages, 
endpoints and objectives added for stage 2. 


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Section 3.1 Study Overview updated to a Phase 2
dose-finding study.  Added the number of 
additional participants to be enrolled, the 
additional dose to be studied, the number of 
participants required were increased and the 
duration of the study was extended.  
Section 3.1: Removed study to be conducted in 
the US.  Rationale: Study may be conducted in 
the US, and outside the US. 
Added Figure 2 to show the revisions to the 
original study schematic.
Section 4.2 Exclusion criteria: Excluded 
participants previously exposed to anti-beta 
Interferon.  Rationale: Study is continuing, 
previously enrolled participants are excluded.
Section 5.2: Breaking the Blind: Noted that an 
additional interim analysis may be conducted for 
internal decision making.
Section 5.4.1: Dosage Forms and Packaging: 
Removed duplicate information.  Added vials 
will be boxed as 6 vials per package.
Section 5.4.2: Preparation and Dispensing: 
Updated to note doses.
Section 6.2.3 Added information regarding 
Alternative measures during public emergencies. 
At this time detailed information will be provided 
under separate cover for this study.  Also added 
Appendix 12 for some of the options that may be 
implemented, during a public emergency. 
Rationale: Due to COVID-19.
Section 7.1 Photography: clarification made to 
the wording. 
Section 9.1 Sample Size Determination: split into 
2 subsections for Stage 1 and Stage 2. Added 
sample size rationale for Stage 2. 
Section 9.2: Added, After the treatment period is 
completed for all the participants, some members 


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of the study team will be unblinded so that a 
report for the corresponding data can be 
generated.  Rationale: To continue business 
planning.
Section 9.2.1: Split into 2 subsections for Stage 1 
and Stage 2. In Section 9.2.1.2, added 
description for analyses of primary endpoints for
Stage 2.
Section 9.2.2: Split into 2 subsections for Stage 1 
and Stage 2. In Section 9.2.2.2, added 
description for analyses of secondary endpoints 
for Stage 2.
Section 9.2.3: Added additional 
 
; also split 
into 2 subsections for Stage 1 and Stage 2. 
Added description of other endpoints for Stage 2.
Section 9.3: Split into 2 subsections for Stage 1 
and Stage 2.
Section 9.4: Added text: “Safety analyses will be 
reported for Stage 1 and for Stage 1 and 2
combined as described in Section 2.”
Section 9.5.1: Interim Analysis Section updated 
to allow for potential additional interim analysis 
at a future date for business decision planning.
Section 9.6: Data Monitoring Committee: 
Updated language that if an interim analysis 
occurs, the unblinded internal review committee 
will be responsible for reviewing the data.
Appendix 12 Added: Alternative Measures 
During Public Emergencies: Added appendix for 
collecting protocol procedures during public 
emergencies.
Amendment 2
18 December 2019
Protocol amended to add an interim analysis after 
the last subject randomized completes study 
Visit 6, Week 12, (primary endpoint) for the 
purpose of early internal decision making.  
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Section 5.2: Breaking the blind: added 
information to this section that an interim 
analysis will be performed, and a separate 
internal review committee will be reviewing 
unblinded data separate from the study team.
Section 9.5: 
Added sub headers 9.5.1 and 9.5.2.
9.5.1 Analysis for Internal Decision Making: 
Added that an interim analysis will occur after 
the last subject randomized completes study 
Visit 6, Week 12, (primary endpoint).  Added 
that an internal review committee separate from 
the blinded study team will review efficacy and 
safety data for internal decision making.
 
 
 
 
 
 
 
Amendment 1
12 March 2018
The title of 5D itch scale was changed to 5D 
Pruritus Scale throughout the document
Rationale: Incorrect title was previously 
recorded. 
SOA:
ECG added to screening in addition to baseline 
ECG. 
Rationale: Results needed for 
inclusion/exclusion criteria.
Footnote “S” revised from one hour post dose to 
“post dose” for PK collection, and also clarified 
that the PK collection should be taken from the 
opposite arm of administration of drug.
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Rationale: Clarified time of PK collection 
after study drug administration.
4.1 Inclusion Criteria:
Inclusion criteria #2 revised; changed the age 
from ≤75 to ≤80 years of age.
Rationale: To include more 
dermatomyositis subjects.
4.2 Exclusion Criteria:
Exclusion criteria #15, added (with the exception 
of topical calcineurin inhibitors).
Section 4.4.2:
Modified Contraception language per Global 
approved SOP deviation dated 7/18/17.
Section 5.1:
Un-blinded personnel was changed to blinded 
personnel.
Rationale: For this study, the study 
coordinator who is blinded will randomize 
the subject. No un-blinded information is 
available to the blinded study coordinator. 
Section 5.5: Added “approximately” to the 
sentence, Blinded IV PF-06823859 or placebo 
will be administered at the investigative site or 
clinic over the course of “approximately” 
60 minutes as an IV infusion.
Rationale: To reduce protocol deviations.
Section 5.8.5:
Added 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 per day 
as per protocol Section 5.8.4.1.  Also added: 
There is no need to change the IVIG dosing 
schedule or adjust the IVIG dosing schedule 
related to investigational product administration.


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Rationale: Clarification provided on 
whether or not pre dosing with steroids was 
permitted related to IVIG dosing, and to 
note that IVIG dosing schedule should not 
be revised according to investigational drug 
administration.
Section 5.8.5.1:
Removed recording of steroid usage in a diary.
Rationale: Subjects are required to be on a 
stable dose of steroids, no justification for a 
subject diary.  
Section 6.1:
Added screening ECG in addition to Day 1 visit.
Rationale: ECG added to screening to 
ensure eligibility criteria were met, prior to 
Day 1.
Section 6.2.1: 
Added “ECG (Day 1, Visits 4, 5, 6, EOS and ET 
only)”: 
Rationale: Updated to align with the 
Schedule of Assessments.
Section 7.1:
Added Photography.
Rationale: Many research offices use 
photography in their standard of practice.
Section 7.5.10:
Typo corrected, (3 mm and 5 mm) to (3 mm to 
5 mm)
Rationale: Typo.
Section 7.9:
Removed lipid profile panel requires a minimum 
fast of 8 hours.
Rationale: Per team discussion, fasting is 
not required for the lipid panel.
Appendix 11:
Added under thalidomide, tacrolimus or 
mizoribine…Prohibited; any form of tacrolimus 


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or any form of topical calcineurin inhibitors 
(TCI). 
Rationale: This class of medication is 
prohibited.
Appendix 11:
Pre medication with corticosteroids for IVIG is 
permitted.
Rationale: to align with Section 5.8.5.
Appendix 6:
Added the acute version of the SF36.
Rationale:  The non-acute version was 
previously placed in the protocol by error.
Several additional minor changes and sentence 
revisions were made throughout the document.
Rationale: Revisions were made for the 
purposes of clarification and to correct 
minor grammatical or spelling errors.” 
Original protocol
10 May 2017
Not applicable (N/A)
This amendment incorporates all revisions to date, including amendments made at the
request of country health authorities and IRBs/ECs.


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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................25
LIST OF FIGURES .................................................................................................................25
APPENDICES .........................................................................................................................25
SCHEDULE OF ACTIVITIES (STAGE 1 AND STAGE 2) .................................................27
SCHEDULE OF ACTIVITIES (AMENDED STAGE 2).......................................................32
SCHEDULE OF ACTIVITIES (STAGE 3)............................................................................37
1. INTRODUCTION ...............................................................................................................45
1.1. Mechanism of Action/Indication.............................................................................45
1.2. Background and Rationale ......................................................................................45
1.2.1. Rationale for DM........................................................................................45
1.3. Nonclinical Pharmacokinetics.................................................................................46
1.4. Nonclinical Safety Data ..........................................................................................46
1.5. Clinical Safety Profile .............................................................................................47
1.5.1. Safety (FIH C0251001) ..............................................................................47
1.5.2. Pharmacokinetics Summary for C0251001................................................48
1.5.3. Immunogenicity Results for C0251001......................................................49
1.5.4. Summary of Benefits and Risks .................................................................49
1.6. Dose Selection Rationale ........................................................................................50
1.7. Banked Biospecimens .............................................................................................51
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................52
2.1. Stage 1, Objectives and Endpoints..........................................................................52
2.2. Stage 2, Objectives and Endpoints..........................................................................53
2.3. Amended Stage 2, Objectives and Endpoints .........................................................54
2.4. Stage 3, Objectives and Endpoints..........................................................................55
3. STUDY DESIGN.................................................................................................................57
3.1. Study Overview.......................................................................................................57
4. PARTICIPANT ELIGIBILITY...........................................................................................63
4.1. Inclusion Criteria, Stage 1 and Stage 2 ...................................................................63
4.2. Exclusion Criteria, Stage 1 and Stage 2 ..................................................................65
4.3. Inclusion Criteria, Amended Stage 2 ......................................................................72
4.4. Exclusion Criteria, Amended Stage 2 .....................................................................72


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4.5. Inclusion Criteria, Stage 3.......................................................................................72
4.6. Exclusion Criteria, Stage 3......................................................................................74
4.7. Randomization Criteria ...........................................................................................80
4.8. Lifestyle Requirements ...........................................................................................80
4.8.1. Surgery........................................................................................................80
4.8.2. Contraception..............................................................................................81
4.9. Sponsor’s Qualified Medical Personnel..................................................................81
5. STUDY TREATMENTS.....................................................................................................82
5.1. Allocation to Treatment ..........................................................................................82
5.2. Breaking the Blind ..................................................................................................82
5.3. Participant Compliance ...........................................................................................82
5.4. Investigational Product Supplies.............................................................................83
5.4.1. Dosage Form(s) and Packaging..................................................................83
5.4.2. Preparation and Dispensing........................................................................83
5.5. Administration.........................................................................................................83
5.5.1. Infusion Discontinuation ............................................................................83
5.6. Investigational Product Storage ..............................................................................84
5.7. Investigational Product Accountability...................................................................85
5.7.1. Destruction of Investigational Product Supplies ........................................85
5.8. Concomitant Treatment(s).......................................................................................85
5.8.1. Prior Treatments .........................................................................................85
5.8.2. Prohibited Concomitant Medications .........................................................86
5.8.3. Permitted Concomitant Medications ..........................................................86
5.8.4. Pre Medication use on the day of IVIG Administration.............................86
5.8.5. Corticosteroids............................................................................................86
5.8.6. Guidance for Investigators..........................................................................87
5.9. Rescue Medication ..................................................................................................87
6. STUDY PROCEDURES .....................................................................................................87
6.1. Screening.................................................................................................................87
6.2. Study Period ............................................................................................................88
6.2.1. Treatment Period (Stage 1 and 2) ...............................................................88
6.2.2. Treatment Period (Amended Stage 2) ........................................................89


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6.2.3. Treatment Period for Stage 3......................................................................90
6.2.4. Follow-up Visits for Stage 2.......................................................................92
6.2.5. Follow-up Visits for Amended Stage 2 ......................................................93
6.2.6. Follow-up Visits for Stage 3.......................................................................94
6.2.7. Unscheduled Visits.....................................................................................95
6.2.8. Alternative Measures During a Public Emergency ....................................95
7. ASSESSMENTS..................................................................................................................97
7.1. Photography ............................................................................................................97
7.2. Pregnancy Testing...................................................................................................98
 
7.5. Safety Assessments ...............................................................................................100
7.5.1. Chest X-RAY............................................................................................100
7.5.2. Electrocardiogram.....................................................................................100
7.5.3. Vital Signs ................................................................................................101
7.5.4. Medical History ........................................................................................101
7.5.5. Physical Examinations..............................................................................102
7.5.6. Height and Weight....................................................................................102
7.5.7. Tuberculosis (TB) Screening and Monitoring..........................................102
7.5.7.1. Interferon Gamma Release Assay (IGRA) Tuberculin Test ...102
7.5.8. Monitoring for Infections .........................................................................103
7.5.9. Viral Surveillance .....................................................................................103
7.5.10. Biopsies...................................................................................................104
7.5.11. Infusion Site Reaction Assessment.........................................................104
7.6. Rater Qualifications...............................................................................................104
7.6.1. CDASI ......................................................................................................104
7.6.2. MMT-8 Stage 3.........................................................................................105
7.6.3. MDAAT Stage 3.......................................................................................105
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7.7.2. 5-D Pruritus Scale.....................................................................................105
7.7.3. Dermatology and Life Quality Index (DLQI) ..........................................106
7.7.4. Health Assessment Questionnaire – Disability Index (HAQ-DI) start.....106
7.7.5. EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L) and EQ-VAS..................106
7.7.6. Patient’s Global Assessment (PtGA)........................................................107
7.7.8. Functional Assessment of Chronic Illness Therapy - fatigue (FACIT-
F)....................................................................................................................107
7.7.9. Stage 2 PRO Measures .............................................................................107
7.7.10. Amended Stage 2 PRO Measures...........................................................108
7.7.11. Stage 3 PRO Measures ...........................................................................108
7.8. Physician Clinician Assessment............................................................................108
7.8.1. Physician Global Assessment (PhGA, Visual Analogue Scale VAS)......108
7.9. Total Improvement Score for Stage 3 ...................................................................109
7.10. Clinical Laboratory Tests....................................................................................109
7.11. Pharmacodynamics (PD).....................................................................................111
7.11.1. Samples for IP-10 Analysis ....................................................................111
7.11.2. Samples for hsCRP Analysis..................................................................111
7.11.3. Samples for MX-A Analysis ..................................................................112
7.11.6. Gene Signature Panel..............................................................................112
7.13. Shipment of Pharmacokinetic Samples...............................................................113
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8. ADVERSE EVENT REPORTING....................................................................................114
8.1. Requirements.........................................................................................................114
8.1.1. Additional Details on Recording Adverse Events on the CRF.................116
8.1.2. Eliciting Adverse Event Information........................................................116
8.1.3. Withdrawal from the Study Due to Adverse Events (see also the 
Participant Withdrawal (Early Termination) section)....................................116
8.1.4. Time Period for Collecting AE/SAE Information....................................116
8.1.4.1. Reporting SAEs to Pfizer Safety.............................................116
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF ...............117
8.1.5. Causality Assessment ...............................................................................117
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ................117
8.2. Definitions.............................................................................................................117
8.2.1. Adverse Events.........................................................................................117
8.2.2. Abnormal Test Findings ...........................................................................118
8.2.3. Serious Adverse Events ............................................................................119
8.2.4. Hospitalization..........................................................................................119
8.3. Severity Assessment..............................................................................................120
8.4. Special Situations ..................................................................................................121
8.4.1. Protocol -Specified Serious Adverse Events............................................121
8.4.2. Potential Cases of Drug -Induced Liver Injury.........................................121
8.4.3. Exposure to the Investigational Product During Pregnancy or 
Breastfeeding, and Occupational Exposure...................................................123
8.4.3.1. Exposure during Pregnancy ....................................................123
8.4.3.2. Exposure during Breastfeeding ...............................................124
8.4.3.3. Occupational Exposure ...........................................................124
8.4.4. Medication Errors .....................................................................................125
8.5. Medication Errors..................................................................................................125
9. DATA ANALYSIS/STATISTICAL METHODS.............................................................126
9.1. Sample Size Determination...................................................................................126
9.1.1. Sample Size Determination in Stage 1 .....................................................126
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9.1.2. Sample Size Determination in Stage 2 .....................................................127
9.1.3. Sample Size Determination in Stage 3 .....................................................127
9.2. Efficacy Analysis ..................................................................................................128
9.2.1. Analysis of the Primary Endpoint.............................................................129
9.2.1.1. Analysis of Primary Endpoint in Stage 1................................129
9.2.1.2. Analysis of Primary Endpoint in Stage 2................................129
9.2.1.3. Analysis of Primary Endpoint in Stage 3................................130
9.2.2. Analysis of Secondary Endpoints.............................................................130
9.2.2.1. Analysis of the Secondary Endpoints in Stage 1.....................130
9.2.2.2. Analysis of the Secondary Endpoints in Stage 2.....................130
9.2.2.3. Analysis of the Secondary Endpoints in Stage 3.....................130
9.2.3.2. Analysis of Other Endpoints in Stage 2 ..................................131
9.4. Safety Analysis......................................................................................................132
9.4.1. Adverse Events and Suicidality Assessments...........................................133
9.4.2. Electrocardiogram.....................................................................................133
9.5. Interim Analyses ...................................................................................................133
9.5.1. Analysis for Internal Decision Making.....................................................133
10. QUALITY CONTROL AND QUALITY ASSURANCE...............................................134
11. DATA HANDLING AND RECORD KEEPING ...........................................................135
11.1. Case Report Forms/Electronic Data Record .......................................................135
11.2. Record Retention.................................................................................................135
12. ETHICS............................................................................................................................136
12.1. Institutional Review Board/Ethics Committee....................................................136
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12.2. Ethical Conduct of the Study ..............................................................................136
12.3. Participant Information and Consent...................................................................136
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP .........................................................................................................................137
13. DEFINITION OF END OF TRIAL.................................................................................137
13.1. End of the Trial ...................................................................................................137
14. SPONSOR DISCONTINUATION CRITERIA ..............................................................137
15. PUBLICATION OF STUDY RESULTS........................................................................137
15.1. Communication of Results by Pfizer ..................................................................137
15.2. Publications by Investigators ..............................................................................138
16. REFERENCES ................................................................................................................140
LIST OF TABLES
Table 1.
Laboratory Tests .....................................................................................110
Table 2.
Additional Lab Testing...........................................................................111
Table 3.
Estimated Half-widths of 90% Confidence Intervals for the 
Difference in TIS between Active and Placebo at Week 12 ..................128
LIST OF FIGURES
Figure 1.
Study C0251002 Design PF-06823859 (Stage 1).....................................59
Figure 2.
Study C0251002 Design PF-06823859 Stage 2 .......................................59
Figure 3.
Study C0251002 Design PF-06823859 Amended Stage 2.......................60
Figure 4.
Study C0251002 Design PF-06823859 Stage 3 .......................................61
Figure 5.
Amended Stage 2 with the Option of Going into the OLE Study ............62
Figure 6.
Stage 3 with the Option of Going into the OLE Study.............................63
APPENDICES
Appendix 1. Abbreviations....................................................................................................144
Appendix 2. CDASI...............................................................................................................150
Appendix 3. Physician Global Assessment (PhGA, VAS)....................................................151
Appendix 4. Personal Health Questionnaire Eight-Item Depression Measure (PHQ-8) .......152
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Appendix 8. Dermatology Life Quality Index.......................................................................164
Appendix 9. 5D Pruritus Scale...............................................................................................165
Appendix 10. EQ-5D-5L AND EQ-VAS..............................................................................166
Appendix 11. FACIT-F Scale................................................................................................169
Appendix 12. 12 HAQ...........................................................................................................170
Appendix 13. Patient Global Assessment (PtGA).................................................................173
Appendix 14. Guidelines for Participant Safety Monitoring and Discontinuation................174
Appendix 15. Time needed for Washout of Prohibited Medication or Medication 
Stabilization Prior to Day 1 ....................................................................176
Appendix 16. List of Prohibited and Permitted Concomitant Medications...........................178
Appendix 17. Alternative Measures During Public Emergencies .........................................180
Telehealth Visits (if applicable)...................................................................180
Home Health Visits (If applicable) ..............................................................181
Laboratory Testing: (If applicable)..............................................................181
Electrocardiograms (If applicable)...............................................................182
Adverse Events and Serious Adverse Events...............................................182
Appendix 19. Muscle Enzymes .............................................................................................184
Appendix 20. MDAAT..........................................................................................................185
Appendix 21. MMT-8............................................................................................................188
Appendix 22. TIS using Core Set Measures in DM ..............................................................189
Appendix 23. Muscle Damage Index, MDI...........................................................................190
Appendix 24. CTFG Guidelines34 Regarding Contraception for Germany...........................191
Appendix 25. Contraceptive and Barrier Guidance...............................................................192
Male Participant Reproductive Inclusion Criteria........................................192
Female Participant Reproductive Inclusion Criteria....................................192
Women of Childbearing Potential................................................................193
Contraception Methods................................................................................194
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SCHEDULE OF ACTIVITIES (STAGE 1 AND STAGE 2)  
This SoA pertains to the DM population with focus on skin disease. Stage 1 enrolled participants to 600 mg or placebo.  Stage 2 
enrolled participants to 600 mg, 150 mg or placebo. 
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to the STUDY PROCEDURES and 
ASSESSMENTS sections 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 on the schedule of activities table, in order to 
conduct evaluations or assessments required to protect the well-being of the participant.
Protocol Activity
Screenin
g
Treatment
Follow-up
Visit identifier (Study Visit)
1
2
3
4
5
6
7
8
9
10
Participant withdrawal or 
Early Terminationa
Study Day/Week
Days
-35 to -1
Baseline Day 1
Week 1
Day 8
Week 4
Day 29
Week 8
Day 57
Week 12
Day 85
Week 16 
Day 113
Week 20 
Day 141
Week 24
Day 169
Week 28 
Day 197
EOS
N/A
Visit Window
None
None
±3 days
Screening Assessments
Informed consent
X
Inclusion/exclusion criteria
X
X
Demography
X
Medical history
X
Xb
DM History
X
Prior DM medication history
X
Xb
Prior Non DM medications
X
Xb
Clinical reported outcomes
CDASI Score
X
X
X
X
X
X
X
X
X
X
PHQ-8 assessmentc
X
Physician global assessment, 
(PhGA)e
X
X
X
X
X
X
X
X
X
X
Patient Reported Outcomes
5D Pruritus Scalef
X
X
X
X
X
X
X
X
X
X
SF36 V2 Acutef
X
X
X
X
X
X
DLQIf
X
X
X
X
X
X
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Protocol Activity
Screenin
g
Treatment
Follow-up
Visit identifier (Study Visit)
1
2
3
4
5
6
7
8
9
10
Participant withdrawal or 
Early Terminationa
Study Day/Week
Days
-35 to -1
Baseline Day 1
Week 1
Day 8
Week 4
Day 29
Week 8
Day 57
Week 12
Day 85
Week 16 
Day 113
Week 20 
Day 141
Week 24
Day 169
Week 28 
Day 197
EOS
N/A
Visit Window
None
None
±3 days
Medical Assessments
Vital Signs (BP, HR, Pulse, 
Respirations and temperature)g
X
X
X
X
X
X
X
X
X
X
X
Weighth
X
X
X
X
X
Heighth
X
Complete physical examinationi
X
X
X
X
Targeted physical examinationi
X
X
X
X
X
X
X
ECG
X
X
X
X
X
X
X
Chest X-Rayj
X
Skin Biopsiesk
X
X
Contraception check 
X
X
X
X
X
X
X
X
X
X
X
Laboratory Safety Assessments
Safety Labs/Urinel
X
X
X
X
X
X
X
X
X
X
Urine β-hCG
(conducted at site)m
X
X
X
X
X
X
X
X
X
X
Serum β-hCGm
X
Follicle stimulating hormone 
FSH (WONCBP only)
X
Viral surveillance (eg, CMV, 
VZV, EBV, HHV6, HSV-1/2)n
X
X
X
X
X
X
HIV, HBsAg, HBcAb, 
HCVAbo
X
Quantiferon® TB Gold testp
X
 
Pharmacokinetic (PK)/serum
Xs
X
Xs
Xs
X
X
X
X
X
X
IVIG sample collection
Xx
Xx
Xx
Banked Biospecimens
Prep B1.5 plasma
X
X
X
X
Banked Prep B2 serum 
X
X
X
X
Banked Prep DI genomic 
samplet
X
Banked Prep R1 whole blood
X
X
X
X
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Protocol Activity
Screenin
g
Treatment
Follow-up
Visit identifier (Study Visit)
1
2
3
4
5
6
7
8
9
10
Participant withdrawal or 
Early Terminationa
Study Day/Week
Days
-35 to -1
Baseline Day 1
Week 1
Day 8
Week 4
Day 29
Week 8
Day 57
Week 12
Day 85
Week 16 
Day 113
Week 20 
Day 141
Week 24
Day 169
Week 28 
Day 197
EOS
N/A
Visit Window
None
None
±3 days
Biomarkersu
Blood for Muscle and Bone 
Biomarkers
X
X
X
X
X
 
IP-10
X
X
X
X
X
X
X
X
X
MX-A
X
X
X
X
X
X
X
X
X
hsCRP
X
X
X
X
X
X
X
X
X
Gene signature panel
X
X
X
X
X
X
X
X
X
Investigational administration
Investigational treatment 
administration
Xv,w
X
X
Infusion Site Reaction
X
X
X
X
Medications and Adverse events
DM concomitant medications
X
→
→
→
→
→
→
→
X
X
Concomitant Medications and 
Treatment(s)
X
→
→
→
→
→
→
→
X
X
Serious and non-serious 
adverse event monitoring
X
X
→
→
→
→
→
→
→
X
X
Abbreviations: →= ongoing/continuous event;
; AE = adverse event; β-hCG = beta-human chorionic gonadotropin; BP = blood
pressure; CDASI = Cutaneous Dermatomyositis Disease Area and Severity Index; CMV = cytomegalovirus; CRF = Case Report Form;
; CT = computed tomography;DLQI=Dermatology and Life Quality Index; DM = Dermatomyositis; EBV = Epstein-Barr virus; 
ECG = electrocardiogram; EOS = end of study; EOT = end of treatment; EW = Early Withdrawal; FSH = follicle stimulating hormone; HEENT = head, eyes,
ears, nose and throat; Hep B = Hepatitis B; HBcAb = hepatitis B core antibody; HBsAg = hepatitis B surface antigen; HCVAb = hepatitis C virus antibody;
HHV6= human herpes Virus; HIV = human immunodeficiency virus; HR = heart rate; hsCRP = high-sensitivity C-reactive protein; HSV-1 = herpes simplex virus
type 1; HSV-2 = herpes simplex virus type 2;
 beta; IP = investigational product;IP-10 = Interferon gamma-induced protein 10;
IRT = interactive response technology; IVIG =intravenous immune globulin; MRI = magnetic resonance imaging; N/A=Not Applicable; 
 
; PD = Pharmacodynamic; PE=Physical Exam; PhGA = Physician Global Assessment; PHQ-8 = Patient Health Questionnaire 8-Item Depression Measure;
PK = pharmacokinetic; SF-36 = The Short Form (36) Health Survey; TB = tuberculosis; VZV = varicella zoster virus; WOCBP = women of childbearing
potential; WONCBP = women of non-childbearing potential.
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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.
b.
Review and collect any changes from screening.
c.
The PHQ-8 will be used at the screening visit only.  If the PHQ-8 total score is ≥15 at screening the participant will be excluded from the study.
d.
 
 
  
 Section 7.4.
e.
Physician’s Global Assessment (PhGA); This assessment should be completed by the same physician completing the CDAI.
f.
Patient reported outcomes (5D Pruritus Scale, SF-36 v2, DLQI) are to be completed at the clinic prior to other clinical assessments.  These need to be 
completed in the following order, 5D Pruritus Scale; SF-36 v2; and last DLQI.
g.
Vital Signs include blood pressure, heart rate (pulse), respirations 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 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.  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.
j.
Chest x-ray; or other appropriate diagnostic image already collected (ie, CT scan with or without contrast or MRI) may be accepted if completed within 
12 weeks prior to Day 1).  Official reading must be located in the source documentation.
k.
Refer to lab manual for preparation of punch skin biopsies.
l.
Laboratory tests may be repeated once during the 5-week screening period; the last value will be used to determine participant eligibility.
m. Serum/urine pregnancy tests for WOCBP; serum pregnancy test must be performed at screening for all WOCBP as defined in the eligibility criteria (if serum 
pregnancy test is borderline positive, the central laboratory will run a FSH test to confirm menopause if the participant has missed her periods <12 months); 
urine pregnancy test must be performed at baseline for all WOCBP prior to dosing with investigational product and at all subsequent visits.
n.
In addition to time points specified, a blood sample for viral surveillance may also be taken at the time of an AE, as clinically appropriate.
o.
Confirmation and documentation of negative HIV test result within 3 months prior to screening is acceptable. 
p.
Additional TB testing is allowed at any time if requested by the Investigator, the Sponsor and/or if there is a suspicion of TB reactivation or new TB 
infection.  The following are acceptable IGRA assays: In-Tube test (QFT-GIT), and QuantiFERON®-TB Gold test, (QFT-G).
q.
r.
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 3 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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s.
At dosing visits, PK samples will be collected preferably after vital signs data and within approximately 30 minutes prior to dosing and post-dose (at the end 
of infusion in the opposite arm that the infusion was administered).
t.
If not collected on the designated collection day, collect at the next available time point when biospecimens are being collected in conjunction with a 
participant visit (For PREP D-1).
u.
On the days of investigational drug administration, (Day 1, Week 4 and Week 8) biomarkers will be collected prior to investigational drug administration.
v.
All Day 1 procedures should be completed prior to investigational treatment administration, with the exception of the infusion site reaction.
w.
Once the infusion has completed, all participants will be monitored for an additional 60 minutes post investigational treatment administration.
x.
All participants who are on IVIG concomitantly will have a pre-dose blood sample collected.  See Section 7.15. 


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SCHEDULE OF ACTIVITIES (AMENDED STAGE 2)
This SoA focuses on DM participants with skin disease. The difference from Stage 2 is that in the Amended Stage 2, all participants 
receive 12 weeks of active study drug, and provide 2 additional skin biopsies at Week 24. Study participation is approximately 
45 weeks in duration, including the screening period. 
The schedule of activities table provides an overview of the protocol visits and procedures.  Refer to the STUDY PROCEDURES and 
ASSESSMENTS sections 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 on the schedule of activities table, in order 
to conduct evaluations or assessments required to protect the well-being of the participant.
Protocol Activity
Screening
Treatment Period  
Follow-up Period
Visit identifier (Study Visit)
1
2
3
4
5
6
7
8
9y
10
11
12
13r
Participant
withdrawal or 
Early 
Terminationa
Study Day/Week
Days
-35 to -1
Baseline 
Day 1
Week 
1
Day 8
Week 4
Day 29
Week 
8
Day 
57
Week 
12
Day
85
Week 
16 
Day 
113
Week 20 
Day 141
Week 24y
Day 169
Week 
28 Day 
197
Week 32
Day 225
Week 
36
Day 
253
Week 
40 
Day 
281
EOS
N/A
Visit Window
None
None
±3 days
Screening Assessments
Informed consent
X
Inclusion/exclusion criteria
X
X
Demography
X
Medical history
X
Xb
DM History
X
Prior DM medication history
X
Xb
Prior Non DM medications
X
Xb
Clinical Reported Outcomes
CDASI Score
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PHQ-8 assessmentc
X
Physician Global Assessment, (PhGA, 
VAS)e
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient Reported Outcomesf
PtGA
X
X
X
X
X
X
X
X
X
X
X
X
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Protocol Activity
Screening
Treatment Period  
Follow-up Period
Visit identifier (Study Visit)
1
2
3
4
5
6
7
8
9y
10
11
12
13r
Participant
withdrawal or 
Early 
Terminationa
Study Day/Week
Days
-35 to -1
Baseline 
Day 1
Week 
1
Day 8
Week 4
Day 29
Week 
8
Day 
57
Week 
12
Day
85
Week 
16 
Day 
113
Week 20 
Day 141
Week 24y
Day 169
Week 
28 Day 
197
Week 32
Day 225
Week 
36
Day 
253
Week 
40 
Day 
281
EOS
N/A
Visit Window
None
None
±3 days
HAQ-DI
X
X
X
X
X
X
X
X
X
X
X
X
5-D Pruritus Scale
X
X
X
X
X
X
X
X
X
X
X
X
SF-36 v2 Acute
X
X
X
X
X
X
X
X
DLQI
X
X
X
X
X
X
X
X
X
EQ-5D-5L & EQ-VAS
X
X
X
X
X
X
Medical Assessments
Vital Signs (BP, HR, Pulse, Respirations 
and temperature)g
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weighth
X
X
X
X
X
X
Heighth
X
X
X
Complete physical examinationi
X
X
X
X
X
Targeted physical examinationi
X
X
X
X
X
X
X
X
X
ECG
X
X
X
X
X
X
X
X
X
X
Chest X-Rayj
X
Skin Punch Biopsiesk
X
X
X
Contraception check 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Assessments
Safety Labs/Urinel
X
X
X
X
X
X
X
Xz
X
X
X
X
X
Urine β-hCG
(conducted at site)m
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum β-hCGm
X
Follicle stimulating hormone FSH 
(WONCBP only)
X
Viral surveillance (eg, CMV, VZV, EBV, -
HHV6, HSV-1/2)n
X
X
X
X
X
X
X
X
X
HIV, HBsAg, HBcAb, HCVAbo
X
Quantiferon® TB Gold testp
X
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Protocol Activity
Screening
Treatment Period  
Follow-up Period
Visit identifier (Study Visit)
1
2
3
4
5
6
7
8
9y
10
11
12
13r
Participant
withdrawal or 
Early 
Terminationa
Study Day/Week
Days
-35 to -1
Baseline 
Day 1
Week 
1
Day 8
Week 4
Day 29
Week 
8
Day 
57
Week 
12
Day
85
Week 
16 
Day 
113
Week 20 
Day 141
Week 24y
Day 169
Week 
28 Day 
197
Week 32
Day 225
Week 
36
Day 
253
Week 
40 
Day 
281
EOS
N/A
Visit Window
None
None
±3 days
Pharmacokinetic (PK)/serums
X
X
X
X
X
X
X
Xz
X
X
X
X
X
IVIG sample collectionx
X
X
X
X
X
X
Banked Biospecimens
Prep B1.5 plasma
X
X
X
X
X
X
X
X
Banked Prep B2 serum 
X
X
X
X
X
X
X
X
Banked Prep D1 genomic samplet
X
Banked Prep R1 whole blood
X
X
X
X
X
X
X
X
Biomarkersu
Blood for Muscle and Bone Biomarkers
X
X
X
X
X
X
X
X
IP-10
X
X
X
X
X
X
X
X
X
X
X
X
MX-A
X
X
X
X
X
X
X
X
X
X
X
X
hsCRP
X
X
X
X
X
X
X
Xz
X
X
X
X
X
Gene signature panel
X
X
X
X
X
X
X
X
X
X
X
X
X
Investigational Treatment 
Administration
Investigational treatment administrationw
Xu,v
Xu
Xu
Xu
Xu
Xu
Infusion Site Reaction
X
X
X
X
X
X
Medications and Adverse Events
DM concomitant medications
X
→
→
→
→
→
→
→
→
→
X
X
Concomitant Medications and Treatment(s)
X
→
→
→
→
→
→
→
→
→
X
X
Serious and non-serious adverse event 
monitoring
X
X
→
→
→
→
→
→
→
→
→
→
X
X
Abbreviations: →= See (Stage 2): Additional assessments added: 5-D Pruritus Scale = 5-Dimensions Pruritus Scale; EQ-5D-5L =European Quality of Life Five 
Dimension, Five Level Scale; EQ-VAS = EuroQol Visual Analogue Scale; FACIT-F = Functional Assessment of Chronic Illness Therapy – Fatigue;
HAQ-DI = Health Assessment Questionnaire Disability Index; PtGA = Patient Global Assessment; 
 
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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.
b.
Review and collect any changes from screening.
c.
The PHQ-8 will be used at the screening visit only.  If the PHQ-8 total score is ≥15 at screening the participant will be excluded from the study.
d.
 
 
  
e.
Physician’s Global Assessment (PhGA, VAS); This assessment should be completed by the same physician completing the CDASI.
f.
Patient reported outcomes (PtGA, HAQ-DI, 5-D Pruritus Scale, 
, SF 36 v2 acute, DLQI, 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, 5-D Pruritus Scale, 
 
, SF 36 v2 acute, DLQI, EQ-5D-5L & EQ-VAS.
g.
Vital Signs include blood pressure, heart rate (pulse), respirations 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 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. 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.
j.
Chest x-ray; or other appropriate diagnostic image already collected (ie, CT scan with or without contrast or MRI) may be accepted if completed within 
12 weeks prior to Day 1). Official reading must be located in the source documentation.
k.
Refer to lab manual for preparation of punch skin biopsies. There is a -6 day screening window at Day 1 for punch biopsies.  At Week 12 and Week 24, a -/+ 
6 day window is permitted to obtain skin punch biopsies. 
l.
Laboratory tests may be repeated once during the 5-week screening period; the last value will be used to determine participant eligibility.
m. Serum/urine pregnancy tests for WOCBP; serum pregnancy test must be performed at screening for all WOCBP as defined in the eligibility criteria (if serum 
pregnancy test is borderline positive, the central laboratory will run a FSH test to confirm menopause if the participant has missed her periods <12 months); 
urine pregnancy test must be performed at baseline for all WOCBP prior to dosing with investigational product and at all subsequent visits.
n.
In addition to time points specified, a blood sample for viral surveillance may also be taken at the time of an AE, as clinically appropriate.
o.
Confirmation and documentation of negative HIV test result within 3 months prior to screening is acceptable.
p.
Additional TB testing is allowed at any time if requested by the Investigator, the Sponsor and/or if there is a suspicion of TB reactivation or new TB 
infection.  The following are acceptable IGRA assays: In-Tube test (QFT-GIT), and QuantiFERON®-TB Gold test, (QFT-G).
q.
On the days of investigational drug administration, ADA and Nab will be collected prior to investigational drug administration.
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r.
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 3 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.
s.
At dosing visits, PK samples will be collected preferably after vital signs data and within approximately 30 minutes prior to dosing and post-dose (at the end 
of infusion in the opposite arm that the infusion was administered).
t.
If not collected on the designated collection day, collect at the next available time point when biospecimens are being collected in conjunction with a 
participant visit (For PREP D-1).
u.
On the days of investigational drug administration, biomarkers will be collected prior to investigational drug administration.
v.
All Day 1 procedures should be completed prior to investigational treatment administration, with the exception of the infusion site reaction.
w.
Once the infusion has completed, all participants will be monitored for an additional 60 minutes post investigational treatment administration.
x.
All participants who are on IVIG concomitantly will have a pre-dose blood sample collected.  See Section 7.15.
y.
All participants who complete the treatment period in this study up through and including (Visit 9, Week 24), will have the opportunity to continue treatment 
in the open label extension C0251008 protocol. Participants whom have completed the treatment period and have not had any significant protocol 
deviations, or safety events will be eligible.  Participants will also have the opportunity to continue into the follow up period and complete the C0251002 
study instead of enrolling into open label extension C0251008.  
z.
All participants continuing to the open label extension C0251008 study should use the DAY 1 C0251008 Lab kit.  Please see lab manual for specific 
instructions.


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Page 37
SCHEDULE OF ACTIVITIES (STAGE 3)
This SoA focuses on DM participants with moderate muscle disease.  The approximate study duration is 45 weeks including the 
screening period. Participants enrolling in Stage 3 will not provide any skin or muscle biopsies.  
The schedule of activities table provides an overview of the protocol visits and procedures. Refer to the STUDY PROCEDURES and
ASSESSMENTS sections 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 on the schedule of activities table, in order 
to conduct evaluations or assessments required to protect the well-being of the participant.
Protocol 
Activity
Screening
Treatment Period
Follow-up Period
Visit 
identifier 
(Study Visit)
1
2
3
4
5
6
7
8
9y
10
11
12
13
Participant
withdrawal or 
Early 
Terminationa
Study 
Day/Week
Days
-35 to -1
Baseline 
Day 1
Week 
1
Day 8
Week 4
Day 29
Week 8
Day 57
Week 12
Day 85
Week 
16 
Day 
113
Week 20 
Day 141
Week 
24y
Day 169
Week 28 
Day 197
Week 32
Day 225
Week 36
Day 253
Week 40 
Day 281
EOSr
N/A
Visit Window
None
None
±3 days
Screening Assessments
Informed 
consent
X
Inclusion/excl
usion criteria
X
X
Demography
X
Medical 
history
X
Xb
DM History
X
Prior DM 
medication
history
X
Xb
Prior Non DM 
medications
X
Xb
X
Clinical Reported Outcomes
CDASI Score
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PHQ-8 
assessmentc
X


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Protocol 
Activity
Screening
Treatment Period
Follow-up Period
Visit 
identifier 
(Study Visit)
1
2
3
4
5
6
7
8
9y
10
11
12
13
Participant
withdrawal or 
Early 
Terminationa
Study 
Day/Week
Days
-35 to -1
Baseline 
Day 1
Week 
1
Day 8
Week 4
Day 29
Week 8
Day 57
Week 12
Day 85
Week 
16 
Day 
113
Week 20 
Day 141
Week 
24y
Day 169
Week 28 
Day 197
Week 32
Day 225
Week 36
Day 253
Week 40 
Day 281
EOSr
N/A
Visit Window
None
None
±3 days
Physician 
Global 
Assessment, 
(PhGA, VAS, 
VAS)e
X
X
X
X
X
X
X
X
X
X
X
X
X
X
MMT-8 Score
X
X
X
X
X
X
X
X
X
X
X
X
X
MDI
X
Myositis 
Disease 
Activity 
Assessment 
Tool 
(MDAAT)
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient Reported Outcomesf
PtGA
X
X
X
X
X
X
X
X
X
X
X
X
X
HAQ-DI
X
X
X
X
X
X
X
X
X
X
X
X
5-D Pruritus 
Scale
X
X
X
X
X
X
X
X
X
X
X
X
 
 
FACIT-F
X
X
X
X
X
X
X
X
X
SF-36 v2
Acute
X
X
X
X
X
X
X
X
EQ-5D-5L & 
EQ-VAS
X
X
X
X
X
X
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Protocol 
Activity
Screening
Treatment Period
Follow-up Period
Visit 
identifier 
(Study Visit)
1
2
3
4
5
6
7
8
9y
10
11
12
13
Participant
withdrawal or 
Early 
Terminationa
Study 
Day/Week
Days
-35 to -1
Baseline 
Day 1
Week 
1
Day 8
Week 4
Day 29
Week 8
Day 57
Week 12
Day 85
Week 
16 
Day 
113
Week 20 
Day 141
Week 
24y
Day 169
Week 28 
Day 197
Week 32
Day 225
Week 36
Day 253
Week 40 
Day 281
EOSr
N/A
Visit Window
None
None
±3 days
Medical Assessments
Vital Signs 
(BP, HR, 
Pulse, 
Respirations 
and 
temperature)g
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weighth
X
X
X
X
X
X
Heighth
X
X
X
Complete 
physical 
examinationi
X
X
X
X
X
Targeted 
physical 
examinationi
X
X
X
X
X
X
X
X
X
X
ECG
X
X
X
X
X
X
X
X
X
X
Chest X-Rayj
X
Contraception 
checkk
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Safety Assessments
Safety 
Labs/Urinel
X
X
X
X
X
X
X
Xz
X
X
X
X
X
Urine -hCG
(conducted at 
site)m
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum 
-hCGm
X


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Page 40
Protocol 
Activity
Screening
Treatment Period
Follow-up Period
Visit 
identifier 
(Study Visit)
1
2
3
4
5
6
7
8
9y
10
11
12
13
Participant
withdrawal or 
Early 
Terminationa
Study 
Day/Week
Days
-35 to -1
Baseline 
Day 1
Week 
1
Day 8
Week 4
Day 29
Week 8
Day 57
Week 12
Day 85
Week 
16 
Day 
113
Week 20 
Day 141
Week 
24y
Day 169
Week 28 
Day 197
Week 32
Day 225
Week 36
Day 253
Week 40 
Day 281
EOSr
N/A
Visit Window
None
None
±3 days
Follicle 
stimulating 
hormone 
FSHm
(WONCBP
only)
X
Viral 
surveillance 
(eg, CMV, 
VZV, EBV, 
HHV6, 
HSV-1/2)n
X
X
X
X
X
X
X
X
X
HIV, HBsAg, 
HBcAb, 
HCVAbo
X
Quantiferon®
TB Gold testp
X
Pharmacokine
tic 
(PK)/serums
X
X
X
X
X
X
X
Xz
X
X
X
X
X
IVIG sample 
collectionx
X
X
X
X
X
X
Banked Biospecimens
Prep B1.5 
plasma
X
X
X
X
X
X
X
X
Banked Prep 
B2 serum 
X
X
X
X
X
X
X
X
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Final Protocol Amendment 6, 20 September 2021 
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Page 41
Protocol 
Activity
Screening
Treatment Period
Follow-up Period
Visit 
identifier 
(Study Visit)
1
2
3
4
5
6
7
8
9y
10
11
12
13
Participant
withdrawal or 
Early 
Terminationa
Study 
Day/Week
Days
-35 to -1
Baseline 
Day 1
Week 
1
Day 8
Week 4
Day 29
Week 8
Day 57
Week 12
Day 85
Week 
16 
Day 
113
Week 20 
Day 141
Week 
24y
Day 169
Week 28 
Day 197
Week 32
Day 225
Week 36
Day 253
Week 40 
Day 281
EOSr
N/A
Visit Window
None
None
±3 days
Banked Prep 
D1 genomic
samplet
X
Banked Prep 
R1 whole 
blood
X
X
X
X
X
X
X
X
Biomarkersu
Blood for 
Muscle and 
Bone 
Biomarkers
X
X
X
X
X
X
X
X
 
 
IP-10
X
X
X
X
X
X
X
X
X
X
X
X
MX-A
X
X
X
X
X
X
X
X
X
X
X
X
hsCRP
X
X
X
X
X
X
X
Xz
X
X
X
X
X
Gene 
signature 
panel
X
X
X
X
X
X
X
X
X
X
X
X
X
Investigational administration
Investigational 
treatment 
administration
w
Xu,v
Xu
Xu
Xu
Xu
Xu
Infusion Site 
Reaction
X
X
X
X
X
X
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Page 42
Protocol 
Activity
Screening
Treatment Period
Follow-up Period
Visit 
identifier 
(Study Visit)
1
2
3
4
5
6
7
8
9y
10
11
12
13
Participant
withdrawal or 
Early 
Terminationa
Study 
Day/Week
Days
-35 to -1
Baseline 
Day 1
Week 
1
Day 8
Week 4
Day 29
Week 8
Day 57
Week 12
Day 85
Week 
16 
Day 
113
Week 20 
Day 141
Week 
24y
Day 169
Week 28 
Day 197
Week 32
Day 225
Week 36
Day 253
Week 40 
Day 281
EOSr
N/A
Visit Window
None
None
±3 days
Medications and Adverse events
DM 
concomitant 
medications
X
→
→
→
→
→
→
→
→
→
→
X
X
Concomitant 
Medications 
and 
Treatment(s)
X
→
→
→
→
→
→
→
→
→
→
X
X
Serious and 
non-serious 
adverse event 
monitoring
X
X
→
→
→
→
→
→
→
→
→
→
X
X
Abbreviations: See Stage 1 and Stage 2 and Amended Stage 2 SoA; HAQ-D1-Health Assessment Questionnaire and Disease Index, MDAAT- Myositis Disease 
Activity Assessment Tool, MMT-8- Manual Muscle Testing-8 designated muscles, PtGA-Patient Global Assessment.
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.
b.
Review and collect any changes from screening.
c.
The PHQ-8 will be used at the screening visit only.  If the PHQ-8 total score is ≥15 at screening the participant will be excluded from the study.
d.
The CSSRS will be used to assess suicidal ideation and behavior during the conduct of the study.  The first assessment will be completed on Day 1 of the 
study prior to dosing to obtain a baseline assessment.  At any postday 1 visits, if there are “yes” answers on items 4, 5 or on any suicidal behavior question of 
the CSSRS, the participant will be discontinued from treatment and referred to a mental health professional for appropriate evaluation and treatment.  Please 
see Section 7.4.
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, 5-D Pruritus Scale,
 FACIT-F, 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, 5-D Pruritus Scale, 
 FACIT-F, SF-36 v2 acute, EQ-5D-5L & EQ-VAS.
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Final Protocol Amendment 6, 20 September 2021 
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Page 43
g.
Vital Signs include blood pressure, heart rate (pulse), respirations 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 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.  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.
j.
Chest x-ray; or other appropriate diagnostic image already collected (ie, CT scan with or without contrast or MRI) may be accepted if completed within 
12 weeks prior to Day 1).  Official reading must be located in the source documentation.
k.
Contraception check should be completed and documented in source.
l.
Laboratory tests may be repeated once during the 5-week screening period; the last value will be used to determine participant eligibility.
m. Serum/urine pregnancy tests for WOCBP; serum pregnancy test must be performed at screening for all WOCBP as defined in the eligibility criteria (if serum 
pregnancy test is borderline positive, the central laboratory will run a FSH test to confirm menopause if the participant has missed her periods <12 months); 
urine pregnancy test must be performed at baseline for all WOCBP prior to dosing with investigational product and at all subsequent visits.
n.
In addition to time points specified, a blood sample for viral surveillance may also be taken at the time of an AE, as clinically appropriate.
o.
Confirmation and documentation of negative HIV test result within 3 months prior to screening is acceptable. 
p.
Additional TB testing is allowed at any time if requested by the Investigator, the Sponsor and/or if there is a suspicion of TB reactivation or new TB 
infection.  The following are acceptable IGRA assays: In-Tube test (QFT-GIT), and QuantiFERON®-TB Gold test, (QFT-G).
q.
On the days of investigational drug administration, (Day 1, Week 4, Week 8, Week 12, and Week 20) ADA and Nab will be collected prior to investigational 
drug administration.
r.
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 3 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.
s.
At dosing visits, PK samples will be collected preferably after vital signs data and within approximately 30 minutes prior to dosing and post-dose (at the end 
of infusion in the opposite arm that the infusion was administered).
t.
If not collected on the designated collection day, collect at the next available time point when biospecimens are being collected in conjunction with a 
participant visit (For PREP D-1).
u.
On the days of investigational drug administration, (Day 1, Week 4, Week 8, Week 12, Week 16 and Week 20) biomarkers will be collected prior to 
investigational drug administration.
v.
All Day 1 procedures should be completed prior to investigational treatment administration, with the exception of the infusion site reaction.
w.
Once the infusion has completed, all participants will be monitored for an additional 60 minutes post investigational treatment administration.
x.
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y.
All participants who complete the treatment period in this study up through and including (Visit 9, Week 24), will have the opportunity to continue treatment 
in the open label extension C0251008 protocol. Participants whom have completed the treatment period and have not had any significant protocol 
deviations, or safety events will be eligible.  Participants will also have the opportunity to continue into the follow up period and complete the C0251002 
study instead of enrolling into open label extension C0251008.
z.
All participants continuing to the open label extension C0251008 study should use the DAY 1 C0251008 Lab kit.  Please see lab manual for specific 
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1. INTRODUCTION
Dermatomyositis, (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
DM has no known cure and there are no widely approved treatments.  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, mycophenolate mofetil, (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 well documented.  Other novel 
approaches have emerged as potential treatment, including tacrolimus (broadly 
immunosuppressive drug developed for transplant use), intravenous immunoglobulin, and 
rituximab, following positive outcomes in some case studies.  However, additional 
randomized controlled trials with these treatments are needed to guide clinical practice.3
Consequently, DM remains a disease with very high unmet medical need, and development 
of safe and effective therapies is warranted. 
1.1. Mechanism of Action/Indication
PF-06823859 is a potent, selective, humanized immunoglobulin G1(IgG1) neutralizing 
antibody directed against the human soluble cytokine interferon-beta (IFNβ), a member of 
the type I interferon (IFN) family of cytokines.  PF-06823859 is in development for the 
treatment systemic lupus erythematous (SLE) with added potential for therapeutic benefit in 
DM.
1.2. Background and Rationale 
 
 
 
  
 
 
  
 
 
 
 
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1.3. Nonclinical Pharmacokinetics 
After single intravenous (IV) doses of PF-06823859 at 10 and 200 mg/kg administered to 
cynomolgus monkeys, serum exposures were typical for an IgG1 monoclonal antibodies,
(mAb) dosed to monkeys.  The mean plasma clearance (CL) ranged from 0.00439 to 
0.00502 L/day/kg, the mean volume at steady state (Vss) ranged from 0.0747 to 0.0823 L/kg, 
and the mean apparent half-life ranged from 11.4 to 14.0 days.  Subcutaneous (SC) 
bioavailability was approximately 87% following a single 10 mg/kg dose of PF-06823859.  
The pharmacokinetic (PK) profiles of PF-06823859 in the cynomolgus monkey were typical 
for a human IgG mAb in monkeys.  In the pivotal repeat dose monkey toxicity study with
20 mg/kg SC, 100 mg/kg SC or 500 mg/kg IV doses of PF-06823859, there were no apparent 
sex-related- differences observed in systemic exposure.  Systemic exposures were higher on 
Day 85 compared to Day 1 for all dose groups, and exposures increased with increasing dose 
in the SC dose groups.  The incidence of Anti-Drug Antibody (ADA) induction across all 
dose groups administered PF-06823859 via either repeat IV or SC dosing in cynomolgus 
monkeys was 36%. 
Additional information for this compound may be found in the single reference safety 
document (SRSD), which for this study is the Investigator’s Brochure (IB).
1.4. Nonclinical Safety Data
In the in vitro Fc receptor (FcR) and complement protein C1q binding assays, PF-06832859 
did not bind to C1q, suggesting an inability to activate the classical complement pathway and 
induce complement dependent cytotoxicity (CDC), and the FcR binding data demonstrated 
that PF-06823859 had low potential to elicit antibody-dependent cell-mediated cytotoxicity
(ADCC) activity.  PF-06823859 did not elicit test article-related release of 3 human pro 
inflammatory cytokines tumor necrosis factor alpha, (TNFα), Interleukin 6, (IL6), and 
Interferon gamma, (IFNγ) in the in vitro soluble phase cytokine release assay.  PF-06823859 
did not cause suppression of the influenza antigen-specific proliferative response in the 
human lymphocyte activation (HuLA) assay.  In the herpes simplex virus-1 (HSV-1) assay, 
incubation of human dermal fibroblasts with PF-06823859 resulted in a dose dependent 
inhibition of IFNβ-mediated suppression of HSV-1 replication.  In the good laboratory 
practice (GLP) compliant tissue cross-reactivity study, staining patterns with PF-06823859 
overlapped between cynomolgus and human tissues, with some exceptions primarily in 
epithelial subtypes.  The majority of staining observed was cytoplasmic, which is not 
expected to be accessible to the test article in vivo. 
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Based on binding and functional assessments across species (ie, mice, rats, rabbits, & 
cynomolgus monkeys), the only pharmacologically relevant species for toxicity testing is the 
cynomolgus monkey.  In a GLP-compliant toxicity study, PF-06823859 was not associated 
with any adverse test article-related findings when administered to sexually-mature male and 
female cynomolgus monkeys once weekly via IV or SC routes up to 500 mg/kg/dose for up 
to 14 weeks.  There were no test article-related effects on the cardiovascular system based on 
electrocardiography and heart rate evaluations, nor were there any test-article related effects 
in male or female reproductive tissues evaluated in the repeat-dose toxicity study in 
sexually-mature cynomolgus monkeys. 
Compared with baseline, test article-related, nonadverse increases in serum globulin and 
subsequent nonadverse decreases in albumin:globulin ratio were noted on Days 29 and 92 in 
animals administered 500 mg/kg/dose (IV).  This increase in serum globulin was attributed to 
the presence of high concentrations of PF-06823859 (an immunoglobulin) and was no longer 
present at the end of the 8-week recovery phase, consistent with the low concentrations of 
PF-06823859 in the serum at this time.  The no observed adverse effect level (NOAEL) in 
this 14 week GLP-compliant repeat-dose toxicity study was 500 mg/kg/dose (IV). In the 
500 mg/kg/dose group (IV), the mean serum concentration maximum, (Cmax) (males and 
females combined) was 25,600 µg/mL and the mean area under the curve, (AUC)168 (males 
and females combined) was 2,430,000 µg•h/mL on Day 85 (Week 13).  The mean average 
concentration (Cav) was 14,500 µg/mL.  There were no sex-related differences in systemic 
exposure.  In conclusion, the nonclinical safety profile of PF-06823859 has been adequately
characterized in vitro and in vivo in cynomolgus monkey to support progression into clinical
trials up to 3 months in duration.
Additional information for this compound may be found in the single reference safety 
document (SRSD), which for this study is the Investigator’s Brochure (IB).
1.5. Clinical Safety Profile
1.5.1. Safety (FIH C0251001)
A first in human (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 Participants) has currently completed all 
dosing with all participants in the follow-up period of the study and expected to complete in 
August 2017.  This study consisted of a total of 8 dosing cohorts.  There were 5 cohorts of 
single 30 mg IV, 100 mg IV, 300 mg IV, 900 mg IV and 2000 mg IV doses.  The last 
3 cohorts were multiple dose cohorts consisting of 100 mg x 3 subcutaneous (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). 


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As of 07 April 2017, a total of 48 participants have received at least one dose of 
PF-06823859.  Preliminary data from this study suggest that PF-06823859 is generally well 
tolerated and safe
 
 The most common adverse events were upper respiratory 
tract infection and headache.  These adverse events were generally mild and resolved without 
further intervention.  No serious adverse event, (AE) or death occurred during the study.
One participant experienced an injection site reaction (ISR) after each of the 100 mg SC 
dosing 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 1.5.3).
Overall, there was no apparent difference in the total rate of adverse events between the 
participants treated with the active investigational product (IP) compared to placebo and no 
apparent dose relationship with the doses of the IP.  However, the rate of mild upper 
respiratory tract infection appears to be higher in participants treated with PF-06823859.
There were no clinically significant changes in electrocardiogram (ECG), vital signs or 
laboratory abnormalities. 
In conclusion, PF-06823859 was generally well tolerated and safe in healthy participants and 
the preliminary data from this FIH study supports continued clinical development of 
PF-06823859.  Further details are provided in the current PF-06823859 Investigator’s 
Brochure.
 
 
 
  
 
 
 
 
 
 
 
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1.5.3. Immunogenicity Results for C0251001
Note the data analysis provided in this section is based on preliminary immunogenicity data.  
A tiered approach for screening, characterization and Anti-Drug Antibody (ADA) titer 
assessment of serum samples was adopted to characterize immunogenicity.  As of 07 April
2017, the treatment related overall ADA incidence rate was 12% (5 of 43 participants).  
Following PF-06823859 administration, 3 adult healthy participants in the single dose groups
(2 in 30 mg IV group and 1 in 900 mg IV group) and 2 participants in repeat dose groups 
(1 in 100 mg SC and 1 in 300 mg SC) were found to have treatment-related ADA responses. 
The ADA positive participant in 100 mg SC repeat dose group had injection site reaction 
after each of the 3 doses.  None of the other participants experienced clinical signs or 
symptoms consistent with an immune response.  The ADA titer in all 5 participants had 
returned to baseline at the time of discharge and did not result in a discernible impact on PK.  
Currently, neutralizing antibody (NAb) assay is under development.
1.5.4. Summary of Benefits and Risks
Based on the clinical data from the FIH study (C0251001) 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 particpants with DM.
As previously noted, DM is a rare disease with higher prevalence in females than males.  
Therefore, the trial objectives cannot be met without inclusion of women of childbearing 
potential (WoCBP).  Nonclinical data to date (Section 1.4) has not identified any risk to 
reproductive organs in sexually mature cynomolgus monkeys, the pharmacologically relevant 
species.  Given that an enhanced pre- and postnatal development study (ePPND) will be 
conducted later in development, this protocol that allows enrollment of Women of child 
bearing potential, (WoCBP) has stringent requirements to mitigate unintended exposures 
(pregnancy testing and use of contraceptives). 
There is a theoretical risk that alterations in bone may occur based on published observations 
of osteopenia in mice genetically deficient in IFNb.10 The potential for bone effects was 
assessed in the 3-month good laboratory practice (GLP) toxicity study in sexually mature 
cynomolgus monkeys, and there were no microscopic findings in bone, nor alterations in 
circulating bone-related biomarkers. However, the potential for bone effects in 
developing/growing bones has not been specifically assessed in growing animals. This risk
is considered to be low given the lack of observed effects in the (GLP) toxicity study as well 
as the limited duration of total exposure to PF-06823859 in this planned DM study.  While 
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appropriate risk mitigation has been employed, possible risks will be communicated to study 
participants in the ICD.
1.6. Dose Selection Rationale
 
A formal interim analysis occurred in April 2020 by an unblinded internal review committee 
independent from the blinded study team.  An internal decision was made to add an
additional dose, 
  None of the blinded study 
team members were involved with the data or the decision made at the time of the interim 
analysis.  In stage 2, following the interim analysis, participants will be randomly assigned to 
receive
that will be administered intravenously 
 
 4 weeks, for a total of 3 doses.  
All participants enrolled in the Amended Stage 2 of the study will receive active study drug
with the fixed sequence design.  Participants will be randomly assigned to receive 
 
every 4 weeks.  
Participants who start the study on 
 will have a 
prespecified dose change to placebo at Week 12, and participants who are on placebo will 
have a prespecified dose change to active study drug at Week 12. Participants will thus 
 
during the treatment period.
Stage 3 participants will be randomly assigned to receive 
 with the fixed 
sequence design. Participants who start the study on active study drug will have a 
prespecified dose change to placebo at Week 12, and participants who are on placebo will 
have a prespecified dose change to active study drug at Week 12. Participants will thus 
receive 3 consecutive doses of 
and 3 consecutive doses of 
placebo for a total of 6 doses during the treatment period.  Doses will be administered 
intravenously over one hour every 4 weeks.
PK and PK/PD approaches were considered using the data available to date to guide selection 
of the proposed dose and dose regimen.  
 
 
 
 
 
 
 
 
 
 
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A 
 for a total of 2 doses was previously tested in healthy 
participants and was considered safe based on data from Study C0251001.  
 
 
 
 
 
 
 
 
 
 
 
Additional information for this compound may be found in the single reference safety 
document (SRSD), which for this study is the investigator brochure (IB). 
 
 
 
 
 
 
 
 
 
. 
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(
 
 
 
2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Stage 1, Objectives and Endpoints
Primary Objective(s):
Primary Endpoint(s):
•
To evaluate the efficacy of PF-06823859 in adult 
participants with moderate to severe DM.
•
Change from baseline in CDASI activity score 
at Week 12.
Secondary Objective(s):
Secondary Endpoint(s):
•
To evaluate the efficacy of PF-06823859 over 
time.
•
To determine the safety, and tolerability, of 
PF-06823859.
•
Absolute values and change from baseline of 
CDASI activity and CDASI damage scores at 
all scheduled time points. (Exception: The 
change from baseline in CDASI activity score 
at Week 12 is a primary endpoint).
•
Incidence of adverse events (AEs) laboratory 
abnormalities, changes in vital signs, and 
electrocardiogram (ECG) findings.
Exploratory Objectives (s)
Exploratory Endpoints(s)
•
To characterize pharmacokinetics (PK) of 
PF-06823859.
•
To characterize pharmacodynamics (PD) effects 
of PF-06823859.
•
To evaluate the effects of PF-06823859 on 
patient-reported outcomes (PROs) and physician 
global assessment (PhGA, VAS) over time.
•
To evaluate the effects of PF-06823859 on 
CDASI sub-scores.
•
Plasma concentration of PF-06823859. 
•
Absolute values and change from baseline in 
the values of selected biomarkers (Gene 
signature panel in blood and tissue; Human 
Myxovirus A (MXA), interferon 
gamma-induced protein 10 (IP-10), 
 
highly sensitive C-reactive protein, (hsCRP), 
muscle and bone blood biomarkers, 
autoantibody concentrations in serum/plasma) 
at all scheduled time points.
•
Absolute values and change from baseline in 
the values of the PhGA, VAS, PROs (the short 
form (SF36) Health Survey, Dermatology and 
Life Quality Index (DLQI), 5D Pruritus Scale, 
at all scheduled time points.
•
Absolute values and change from baseline
values of the sub-scores of CDASI activity and 
CDASI damage scores at all scheduled time 
points.
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2.2. Stage 2, Objectives and Endpoints
Primary Objective(s):
Primary Endpoint(s):
•
To estimate the efficacy of PF-06823859 in adult 
participants with moderate to severe DM across
two stages.
•
Change from baseline in CDASI activity score 
at Week 12. 
Secondary Objective(s):
Secondary Endpoint(s):
•
To estimate the efficacy of PF-06823859 over 
time across two Stages.
•
To determine the safety, and tolerability, of 
PF-06823859 across two Stages.
•
Absolute values and change from baseline of 
CDASI activity and CDASI damage scores at 
all scheduled time points. (Exception: The 
change from baseline in CDASI activity score 
at Week 12 is a primary endpoint).
•
Incidence of adverse events (AEs) laboratory 
abnormalities, changes in vital signs, and 
electrocardiogram (ECG) findings.
Exploratory Objectives (s)
Exploratory Endpoints(s)
•
To characterize pharmacokinetics (PK) of 
PF-06823859 across the two stages.
•
To characterize pharmacodynamics (PD) effects 
of PF-06823859 across the two stages.
•
To estimate the effects of PF-06823859 on 
patient-reported outcomes (PROs) and physician 
global assessment (PhGA, VAS) over time across 
the two stages.
•
To estimate the effects of PF-06823859 on 
CDASI sub-scores across the two stages.
•
Plasma concentration of PF-06823859. 
•
Absolute values and change from baseline in 
the values of selected biomarkers (Gene 
signature panel in blood and tissue; Human 
Myxovirus A (MXA), interferon 
gamma-induced protein 10 (IP-10), 
, 
highly sensitive C-reactive protein, (hsCRP), 
muscle and bone blood biomarkers, 
autoantibody concentrations in serum/plasma) 
at all scheduled time points.
•
Absolute values and change from baseline in 
the values of the PhGA, VAS, PROs (the short 
form (SF36) Health Survey, Dermatology and 
Life Quality Index (DLQI), 5D Pruritus Scale, 
at all scheduled time points. 
•
Absolute values and change from baseline 
values of the sub-scores of CDASI activity and 
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CDASI damage scores at all scheduled time 
points. 
 
 
 
 
 
 
 
 
2.3. Amended Stage 2, Objectives and Endpoints 
Primary Objective(s):
Primary Endpoint(s):
To estimate the efficacy of PF-06823859 in adult 
participants with moderate to severe DM across 
Stage 1 and Stage 2.
•
Change from baseline in CDASI activity score 
at Week 12. 
Secondary Objective(s):
Secondary Endpoint(s):
•
To estimate the efficacy of PF-06823859 over 
time across Stage 1 and Stage 2.
•
To determine the safety, and tolerability, of 
PF-06823859 across Stage 1 and Stage 2.
•
Absolute values and change from baseline of 
CDASI activity and CDASI damage scores at 
all scheduled time points. (Exception: The 
change from baseline in CDASI activity score 
at Week 12 is a primary endpoint).
•
Incidence of adverse events (AEs) laboratory 
abnormalities, changes in vital signs, and 
electrocardiogram (ECG) findings.
Exploratory Objectives (s)
Exploratory Endpoints(s)
•
To characterize pharmacokinetics (PK) of 
PF-06823859 across Stage 1 and Stage 2.
•
To characterize pharmacodynamics (PD) effects 
of PF-06823859 across Stage 1 and Stage 2.
•
To estimate the effects of PF-06823859 on the 
Physician Global Assessment (PhGA, VAS)
across Stage 1 and Stage 2.
•
Plasma concentration of PF-06823859. 
•
Absolute values and change from baseline in 
the values of selected biomarkers (Gene 
signature panel in blood and tissue; Human 
Myxovirus A (MXA), interferon 
gamma-induced protein 10 (IP-10), 
highly sensitive C-reactive protein, (hsCRP), 
muscle and bone blood biomarkers, 
autoantibody concentrations in serum/plasma) 
at all scheduled time points.
•
Absolute values and change from baseline in 
the values of the PhGA, VAS at all scheduled 
time points.
•
Absolute values and change from baseline in 
the values of PROs including the Patient 
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•
To estimate the effects of PF-06823859 on 
patient-reported outcomes (PROs) over time
across Stage 1 and Stage 2.
•
To estimate the effects of PF-06823859 on 
CDASI sub-scores across Stage 1 and Stage 2.
Global Assessment (PtGA), the Health 
Assessment Questionnaire – Disability Index 
(HAQ-DI), the 5-D Pruritus Scale, 
 
, the 
Short Form (SF-36 v2 Acute), the 
Dermatology and Life Quality Index (DLQI)
and the European Quality of Life Five
Dimension, Five Level Scale (EQ-5D-5L) & 
EQ Visual Analogue Scale (EQ-VAS) at all 
scheduled time points. 
•
Absolute values and change from baseline 
values of the sub-scores of CDASI activity and 
CDASI damage scores at all scheduled time 
points. 
 
 
 
 
 
 
 
 
 
 
 
2.4. Stage 3, Objectives and Endpoints
Primary Objective(s):
Primary Endpoint(s):
•
To evaluate the safety and tolerability of 
PF-06823859 in adult DM participants with 
moderate to severe active muscle disease.
•
Incidence of adverse events (AEs) laboratory 
abnormalities, changes in vital signs, and 
electrocardiogram (ECG) findings.
Secondary Objective(s):
Secondary Endpoint(s):
•
To evaluate the efficacy of PF-06823859 over 
time in adult DM participants with moderate
active muscle disease.
•
Total Improvement Score (TIS) at Week 12 and 
intermediate scheduled time points.
•
Change from baseline in the core Set Measures 
(CSM) of the TIS including PGA, PtGA, MMT, 
HAQ-DI, muscle enzymes, and extra-muscular 
activity, (MDAAT).
•
Absolute values and change from baseline of 
CDASI activity and CDASI damage scores at 
all scheduled time points. 
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Exploratory Objectives (s)
Exploratory Endpoints(s)
•
To characterize PK of PF-06823859 in adult DM 
participants with active muscle disease. 
•
To characterize the PD of PF-06823859 in adult 
DM participants with active muscle disease.
•
To estimate the effects of PF-06823859 on the 
physician global assessment (PhGA, VAS) over 
time.
•
To estimate the effects of PF-06823859 on 
patient-reported outcomes (PROs) over time.
 
 
•
Plasma concentrations of PF-06823859.
•
Absolute values and change from baseline in 
the values of selected biomarkers (Gene 
signature panel in blood; Human Myxovirus A 
(MXA), interferon gamma-induced protein 10 
(IP-10), 
 highly sensitive C-reactive 
protein, (hsCRP), muscle and bone blood 
biomarkers, autoantibody concentrations in 
serum/plasma) at all scheduled time points.
•
Absolute values and change from baseline in 
the values of the PhGA, VAS at all scheduled 
time points.
•
Absolute values and change from baseline in 
the values of PROs including the Patient Global 
Assessment (PtGA), the Health Assessment 
Questionnaire – Disability Index (HAQ-DI), the 
5-D Pruritus Scale, 
 
 
the Functional 
Assessment of Chronic Illness Therapy –
Fatigue (FACIT-F), the Short Form (SF-36 v2
Acute), and the European Quality of Life Five 
Dimension, Five Level Scale (EQ-5D-5L) & 
EQ Visual Analogue Scale (EQ-VAS) at all 
scheduled time points. 
 
 
 
 
 
 
 
 
 
 
 
 
 
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3. STUDY DESIGN
3.1. Study Overview
Stage 1 was a multi-center Phase 2A study planned to be conducted in approximately 
30 adult participants with moderate to severe DM.  Thirty two participants were randomized 
in order to collect data from 24 participants who completed the study.  Each participant was 
to take part in the study for a period of approximately 9 months.  After the 35 day screening 
period, participants who were eligible enrolled into the study and were randomized in a 
blinded manner, 2:1 (Active:Placebo) ratio.  Investigational drug or placebo administration 
took place on Day 1, Week 4 and Week 8 of the study.  Participants then entered a 5-month 
follow-up period. 
In Stage 2, with the addition of 1 lower dose arm, this study then became a
 
 
Participants will receive study drug, (active or placebo) on 
Day 1, Week 4, (Visit 4), and Week 8, (Visit 5).  At Week 12, (Visit 6) is the scheduled 
primary endpoint of the study.  
The study was further amended, and Stage 2 became “Amended Stage 2” changing the study
to a fixed sequence design. In this design participants will be randomized to a treatment 
sequence at Day 1. The treatment sequence (Active -> Placebo or Placebo ->Active) will 
dictate whether the participant will receive active study drug during Day 1 to Week 12 or 
active study drug during Week 12 to Week 20. Although dosing is completed at Week 20, 
the treatment period goes through to Week 24. There is no washout in between the dose 
changes (Day 1 to Week 12 and Week 12 to Week 20) for this design. Another key feature is 
that this design will allow placebo subjects to receive active treatment at some timepoint 
during the study. No re-randomization will occur at Week 12.  Participants who start the 
study on active study drug
will have a prespecified dose change to 
placebo at Week 12, and participants who are on placebo will have a prespecified dose 
change to active study drug at Week 12.  The placebo participants will receive prespecified
doses of either 
, in order to maintain equal distribution of these doses.
There will be no unblinding or interruption of dosing during the treatment period.  Each 
participant will receive 3 consecutive doses of active study drug and 3 consecutive doses of 
placebo during the trial. The dose change between active and placebo in this fixed sequence 
design will provide each participant 12 weeks of active drug.  The participant, study doctor, 
or sponsor will not know what the participant is assigned to during the treatment period. The 
end of the treatment period is at Week 24, although the last dose is administered at the 
Week 20 visit (Visit 8).  All participants will then enter a 4 month follow-up period (the 
interval between the last dose and the end of the follow-up period is 5 months). 
Participants who entered Stage 2 prior to Amendment 4 will follow the design and SoA of 
Amendment 3, which is Stage 2. Statistical analyses including Stage 2 endpoints will 
involve data from the original Stage 2 of Amendment 3 and the Amended Stage 2 of
Amendment 4, as appropriate.
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In Amendment 4, an additional DM cohort of 8 to 16 participants with active moderate 
muscle involvement (MMT-8 ≤136/150) will be enrolled. This cohort is referred to as 
Stage 3. Participants in this cohort are allowed to have any amount of skin involvement, as
no specific CDASI score is required. All participants who meet eligibility criteria for 
(Stage 3) will be randomized to receive either PF-06823859 600 mg active study drug or 
placebo. This study design is similar to the Amended Stage 2 as all participants will receive 
their dosing assignment at Day 1 in a fixed sequence manner for the duration of the treatment 
period. The treatment period will consist of 6 dosing’s occurring at Day 1, Week 4, (Visit 4), 
Week 8, (Visit 5), Week 12 (Visit 6), Week 16 (Visit 7), and Week 20, (Visit 8).  Each 
participant will receive 3 consecutive doses of active study drug and 3 consecutive doses of 
placebo. At Week 12 (Visit 6), participants will be switched to the opposite treatment arm 
from what they were randomly assigned to at Day 1, Week 4 and Week 8. The  study design 
permits all participants to receive active study drug in a blinded manner. The dose change 
between active and placebo will provide each participant 12 weeks of active drug.  The end 
of the treatment period is at Week 24, although the last dose is administered at the Week 20 
visit (Visit 8).  All participants will then enter a 4 month follow-up period (the interval 
between the last dose and the end of the follow-up period is 5 months). 
If a participant meets eligibility criteria for both Amended Stage 2 and Stage 3, the 
participant will be enrolled in Stage 3 unless the enrollment maximum for Stage 3 has been 
reached, at which point the participant would enroll in the Amended Stage 2.
Amendment 5 contained updates specific to Germany only. Germany is following the 
contraceptive guidelines related to CTFG guidelines, see Appendix 24.
Amendment 6; participants currently active in the C0251002 study at the time the open label 
extension study (C0251008) is approved, will have the opportunity to receive 24 additional 
weeks of treatment.  Study participants will be eligible if they have completed the treatment 
period up through and including Visit 9, Week 24 and have not had any significant protocol 
deviations, or safety events. The participant can also select to continue into the follow up 
period of the C0251002 study for completion instead of enrolling into open label extension 
C0251008.  
The overall duration of the C0251002 study will be approximately 69 months from first 
subject first visit, (FSFV) to last subject last visit, (LSLV) and will be conducted at 
approximately 35-40 investigative sites. Overall, approximately 76 participants will be 
randomized into this study.


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Figure 1.
Study C0251002 Design PF-06823859 (Stage 1)
* Stage 1, study randomized 32 participants.
Figure 2.
Study C0251002 Design PF-06823859 Stage 2


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Figure 3.
Study C0251002 Design PF-06823859 Amended Stage 2


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Figure 4.
Study C0251002 Design PF-06823859 Stage 3


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Figure 5.
Amended Stage 2 with the Option of Going into the OLE Study


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Figure 6.
Stage 3 with the Option of Going into the OLE Study
4. PARTICIPANT ELIGIBILITY 
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.
Participant eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before participants are included in the study. 
4.1. Inclusion Criteria, Stage 1 and Stage 2
Participants must meet all of the following inclusion criteria to be eligible for enrollment into 
the study:
1. Evidence of a personally signed and dated informed consent document indicating that 
the participant has been informed of all pertinent aspects of the study. 
2. Male and or female participants between the ages of ≥18 and ≤80 years old at the 
time of signing the informed consent.


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3. Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) Activity
Score, v2-a (See Appendix 2) (Activity ≥14, and have failed at least 1 standard of 
care systemic treatment, (eg, corticosteroids).
4. Confirmation of DM by the investigator and two of the following:
a.
Gottron’s papules;
b. Gottron’s sign;
c.
Heliotrope eruption;
d. Nailfold changes, (dilated capillary loops, capillary dropout, cuticular 
hypertrophy and/or rugged cuticles;
e.
Photo distributed violaceous erythema, (skin that is exposed to sunlight and 
appears purplish/reddish, and patchy in appearance;
f.
Positive DM serology (eg, anti-transcriptional intermediary 
factor-1(TIF1-gamma), Nuclear matrix protein 2 (NXP2), 
Nucleosome-remodelling deacetyalse complex, (Mi2), Melanoma 
differentiation-associated gene 5, (MDA5), Small ubiquitin-like modifier 
activating enzyme ½, (SAE ½), or anti-tRNA synthetase).
Note: Concurrent myositis or a history of myositis that is in remission is permitted
5. Participant has had a standard work up for dermatomyositis (prior to) baseline.
a.
Stable interstitial lung disease related to DM that is not severe in the opinion of 
the investigator is allowed, ie, no supplemental oxygen permitted.
b. If their DM diagnosis is within 2 years of the screening visit, then they must have 
completed either:

Age appropriate malignancy screening eg, computerized tomography, (CT) of 
the chest/abdomen/pelvis if indicated; 
or

PET CT of chest/abdomen/pelvis at least once by the baseline visit.
6. Willing to provide 6 skin punch biopsies; (4) skin punch biopsies at pre-dose Day 1, 
Visit 2, and (2) skin punch biopsies at Week 12. 
7. Male participants able to father children and female participants of childbearing 
potential must agree to adhere to the methods of contraception listed in Appendix 25
throughout the duration of the study, including the follow-up period until the end of 
study.


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
Participants in Germany: Please refer to guidelines for Contraceptive, located in 
Appendix 24.
8. Female participants of non-childbearing potential must meet at least 1 of the 
following criteria:
a.
Achieved postmenopausal status, defined as follows: cessation of regular menses 
for at least 12 consecutive months with no alternative pathological or 
physiological cause; status may be confirmed with a serum follicle-stimulating 
hormone (FSH) level confirming the postmenopausal state;
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy; 
c.
Have medically confirmed ovarian failure. 
All other female participants (including female participants with tubal ligations) are 
considered to be of childbearing potential. 
9. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and 
other study procedures.
4.2. Exclusion Criteria, Stage 1 and Stage 2
Participants with any of the following characteristics/conditions will not be included in the 
study:
1. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or 
participants who are Pfizer employees, including their family members, directly 
involved in the conduct of the study.
2. Other acute or chronic medical or psychiatric condition including recent (within the 
past year) or active suicidal ideation or behavior or laboratory abnormality that may 
increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the participant inappropriate for entry into 
this study.
3. Any psychiatric condition including recent or active suicidal ideation or behavior that 
meets any of the following criteria:

Clinically significant depression by Patient Health Questionnaire 8- item 
depression measure (PHQ-8) total score ≥15 (Appendix 4) (completed during the 
screening visit).


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•
Suicidal ideation associated with actual intent and a method or plan in the past 
year: “Yes” answers on items 4 or 5 of
 
.
•
Previous history of suicidal behaviors in the past 5 years: “Yes” answer
 
 
•
Any lifetime history of serious or recurrent suicidal behavior.
•
The presence of any current major psychiatric disorder that is not explicitly 
permitted in the inclusion/exclusion criteria.
•
In the opinion of the investigator, exclusion is required.
4. Intake of >15 mg oral prednisone/day, or equivalent.
5. Drug induced myopathy, metabolic myopathy, muscular dystrophy, cancer associated 
DM, mixed connective tissue disease-associated DM, (eg, overlap syndrome).
6. Significant concurrent disease or conditions other than DM that may influence 
response to the study drug or safety.
7. Abnormal labs:
•
Hemoglobin <10 g/dL;
•
Neutrophils <1.0 x 109/L;
•
Lymphocytes <500 cells/uL;
•
Platelets <75 x 109/L;
•
Creatinine clearance <60 ml/min according to modified Cockcroft-Gault equation;
•
Alkaline phosphatase >2.5 x upper normal limit;
•
Total bilirubin ≥1.5 x upper limit of normal.
Note: Elevation of aspartate aminotransferase (AST), alanine aminotransferase
(ALT), lactate dehydrogenase (LDH) , creatinine kinase (CK) or aldolase
due to muscle involvement (in the opinion of the investigator) are allowed if 
gamma glutamyl transferase, GGT <1.5 upper limit normal.
CCI
CCI


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Note: Screening laboratory tests with abnormal results may be repeated once to 
confirm abnormal results within the 5-week screening period.  If results 
return to normal within the 5-week screening period, the participant may 
enter the study. 
8. Participation in other studies involving investigational drug(s) within 30 days prior to 
study entry.  For biologics, 5 half-lives or 180 days preceding the first dose of the 
investigational product (whichever is longer).  This applies prior to study entry and/or 
during study participation. 
9. Pregnant female participants; breastfeeding female participants; fertile male
participants and female participants of childbearing potential who are unwilling or 
unable to adhere to the methods of contraception listed in Appendix 25 for the 
duration of the study and for 5 months after the after the last dose of investigational 
product. 

Participants in Germany: please see guidelines for Contraception Methods in
Appendix 24.
10. Have received the following within 180 days of Day 1:

A biologic investigational agent.  An investigational agent is defined as any drug 
not approved for sale in the country in which it is being used.

IV or oral cyclophosphamide, belimumab or any anti-B-Lymphocyte Stimulator 
(anti-BLyS or anti-B-cell activating factor [anti-BAFF] agent). 

Required 3 or more courses of systemic corticosteroids for concomitant 
conditions (eg, asthma, Crohn’s disease, ulcerative colitis, systemic vasculitis, 
atopic dermatitis). 
11. Have received the following within 90 days of Day 1:

Anti-TNF therapy (eg, infliximab, etanercept, adalimumab).

High dose oral corticosteroids (>100 mg/day prednisone or equivalent) or pulse 
IV doses.

Plasmapheresis.
12. Have received the following within 60 days of Day 1:

Any intra muscular (IM) or IV steroid injection.

Tofacitinib or any other Janus kinase (JAK) inhibitors.


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
Any change in dose of an immunosuppressive/immunomodulatory or antimalarial 
agent. Dose must be stable for 60 days prior to Day 1 and remain stable through 
Week 12.

Inhaled immunosuppressive agents can be used during the study however must be 
on a stable dose 60 days prior to Day 1 and remain stable through Week 12.
(Immunosuppressive ophthalmic drops are allowed without any restrictions). 

Disease -modifying antirheumatic drugs (DMARD)s, (methotrexate, 
sulfasalazine, hydroxychloroquine, and leflunomide). Less frequently used 
medications include gold salts, azathioprine, and cyclosporine.  Dose must be 
stable for 60 days prior to Day 1 and remain stable through Week 12.

Participants may be on one of the following cytotoxic agents: methotrexate, 
azathioprine, leflunomide, mycophenolate, or 6 MP, but not on any combination 
of these cytotoxic agents. 
Use of IV or IM antibacterials, antivirals, antifungals, or anti-parasitic agents within 60 days
of Day 1.  Substitution of IM agents for oral agents because of gastro intestinal, (GI)
intolerance may be acceptable, as long as it does not otherwise meet the criteria for a serious 
infection (requires hospitalization or use of other IV antibiotics) (See exclusion #24).
13. Have received within 6 weeks of Day 1:

A live (live attenuated) vaccine.
14. Have received any of the following within 30 days of Day 1:

Any intra-articular steroid injection.

Any new, or change in dose of a corticosteroid or equivalent.

Any new, or change in dose of intravenous immunoglobulin (IVIG); (Must be on 
a stable dose for 30 days).

Oral tacrolimus.
15. Have received any of the following within 14 days prior to Day 1:

Stable dose of topical immunosuppressants of any strength used on the scalp is 
permitted throughout the study (With the exception of topical calcineurin 
inhibitors).

Use of oral antibiotics to treat an active infection within 14 days of Day 1.

Topical calcineurin inhibitors.


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16. Have been treated with any B-cell depleting agents such as rituximab (or other 
CD20+ directed therapies, or epratuzumab, or anti-CD52 [alemtuzumab]), or
Transmembrane Activator and CAML Interactor (TACI)-Ig, within 12 months prior 
to Day 1.  In addition, participants that have been treated with rituximab, or TACI-Ig, 
serum total immunoglobulins should be checked prior to study entry.
17. Have a history of a major organ transplant (eg, heart, lung, kidney, liver) or 
hematopoietic stem cell/marrow transplant.
18. Active bacterial, viral, fungal, mycobacterial or other infections (including but not 
limited to tuberculosis [TB] and atypical mycobacterial disease, granulomatous 
disease on chest x-ray).  History of recurrent bacterial, viral, fungal, mycobacterial or 
other infections (including but not limited to TB and atypical mycobacterial disease, 
granulomatous disease on chest x-ray) that would substantially increase the risk to the 
participant if he or she participates in the study.
19. Have clinically significant finding on a chest radiograph (or other appropriate 
diagnostic imaging study previously completed within 12 weeks prior to Day 1 such 
as computed tomography [CT] or magnetic resonance imaging [MRI]) such as the 
presence of TB, general infection, heart failure or malignancy.  Chest imaging must 
be performed during the 5-week screening period or if diagnostic imaging was 
previously completed within 12 weeks prior to Day 1.
20. Infected with Mycobacterium tuberculosis (TB) as defined by any of the following:
A positive Interferon Gamma Release Assay (IGRA) test performed at or within the 
12 weeks prior to Day 1 is exclusionary; a negative test is required for eligibility.  
The following are acceptable IGRA assays: QuantiFERON® TB Gold In-Tube test 
(QFT-GIT) and QuantiFERON® - TB Gold test (QFT-G), and T-spot® TB test.  If 
T-spot® TB test was completed within 12 weeks prior to Day 1, this is acceptable, 
however this test type cannot be offered for participants requiring the test during 
screening, or at any time during the study. 

In participants with a history of Bacillus Calmette-Guérin (BCG) vaccination, the 
IGRA test is strongly recommended since the Mantoux test (tuberculin, purified 
protein derivative [PPD] skin test) may be positive due to vaccination.

If the results of the IGRA are indeterminate, the test may be repeated, and if a 
negative result is obtained, enrollment may proceed.  A positive test on repeat is 
exclusionary.

Participants with repeat indeterminate IGRA results may be enrolled after 
consultation with an infectious disease and/or pulmonary specialist who 
determines that the risk of infection is low (ie, participant would be acceptable for 
immunosuppressant treatment without additional action).


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
Participants who test positive for IGRA, but in the opinion of the principal 
investigator (PI) are at low risk of TB infection, may be referred to an infectious 
disease and/or pulmonary specialist for consultation and potential IGRA test 
repeated once.  Participants will be eligible if the repeat test is negative before the 
randomization and an infectious disease and/or pulmonary specialist determines 
that the risk of infection is low (ie, participant would be acceptable for 
immunosuppressant treatment without additional action).

Chest radiograph taken at screening with changes suggestive of active TB 
infection, unless previously performed and documented within 12 weeks prior to 
Day 1.

A participant who has been treated or is currently being treated for active or latent 
TB infection is to be excluded.

A participant with a history of either untreated or inadequately treated latent or 
active TB infection is to be excluded.
21. Have a history of any lymphoproliferative disorder such as Epstein Barr Virus (EBV) 
related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and 
symptoms suggestive of current lymphatic or lymphoid disease.
22. Have a history (single episode) of disseminated herpes zoster or disseminated herpes 
simplex, or recurrent (more than 1 episode of) localized, dermatomal herpes zoster.
23. Known history of the following viruses:

Human immunodeficiency (HIV) based on documented history with positive 
serological test, or positive HIV serological test at screening. 
Note: a documented negative HIV test within 3 months of screening is acceptable 
and does not need to be repeated. 

Have positive test for hepatitis B surface antigen (HBsAg), total hepatitis B core 
antibody (anti-HBcAb; also called anti-HBc), hepatitis B surface antibody 
(HBsAb), and/or HCV Ab. 

All participants will be screened for HBsAg and HBcAb; participants who are 
HBsAg positive will be screen-failed.  Participants who are HBsAg negative but 
HBcAb positive will be reflex-tested for HBsAb and, if HBsAb positive, may 
enroll; if hepatitis B surface antibody test, (HBsAb) negative, they will be 
screen-failed. Participants who are positive for HCV Ab will be screen-failed.


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24. Have required management of acute or chronic infections as follows:

Currently on any suppressive therapy for a chronic infection (such as 
pneumocystis, cytomegalovirus [CMV], and atypical mycobacteria) that, in the 
opinion of the investigator and sponsor, would place the participant at risk for 
reactivation.  Participants receiving prophylactic therapy for prior outbreaks of 
herpes simplex virus or herpes zoster may be enrolled with the expectation that 
this treatment will continue for the duration of the study.

Hospitalization for treatment of serious infections within 60 days of Day 1, see 
exclusion (#12).
25. Have acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) 
or any history of significant cerebrovascular disease within 24 weeks of screening.  A 
screening 12-lead electrocardiogram (ECG) that demonstrates clinically significant 
abnormalities requiring treatment (eg, acute myocardial infarction, serious tachy- or 
brady- arrhythmias) or that is indicative of serious underlying heart disease 
(eg, cardiomyopathy, major congenital heart disease, low voltage in all leads, 
Wolff-Parkinson-White syndrome).
26. Have cancer or a history of cancer within 5 years of screening (other than adequately 
treated cutaneous basal cell, squamous cell carcinoma, or carcinoma in situ of the 
uterine cervix with no evidence of recurrence within the previous 5 years).
27. Have pre-existing demyelinating disorder such as multiple sclerosis, or other severe 
neurological deficits.
28. Have current alcohol and/or drug abuse, or a history of, in the past 2 years which, in 
the opinion of the investigator, could create a risk for the participant’s health or 
protocol adherence.
29. Have had major surgery within 4 weeks of screening, or scheduled to occur during 
the study, excluding diagnostic surgery.
30. Previous treatment with total lymphoid irradiation.
31. Grade 3 or greater laboratory abnormality based on the Common Terminology 
Criteria for Adverse Events (CTCAE) v 4.03 (Appendix 14) except the following that 
are allowed: Participants with abnormal aspartate aminotransferase (AST), alanine 
aminotransferase (ALT), lactate dehydrogenase (LDH), aldolase, and CK lab values 
if these values are determined by the investigator to be related to muscle involvement, 
and if glutamyl transferase (GGT) <1.5 upper limit normal.
32. Known exposure to anti-beta Interferon, (PF-06823859) or any type of anti-beta 
interferon therapy.


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4.3. Inclusion Criteria, Amended Stage 2 
If a participant meets eligibility for both the Stage 2, (skin focused cohort) and the Stage 3, 
(muscle disease cohort) the patient should be placed in the Stage 3 muscle disease cohort.
All inclusion criteria is the same as Stage 1 and Stage 2 with the exception to Inclusion 
Criteria #6.
6. Willing to provide at least (8) vs. 6 skin punch biopsies; (4) skin punch biopsies at 
pre-dose Day 1 Visit 2, (2) skin punch biopsies at Week 12, Visit 6 and (2) skin 
punch biopsies at Week 24 Visit 9.
4.4. Exclusion Criteria, Amended Stage 2
All exclusion criteria is the same as Stage 1 and Stage 2 with the exception of Exclusion 
Criterion #7 Abnormal labs and Exclusion Criterion #12 related to stable dosing of 
concomitant medications:
Exclusion Criterion #7:

Hemoglobin <9 g/dL;

Creatinine clearance <50 mL/min according to modified Cockcroft-Gault equation.
Exclusion Criterion #12: 

Any change in dose of an immunosuppressive/immunomodulatory or antimalarial 
agent. Dose must be stable for 60 days prior to Day 1 and remain stable through 
Week 24.

Inhaled immunosuppressive agents can be used during the study however must be on 
a stable dose 60 days prior to Day 1 and remain stable through Week 24.
(Immunosuppressive ophthalmic drops are allowed without any restrictions). 

Disease -modifying antirheumatic drugs (DMARD)s, (methotrexate, sulfasalazine, 
hydroxychloroquine, and leflunomide).  Less frequently used medications include 
gold salts, azathioprine, and cyclosporine.  Dose must be stable for 60 days prior to 
Day 1 and remain stable through Week 24.
4.5. Inclusion Criteria, Stage 3
1. Evidence of a personally signed and dated informed consent document indicating that 
the participant has been informed of all pertinent aspects of the study. 
2. Male and or female participants between the ages of ≥18 and ≤80 years old at the 
time of signing the informed consent.
3. Meets one of the following two criteria:


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
MMT-8 ≤136/150 and PhGA, VAS ≥3 cm (0-10 cm) by visual analog scale 
(VAS) (Appendix 21).

Sum of PhGA, VAS, PtGA, and extramuscular global assessment VAS scores
(Appendix 20) is ≥10 cm (0-10 cm) VAS for each).
4. Participant has failed at least two or more adequate courses of an immunosuppressive 
agent or immunomodulatory agent, including IVIG, at a dose known to be effective 
for rheumatologic diseases.
5. Participant has had a standard work up for dermatomyositis (prior to) baseline. 
a.
Stable interstitial lung disease related to DM that is not severe in the opinion of 
the investigator is allowed, ie, no supplemental oxygen permitted.
b. If their DM diagnosis is within 2 years of the screening visit, then they must have 
completed either:

Age appropriate malignancy screening eg, computerized tomography, (CT) of 
the chest/abdomen/pelvis if indicated;
or

PET CT of chest/abdomen/pelvis at least once by the baseline visit.
6. Male participants able to father children and female participants of childbearing 
potential must agree to adhere to the methods of contraception. See Appendix 25
throughout the duration of the study, including the follow-up period until the end of 
study.

Participants in Germany: please see guidelines for Contraception Methods in 
Appendix 24.
7. Female participants of non-childbearing potential must meet at least 1 of the 
following criteria:
a.
Achieved postmenopausal status, defined as follows: cessation of regular menses 
for at least 12 consecutive months with no alternative pathological or 
physiological cause; status may be confirmed with a serum follicle-stimulating 
hormone (FSH) level confirming the postmenopausal state.
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy.
c.
Have medically confirmed ovarian failure. 
d. All other female participants (including female participants with tubal ligations) 
are considered to be of childbearing potential. 


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8. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and 
other study procedures.
4.6. Exclusion Criteria, Stage 3
1. Investigator site staff members directly involved in the conduct of the study and their 
family members, site staff members otherwise supervised by the investigator, or 
participants who are Pfizer employees, including their family members, directly 
involved in the conduct of the study.
2. Other acute or chronic medical or psychiatric condition including recent (within the 
past year) or active suicidal ideation or behavior or laboratory abnormality that may 
increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the participant inappropriate for entry into 
this study.
3. Any psychiatric condition including recent or active suicidal ideation or behavior that 
meets any of the following criteria:

Clinically significant depression by Patient Health Questionnaire 8- item 
depression measure (PHQ-8) total score ≥15 (Appendix 4) (completed during the 
screening visit).

Suicidal ideation associated with actual intent and a method or plan in the past 
year: “Yes” answers on items 4 or 5 of Columbia-Suicide Severity Rating Scale 
during the conduct of the study (C-SSRS; Appendix 5) (completed prior to Day 1 
Dosing).

Previous history of suicidal behaviors in the past 5 years: “Yes” answer (for 
events that occurred in the past 5 years) to any of the suicidal behavior items of 
the C-SSRS; Appendix 6).

Any lifetime history of serious or recurrent suicidal behavior.

The presence of any current major psychiatric disorder that is not explicitly 
permitted in the inclusion/exclusion criteria.

In the opinion of the investigator, exclusion is required.
4. Intake of >20 mg oral prednisone/day, or equivalent.
5. Drug induced myopathy, metabolic myopathy, muscular dystrophy, cancer associated 
DM, mixed connective tissue disease-associated DM, (eg, overlap syndrome) and 
polymyositis. 


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6. Significant concurrent disease or conditions other than DM that may influence 
response to the study drug or safety. 
7. Abnormal labs:

Hemoglobin <9 g/dL;

Neutrophils <1.0 x 109/L;

Lymphocytes <500 cells/uL;

Platelets <75 x 109/L;

Creatinine clearance <50 ml/min according to modified Cockcroft-Gault equation;

Alkaline phosphatase >2.5 x upper normal limit; 

Total bilirubin ≥1.5 x upper limit of normal.
Note: Elevation of aspartate aminotransferase (AST), alanine aminotransferase
(ALT), lactate dehydrogenase (LDH), creatinine kinase (CK) or aldolase 
due to muscle involvement (in the opinion of the investigator) are allowed if 
gamma glutamyl transferase, GGT <1.5 upper limit normal.
Note: Screening laboratory tests with abnormal results may be repeated once to 
confirm abnormal results within the 5-week screening period.  If results 
return to normal within the 5-week screening period, the participant may 
enter the study. 
8. Participation in other studies involving investigational drug(s) within 30 days prior to 
study entry.  For biologics, 5 half-lives or 180 days preceding the first dose of the 
investigational product (whichever is longer).  This applies prior to study entry and/or 
during study participation. 
9. Pregnant female participants; breastfeeding female participants; fertile male 
participants and female participants of childbearing potential who are unwilling or 
unable to adhere to the methods of contraception. See Appendix 25 as outlined in this 
protocol for the duration of the study and for 5 months after the after the last dose of 
investigational product. 
10. Have received the following within 180 days of Day 1: (See Appendix 15 and 
Appendix 16).

A biologic investigational agent.  An investigational agent is defined as any drug 
not approved for sale in the country in which it is being used.


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
IV or oral cyclophosphamide, belimumab or any anti-B-Lymphocyte Stimulator 
(anti-BLyS or anti-B-cell activating factor [anti-BAFF] agent). 

Required 3 or more courses of systemic corticosteroids for concomitant 
conditions (eg, asthma, Crohn’s disease, ulcerative colitis, systemic vasculitis, 
atopic dermatitis). 
11. Have received the following within 90 days of Day 1: (See Appendix 15 and 
Appendix 16).

Anti-TNF therapy (eg, infliximab, etanercept, adalimumab).

High dose oral corticosteroids (>100 mg/day prednisone or equivalent) or pulse 
IV doses. 

Plasmapheresis.
12. Have received the following within 60 days of Day 1: (See Appendix 15 and 
Appendix 16).

Any intra muscular (IM) or IV steroid injection. (same as above).

Tofacitinib or any other Janus kinase (JAK) inhibitors.

Any change in dose of an immunosuppressive/immunomodulatory or antimalarial 
agent.  Dose must be stable for 60 days prior to Day 1 and remain stable through 
Week 24.

Inhaled immunosuppressive agents can be used during the study for ILD related 
to DM; however, must be on a stable dose 60 days prior to Day 1 and remain 
stable through Week 24.  (Immunosuppressive ophthalmic drops are allowed 
without any restrictions). 

Disease -modifying antirheumatic drugs (DMARD)s, (methotrexate, 
sulfasalazine, hydroxychloroquine, and leflunomide).  Less frequently used 
medications include gold salts, azathioprine, and cyclosporine.  Dose must be 
stable for 60 days prior to Day 1 and remain stable through Week 24.

Participants may be on one of the following cytotoxic agents: methotrexate, 
azathioprine, leflunomide, mycophenolate, or 6 MP, but not on any combination 
of these cytotoxic agents. 
Use of IV or IM antibacterials, antivirals, antifungals, or anti-parasitic agents within 60 days 
of Day 1.  Substitution of IM agents for oral agents because of gastro intestinal, (GI) 
intolerance may be acceptable, as long as it does not otherwise meet the criteria for a serious 
infection (requires hospitalization or use of other IV antibiotics) (See exclusion #24).


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13. Have received within 6 weeks of Day 1: (See Appendix 15 and Appendix 16).

A live (live attenuated) vaccine.
14. Have received any of the following within 30 days of Day 1: (See Appendix 15 and 
Appendix 16).

Any intra-articular steroid injection.

Any new, or change in dose of a corticosteroid or equivalent.

Any new, or change in dose of intravenous immunoglobulin (IVIG); (Must be on 
a stable dose for 30 days).

Oral tacrolimus.
15. Have received any of the following within 14 days prior to Day 1: (See Appendix 15
and Appendix 16).

Use of oral antibiotics to treat an active infection within 14 days of Day 1.

Topical calcineurin inhibitors.
16. Have been treated with any B-cell depleting agents such as rituximab (or other 
CD20+ directed therapies, or epratuzumab, or anti-CD52 [alemtuzumab]), or 
Transmembrane Activator and CAML Interactor (TACI)-Ig, within 12 months prior 
to Day 1. In addition, participants that have been treated with rituximab, or TACI-Ig, 
serum total immunoglobulin should be checked prior to study entry.
17. Have a history of a major organ transplant (eg, heart, lung, kidney, liver) or 
hematopoietic stem cell/marrow transplant.
18. Active bacterial, viral, fungal, mycobacterial or other infections (including but not 
limited to tuberculosis [TB] and atypical mycobacterial disease, granulomatous 
disease on chest x-ray).  History of recurrent bacterial, viral, fungal, mycobacterial or 
other infections (including but not limited to TB and atypical mycobacterial disease, 
granulomatous disease on chest x-ray) that would substantially increase the risk to the 
participant if he or she participates in the study.
19. Have clinically significant finding on a chest radiograph (or other appropriate 
diagnostic imaging study previously completed within 12 weeks prior to Day 1 such 
as computed tomography [CT] or magnetic resonance imaging [MRI]) such as the 
presence of TB, general infection, heart failure or malignancy.  Chest imaging must 
be performed during the 5-week screening period or if diagnostic imaging was 
previously completed within 12 weeks prior to Day 1.


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20. Infected with Mycobacterium tuberculosis (TB) as defined by any of the following:
A positive Interferon Gamma Release Assay (IGRA) test performed at or within the 
12 weeks prior to Day 1 is exclusionary; a negative test is required for eligibility.  
The following are acceptable IGRA assays: QuantiFERON® TB Gold In-Tube test 
(QFT-GIT) and QuantiFERON® - TB Gold test (QFT-G), and T-spot® TB test.  If 
T-spot® TB test was completed within 12 weeks prior to Day 1, this is acceptable, 
however this test type cannot be offered for participants requiring the test during 
screening, or at any time during the study. 

In participants with a history of Bacillus Calmette-Guérin (BCG) vaccination, the 
IGRA test is strongly recommended since the Mantoux test (tuberculin, purified 
protein derivative [PPD] skin test) may be positive due to vaccination.

If the results of the IGRA are indeterminate, the test may be repeated, and if a 
negative result is obtained, enrollment may proceed.  A positive test on repeat is 
exclusionary.

Participants with repeat indeterminate IGRA results may be enrolled after 
consultation with an infectious disease and/or pulmonary specialist who 
determines that the risk of infection is low (ie, participant would be acceptable for 
immunosuppressant treatment without additional action).

Participants who test positive for IGRA, but in the opinion of the principal 
investigator (PI) are at low risk of TB infection, may be referred to an infectious 
disease and/or pulmonary specialist for consultation and potential IGRA test 
repeated once.  Participants will be eligible if the repeat test is negative before the 
randomization and an infectious disease and/or pulmonary specialist determines 
that the risk of infection is low (ie, participant would be acceptable for 
immunosuppressant treatment without additional action).

Chest radiograph taken at screening with changes suggestive of active TB 
infection, unless previously performed and documented within 12 weeks prior to 
Day 1.

A participant who has been treated or is currently being treated for active or latent 
TB infection is to be excluded.

A participant with a history of either untreated or inadequately treated latent or 
active TB infection is to be excluded.
21. Have a history of any lymphoproliferative disorder such as Epstein Barr Virus (EBV) 
related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and 
symptoms suggestive of current lymphatic or lymphoid disease.


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22. Have a history (single episode) of disseminated herpes zoster or disseminated herpes 
simplex, or recurrent (more than 1 episode of) localized, dermatomal herpes zoster.
23. Known history of the following viruses:

Human immunodeficiency (HIV) based on documented history with positive 
serological test, or positive HIV serological test at screening. 
Note: a documented negative HIV test within 3 months of screening is acceptable 
and does not need to be repeated. 

Have positive test for hepatitis B surface antigen (HBsAg), total hepatitis B core 
antibody (anti-HBcAb; also called anti-HBc), hepatitis B surface antibody 
(HBsAb), and/or HCV Ab. 

All participants will be screened for HBsAg and HBcAb; participants who are 
HBsAg positive will be screen-failed.  Participants who are HBsAg negative but 
HBcAb positive will be reflex-tested for HBsAb and, if HBsAb positive, may 
enroll; if hepatitis B surface antibody test, (HBsAb) negative, they will be 
screen-failed. Participants who are positive for HCV Ab will be screen-failed.
24. Have required management of acute or chronic infections as follows:

Currently on any suppressive therapy for a chronic infection (such as 
pneumocystis, cytomegalovirus [CMV], and atypical mycobacteria) that, in the 
opinion of the investigator and sponsor, would place the participant at risk for 
reactivation.  Participants receiving prophylactic therapy for prior outbreaks of 
herpes simplex virus or herpes zoster may be enrolled with the expectation that 
this treatment will continue for the duration of the study.

Hospitalization for treatment of serious infections within 60 days of Day 1, see 
exclusion (#12).
25. Have acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) 
or any history of significant cerebrovascular disease within 24 weeks of screening.  A 
screening 12-lead electrocardiogram (ECG) that demonstrates clinically significant 
abnormalities requiring treatment (eg, acute myocardial infarction, serious tachy- or 
brady- arrhythmias) or that is indicative of serious underlying heart disease 
(eg, cardiomyopathy, major congenital heart disease, low voltage in all leads, 
Wolff-Parkinson-White syndrome).
26. Have cancer or a history of cancer within 5 years of screening (other than adequately 
treated cutaneous basal cell, squamous cell carcinoma, or carcinoma in situ of the 
uterine cervix with no evidence of recurrence within the previous 5 years).
27. Have pre-existing demyelinating disorder such as multiple sclerosis, or other severe 
neurological deficits.


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28. Have current alcohol and/or drug abuse, or a history of, in the past 2 years which, in 
the opinion of the investigator, could create a risk for the participant’s health or 
protocol adherence.
29. Have had major surgery within 4 weeks of screening, or scheduled to occur during 
the study, excluding diagnostic surgery.
30. Previous treatment with total lymphoid irradiation.
31. Grade 3 or greater laboratory abnormality based on the Common Terminology 
Criteria for Adverse Events (CTCAE) v 4.03 (See Appendix 14) except the following 
that are allowed: Participants with abnormal aspartate aminotransferase (AST), 
alanine aminotransferase (ALT), lactate dehydrogenase (LDH), aldolase, and CK lab 
values if these values are determined by the investigator to be related to muscle 
involvement, and if glutamyl transferase (GGT) <1.5 upper limit normal.
32. Known exposure to anti-beta Interferon, (PF-06823859) or any type of anti-beta 
interferon therapy.
33. Participant has severe muscle damage defined as a global muscle damage score >5 on 
a 10 cm VAS scale which is a component on the Myositis Damage Index (MDI) 
Appendix 23.
4.7. Randomization Criteria 
Participants will be randomized after successfully meeting all eligibility requirements.
4.8. Lifestyle Requirements 
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 Section 4.8.2 and 
Appendix 25. 
4.8.1. Surgery
During the study, no elective surgery should occur without first consulting with the sponsor.  
Preferably, elective surgery should occur 4 weeks before the study screening visit or 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 investigational product prior to the surgical procedure.  In general, 
planned surgical procedures should not be performed unless the investigational product 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.


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4.8.2. 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 Appendix 25
and study sites participating in Germany please see Appendix 24).
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 25 and study sites from Germany see Appendix 24) 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 1 of the selected methods of contraception) 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.
In Germany, CTFG guidelines will be followed, where one highly effective method of 
contraception must be used, see Appendix 24. The investigator will document the 
conversation, and the participant’s affirmation, in the participant’s chart.  
4.9. 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 Study Team on Demand (STOD), 
STOD@pfizer.com. 
To facilitate access to appropriately qualified medical personnel on study-related medical 
questions or problems, participants are provided with a contact card.  The contact card 
contains, at a minimum, protocol and investigational product identifiers, participant study 
numbers, contact information for the investigator site, and contact details for a contact center 
in the event that the investigator site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
participant’s participation in the study. The contact number can also be used by investigator
staff if they are seeking advice on medical questions or problems; however, it should be used
only in the event that the established communication pathways between the investigator site 
and the study team are not available. It is therefore intended to augment, but not replace, the 
established communication pathways between the investigator site and the study team for 
advice on medical questions or problems that may arise during the study.  The contact 
number is not intended for use by the participant directly, and if a participant calls that 
number, he or she will be directed back to the investigator site.


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5. STUDY TREATMENTS
For the purposes of this study, and per International Conference on Harmonisation (ICH)
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient or placebo being tested or used as a reference/comparator in a clinical trial, 
including a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use (ICH E6 1.33).
For this study, the investigational product will be administered intravenously over 
approximately one hour.  Investigational product will be administered every 4 weeks, each 
participant receiving 3 doses of investigational product.
5.1. Allocation to Treatment
Allocation of participants to treatment/ or placebo will proceed through the use of an 
interactive response technology (IRT) system or (interactive Web-based response [IWR].  
The blinded personnel will be required to enter or select information including but not 
limited to the user’s identification (ID) and password, the protocol number and the 
participant number.  The blinded person will then be provided with a randomization number, 
and dispensable unit (DU) or container number when investigational product is being 
supplied via the IRT system.  It is noted that all of the information shown in the IRT system 
during drug assignment, and on the relevant confirmation report, is blinded information.  The 
IRT system will provide a confirmation report containing the participant number, 
randomization number, and DU or container number assigned.
The study specific IRT reference manual will provide the contact information and further 
details on the use of the IRT system.
5.2. Breaking the Blind
This study will be double blinded, (Sponsor, Investigator and participant will all be and 
remain blinded throughout the duration of the study). An interim analysis may be conducted 
for internal decision making. An internal review committee, (IRC) separate from the blinded 
study team will review safety and efficacy data.
At the initiation of the study, the investigator site will be instructed on the method for 
breaking the blind.  The method will be an electronic process.  Blinding codes are able to be 
broken in exceptional circumstances when knowledge of the actual treatment code is 
absolutely essential for further management of the participant. If the situation allows, 
investigators are encouraged to discuss with the sponsor’s medical monitor if they believe 
unblinding is necessary, however, under no circumstances should unblinding be delayed in 
an emergency situation. When the blinding code is broken, the reason must be fully 
documented and entered on the case report form (CRF).
5.3. Participant Compliance
All doses of investigational product will be administered by the appropriately designated 
study staff at the investigator site. 


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5.4. Investigational Product Supplies
5.4.1. Dosage Form(s) and Packaging
 
 
 
Placebo for
 
sealed with a stopper and a flip off 
aluminum seal. 
The vials will be packed into cartons containing 6 vials per carton.
5.4.2. Preparation and Dispensing
Once eligibility has been confirmed through the screening period process, each participant 
will be randomized. The investigational product will be dispensed using an interactive 
response technology, (IRT) drug management system at each dispensing visit. A qualified 
staff member will dispense the investigational product via unique container numbers on the 
label provided, in quantities appropriate for the dose assignment.
See the IP manual for instructions on how to prepare the investigational product for 
administration. Investigational product 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. 
PF-06823859 doses and placebo will be prepared by qualified unblinded site personnel 
according to the IP manual. The investigational product will be administered to participants
in a blinded manner.
5.5. Administration
Blinded IV PF-06823859 or placebo will be administered at the investigative site or clinic 
over the course of 
 
 has completed, all participants will be monitored for an additional 
60 minutes post investigational treatment administration.
5.5.1. Infusion Discontinuation
•
If a participant experiences symptoms typical of an allergic reaction, the study drug 
administration should be discontinued immediately and permanently. 
•
If a participant experiences symptoms typical of infusion reactions 
(eg, lightheadedness, nausea, chills, fever), the study drug 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, 
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then the study drug 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.
5.6. Investigational Product Storage 
The investigator, or an approved representative, eg, pharmacist, will ensure that all 
investigational products are stored in a secured area with controlled access under required 
storage conditions and in accordance with applicable regulatory requirements. 
Investigational product should be stored in its original container and in accordance with the 
label. 
See the IP manual for complete information on storage conditions, handling and stability of 
the product. 
Any storage conditions stated in the single reference safety document (SRSD) 
(eg, Investigator’s Brochure [IB]) will be superseded by the storage conditions stated on the 
product label. 
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated, and/or room temperature products).  This should be 
captured from the time of investigational product receipt throughout the study.  Even for 
continuous monitoring systems, a log or site procedure that ensures daily evaluation for 
excursions should be available.  The intent is to ensure that the minimum and maximum 
temperature is checked each business day to confirm that no excursion occurred since the last 
evaluation and to provide the site with the capability to store or view the minimum/maximum 
temperature for all nonworking days upon return to normal operations.  The operation of the 
temperature monitoring device and storage unit (for example, refrigerator), as applicable, 
should be regularly inspected to ensure it is maintained in working order. 
Any excursions from the product label storage conditions should be reported to Pfizer upon 
discovery.  The site should actively pursue options for returning the product to the storage 
conditions as described in the labeling, as soon as possible.  Deviations from the storage 
requirements, including any actions taken, must be documented and reported to Pfizer. 
Once an excursion is identified, the investigational product must be quarantined and not used 
until Pfizer provides documentation of permission to use the investigational product.  It will 
not be considered a protocol deviation if Pfizer approves the use of the investigational 
product after the temperature excursion.  Use of the investigational product prior to Pfizer
approval will be considered a protocol deviation.  Specific details regarding information the 
site should report for each excursion will be provided to the site. 


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Receipt of materials, door opening and closing, and other routine handling operations where 
the product(s) are briefly out of the temperature range described in the labeling are not 
considered excursions.
5.7. Investigational Product Accountability 
The investigator site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.  All investigational products will be 
accounted for using a drug accountability form/record.
5.7.1. Destruction of Investigational Product Supplies 
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (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 investigational product.
5.8. Concomitant Treatment(s)
5.8.1. Prior Treatments
The indication for use, total daily dose, route of administration, and start and stop dates for 
all prior medications (including prescription medications and treatments, vaccinations, 
nonprescription medications, nondrug treatments and dietary supplements) received within 
30 days prior to obtaining informed consent for the study will be recorded on the CRF.
For a list of prohibited and permitted concomitant medications refer to Appendix 15 and 
Appendix 16 Concomitant Treatment(s)
Participants will abstain from concomitant treatments as described in the Inclusion and 
Exclusion sections of the protocol.
Participants enrolling in the study are permitted to be on a stable DM treatment prior to 
Day 1 investigational treatment, as long as it is permitted treatment.  All concomitant 
treatments taken during the study must be recorded in study records with indication for use, 
total daily dose, and start and stop dates of administration. 
All participants will be questioned about concomitant treatment at each site visit. 
Medications that are taken during the 5-week screening period (after informed consent is 
obtained and before the first dose of investigational product) will be documented as prior 
medications.  Medications taken after the first dose of investigational product has been 
administered will be documented as concomitant 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.  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).  Herbals with 
unknown properties or those herbals that are known to have an effect on drug metabolism 
(eg, St. John’s Wort) must be discontinued at least 1 week or 5 half-lives (whichever is 
longer) before the first dose of investigational product.
5.8.2. Prohibited Concomitant Medications
Please See Appendix 15 and Appendix 16.
5.8.3. Permitted Concomitant Medications
Please See Appendix 15 and Appendix 16. 
5.8.4. Pre Medication use on the day of IVIG Administration
For participants who enroll in the study who are on 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 per day as per protocol Section 5.8.5.
There is no need to change the IVIG dosing schedule or adjust the IVIG dosing schedule 
related to investigational product administration.
5.8.5. Corticosteroids
For Stage 1, 2, a stable dose of ≤15 mg/day of corticosteroids or equivalent are permitted 
during the study through Week 12, Visit 6. After Week 12 as per the investigator’s 
discretion tapering of steroids may occur. The decision of tapering the steroids is entirely up 
to the study investigator and any change in the steroid dose should be recorded on the 
concomitant steroid page.  
For Amended Stage 2, a stable dose of ≤15 mg/day of corticosteroids or equivalent are 
permitted during the study through Week 24, Visit 9. After Week 24 as per the investigator’s 
discretion tapering of steroids may occur. The decision of tapering the steroids is entirely up 
to the study investigator and any change in the steroid dose should be recorded on the 
concomitant steroid page.  Please note if the participant is considering entering the open label 
extension study, please refrain from tapering steroids until the participant has been in the 
open label study for 4 weeks.  


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For Stage 3, a stable dose of ≤20 mg/day of corticosteroid’s or equivalent are permitted
during the study through Week 24, Visit 9. After Week 24 as per the investigator’s 
discretion tapering of steroids may occur. The decision of tapering the steroids is entirely up 
to the study investigator and any change in the steroid dose should be recorded on the 
concomitant steroid page. Please note if the participant is considering entering the open label 
extension study, please refrain from tapering steroids until the participant has been in the 
open label study for 4 weeks.  
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. 
5.8.6. Guidance for Investigators
During the course of the study, those participant who experience a severe flare requiring new 
or increased doses of immunosuppressants (including new or increased doses of 
corticosteroids beyond what is permitted or hospitalization), will be discontinued from the 
treatment period of the study and placed in the follow-up period, and therefore, will receive 
no further investigational product. Rescue therapy may be administered as clinically 
necessary. 
5.9. Rescue Medication 
After a participant enters the follow up period, or prematurely withdrawn from the study for 
any reason, medically necessary treatments for DM will be allowed.  The previous prohibited 
medications will no longer apply.
6. STUDY PROCEDURES 
6.1. Screening
For screening procedures, see Schedule of Activities and ASSESSMENTS section.
Participants will be screened within 35 days prior to administration of investigational product 
to confirm that they meet the participant eligibility criteria for the study.  The investigator (or 
appropriate delegate at the investigator site) will obtain informed consent from each 
participant in accordance with the procedures described in Section 12.3.  Screening visits 
may occur over multiple visits to achieve all of the required testing.
Screening laboratory tests with abnormal results may be repeated once to confirm abnormal 
results.  The last value (most recent value obtained) will be used to determine eligibility.  If 
results return to normal within the 5-week screening period, the participant may enter the 
study. 
Rescreening:
Participants who do not meet the eligibility criteria (ie, screen failure) may be re-screened 
once at a later date.  Any participant who is re-screened must be re-consented and receive a 
new participant number.  All activities required for the screening visit must be repeated.


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6.2. Study Period
6.2.1. Treatment Period (Stage 1 and 2)
The treatment period will begin on Day 1 and consist of 4 scheduled visits, (Visits 2-5).  
From Day 1, where investigational treatment or placebo is received, a scheduled visit will 
occur in 7 days (±) 3 days, to follow up with the participant after the first investigational 
drug/placebo administration. For all other visits the participant will be seen every 4 weeks
from Day 1.  Investigational treatment will be received at Visits 2 (Day 1), Visits 4 and 5.  
During the treatment period visits, the following assessments may occur:
•
Investigational drug or placebo administered.
•
Skin biopsy (4).  (After randomization prior to first dose of investigational/placebo 
treatment) Day 1, Visit 2.
•
CDASI assessment.
•
•
Physicians Global Assessment.
•
Vital signs, (Blood pressure, (BP), Heart Rate, (HR), Pulse, respirations and 
temperature).
•
Weight.
•
Targeted Physical examination.
•
ECG, (Day 1, Visits 4, 5, 6, End of Study or Early termination).
•
Blood & urine collection for safety laboratory testing.
•
Males and females, (contraception check).
•
All females Urine Pregnancy test.
•
Blood collection for various biomarkers, (IP-10, MX-A, 
 
 hsCRP, Gene signature panel).
•
•
•
Patient reported outcomes, 5D Pruritus Scale, SF36 V2 Acute, and DLQI.
•
Recording of any new concomitant medications, DM concomitant medications or 
changes in ongoing concomitant medications, or DM concomitant medications.
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•
Collection for Viral Surveillance.
•
Check for Infusion site reactions.
•
Collection of any serious and non-serious adverse events.
•
Genomic Banked biospecimen (Prep D1) If missed, the site may collect at the next
available time point when biospecimens are being collected in conjunction with a 
participant visit.
Please see the Schedule of Assessments for specific details on which procedures will occur at 
each visit. 
6.2.2. Treatment Period (Amended Stage 2)
The treatment period will begin on Day 1 and consist of 8 scheduled treatment visits, 
(Visits 2-8).  The first dose of investigational treatment or placebo will be administered on 
Day 1. Following Day 1, a scheduled visit will occur in 7 days (±) 3 days. Otherwise, 
monthly visits will occur to the end of the follow-up period after the first dose administration.  
Investigational treatment will be received at Visit 2 (Day 1), Visit 4 (Week 4), Visit 5 
(Week 8), Visit 6 (Week 12),  Visit 7 (Week 16) and Visit 8 (Week 20).  The end of the 
treatment period is at Week 24. Once Week 24 has been completed, eligible participants will 
have the opportunity to enter the open label extension study or may continue into the 
follow up period. 
During the treatment period visits, the following assessments may occur: For more details 
please follow the SoA.
•
Investigational drug or placebo administered through Visit 8. 
•
Punch Skin biopsy (4), (-6 days prior to randomization Day 1, Visit 2).
•
Punch Skin biopsy (2), (±6 days, Week 12, Visit 6).
•
Punch Skin biopsy (2), (±6 days, Week 24, Visit 9).
•
CDASI assessment.
•
•
Physicians Global Assessment.
•
Vital signs, (Blood pressure, (BP), Heart Rate, (HR), Pulse, respirations and 
temperature).
•
Weight.
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•
Targeted Physical examination.
•
Complete Physical examination.
•
ECG, (Day 1, Visits 4, 5, 6, 7, 8, 9, End of Study Visit 13, or Early termination).
•
Blood & urine collection for safety laboratory testing.
•
Males and females, (contraception check).
•
All females Urine Pregnancy test. 
•
Blood collection for various biomarkers, (IP-10, MX-A, 
 
 hsCRP, Gene signature panel).
•
•
•
Patient reported outcomes, PtGA, HAQ-DI, DLQI, 5D Pruritus Scale, 
 
, SF36 V2 Acute, and EQ-5D-5L, EQ-VAS.
•
Recording of any new concomitant medications, DM concomitant medications or 
changes in ongoing concomitant medications.
•
Collection for Viral Surveillance.
•
Check for Infusion site reactions. 
•
Collection of any serious and non-serious adverse events.
•
 If missed, the site may collect at the next 
available time point when biospecimens are being collected in conjunction with a 
participant visit. For more details please follow the SoA.
6.2.3. Treatment Period for Stage 3
The treatment period will begin on Day 1 and consist of 8 scheduled visits, (Visits 2-8).  The 
first dose of investigational treatment or placebo will be administered on Day 1. Following 
Day 1, a scheduled visit will occur in 7 days (±) 3 days.  Otherwise, monthly visits will occur
to the end of the follow-up period after the first dose administration.  Investigational 
treatment will be received at Visit 2 (Day 1), Visit 4 (Week 4), Visit 5 (Week 8), Visit 6 
(Week 12),  Visit 7 (Week 16) and Visit 8 (Week 20). The end of the treatment period is at 
Week 24. Once Week 24 has been completed, eligible participants will have the opportunity 
to enter the open label extension study or they may continue into the follow up period. 
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During the treatment period visits, the following assessments may occur: For more details 
please follow the SoA.
•
Investigational drug or placebo administered through Visit 8. 
•
CDASI assessment.
•
•
MMT-8 assessment (See Appendix 21).
•
Physicians Global Assessment, PhGA, VAS (See Appendix 3).
•
Myositis Disease Activity Assessment Test, MDAAT(See Appendix 20).
•
Recording of Muscle Enzymes (See Appendix 19).
•
Vital signs, (Blood pressure, (BP), Heart Rate, (HR), Pulse, respirations and 
temperature).
•
Weight.
•
Complete Physical Exam.
•
Targeted Physical Exam.
•
ECG, (Day 1, Visits 4, 5, 6, 7, 8, 9, End of Study Visit 13, or Early termination).
•
Blood & urine collection for safety laboratory testing, (including muscle enzymes).
•
Males and females, (contraception check).
•
All females Urine Pregnancy test. 
•
Blood collection for various biomarkers, (IP-10, MX-A, 
 
 hsCRP, Gene signature panel).
•
•
•
Patient reported outcomes in the following order, PtGA, HAQ-DI, 5D Pruritus Scale, 
 FACIT-F, SF36 V2 Acute, and EQ-5D-5L, 
EQ-VAS. 
•
Recording of any new concomitant medications, DM concomitant medications or 
changes in ongoing concomitant medications.
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•
Collection for Viral Surveillance.
•
Check for Infusion site reactions. 
•
Collection of any serious and non-serious adverse events.
6.2.4. Follow-up Visits for Stage 2
Due to the investigational drug’s half-life of approximately 28 days, 5 follow-up visits, 
(Visits 6-10) will be conducted monthly.  During the follow up period, the participant will 
have the following assessments and procedures completed.  Please see Schedule of 
Assessments for specific details on which procedures will occur at each visit.
•
Punch Skin biopsy (2), (Week 12, Visit 6).
•
CDASI assessment.
•
•
Physicians Global Assessment.
•
Vital signs, (Blood pressure, (BP), Heart Rate, (HR), Pulse, respirations and 
temperature).
•
Weight.
•
Targeted Physical examination.
•
Complete Physical examination.
•
ECG, (Visit 12, End of Study Visit 10), or Early termination).
•
Blood & urine collection for safety laboratory testing.
•
Males and females, (contraception check).
•
All females Urine Pregnancy test. 
•
Blood collection for various biomarkers, (IP-10, MX-A, 
 
, hsCRP, Gene signature panel).
•
•
•
Patient reported outcomes, 5D Pruritus Scale, SF36 V2 Acute, DLQI and EQ-5D-5L.
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•
Recording of any new concomitant medications, DM concomitant medications or 
changes in ongoing concomitant medications, 
•
Collection for Viral Surveillance.
•
Collection of any serious and non-serious adverse events.
•
Genomic Banked biospecimen (Prep D1) If missed, the site may collect at the next
available time point when biospecimens are being collected in conjunction with a 
participant visit.
6.2.5. Follow-up Visits for Amended Stage 2
Due to the investigational drug’s half-life of approximately 28 days, 4 follow-up visits will 
occur after completing the treatment period, Week 24, (Visit 9) and will be conducted every 
4 weeks.  The last dose is administered at Week 20 which provides a 5 month interval to the 
end of the study.  During the follow up period, the participant will have the following 
assessments and procedures completed.  Please see Schedule of Assessments for specific 
details on which procedures will occur at each visit.
•
Punch Skin biopsy (2), (± 6 days, Week 24, Visit 9).
•
CDASI assessment.
•
•
Physicians Global Assessment.
•
Vital signs, (Blood pressure, (BP), Heart Rate, (HR), Pulse, respirations and 
temperature).
•
Weight.
•
Height.
•
Targeted Physical examination.
•
Complete Physical examination.
•
ECG, (Visit 9, End of Study Visit 13), or Early termination).
•
Blood & urine collection for safety laboratory testing.
•
Males and females, (contraception check).
•
All females Urine Pregnancy test. 
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•
Blood collection for various biomarkers, (IP-10, MX-A, 
 
, hsCRP, Gene signature panel).
•
•
•
Patient reported outcomes, PtGA, HAQ-DI, DL,QI, Pruritus Scale, 
, SF36 V2 Acute, and EQ-5D-5L, EQ-VAS.
•
Recording of any new concomitant medications, DM concomitant medications or 
changes in ongoing concomitant medications.
•
Collection for Viral Surveillance.
•
Collection of any serious and non-serious adverse events.
6.2.6. Follow-up Visits for Stage 3
Due to the investigational drug’s half-life of approximately 28 days, 4 follow-up visits will 
occur after completing the treatment period, Week 24,(Visit 9) and will be conducted every 
4 weeks. The last dose is administered at Week 20 which provides a 5 month interval to the 
end of the study. During the follow up period, the participant will have the following 
assessments and procedures completed.  Please see Schedule of Assessments for specific 
details on which procedures will occur at each visit.
•
CDASI assessment (See Appendix 2).
•
•
MMT-8 assessment (See Appendix 21).
•
Pt Global Assessment (PtGA) (See Appendix 13).
•
Physicians Global Assessment, (PhGA, VAS) (See Appendix 3).
•
Myositis Disease Activity Assessment Test, (MDAAT) (See Appendix 20).
•
Recording of Muscle Enzymes (See Appendix 19).
•
Vital signs, (Blood pressure, (BP), Heart Rate, (HR), Pulse, respirations and 
temperature).
•
Weight.
•
Height
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•
Complete Physical Exam.
•
Targeted Physical Exam.
•
ECG, (Visit 9, End of Study Visit 13, or Early Termination).
•
Blood & urine collection for safety laboratory testing, (including muscle enzymes).
•
Males and females, (contraception check).
•
All females Urine Pregnancy test. 
•
Blood collection for various biomarkers, (IP-10, MX-A, 
 
 hsCRP, Gene signature panel).
•
•
•
Patient reported outcomes in the following order, PtGA, HAQ-DI, 5-D Pruritus Scale, 
 FACIT-F, SF36 V2 Acute, and EQ-5D-5L and 
EQ-VAS. 
•
Recording of any new concomitant medications, DM concomitant medications or 
changes in ongoing concomitant medications.
•
Collection for Viral Surveillance.
•
Collection of any serious and non-serious adverse events.
6.2.7. Unscheduled Visits
At any time during the conduct of the study a participant may be brought in for an 
unscheduled study visit.  This may be related to a lab value, or per the investigator’s 
discretion. 
6.2.8. Alternative Measures During a Public Emergency 
The implementation of alternative measures during public emergencies should be consistent 
with the protocol to the extent possible if feasible. A separate document will be provided 
which outlines specific details in collecting procedures according to this protocol.  Please 
also reference Appendix 17 for options that may be available to continue the conduct of the 
study.
Participant Withdrawal (Early Termination) The early termination visit only applies to 
participant who are randomized and then are prematurely withdrawn from the study. 
Contraception should also be continued for a minimum of 5 months from the last dose of 
investigational product. 
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It may be appropriate for the participant to return to the clinic for final safety assessments to 
be scheduled as early as practically feasible following the decision to withdraw from the 
study.  Participants should be questioned regarding their reason for withdrawal.  At the early 
withdrawal visit, every effort must be made to complete the assessments according to the 
early withdraw visit in the SOA. The site should follow the applicable SOA the participant
has been following during their participation in the study. 
Lack of completion of all or any of the early termination procedures will not be viewed as 
protocol deviations so long as the participant safety was preserved.
Withdrawal of consent
Participants who request to discontinue receipt of study treatment 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 investigational product or also from study 
procedures and/or post treatment study follow-up, and entered on the appropriate CRF page. 
In the event that 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.
Lost to follow-up: 
All reasonable efforts must be made to locate participants to determine and report their 
ongoing status. This includes follow-up with persons authorized by the participant as noted 
above. Lost to follow-up is defined by the inability to reach the participant after a minimum 
of 2 documented phone calls, faxes, or e-mails as well as lack of response by the participant
to 1 registered mail letter. All attempts should be documented in the participant’s medical 
records. If it is determined that the participant has died, the site will use locally permissible 
methods to obtain the date and cause of death. If the investigator’s use of a third-party 
representative to assist in the follow-up portion of the study has been included in the 
participant’s informed consent, then the investigator may use a sponsor-retained third-party 
representative to assist site staff with obtaining the participant’s contact information or other 
public vital status data necessary to complete the follow-up portion of the study. The site 
staff and representative will consult publicly available sources, such as public health 
registries and databases, in order to obtain updated contact information. If, after all attempts, 
the participant remains lost to follow-up, then the last-known-alive date as determined by the 
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Participants may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety (see also the 
Withdrawal From the Study Due to Adverse Events section) or behavioral reasons, or the 
inability of the participant to comply with the protocol-required schedule of study visits or 
procedures at a given study site.
If a participant does not return for a scheduled visit, every effort should be made to contact 
the participant. The Investigator or designee should attempt to contact the participant twice.  
After two attempts, study site staff may send a registered letter.  If no response is received 
from the participant, the participant will be considered lost to follow up.  All attempts to 
contact the participant and information received during contact attempts must be documented 
in the participant’s medical record.  In any circumstance, every effort should be made to 
document participant outcome, if possible.  The investigator should inquire about the reason 
for withdrawal, request that the participant return for a final visit, if applicable, and follow-up 
with the participant regarding any unresolved adverse events (AEs).
If the participant withdraws from the study, and also withdraws consent 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.
Participants who withdraw from the study may be replaced at the discretion of the 
investigator upon consultation with the sponsor. 
7. ASSESSMENTS
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances outside of the control of the investigator that may make it unfeasible to 
perform the test. In these cases the investigator will 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 this and any corrective and preventive actions 
that he or she has taken to ensure that normal processes are adhered to as soon as possible.
The study team will 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.
7.1. 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 
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7.2. Pregnancy Testing
All pregnancy tests used in this study, either urine or serum, must have a sensitivity of at 
least 5 mlU/ml and must be performed by a certified laboratory.  For female participants of 
childbearing potential, 2 negative pregnancy tests are required before receiving 
investigational product (1 negative pregnancy test at screening and 1 at the baseline visit 
immediately before investigational product administration).  Following a negative pregnancy 
test result at screening, appropriate contraception according to Appendix 25 or Appendix 24
for participants from Germany must be commenced and the second negative pregnancy test 
result will then be required at the baseline visit and within 5 days after the first day of the 
menstrual period (counting the first day of the menstrual period as Day 1) before the 
participant may receive the investigational product.  In the absence of regular menstrual 
bleeding, the study candidate should have used contraception according to Appendix 25 or 
Appendix 24 for Germany participants for at least 1 month before the second pregnancy test.  
Pregnancy tests will be repeated at every visit including treatment and follow-up visits, and 
at the end of the study to confirm that the participant has not become pregnant during the 
study.  Pregnancy tests will also be conducted whenever 1 menstrual cycle is missed during 
the active treatment period and/or when potential pregnancy is otherwise suspected, and may 
be repeated if requested by institutional review boards (IRBs)/ethics committees (ECs) or if 
required by local regulations.  In the case of a confirmed pregnancy, the participant will be 
withdrawn from administration of investigational product but should remain in the study for 
the early withdrawal visit.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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•
 
 
•
 
 
•
 
 
 
 
 
 
 
 
 
 
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7.5. Safety Assessments
Safety will be assessed by the spontaneous reporting of AEs, physical examinations and 
clinical laboratory results.  Unscheduled safety assessments may be performed at any time 
during the study to assess any perceived safety concerns.  Investigators and Pfizer Clinicians 
will review individual participant data throughout the conduct of the study to ensure the
well-being of study participants.
7.5.1. Chest X-RAY
Chest radiograph (posterior-anterior and lateral views are recommended, however, local 
guidelines should be followed).  If another diagnostic image (ie, CT or MRI was already 
completed within 12 weeks prior to Day 1, this may be accepted).  The image will show no 
evidence of current, active TB or previous inactive TB, general infections, heart failure or 
malignancy, and must be read by a qualified radiologist. Documentation of the official 
reading must be located and available in the source documentation.
7.5.2. Electrocardiogram
Single 12-lead ECGs should be collected at times specified in the Schedule of Activities.
All scheduled ECGs should be performed after the participant has rested quietly for at least 
10 minutes in a supine position and prior to any blood collection procedures.
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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.
7.5.3. Vital Signs
Vital signs (blood pressure, heart rate [pulse], respirations and temperature) will be measured
after approximately 5 minutes of rest as indicated in the Schedule of Activities.
Blood pressure (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.
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.
7.5.4. Medical History
A complete medical history will be taken including onset of DM disease.  The clinical 
involvement of additional organs, (ie, lung, heart, liver) and prior DM treatments will be 
recorded.  Participants should have had a standard work up for dermatomyositis (prior to) 
baseline.  Stable interstitial lung disease related to DM that is not severe in the opinion of the 
investigator is allowed, ie, no supplemental oxygen permitted.  If their DM diagnosis is 
within 2 years of the screening visit, then they must have completed either age appropriate 
malignancy screening and a CT of the chest/abdomen/pelvis; or Positron emission 
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7.5.5. Physical Examinations
Complete physical examination (PE) must be performed by the investigator, sub-investigator 
or a qualified health professional per local guidelines.  Complete PE consists of assessments 
of general appearance, skin, head, eyes, ears, nose and throat (HEENT), heart, lungs, breast 
(optional), abdomen, external genitalia (optional), extremities, neurologic function, back, and 
lymph nodes.
Targeted PE must be performed by the investigator, sub-investigator or a qualified health 
professional per local guidelines.  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.
Complete and targeted physical examinations are performed at various time points, see 
Schedules of Activities.
7.5.6. 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 times according to the SOA. Weight will 
continue to be assessed and recorded at various time points, see Schedules of Activities.
7.5.7. Tuberculosis (TB) Screening and Monitoring
7.5.7.1. Interferon Gamma Release Assay (IGRA) Tuberculin Test
Participants should be screened for TB using an Interferon gamma release assay (IGRA) per 
local guidelines. IGRA will be tested during screening or within 12 weeks prior to Day 1. 
The following are acceptable IGRA assays: In-Tube test (QFT-GIT) and QuantiFERON®-TB 
Gold test (QFT-G).  If T-spot®TB test was completed within 12 weeks prior to Day 1, this is 
acceptable, however this test type cannot be offered for participants requiring the test during 
screening, or treatment. 
Site personnel should follow the processing and analyses steps based on the assay chosen.  
Ensure incubation steps are followed as appropriate. Documentation of IGRA product used 
and the test result must be in the participant’s source documentation.
If the results of the IGRA are indeterminate, the test may be repeated, and if a negative result 
is obtained, enrollment may proceed. A positive test on repeat is exclusionary.
Participants with repeat indeterminate IGRA results may be enrolled after consultation with 
an infectious disease and/or pulmonary specialist who determines that the risk of infection is 
low (ie, participant would be acceptable for immunosuppressant treatment without additional 
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There is no additional scheduled testing for TB after screening.  However, if at any time the 
participant has signs or symptoms associated with TB, the investigator should complete 
additional TB testing to ensure TB activation has not occurred. 
Refer to lab manual for any additional processing information and shipping instructions.
7.5.8. Monitoring for Infections
Participants will be monitored for development of any infection (viral, bacterial, and fungal).  
Infections will be classified as either treated or non-treated infections.  All treated infections 
occurring during the study require identification of the causative organism, if feasible, 
whether by culture, antigen assay, serology, etc. (as appropriate) and the results (eg, any 
identified organisms or absence of growth) recorded in the CRF.
Treated infections are infections that:

Require antimicrobial therapy by any route of administration or;

Require any surgical intervention (eg, incision and drainage).
Treated infections will be further classified as serious or non-serious.  Serious infections are 
treated infections that:

Require parenteral antimicrobial therapy or;

Required hospitalization for treatment or;

Meet other criteria that require the infection to be classified as a SAE.
A participant who experiences a serious infection should be discontinued from treatment. A 
serious infection should be reported as a SAE and should be listed as the reason for 
discontinuation in the CRF.  All serious infections occurring during the study should undergo 
appropriate laboratory investigations, including culture, and the results (eg, any identified 
organisms or absence of growth) be recorded in the CRF.
7.5.9. Viral Surveillance
Blood sample for possible analysis of cytomegalovirus (CMV), Epstein-Barr virus (EBV), 
herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2) and
varicella-zoster virus (VZV), Human Herpes Virus 6 (HHV6) and other viruses will be 
collected according to the times outlined in the Schedule of Activities. Additional sample 
collection instructions will be provided in the laboratory manual.
Note: Due to long turnaround time, the retrospective nature of these labs might make their 
reporting time quite delayed.
In addition to time points specified, a blood sample for viral surveillance sample may also be 
taken at the time of an AE, as clinically appropriate.


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7.5.10. Biopsies 
Punch biopsy is considered the primary technique for obtaining diagnostic full -thickness 
skin specimens. During this study punch biopsies (4 mm each) will be collected from all 
participants in the Stage 1, 2, and Amended Stage 2 of the study. Four punch biopsies will 
be collected at baseline Day 1.  Two biopsies from an active skin lesion and two biopsies 
from skin that is healthy and free of any skin lesions, or discoloration. At Week 12, two 
biopsies will be collected from the same area as the baseline biopsies for the active lesion. 
For additional information on acceptable body locations for punch biopsy, please see the lab 
manual. 
For participants enrolled in the Amended Stage 2 part of the study, an additional 2 biopsies 
will be collected at Week 24, Visit 9. Biopsies should be collected from the same active 
lesion area as previously collected. All biopsies will be analyzed to see if there are any 
changes from the baseline biopsies in an 
manner, after study treatment. 
Additional information on the collection and processing of the skin biopsies will be provided 
in the lab manual under separate cover. Histology and immunohistochemistry will be 
performed on tissue slices to understand changes in tissue morphology. RNA will be 
extracted to understand gene expression changes following treatment.
7.5.11. Infusion Site Reaction Assessment
Infusion site reactions will be assessed according to the Schedule of Activities.  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.
7.6. Rater Qualifications
7.6.1. CDASI
The primary and secondary endpoints for this study assess changes in the modified CDASI,14
activity score as well as the individual components.
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 
individual complete the Physician Global Assessment (PhGA, VAS) for consistency 
(See Appendix 3).
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7.6.2. MMT-8 Stage 3
This partially validated tool assesses muscle strength using manual muscle testing (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.
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. (See Appendix 21).
7.6.3. MDAAT Stage 3
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. 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.  (See 
Appendix 20) 
7.7. 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 patient 
reported outcomes used in this study. 
7.7.1. The Short Form -36 Version 2, Acute (SF-36 v2 acute)
The Short Form (36) Health Survey (SF-36) version 2, acute is a 36 item generic health 
status measure.15,16,17  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 physical component scores (PCS) and mental component 
scores (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.  A copy of the SF-36 version 2, acute questionnaire 
can be found in Appendix 7.
7.7.2. 5-D Pruritus Scale
The 5-D Pruritus Scale measures five dimensions of itch: degree, duration, direction, 
disability and distribution.18 This patient-reported questionnaire is a multidimensional Likert 
response instrument designed to evaluate several components of chronic pruritus, including 
the areas of the body affected, itch intensity, course of itch through the day, impact on sleep 
and activities of daily living and disability induced by the pruritus and whether or not the 
symptom has changed in the past two weeks and would provide pruritus assessments 


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complementary to the unidimensional itch instruments, which for example measure intensity 
without impact on quality of life daily.19,20,21,22,23  The 5-D Pruritus Scale was validated in 
participants with dermatological and systemic diseases and has a recall period of two 
weeks.22 The 5-D Pruritus Scale will be collected as indicated in the Schedule of Activities.  
A copy of the scale can be found in Appendix 9.
7.7.3. Dermatology and Life Quality Index (DLQI)
The DLQI (Dermatology and Life Quality Index) is a 10-item, validated patient-reported 
questionnaire used in clinical practice and clinical trials to assess the impact of skin 
conditions on quality of life.  This 10-item questionnaire is applicable to participants with 
various skin diseases and has a recall period of one Week24.  The DLQI is calculated by 
summing the score of each question resulting in a minimum of 0 to maximum of 30, with a 
higher score indicating a greater QoL impairment.  Using a Likert scale, this questionnaire 
assesses symptoms and feelings, daily activities, leisure, work and school, personal 
relationships, and distress as related to the participant’s skin condition.  The DLQI will be 
collected as indicated in the Schedule of Activities.  A copy of the DLQI can be found in 
Appendix 8. 
7.7.4. Health Assessment Questionnaire – Disability Index (HAQ-DI) start
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.25
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. A copy of the HAQ-DI questionnaire can be found in Appendix 12.
 
 
 
 
 
 
 
 
 
 
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7.7.6. Patient’s Global Assessment (PtGA) 
The Patient’s Global Assessment (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 visual analog scale (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.29,30 The PtGA will be collected as 
indicated in the Schedule of Activities. A copy of PtGA questionnaire can be found in 
Appendix 13.
 
 
 
 
 
 
 
 
 
7.7.8. Functional Assessment of Chronic Illness Therapy - fatigue (FACIT-F)
The Functional Assessment of Chronic Illness Therapy - fatigue (FACIT-F) scale is a 
13-item instrument to measure fatigue or tiredness and its impact on a patient's daily 
activities and functioning. The FACIT-F includes items such as tiredness, weakness, lack of 
energy, and the impact of these feelings on daily functioning (eg, sleeping, and social 
activities). The content validity and psychometric properties of the instrument have been 
established in different chronic conditions including rheumatoid arthritis, psoriatic arthritis, 
systemic lupus erythematosus etc. Each item is scored from 0 to 4 with 0 representing “Not 
at all” to 4 as “Very much”. To score the FACIT-F, all items are summed to create a single 
fatigue score with a range from 0 to 52. Items are reverse scored when appropriate to 
provide a scale in which higher scores represent better functioning or less fatigue. The 
FACIT-F will be collected as indicated in the Schedule of Activities. A copy of the 
FACIT-F can be found in Appendix 11.
For this study, participants in Stage 2, the Amended Stage 2, and Stage 3 will complete the 
patient reported outcomes in the following order, prior to any other clinical assessments:
7.7.9. Stage 2 PRO Measures
1. 5D Pruritus Scale.
2. SF-36 v2 acute.
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3. DLQI.
7.7.10. Amended Stage 2 PRO Measures
1. PtGA.
2. HAQ-DI.
3. 5-D Pruritus Scale.
5. SF-36 v2 acute.
6. DLQI.
7.7.11. Stage 3 PRO Measures 
1. PtGA.
2. HAQ-DI.
3. 5-D Pruritus Scale.
5. FACIT-F.
6. SF-36 v2 acute.
The DLQI and the FACIT-F need to be assessed only in the skin cohort and the muscle 
cohort, respectively. 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 chronological order for both the cohorts as listed above.  
These patient reported outcomes should be completed prior to any other clinical 
activities and checked by site staff for completeness.
7.8. Physician Clinician Assessment
7.8.1. Physician Global Assessment (PhGA, Visual Analogue Scale VAS)
The Physician Global Assessment (PhGA, VAS) is an assessment of the participant’s general 
health status rather than the disease activity in a specific organ (Appendix 3).  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 
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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 CDASI.
7.9. Total Improvement Score for Stage 3
There are 6 core set measures that comprise the total improvement score. These components 
are the physician global activity assessment, the patient global activity assessment, MMT-8 
score, HAQ- DI score, the myositis disease activity assessment tool, (MDAAT), and the 
participant’s most elevated muscle enzymes. The total improvement score is the sum of all 
6 improvement scores associated with the change in each core set measure.  See 
Appendix 22. 
7.10. Clinical Laboratory Tests
The following laboratory tests will be performed at time points defined in the Schedule of 
Activities.  Sample collection, labeling, storage and shipping instructions can be found in the 
laboratory manual.
Additional blood samples may need to be collected at times not specified in the protocol
(eg, replacement of clotted or compromised specimens, or repeat of clinically significant out 
of range laboratory results.
Laboratory tests may be repeated once during screening; the last value will be used to 
determine participant eligibility.  Unscheduled clinical labs may be obtained at any time 
during the study to assess any perceived safety concerns at the investigator’s discretion.  All 
laboratory tests with clinically important changes from baseline identified after 
administration of investigational product will be followed until the value stabilizes.
For samples that are collected for safety labs or pharmacokinetics, sample that remains after 
the intended analysis may be used to better understand potential adverse events.


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Table 1.
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) 
Reticulocyte count (%, Abs) 
PT/PTT
BUN and Creatinine 
Creatine Phosphokinase
Glucose (fasting & non fasting) 
Sodium
Potassium 
Chloride 
Calcium
Total CO2 (Bicarbonate) 
AST, ALT
LDH
Aldolase
CKMB (Only if CPK is 
elevated)
Total Indirect and Direct 
Bilirubin
Alkaline phosphatase 
Uric acid
Albumin Total protein
Lipid Profile Panel:a
Total Cholesterol
LDL-Cholesterol (direct) 
HDL-Cholesterol 
Triglycerides
pH
Glucose (qual) 
Protein (qual) 
Blood (qual) 
Ketones 
Nitrites
Leukocyte esterase 
Microscopyb
Spot Urine (Upr:Ucr)e
HBsAgc
HBcAbc
HCVAbc
HIVc
HepB reflex,c if applicable
-hCGd
FSHd
(QFT-GIT or QFT-G)
Viral surveillance (may 
include)
CMV 
EBV
HSV-1 and HSV-2 
VZV, HHV6
a.
Lipid profile panel will be completed on Day 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, 
and Week 28 (and if applicable, at participant withdrawal/early withdrawal and post-withdrawal visits). 
b.
Only if urine dipstick is positive for blood or protein.
c.
At screening only; confirmation and documentation of negative HIV test result within 3 months prior to 
screening is acceptable.
d.
Serum/urine pregnancy tests for (WOCBP); serum pregnancy test must be performed at screening for all
WOCBP as defined in the eligibility criteria (if serum pregnancy test is borderline positive, the central
laboratory will run a FSH test to confirm menopause if the participant has missed her periods <12 months);
urine pregnancy test must be performed at baseline for all WOCBP prior to dosing with investigational
product and at all subsequent visits. FSH for women of non-child bearing potential, (WONCBP) only; at
screening only.
e.
Spot Urine Protein and creatinine.


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Table 2.
Additional Lab Testing
Gene signature panel
Refer to the schedule of activities for collection times.
a.
Several exploratory biomarkers will be collected at specified time 
points.  Some will be evaluated in real time; others stored for 
future analysis.
  
 
 
 
 
 
 
 
 
 
 
 
 
7.11.1. Samples for IP-10 Analysis
Blood samples to provide serum for the analysis of IP-10 will be collected into appropriately 
labeled tubes according to the times outlined in the Schedule of Activities.
7.11.2. 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.
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7.11.3. Samples for MX-A Analysis
Whole blood samples for the analysis of MXA will be collected into appropriately labeled 
tubes according to the times outlined in the Schedule of Activities.
 
 
7.11.6. Gene Signature Panel
Blood samples to be assayed with a gene signature panel will be collected into appropriately 
labeled tubes according to the times outlined in the Schedule of Activities. 
 
 
 
 
 
 
 
 
 
 
 
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7.13. 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. Placebo 
samples may be assayed in the event of suspected error in participant randomization. Refer 
to the central laboratory manual for further information.
7.14. Immunogenicity 
 
 
 
 
 
 
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8. ADVERSE EVENT REPORTING
8.1. Requirements
The table below summarizes the requirements for recording safety events on the CRF and for 
reporting safety events on the Clinical Trial (CT) Serious Adverse Event (SAE) Report Form 
to Pfizer Safety.  These requirements are delineated for 3 types of events: (1) SAEs; 
(2) non-serious adverse events (AEs); and (3) exposure to the investigational product under 
study during pregnancy or breastfeeding, and occupational exposure. 
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Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Non-serious AE
All
None
Exposure to the 
investigational product 
under study during 
pregnancy or 
breastfeeding, and 
occupational exposure
All (regardless of whether 
associated with an AE), 
except occupational 
exposure
Exposure during pregnancy, 
exposure via breastfeeding, 
occupational exposure 
(regardless of whether 
associated with an AE)
All observed or volunteered events regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
paragraphs.
Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report 
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study.  In particular, if the SAE is fatal or life-threatening, 
notification to Pfizer Safety must be made immediately, irrespective of the extent of available 
event information. This time frame also applies to additional new (follow-up) information on 
previously forwarded reports.  In the rare situation that the investigator does not become 
immediately aware of the occurrence of an event, the investigator must report the event 
within 24 hours after learning of it and document the time of his/her first awareness of the 
event.
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see Section 8.2.3).  In addition, the investigator may be requested by Pfizer Safety to obtain 
specific follow-up information in an expedited fashion.  This information is more detailed 
than that recorded on the CRF.  In general, this 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.  Any pertinent additional information must be reported on the CT SAE Report Form; 
additional source documents (eg, medical records, CRF, laboratory data) are to be sent to 
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As part of ongoing safety reviews conducted by the sponsor, any non-serious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study.
8.1.1. Additional Details on Recording Adverse Events on the CRF
All events detailed in the table above will be recorded on the AE page(s) of the CRF.  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.
8.1.2. Eliciting Adverse Event Information
The investigator is to record on the CRF all directly observed AEs and all AEs spontaneously 
reported by the study participant.  In addition, each study participant will be questioned about 
the occurrence of AEs in a non-leading manner.
8.1.3. Withdrawal from the Study Due to Adverse Events (see also the Participant
Withdrawal (Early Termination) section)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF. 
When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported, as appropriate, on the CT SAE Report Form, in accordance with 
the Requirements section above.
8.1.4. Time Period for Collecting AE/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 investigational product), through and including 
a minimum of 5 months after the last administration of the investigational product.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
8.1.4.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a participant during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form.


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SAEs occurring in a participant after the active collection period has ended are reported to 
Pfizer Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to investigational 
product must be reported to Pfizer Safety.
Follow up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment.
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF
During the active collection period, both non-serious AEs and SAEs are recorded on the 
CRF.
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
8.1.5. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious); the investigator must record the causal relationship on the CRF, and report such 
an assessment in accordance with the SAE reporting requirements, if applicable.  An 
investigator’s causality assessment is the determination of whether there exists a reasonable 
possibility that the investigational product caused or contributed to an AE; generally the facts 
(evidence) or arguments to suggest a causal relationship should be provided.  If the 
investigator does not know whether or not the investigational product caused the event, then 
the event will be handled as “related to investigational product” for reporting purposes, as 
defined by the sponsor.  If the investigator's causality assessment is “unknown but not 
related” to investigational product, this should be clearly documented on study records. 
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.
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations.
8.2. Definitions
8.2.1. Adverse Events
An AE is any untoward medical occurrence in a study participant administered a product or 
medical device; the event need not necessarily have a causal relationship with the treatment 
or usage.  Examples of AEs include, but are not limited to: 

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
Clinically significant signs and symptoms;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease;

Drug abuse;

Drug dependency.
Additionally, AEs may include signs and symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure.
8.2.2. Abnormal Test Findings
Abnormal objective test findings should be recorded as AEs when any of the following 
conditions are met: 

Test result is associated with accompanying symptoms; and/or

Test result requires additional diagnostic testing or medical/surgical intervention; 
and/or

Test result 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; and/or

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Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
recording as an AE.
8.2.3. Serious Adverse Events
A serious adverse event is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect.
Or that is considered to be:

An important medical event.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the participant or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.
Examples of such events are 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.
8.2.4. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility, or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit is assessed for medical importance.
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;


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
Respite care (eg, caregiver relief);

Skilled nursing facilities;

Nursing homes;

Same-day surgeries (as outpatient/same-day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating clinical 
AE is not in itself an SAE.  Examples include:

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
workup of a persistent pretreatment laboratory abnormality);

Social admission (eg, participant has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);

Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Preplanned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual participant.
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as SAEs.  However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE.  For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
AE.
8.3. Severity Assessment
If required on the AE page of the CRF, the investigator will use the adjectives MILD, 
MODERATE, or SEVERE to describe the maximum intensity of the AE.  For purposes 
of consistency, these intensity grades are defined as follows:
MILD
Does not interfere with participant's usual function.
MODERATE
Interferes to some extent with participant's usual function.
SEVERE
Interferes significantly with participant's usual function.


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Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
the participant's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.4. Special Situations
8.4.1. Protocol -Specified Serious Adverse Events
There are no protocol -specified SAEs in this study.  All SAEs will be reported to Pfizer 
Safety by the investigator as described in previous sections, and will be handled as SAEs in 
the safety database. 
8.4.2. 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 drug -induced 
liver injury (DILI).  Participants who experience a transaminase elevation above 3 times the 
upper limit of normal (× ULN) should be monitored more frequently to determine if they are 
an “adaptor” or are “susceptible.”
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (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 lab 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:


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
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).
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, laboratory tests should 
include albumin, creatine kinase (CK), direct and indirect bilirubin, gamma-glutamyl 
transferase (GGT), prothrombin time (PT)/international normalized ratio (INR), total bile 
acids, alkaline phosphatase and acetaminophen drug and/or protein adduct levels.  
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 (either by 
itself or as a co formulated product in prescription or over-the-counter medications), 
recreational drug, 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 and liver imaging 
(eg, biliary tract) 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 liver function test (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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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.  
Information should be provided in the source documentation with rationale related to any lab 
abnormalities.
8.4.3. Exposure to the Investigational Product During Pregnancy or Breastfeeding, and 
Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.4.3.1. Exposure during Pregnancy
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy (EDP) occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the investigational product;

An example of environmental exposure would be a case involving direct contact 
with a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant 
and has been exposed to chemotherapeutic products).

A male has been exposed (eg, because of treatment or environmental exposure) to 
the investigational product prior to or around the time of conception and/or is 
exposed during his partner’s pregnancy.
If a participant or participant’s partner becomes or is found to be pregnant during the 
participant’s treatment with the investigational product, 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.  In addition, the investigator must submit 
information regarding environmental exposure to a Pfizer product in a pregnant woman 
(eg, participant reports that she is pregnant and has been exposed to a cytotoxic product by 
inhalation or spillage) to Pfizer Safety using the EDP supplemental form.  This must be done
irrespective of whether an AE has occurred and within 24 hours of awareness of the 
exposure.  The information submitted should include the anticipated date of delivery 
(see below for information related to termination of pregnancy).
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 


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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 
pre-procedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
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 includes 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 investigational product.
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.
8.4.3.2. Exposure during Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form.  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’s administration, the SAE is reported together with the exposure during breastfeeding.
8.4.3.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.


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An occupational exposure is reported 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 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 is maintained in the investigator site file.
8.4.4. Medication Errors 
Other exposures to the investigational product 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
8.5. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong participant, or at the wrong time, or at the wrong dosage strength 
Medication errors include:

Medication errors involving participant exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating 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 immediately.
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 non-serious, are recorded on an 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.


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9. DATA ANALYSIS/STATISTICAL METHODS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a statistical analysis plan (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. 
At the completion of Stage 1, the team may provide limited summary level (but not patient 
level) data that may be shared externally and internally. This will be considered preliminary 
data and the timing of the data release will be contingent on internal Pfizer procedures to 
maintain data integrity.  During this time, the investigators and select list of individuals from 
the sponsor who interact with the investigators and monitor safety will continue to be blinded 
to individual study treatments through the query resolution of the Stage 1 data. Patient level 
data will not be shared with the investigators until the entire study is complete.
9.1. Sample Size Determination
9.1.1. Sample Size Determination in Stage 1
The primary endpoint is the change from baseline in CDASI activity score at Week 12.  The 
treatment effect is defined as the difference (mean change from baseline at Week 12 in the 
active treatment group minus the mean change from baseline at Week 12 in the placebo 
group) in the mean change of CDASI activity score from baseline at Week 12. A successful 
treatment should decrease CDASI activity score and therefore the desirable value of the 
treatment effect is negative.  The value -5 is viewed as the minimal clinically important value 
of the treatment effect. 
In the comparison of the active treatment arm to placebo, the treatment is declared 
efficacious if both of the following conditions are satisfied:

C1: Estimated value of the treatment effect is lower than -5.

C2: An upper limit of 2-sided 90% confidence interval for the treatment effect is 
below zero.
The standard deviation of the change from baseline in CDASI activity score is assumed to be 
equal to 8 units. This assumption is based on the analysis of the observational data sets 
collected by the researchers at Pfizer’s Center of Therapeutic Innovation and University of 
Pennsylvania. 
A sample size of 24 participants (16 participants in the active and 8 participants in the 
placebo treatment groups) with complete response is expected to provide 80% probability of 
declaring efficacy (satisfying both of the conditions C1 and C2) for the reference value of the 
true treatment effect equal to -8.6 units.
It is assumed that 80% of randomized participants will provide complete responses of 
CDASI activity score at Week 12. 


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9.1.2. Sample Size Determination in Stage 2
The primary endpoint is the change from baseline in CDASI activity score at Week 12. 
Baseline is defined as Day 1. For each active treatment group, the treatment effect is defined 
as the difference (between the active treatment group and the placebo group across the two 
stages) in the mean change of CDASI activity score from baseline at Week 12. The standard 
deviation of the change from baseline CDASI activity score is assumed to be 8 units.
For the comparison of 150 mg PF-06823859 and placebo, assuming a SD of 8 and assuming 
a pooled sample size of approximately 10 and 11 completers respectively across the two 
Stages, we expect the half length of the 90% CI to be 5.75. For the comparison of 600 mg 
PF-06823859 and placebo, assuming a SD of 8 and assuming a pooled sample size of 
approximately 21 and 11 completers respectively across the two Stages, we expect the 
half length of the 90% CI to be 4.90. 
No p-values will be presented for the comparisons listed in the objectives and endpoints of 
Section 2.2 for Stage 2.
9.1.3. Sample Size Determination in Stage 3
The major efficacy endpoint of interest in Stage 3 is the TIS,31 which is a continuous measure 
ranging from 0 to 100. The treatment effect is defined as the difference in mean TIS between 
the active and placebo treatment groups at Week 12. The standard deviation in TIS at Week 
12 is estimated to be between 15 and 25 units.32,33
The DM muscle disease cohort will enroll between 8 and 16 participants randomized 1:1 to 
active and placebo. Table 3 shows the estimated half widths of the 90% confidence intervals 
for the difference in mean TIS between the PF-06823859 600 mg arm and the placebo arm at 
Week 12 across a range of standard deviations and number of completers. For example, if 
10 participants (5 active, 5 placebo) complete the Week 12 assessment and the SD of the TIS 
is 20, the estimated half width of the 90% confidence interval is approximately 20.8.
No p-values will be presented for the comparisons listed in the objectives and endpoints of 
Section 2.4 for the DM muscle cohort.


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Table 3.
Estimated Half-widths of 90% Confidence Intervals for the Difference in 
TIS between Active and Placebo at Week 12
Number of completers 
(active: placebo)
Assumed 
SD of TIS
Half width of 
90% CI
8 (4:4)
15
17.4
20
23.3
25
29.1
10 (5:5)
15
15.6
20
20.8
25
26.0
12 (6:6)
15
14.2
20
19.0
25
23.7
14 (7:7)
15
13.2
20
17.6
25
22.0
16 (8:8)
15
12.3
20
16.4
25
20.6
9.2. Efficacy Analysis
The primary efficacy analysis of Stage 1 and Stage 2 is based on the CDASI activity scores
at Week 12.  The primary efficacy analysis in Stage 3 is based on the TIS at Week 12.
Analysis of efficacy endpoints will be performed for the modified intenttotreat (mITT) 
population, defined as all randomized participants who receive at least 1 dose of 
investigational product.  Formal statistical testing for efficacy will be based on Stage 1 data 
only.
All treatment periods in this study will be conducted in a double blinded fashion. During this 
period, the participants, investigators and sponsor (or designee) will be blinded to
randomized study treatments. After the treatment period is completed for all the participants, 
some members of the study team will be unblinded so that a report for the corresponding data 
can be generated. The participants, investigators, and individuals from the sponsor (or 
designee) who interact with the investigators and monitor safety will continue to be blinded 
to individual study treatments throughout the follow up period of the study. The official 
database release will occur after the last participant completes the last visit. The Clinical 
Study Report (CSR) will be based on the data generated following the database release.


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9.2.1. Analysis of the Primary Endpoint 
9.2.1.1. Analysis of Primary Endpoint in Stage 1
The treatment effect is defined as the difference (mean change from baseline at Week 12 in 
the active treatment group minus the mean change from baseline at Week 12 in the placebo 
group) in the mean change of CDASI activity score from baseline at Week 12. 
The estimates for treatment effect will be obtained by fitting the longitudinal analysis of 
covariance (LANCOVA) model to the CDASI activity score change from baseline.  The 
model will include treatment (active dose and placebo), week and treatment by week 
interaction as fixed effects and baseline value as a covariate.  An unstructured 
variance-covariance matrix will be allowed.
A sensitivity analysis will be based on the analysis of covariance (ANCOVA).  The 
ANCOVA-based estimation of the treatment effect will use the observations collected at 
baseline and Week 12 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.
Estimates and the confidence intervals for treatment effect will be presented for each of these 
methods.
9.2.1.2. Analysis of Primary Endpoint in Stage 2
The treatment effect is defined as the difference (between each active treatment group and 
placebo group across the two stages) in the mean change of CDASI activity score from 
baseline at Week 12.  Baseline is defined as Day 1.
Estimates and 90% CI will be computed. No p-values will be computed for the analysis in 
this stage.
The estimates will be obtained using the same LANCOVA model as described in 
Section 9.2.2.1. 
Data permitting, the secondary analysis for the primary endpoint in Stage 2 will be the 
PF-06823859 exposure-response analysis of the combined data from Stage 1 and Stage 2. 
The Population Modeling Analysis Plan, (PMAP) will describe the evaluation of the
relationship between PF-06823859 exposures and response at Week 12. Analyses developed 
to characterize this exposure-response relationship will not be part of the Clinical Study 
Report (CSR) and may be reported separately.
Additional sensitivity analysis will be described in the SAP.


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9.2.1.3. Analysis of Primary Endpoint in Stage 3
The primary objective in Stage 3 is to determine the safety and tolerability of PF-06823859 
in adult DM participants with moderate muscle disease. No efficacy analyses will be 
performed for the primary endpoint. All safety data will be reported according to sponsor 
standards consistent with the previous stages.
9.2.2. Analysis of Secondary Endpoints
9.2.2.1. Analysis of the Secondary Endpoints in Stage 1
The values of CDASI activity and damage scores at each visit will be summarized by 
descriptive statistics.  The estimates for treatment effect will be obtained by LANCOVA and 
ANCOVA methods described in Section 9.2.1 where the change from baseline of a 
corresponding score (ie, activity or damage score) will be used as a dependent variable.  The 
ANCOVA analysis will be used as supportive analysis.  Estimates and the confidence 
intervals for treatment effect will be presented for each of these methods.
9.2.2.2. Analysis of the Secondary Endpoints in Stage 2
The analyses and summaries of the secondary endpoints in Stage 2 will be the same as those 
in Section 9.2.2.1 except that they will be conducted for the data across the two Stages. No 
p-values will be presented for these analyses.
As a supportive analysis, summaries will also be presented for change from baseline in 
CDASI activity score after 12 weeks of active treatment, which includes pooled data from 
participants who received active treatment from Day 1 to Week 12 (CDASI measured at 
Week 12) and participants who received active treatment from Week 12 to Week 24 (CDASI 
measured at Week 24). This may be compared to the participants receiving placebo during 
the first 12 weeks. Baseline is defined as Day 1 for participants who received active 
treatment from Day 1 to Week 12. Baseline is defined as Week 12 for participants who 
received active treatment from Week 12 to Week 24. Further details will be provided in the 
SAP.
9.2.2.3. Analysis of the Secondary Endpoints in Stage 3
The TIS at baseline is 0 indicating no change. The TIS at post baseline visits is scored as 
relative change from baseline. The absolute value of the TIS at each post baseline visit will 
be summarized by descriptive statistics. The estimates of the treatment effect from Baseline 
to Week 12 will be obtained by LANCOVA where the TIS will be used as a dependent 
variable. The model will include treatment (active dose and placebo), week and treatment by 
week interaction as fixed effects. An unstructured variance-covariance matrix will be 
allowed. 
Estimates and the 90% confidence intervals for treatment effect will be presented. No 
p-values will be presented for these analyses.


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As a supportive analysis, the mean TIS after receiving 12 weeks of active treatment will also 
be estimated among all participants who completed or had the chance to complete the fixed 
sequence using pooled data from participants who received active treatment from Day 1 to 
Week 12 (TIS measured at Week 12) and participants who received active treatment from 
Week 12 to Week 24 (TIS measured at Week 24). This may be compared to the placebo 
during the first 12 weeks. Baseline is defined as Day 1 for participants who received active
treatment from Day 1 to Week 12. Baseline is defined as Week 12 for participants who 
received active treatment from Week 12 to Week 24. Further details will be provided in the 
SAP.
The CSM of the TIS, including PGA, PtGA, MMT, HAQ-DI, muscle enzymes, and 
extra-muscular activity, at each visit will also be summarized by descriptive statistics on the 
absolute scale and change from baseline.
Additionally, the absolute values and change from baseline of CDASI activity and CDASI 
damage scores at all scheduled time points will be summarized by descriptive statistics per 
Section 9.2.2.1.
Further details will be provided in the SAP.
9.2.3. Analysis of Other Endpoints
9.2.3.1. Analysis of Other Endpoints in Stage 1
The values of patient reported outcomes (SF36, DLQI and 5D Pruritus Scale, Severity Score) 
at each visit will be summarized by descriptive statistics.  The estimates for treatment effect 
will be obtained by LANCOVA method described in Section 9.2.1 where the change from 
baseline of a corresponding score will be used as a dependent variable. 
The individual items of the CDASI will be summarized by descriptive statistics.
The detailed analysis of gene signature data and other biomarkers will be described in the 
exploratory analysis plan.
 
 
  
9.2.3.3. Analysis of Other Endpoints in Stage 3
The values of PROs (PtGA, HAQ-Di, 5D Puritus, 
, 
FACIT-F, SF-36V2, and EQ-5D-5L) and PhGA, VAS at each visit will be summarized by 
descriptive statistics.
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9.4. Safety Analysis
The safety analysis population will include all participants who have received at least one 
dose of study drug or placebo.  Safety data will be presented in tabular and/or graphical 
format and summarized descriptively, where appropriate.  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.  Participant listings will be produced for these safety endpoints accordingly.
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Safety analyses will be reported for Stage 1, Stage 1 and 2 combined, and Stage 3 as 
described in Section 2.
9.4.1. 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 Columbia Classification 
Algorithm of Suicide Assessment (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.
9.4.2. Electrocardiogram
Changes from baseline for the ECG parameters (QT interval, heart rate, corrected QT 
interval QTc (QTcB and QTcF versions) and QRS interval 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 post dose QTc values (QTcB or QTcF) and 
maximum increases from baseline in the following categories will be tabulated by treatment:
Borderline (msec) 
Prolonged (msec) 
Absolute Value 
≥450 - <480 
≥480 
Absolute Change 
30-<60
≥60 
In addition, the number of participants with absolute QTc values ≥500 msec will be listed.
9.5. Interim Analyses
9.5.1. Analysis for Internal Decision Making
In stage 1 of the study, an interim analysis was performed when 32 participants were 
randomized and completed Visit 6 (Week 12). Additional interim analyses in later study 
stages may be conducted depending on the enrollment rate. If an additional interim analysis 
is done in the future, an internal review committee (IRC), independent from the blinded study 
team will review efficacy and safety data for business decision planning, if applicable. No 
changes to the conduct of the study will occur. The results of the interim analysis will not be 
shared with the study team, participants, or investigators.
 
 
 
 
 
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10. QUALITY CONTROL AND QUALITY ASSURANCE
Pfizer or its agent will conduct periodic monitoring visits during study conduct to ensure that 
the protocol and Good Clinical Practices (GCPs) are being followed.  The monitors may 
review source documents to confirm that the data recorded on CRFs are accurate.  The 
investigator and institution will allow Pfizer monitors/auditors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification.  This 
verification may also occur after study completion.
During study conduct and/or after study completion, the investigator site may be participant
to review by the IRB/EC, and/or to quality assurance audits performed by Pfizer, or 
companies working with or on behalf of Pfizer, and/or to inspection by appropriate 
regulatory authorities.
The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the investigator site for the inspection and will allow Pfizer 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 Pfizer or its agent.  Before response submission to the regulatory 
authorities, the investigator will provide Pfizer or its agents with an opportunity to review 
and comment on responses to any such findings.
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.
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11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included participant.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring, and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true. Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry. 
In most cases, the source documents are the hospital or the physician participant chart.  In 
these cases, data collected on the CRFs must match the data in those charts. 
In some cases, the CRF may also serve as the source document.  In these cases, a document 
should be available at the investigator site and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document.
11.2. Record Retention
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the 
investigator agrees to keep records, including the identity of all participating participants 
(sufficient information to link records, eg, CRFs and hospital records), all original signed 
informed consent documents, copies of all CRFs, safety reporting forms, source documents, 
and detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, and telephone call reports).  The records should 
be retained by the investigator according to the ICH guidelines, according to local 
regulations, or as specified in the clinical study agreement (CSA), whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or an independent third party arranged by Pfizer. 
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations.


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The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met.
12. ETHICS
12.1. Institutional Review Board/Ethics Committee
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, 
eg, recruitment advertisements, if applicable, from the IRB/EC.  All correspondence with the
IRB/EC should be retained in the investigator file.  Copies of IRB/EC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the participants.  
In that event, the investigator must notify the IRB/EC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Participants (Council for International Organizations 
of Medical Sciences 2002), ICH Guideline for Good Clinical Practice, and the Declaration of 
Helsinki.
12.3. Participant Information and Consent
All parties will ensure protection of participant personal data and will not include participant
names or other identifiable data in any reports, publications, or other disclosures, except 
where required by law.
When study data are compiled for transfer to Pfizer and other authorized parties, participant
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by Pfizer in order to de-identify study participants. The 
investigator 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.  In case of data 
transfer, Pfizer will maintain high standards of confidentiality and protection of participants’
personal data consistent with applicable privacy laws.
The informed consent documents and any participant recruitment materials must be in 
compliance with ICH GCP, local regulatory requirements, and legal requirements, including 
applicable privacy laws.
The informed consent documents used during the informed consent process and any 
participant recruitment materials must be reviewed and approved by Pfizer, approved by the 
IRB/EC before use, and available for inspection.


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The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study and possible risks associated with participation.
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each participant before any study-specific activity is performed. The 
investigator will retain the original of each participant's signed consent document.
12.4. 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 investigational 
product, Pfizer should be informed immediately. 
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 ICH GCP that the investigator becomes aware 
of.
13. DEFINITION OF END OF TRIAL
13.1. End of the Trial 
Last participant last visit (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.
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or investigational product safety problems, or at the 
discretion of Pfizer.  In addition, Pfizer retains the right to discontinue development of 
PF-06823859 at any time.
If a study is prematurely terminated, Pfizer will promptly notify the investigator.  After 
notification, the investigator must contact all participating participants and the hospital 
pharmacy (if applicable) within 7 days.  As directed by Pfizer, all study materials must be 
collected and all CRFs completed to the greatest extent possible.
15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations. 


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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.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in participants) that evaluate the safety and/or efficacy of a 
Pfizer product, regardless of the geographical location in which the study is conducted.  US 
Basic Results are submitted for posting within 1 year of the primary completion date (PCD) 
for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.
PCD is defined as the date that the final participant was examined or received an intervention 
for the purposes of final collection of data for the primary outcome, whether the clinical 
study concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual participants has been removed) on www.pfizer.com 
for Pfizer-sponsored interventional studies at the same time the US Basic Results document 
is posted to www.clinicaltrials.gov.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by the 
principal investigator (PI) of the results of the study based on information collected or 
generated by the PI, whether or not the results are favorable to the Pfizer product.  However, 
to ensure against inadvertent disclosure of confidential information or unprotected 
inventions, the investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “publication”) 
before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before it is submitted 
for publication or otherwise disclosed. If any patent action is required to protect intellectual 
property rights, the investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days.


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The investigator will, on request, remove any previously undisclosed confidential 
information before disclosure, except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.
If the study is part of a multicenter study, the investigator agrees that the first publication is 
to be a joint publication covering all investigator sites, and that any subsequent publications 
by the PI will reference that primary publication. However, if a joint manuscript has not 
been submitted for publication within 12 months of completion or termination of the study at 
all participating sites, the investigator is free to publish separately, participant to the other 
requirements of this section.
For all publications relating to the study, the institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.
If there is any conflict between the CSA and any attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study participants, and the CSA will control as to all 
other issues.


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16. REFERENCES
1.
National Orgnaization of Rare Disease, NORD 2015: http://rarediseases.org/rare-
diseases/dermatomyositis/.  
2.
Myositis Support and Understanding Association Inc. 2010-2017; 
https://understandingmyositis.org/types-of-myositis/dermatomyositis/?gclid=CIXP-
fLSns8CFYM9gQodSZIDlA).  
3.
Fasano S, Alves SC, Isenberg DA. Current pharmacological treatment of idiopathic 
inflammatory myopathies. Expert Rev Clin Pharmacol 2015.
4.
Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. Lancet 2003;
362(9388):971-82.
5.
Salajegheh M, Kong SW, Pinkus JL, et al. Interferon-stimulated gene 15 (ISG15) 
conjugates proteins in dermatomyositis muscle with perifascicular atrophy. Ann Neurol 
2010; 67(1):53-63.
6.
Liao AP, Salajegheh M, Nazareno R, et al. Interferon ß is associated with type 1 
interferon- inducible gene expression in dermatomyositis. Ann Rheum Dis 2011; 
70(5):831-6.
7.
Wong D, Kea B, Pesich R et al. Interferon and biologic signatures in dermatomyositis 
skin: specificity and heterogeneity across dis- eases. PLOS ONE 2012; 7:e29161.
8.
Huard et al., Correlation of Cutaneous Disease Activity with type 1 interferon gene 
signature and interferon in Dermatomyositis; British American Journal of 
Dermatology, article BJD15006.
9.
Malhotra S, Bustamante MF, Perez-Miralles F, et al. Search for specific biomarkers of
IFNbioactivity in patients with multiple sclerosis. PLoS One 2011; 6(8):e23634.
10.
Takayanagi H et al, “RANKL maintains bone homeostasis through c-FOS-dependent 
induction of interferon-b” Nature 18Apr 2002, vol 416, p744.
11.
B Wang, BW Higgs, L Chang, I Vainshtein, Z Liu, K Streicher, M Liang, WI White, 
S Yoo, L Richman, B Jallal, L Roskos and Y Yao.  Pharmacogenomics and 
Translational Simulations to Bridge Indications for an Anti-Interferon-a Receptor 
Antibody, June 2013.
12.
Kroenke K, Strine TW, Spitzer RL, et al. The PHQ-8 as a measure of current
depression in the general population. J Affect Disord 2009;114(1-3):163-173.
13.
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):1035-43XXX.


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14.
C.O. Anyanwu, D.F. Fiorentino,  L. Chung,  C. Dzuong,  Y. Wang,  J. Okawa,  K. Carr,  
K.J. Propert  and Werth. Validation of the Cutaneous Dermatomyositis Disease Area 
and Severity Index: characterizing disease severity and assessing responsiveness to 
clinical change.  British Journal of Dermatology 2015: 173: 890-891.
15.
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(4):40-66.
16.
Ware JE, Snow KK, Kosinski M, et al. 36® Health Survey Manual and Interpretation 
Guide. Boston, MA: New England Medical Center, The Health Institute, 1993.
17.
Ware JE and Sherbourne CD. The MOS 36 Item Short Form Health Survey (SF-36®): 
I. conceptual framework and item selection. Med Care 1992; 30(6):473-83.
18.
Elman S, Hynan LS, Gabriel V, Mayo MJ. The 5-D itch scale: a new measure of
pruritus. Br J Dermatol 2010;162:587e93.
19.
Weisshaar, Elke, Uwe Gieler, Jörg KUpFER, Masutaka Furue, Hidehisa Saeki, and Gil 
YOSIpOVITCH. "Questionnaires to assess chronic itch: a consensus paper of the 
special interest group of the International Forum on the Study of Itch.
"Acta dermato-venereologica 92, no. 5 (2012): 493-496.
20.
Hundley JL, Carroll CL, Lang W, Snively B, Yosipovitch G, Feldman SR, et al. 
Cutaneous symptoms of dermatomyositis significantly impact patients’ quality of life. 
J Am Acad Dermatol. 2006;54(2):217–20.
21.
Shirani Z, Kucenic MJ, Carroll CL, Fleischer AB Jr, Feldman SR, Yosipovitch G, et al. 
Pruritus in adult dermatomyositis. Clin Exp Dermatol. 2004;29(3):273–6.
22.
Pereira, Manuel Pedro, and Sonja Ständer. "Assessment of severity and burden of 
pruritus." Allergology International 66, no. 1 (2017): 3-7.
23.
Ständer, S., Augustin, M., Reich, A., Blome, C., Ebata, T., Phan, N.Q. and 
Szepietowski, J.C., 2013. Pruritus assessment in clinical trials: consensus 
recommendations from the International Forum for the Study of Itch (IFSI) Special 
Interest Group Scoring Itch in Clinical Trials. Acta dermato-venereologica, 93(5), 
pp.509-514.
24.
Rider LG, Werth V P, Huber A M, et al. Measures of adult and juvenile 
dermatomyositis, polymyositis, and inclusion body myositis. Dermatology Life Quality 
Index (DLQI). Arthritis Care Res (Hoboken), 2011. 63 Suppl 11: p. S118-57.
25.
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.


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26.
The EuroQol Group. EuroQol-a new facility for the measurement of health-related 
quality of life. Health Policy. 1990;16(3):199–208.Herdman M, Gudex C, Lloyd A, 
et al. 
27.
Development and preliminary testing of the new five-level version of EQ-5D 
(EQ-5D-5L). Qual Life Res. 2011;20(10):1727–36.
28.
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.
29.
L. G. Rider, Werth V. P., Huber A. M., Alexanderson H., Rao A. P., Ruperto N., 
Herbelin L., Barohn R., Isenberg D., and Miller F. W., Measures of adult and juvenile 
dermatomyositis, polymyositis, and inclusion body myositis: Physician and 
Patient/Parent Global Activity, Manual Muscle Testing (MMT), Health Assessment 
Questionnaire (HAQ)/Childhood Health Assessment Questionnaire (C-HAQ), 
Childhood Myositis Assessment Scale (CMAS), Myositis Disease Activity Assessment 
Tool (MDAAT), Disease Activity Score (DAS), Short Form 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 (Hoboken), 2011. 63 Suppl 
11: p. S118-57.
30.
International Myositis Assessment & Clinical Studies Group (IMACS). Disease Activity 
Core Set Measures.  [cited 2020 Oct 22]; Available from: 
https://www.niehs.nih.gov/research/resources/imacs/diseaseactivity/index.cfm.
31.
Aggarwal R, Rider LG, Ruperto N, et al. 2016 American college of 
rheumatology/European league against rheumatism criteria for minimal, moderate, and 
major clinical response in adult dermatomyositis and polymyositis: an international 
myositis assessment and clinical studies group/paediatric rheumatology international 
trials organisation collaborative initiative. Arthritis & Rheumatology. 
2017;69(5):898-910.
32.
Leclair V, Galindo-Feria AS, Dastmalchi M, et al.  Efficacy and safety of rituximab in 
anti-synthetase antibody positive and negative subjects with idiopathic inflammatory 
myopathy: a registry-based study. Rheumatology. 2019;58(7):1214-1220.
33.
Tjärnlund A, Tang Q, Wick C, et al. Abatacept in the treatment of adult 
dermatomyositis and polymyositis: a randomised, phase IIb treatment delayed-start 
trial. Ann RheumDis. 2018;77(1):55-62.


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34.
Clinical Trial Facilitation and Coordination Group, (CTFG Guidelines) –
Recommendations related to contraception and pregnancy testing in clinical trials 
(Version 1.1, CTFG 21/09/2020).


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Appendix 1. Abbreviations 
This following is a list of abbreviations that may be used in the protocol. 
Abbreviation
Term
%CV
percent coefficient of variation
ADA
Anti-Drug antibody
ADCC
Antibody-dependent cell-mediated cytotoxicity
AE
adverse event
ALC
absolute lymphocyte count
ALT
alanine aminotransferase
ANC
absolute neutrophil count
ANCOVA
Analysis of covariance
anti-TNF
anti-tumor necrosis factor
anti-IFN a
anti-interferon alpha
AST
aspartate aminotransferase
ATP
adenosine tri-phosphate
AUC
area under the curve
AZA
Azathioprine

Beta
-hCG
beta-human chorionic gonadotropin
BA
Bioavailability
BAFF
B-cell activating factor
BBS
Biospecimen Banking System
BCD
Bacille Calmette Guerin
BID
twice a day
BLyS
B-lymphocyte stimulator
BP
blood pressure
Cmax
maximum (or peak) serum concentration
CAV
Concentration average
CDC
Centers for Disease Control
CDASI
Cutaneous Dermatomyositis Disease Area and Severity Index
CDS
core data sheet
CI
confidence interval
CK
creatine kinase
Cl
chlorine
Clq
Chloroquine
CMV
Cytomegalovirus
CNS
central nervous system
COVID-19
Corona Virus Disease 2019
CRF
case report form
CSA
clinical study agreement
CSM
Core Set Measure
CSR
Clinical Study Report
C-SSRS
Columbia-Suicide Severity Rating Scale


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Abbreviation
Term
CT
clinical trial
CT
Computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
CTFG
Clinical Trial Facilitation and Coordination Group
CVA
cerebrovascular accident
DAI
dosage and administration instructions
DDI
drug-drug interaction
DILI
drug-induced liver injury
DLQI
Dermatology and Life Quality Index
DM
Dermatomyositis
DMARDs
disease-modifying antirheumatic drugs
DNA
deoxyribonucleic acid
DU
dispensable unit
EBV
Epstein-Barr virus
EC
ethics committee
ECG
electrocardiogram
EDP
exposure during pregnancy
EDTA
edetic acid (ethylenediaminetetraacetic acid)
EFD
Embryo-Fetal Development
EOS
end of study
EPO
Erythropoietin
ePPND
enhanced pre and postnatal development
EQ-5D-5L & EQ VAS European Quality of Life, 5 Dimenstion, 5 Level Scale and Visual 
Analogue Scale
ET
Early termination
Eudra CT
European Union Drug Regulating Authorities Clinical Trials 
EW
early withdrawal
FACIT-F
Functional Assessment of Chronic Illness Therapy Fatigue Scale
FcR
Fc Receptor
FDA
Food and Drug Administration
FIH
first in human
FSFV
first subject first visit
FSH
follicle-stimulating hormone
GCP
Good Clinical Practice
GGT
gamma-glutamyl transferase
GI
Gastrointestinal
GLMM
generalized linear mixed model
GLP
Good laboratory practice
HAQ-DI
Health Assessment Questionnaire and Disease Index
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody test
HBsAg
hepatitis B surface antigen
HCVAb
hepatitis C virus antibody


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Abbreviation
Term
HEENT
head, eyes, ears, nose and throat
Hep B
hepatitis B
HHV6
Human Herpes Virus 6
HIV
human immunodeficiency virus
HR
heart rate
HRT
hormone replacement therapy
hsCRP
high-sensitivity C-reactive protein
HSV-1
herpes simplex virus type 1
HSV-2
herpes simplex virus type 2
IA 
Intra-articular
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Conference on Harmonisation
ID
Identification
IFN-
Interferon beta
IFNAR 
interferon-α/β receptor
Ig
Immunoglobulin
IgG1
Immunoglobulin G1
IGRA
Interferon-Gamma Release Assays
IL-6
Interlukin 6
IM
Intramuscular
IMACS
International Myostits Assessment & Clinical Studies
IMP
investigational medicinal product
IND
investigational new drug application
INF
Interferon
INR
international normalized ratio
IP
investigational product
IP-10
interferon gamma-induced protein 10
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
IRG
Interferon regulated gene
ISR
Injection site reaction
IUD
intrauterine device
IUS
Intrauterine system
IV
intravenous
IVIG
intravenous immunoglobulin
IVR
interactive voice-based response
IWR
interactive web-based response
JAK
Janus kinase 
K2EDTA
anticoagulant
LANCOVA
longitudinal analysis of covariance
LDH
lactate dehydrogenase


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Abbreviation
Term
LFT
liver function test
LLN
lower limit of normal
LSLV
last subject last visit
MAb
Monoclonal antibody
MAD
multiple ascending dose
MPV
mean platelet volume
MCS
Multiple chemical sensitivity
MDAAT
Myositis Disease Activity Assessment Tool
MDA5
melanoma differentiation-associated gene 5
MDI
Muscle Disease Index
Mi2
myositis specific Autoantibody
mITT
Modified intent to treat 
MMF
Mycophenolic acid
MMT-8
Manual Muscle Testing-8 designated muscle groups
MP
Mycoplasma Pneumoniae
MRI
magnetic resonance imaging
MTX
Methotrexate
MXA-1
Human myxovirus resistance protein 1
N/A
not applicable
NAb
Neutralizing Anti-body
NOAEL
no-observed-adverse-effect-level
NXP2
Nuclear matrix protein
OLE
open label extension
PCD
primary completion date
PCS
physical component scores
PD
Pharmacodynamics
PE
physical examination
PET
positron emission tomography
pH
Potential of Hydrogen
PhGA, VAS
physician global assessment
PHQ-8
Patient Health Questionnaire 8-item depression measure
PI
Principal Investigator
PK
Pharmacokinetics
PMAP
Population Modeling Analysis Plan
PoC
proof-of-concept
PoM
proof-of-mechanism
PPD
purified protein derivative
PR interval
period, in milliseconds, that extends from beginning of P wave 
until beginning of QRS complex
PROMIS
Patient Reported Outcome Measurement Information System
PT
prothrombin time
PtGA
Patient global assessment
PTT
partial thromboplastin time


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Abbreviation
Term
PPT
partial prothrombin time
PRO
patient reported outcome
QD
once a day
QFT-GIT
QuantiFERON-TB Gold In-Tube
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
RNA
ribonucleic acid
RR
respiratory rate
R-R interval
time between beats on ECG
SAD
single ascending dose
SAE
serious adverse event
SAP
statistical analysis plan
SC
Subcutaneous
SCL
Supply Chain Lead
SD
Standard deviation
SF-36
The Short Form (36) Health Survey
SGOT
serum glutamic-oxaloacetic transaminase
SGPT
serum glutamic-pyruvic transaminase
SIB
suicidal ideation and behavior
SoA/SOA
Schedule of Assessments
SoC
standard of care
SLE
Systemic lupus erythematous
SOC
System Organ Class
SOP
standard operating procedure
SRSD
single reference safety document
TACI
transmembrane activator and CAML interactor
Tmax
time drug is present at maximum concentration in serum
TB
Tuberculosis
TBili
Total Bilirubin
TEAE
treatment-emergent adverse event
TIS
Total Improvement Score
TIF
Transcription intermediary factor
TNF
tumor necrosis factor
ULN
upper limit of normal
US
United States
VAS
visual analog scale
Vss
Volume at steady state
VZV
varicella zoster virus
WBC
white blood cell
WOCBP
women of child bearing potential


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Abbreviation
Term
WONCBP
women of non-child bearing potential


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Appendix 2. CDASI


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Appendix 3. Physician Global Assessment (PhGA, VAS)
THE PATIENT’S DERMATOMYOSITIS AT THIS TIME IS:
(PLEASE PLACE A VERTICLE LINEON THE LINE BELOW.)
Very  ______________________________________________ Very
Good
Poor
[Note: Scale will be 100 mm in length]


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Appendix 4. Personal Health Questionnaire Eight-Item Depression Measure (PHQ-8)
Kroenke K, Strine TW, Spitzer RL, et al.  The PHQ-8 as a measure of current depression in the general 
population. J Affect Disord 2009;114(1-3):163-173.


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Appendix 5.
 
CCI


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CCI


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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.


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CCI


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SF-36v2™Health Survey© 1996, 2000 by QualityMetric Incorporated and Medical Outcomes Trust.  All Rights 
Reserved.
SF-36® is a registered trademark of Medical Outcomes Trust.
(SF-36v2 Standard, US Version 2.0).


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McHorney CA, Ware JE, Lu JFR, et al.  The MOS 36Item ShortForm Health Survey (SF36®): III. tests of data 
quality, scaling assumptions and reliability across diverse patient groups.  Med Care 1994; 32(4):4066.  Ware 
JE, Snow KK, Kosinski M, et al. 36® Health Survey Manual and Interpretation Guide. Boston, MA: New 
England Medical Center, The Health Institute, 1993.Ware JE and Sherbourne CD. The MOS 36Item.


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Appendix 8. Dermatology Life Quality Index


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Appendix 9. 5D Pruritus Scale


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Appendix 10. EQ-5D-5L AND EQ-VAS


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Appendix 11. FACIT-F Scale


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Appendix 12. 12 HAQ


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Appendix 13. Patient Global Assessment (PtGA)


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Appendix 14. Guidelines for Participant Safety Monitoring and Discontinuation
These guidelines for participant safety monitoring and discontinuation are to be applied to all 
participants in study C0251002.  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.
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 [prothrombin time] with INR [international normalized 
ratio], 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);

For women of child-bearing potential with any positive urine -hCG test, the 
participant will have study drug interrupted and a serum sample submitted to the 
central laboratory for -hCG testing.
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:

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);


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
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

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 
Appendix 16:
Please refer to Appendix 16 for all inclusive prohibited medication listing.
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 IP 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 months.  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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Appendix 15. Time needed for Washout of Prohibited Medication or Medication 
Stabilization Prior to Day 1
180 days (6 months) prior to DAY 1

B-cell depleting agents, (rituximab, epratuzumab, alemtuzumab, or TACI-Ig).  In 
addition, participants that have been treated with rituximab, or TACI-g, (serum 
total immunoglobulin should be checked prior to study entry);

Investigational biologic agent;

IV or Oral Cyclophosphamide;

Belimumab; or 

Any B-Lymphocyte Stimulator, (BLys or anti BAFF agent).
90 Days (3 months) prior to DAY 1

Anti-TNF therapy, (infliximab, etanercept, adalimumab).

High dose oral corticosteroids (>100 mg/day prednisone, or equivalent) or pulse IV 
doses.

Plasmapheresis.
60 Days (2 months) prior to DAY 1

Any IV or IM steroid injection

Tofacitinib or any other JAK inhibitor

Stable dose of antimalarial agent 60 days, 

Stable dose of immunosuppressive/immunomodulatory agent (60 days) 

INHALED immunosuppressive agents (STABLE 60 days prior to Day 1, dose 
must remain stable during the study)

DMARDs, (methotrexate, sulfasalazine, hydroxychloroquine, and leflunomide.  
Less frequently used medications include gold salts, azathioprine, and 
cyclosporine) Dose must be stable for 60 days and remain stable during the 
treatment.

Participants may be on one of the following cytotoxic agents: Methotrexate,(MTX), 
Azathioprine, (AZA), leflunominde, mycophenolate, or 6- Mercaptopurine (MP), 
but not on any combination of these cytotoxic agents.

Replacement of one immunosuppressive medication or antimalarial drug for 
another may be permitted for safety related issues after discussion with the 
sponsor.


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42 Days (6 weeks prior to Day 1)

Live or attenuated vaccine.
30 Days (1 month prior to Day 1)

Intra articular steroid injection.

Must be on a stable dose of corticosteroid or equivalent for 30 days.

Must be on a stable dose of IVIG for 30 days.

Oral Tacrolimus requires a 30 day washout prior to Day 1 and is prohibited 
throughout the treatment period.
14 Days (2 weeks prior to Day 1)

Topical calcineurin inhibitors, (eg, topical tacrolimus, pimecrolimus) require a 
14 day washout prior to Day 1 and are prohibited throughout the treatment period.

A stable dose of topical immunosuppressant of any strength used on the scalp is 
permitted throughout the study, with the exception of prohibited medications.
Marketed Biologics (prior to Day 1)

Marketed Biologics require a five half-life washout period.


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Appendix 16. List of Prohibited and Permitted Concomitant Medications 
Medications
C0251002 
Treatment Period Day 1-Week 12 (Stage 2)
Treatment Period Day 1-Week 24 
(Amended Stage 2
(Amended Stage 3)
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 24, 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.

No new antimalarial drugs or increase 
in dose is allowed during the 
treatment period.
Permitted
Thalidomide, tacrolimus, or mizoribine
Prohibited

Any form of tacrolimus or any form 
of a topical calcineurin inhibitor, 
(TCI) is not allowed.
Permitted 
Immunosuppressive topical 
Permitted 

Immunosuppressive ointment for the 
scalp.  Stable dose for 14 days prior to 
Day 1.
Permitted
Topical calcineurin inhibitors 
Prohibited
Permitted
Immunosuppressive eye drops
Permitted
Permitted


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Medications
C0251002 
Treatment Period Day 1-Week 12 (Stage 2)
Treatment Period Day 1-Week 24 
(Amended Stage 2
(Amended Stage 3)
Follow-up Period
Investigational or marketed biologics (eg, 
abatacept,  tocilizumab, TNF inhibitors)
Prohibited
Prohibited
Cyclophosphamide or chlorambucil
Prohibited
Permitted
Cyclosporine
Prohibited
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 15 mg or equivalent per 
day as per protocol Section 5.8.5. 
Permitted
Permitted
Note: If you have any questions about the use of a drug, please contact the study team. If 
you see that a specific drug is not listed, but it is in the same drug class as a prohibited drug; 
it should be considered prohibited.


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Appendix 17. 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). 
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 may be performed during a telehealth visit:

Review and record any AEs and SAEs since the last contact.  Refer to Section 8.3, 
and Section 12.4.

Review and record any new concomitant medications or changes in concomitant 
medications since the last contact.

Review and record contraceptive method. Confirm that the participant is adhering to 
the contraception method(s) required in the protocol. Refer to Section 4.8.2 and 
Appendix 25. German participants will follow Appendix 24.

PGA.

CDASI (if applicable).

CSSRS (if applicable).

Patient Reported Outcomes (if applicable).

Study participants must be reminded to promptly notify site staff about any change in 
their health status.


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Home Health Visits (If applicable)
A home health care service will 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.
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 1 of the protocol; not all laboratory collections may be possible.

Hematology;

Chemistry;

Urinalysis;

Viral Surveillance (if applicable);

Pregnancy testing (if applicable);

PK (if applicable).

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 IU/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. 

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 


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be filed in the participant’s source documents/medical records. Relevant data from 
the local laboratory report should be recorded on the CRF.
Electrocardiograms (If applicable)

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. 
Adverse Events and Serious Adverse Events  

If a participant has COVID-19 during the study, this should be reported as an adverse 
event (AE) or serious adverse events (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 
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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CCI
CCI
CCI
CCI
CCCI
CCI
CCI


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Appendix 19. Muscle Enzymes


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Appendix 20. MDAAT


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Appendix 21. MMT-8


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Appendix 22. TIS using Core Set Measures in DM
The total improvement score is the sum of all 6 improvement scores associated with the 
change in each core set measure.  A total improvement score of ≥20 represents minimal 
improvement, a score of ≥40 represents moderate improvement, and a score of 
≥60 represents major improvement.31


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Appendix 23. Muscle Damage Index, MDI
Please assess the severity and extent of damage exhibited by the patient at this time.  To 
assess the severity, please rate your overall assessment of the current disease damage for by
drawing a vertical mark on the 10cm. line according to the following scale: Left end of
line = no evidence of disease damage, Midpoint of line = moderate disease damage,
and -Right end of line = extreme or maximum disease damage.  Please write in NA if the
system cannot be assessed.


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Appendix 24. CTFG Guidelines34 Regarding Contraception for Germany
Birth control methods which may be considered as highly effective:
For the purpose of this guidance, methods that can achieve a failure rate of less than 1% per 
year when used consistently and correctly are considered as highly effective birth control 
methods. Such methods include:
1. Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation:1

Oral;

Intravaginal;

Transdermal.
2. progestogen-only hormonal contraception associated with inhibition of ovulation:1

oral

injectable

implantable.2
3. intrauterine device (IUD).2
4. intrauterine hormone-releasing system (IUS).2
5. bilateral tubal occlusion.2
6. vasectomised partner.2,3
7. sexual abstinence.4
1.
Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the efficacy 
of the contraception method.
2.
Contraception methods that in the context of this guidance are considered to have low user dependency.
3.
Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual 
partner of the WOCBP trial participant and that the vasectomised partner has received medical 
assessment of the surgical success.
4.
In the context of this guidance 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 
treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the subject.


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Appendix 25. Contraceptive and Barrier Guidance
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 months after the last dose of study intervention, 
which corresponds to the time needed to eliminate reproductive safety risk of the study 
intervention. 

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 Appendix 25.4.
Female Participant Reproductive Inclusion Criteria
Female Participant Options:
A female participant is eligible to participate  if she is not pregnant or breastfeeding, and at
least 1 of the following conditions apply.

Is not a WOCBP (see definitions below in Appendix 25.3.
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 5 months after the last dose of study 
intervention, which corresponds to the time needed to eliminate any reproductive 
safety risk of the study intervention. The investigator should evaluate the 


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effectiveness of the contraceptive method in relationship to the first dose of study 
intervention.

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 5 months after the last dose of study intervention, 
which corresponds to the time needed to eliminate any reproductive safety risk of the 
study intervention. 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. 
Women of Childbearing Potential
A woman is considered fertile following menarche and until becoming post menopausal 
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.
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).

SAP_001.pdf: 
Protocol C0251002 (PF-06823859) Statistical Analysis Plan
PFIZER CONFIDENTIAL
Page 1 of 48
Protocol C0251002
A PHASE 2, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY 
TO EVALUATE THE EFFICACY, SAFETY, AND TOLERABILITY OF 
PF-06823859 IN ADULT SUBJECTS WITH DERMATOMYOSITIS
Statistical Analysis Plan 
(SAP)
Version: 5.0 
Date:     09-JUN-2022


Protocol C0251002 (PF-06823859) Statistical Analysis Plan
PFIZER CONFIDENTIAL
Page 2 of 48
TABLE OF CONTENTS 
LIST OF TABLES.....................................................................................................................6
1. VERSION HISTORY............................................................................................................7
2. INTRODUCTION ...............................................................................................................10
2.1. Study Objectives .....................................................................................................10
2.1.1. Study Objectives in Stage 1........................................................................10
2.1.1.1. Primary Objective in Stage 1 ....................................................10
2.1.1.2. Secondary Objectives in Stage 1...............................................10
2.1.1.3. Exploratory Objectives in Stage 1.............................................10
2.1.2. Study Objectives in Stage 2........................................................................10
2.1.2.1. Primary Objectives in Stage 2...................................................10
2.1.2.2. Secondary Objectives in Stage 2...............................................10
2.1.2.3. Exploratory Objectives in Stage 2.............................................11
2.1.3. Study Objectives in Amended Stage 2 .......................................................11
2.1.3.1. Primary Objectives in Amended Stage 2 ..................................11
2.1.3.2. Secondary Objectives in Amended Stage 2 ..............................11
2.1.3.3. Exploratory Objectives in Amended Stage 2 ............................11
2.1.4. Study Objectives in Stage 3........................................................................12
2.1.4.1. Primary Objectives in Stage 3...................................................12
2.1.4.2. Secondary Objectives in Stage 3...............................................12
2.1.4.3. Exploratory Objectives in Stage 3.............................................12
2.2. Study Design ...........................................................................................................13
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS ................................................................................................................14
3.1. Endpoints in Stage 1................................................................................................15
3.1.1. Primary Endpoint in Stage 1.......................................................................15
3.1.2. Secondary Endpoint(s) in Stage 1...............................................................15
3.1.3. Exploratory Endpoints in Stage 1...............................................................15
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3.2. Endpoints in Stage 2................................................................................................16
3.2.1. Primary Endpoint in Stage 2.......................................................................16
3.2.2. Secondary Endpoints in Stage 2 .................................................................16
3.2.3. Exploratory Endpoints in Stage 2...............................................................16
3.3. Endpoints in Amended Stage 2 ...............................................................................17
3.3.1. Primary Endpoint in Amended Stage 2 ......................................................17
3.3.2. Secondary Endpoints in Amended Stage 2.................................................17
3.3.3. Exploratory Endpoints in Amended Stage 2 ..............................................17
3.4. Endpoints in Stage 3................................................................................................18
3.4.1. Primary Endpoint in Stage 3.......................................................................18
3.4.2. Secondary Endpoints in Stage 3 .................................................................18
3.4.3. Exploratory Endpoints in Stage 3...............................................................18
3.5. Other Endpoints.......................................................................................................19
3.6. Baseline Variables...................................................................................................19
4. ANALYSIS SETS ...............................................................................................................19
4.1. Full Analysis Set .....................................................................................................19
4.1.1. Full Analysis Sets in Stage 1, Stage 2, and Amended Stage 2 ...................20
4.1.2. Full Analysis Sets in Stage 3 ......................................................................20
4.2. Per Protocol Analysis Set........................................................................................21
4.2.1. Per Protocol Analysis Set in Stage 1 ..........................................................21
4.2.2. Per Protocol Analysis Set in Stage 2 and Amended Stage 2......................21
4.2.3. Per Protocol Analysis Set in Stage 3 ..........................................................21
4.3. Safety Analysis Set..................................................................................................21
4.4. Other Analysis Sets .................................................................................................22
5. GENERAL METHODOLOGY AND CONVENTIONS....................................................22
5.1. Hypotheses and Decision Rules ..............................................................................22
5.1.1. Hypotheses and Decision Rules in Stage 1.................................................22
5.1.2. Hypotheses and Decision Rules in Stage 2 and Amended Stage 2 ............23
5.1.3. Hypotheses and Decision Rules in Stage 3.................................................23
5.2. General Methods .....................................................................................................23
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5.2.1. Analyses for Continuous Longitudinal Data ..............................................23
5.2.1.1. Longitudinal Analysis of Covariance (LANCOVA) 
Model.................................................................................................23
5.2.1.2. Conventional ANCOVA Model................................................24
5.3. Methods to Manage Missing Data ..........................................................................24
6. ANALYSES AND SUMMARIES ......................................................................................25
6.1. Analyses and Summaries During Stage 1 ...............................................................25
6.1.1. Primary Endpoint in Stage 1.......................................................................25
6.1.1.1. Primary Analysis in Stage 1......................................................25
6.1.1.2. Sensitivity Analyses 1-3 in Stage 1...........................................25
6.1.2. Secondary Endpoint(s) in Stage 1...............................................................26
6.1.2.1. Analysis of Secondary Endpoints in Stage 1 ............................26
6.1.2.2. Sensitivity Analyses 1-3 in Stage 1...........................................27
6.1.3. Exploratory Efficacy Endpoints in Stage 1 ................................................27
 
6.1.3.3. Additional Biomarkers (Gene Signature Panel in Blood 
and Tissue, Muscle Bone and Blood Biomarkers, Autoantibody 
Concentrations in Serum/Plasma) in Stage 1 ....................................29
6.1.3.4. Patient Reported Outcomes (SF36, DLQI, 5D Itch Scale) 
and Physician’s Evaluation of Disease (PhGA), CDASI 
Activity and CDASI Damage Subscores in Stage 1..........................29
6.2. Analyses and Summaries During Stage 2 and Amended Stage 2...........................30
6.2.1. Primary Endpoint in Stage 2 and Amended Stage 2...................................30
6.2.1.1. Primary Analysis in Stage 2 and Amended Stage 2..................30
6.2.1.2. Secondary Analysis in Stage 2 and Amended Stage 2..............31
6.2.1.3. Sensitivity Analyses in Stage 2 and Amended Stage 2.............31
6.2.1.4. Supportive Analyses in Stage 2 and Amended Stage 2 ............31
6.2.2. Secondary Endpoint(s) in Stage 2 and Amended Stage 2 ..........................31
6.2.3. Exploratory Efficacy Endpoints in Stage 2, and Amended Stage 2 ...........31
6.3. Analyses and Summaries During Stage 3 ...............................................................32
6.3.1. Primary Endpoint in Stage 3.......................................................................32
6.3.2. Secondary Endpoint(s) in Stage 3...............................................................32
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6.3.2.1. Total Improvement Score in Stage 3.........................................32
6.3.2.2. Components of the TIS in Stage 3 ............................................33
6.3.2.3. CDASI Activity and CDASI Damage Scores in Stage 3..........34
6.3.3. Exploratory Efficacy Endpoints in Stage 3 ................................................34
6.5. Subset Analyses.......................................................................................................34
6.6. Baseline and Other Summaries and Analyses.........................................................34
6.6.1. Baseline Summaries....................................................................................34
6.6.2. Study Conduct and Subject Disposition .....................................................35
6.6.3. Study Treatment Exposure .........................................................................35
6.6.4. Concomitant Medications and Non-Drug Treatments................................35
6.7. Safety Summaries and Analyses .............................................................................35
6.7.1. Adverse Events...........................................................................................35
6.7.2. Laboratory Data..........................................................................................35
6.7.3. Vital Signs ..................................................................................................36
6.7.4. Electrocardiogram.......................................................................................36
6.7.7. Physical Examination .................................................................................37
6.7.8. Other Safety Data .......................................................................................37
7. INTERIM ANALYSES.......................................................................................................37
7.1. Introduction .............................................................................................................37
8. REFERENCES ....................................................................................................................38
9. APPENDICES .....................................................................................................................39
9.1. Definition and Use of Visit Windows in Reporting................................................39
9.2. CDASI.....................................................................................................................40
9.2.1. The Activity Score (AS).............................................................................41
9.2.2. Damage Score.............................................................................................41
9.3. Additional Information for Safety Endpoints..........................................................42
9.3.1. Adverse Events...........................................................................................42
9.3.2. Laboratory Data..........................................................................................42
9.3.3. Vital Signs ..................................................................................................42
9.3.4. Electrocardiogram.......................................................................................42
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9.4. Patient-Reported Outcomes and physician’s Evaluation of Disease.......................42
9.4.1. SF36: The Short Form Health Survey ........................................................42
9.4.2. DLQI: Dermatology Life Quality Index.....................................................42
9.4.3. 5D Itch Scale...............................................................................................43
9.4.4. PhGA: Physician Global Assessment.........................................................43
9.4.5. PtGA: Patient Global Assessment ..............................................................43
9.4.6. HAQ-DI: Health Assessment Questionnaire and Disease Index................43
9.4.8. EQ-5D-5L & EQ-VAS ...............................................................................44
9.4.9. FACIT-F .....................................................................................................44
9.6. Examples of SAS Code for the LANCOVA and ANCOVA Analyses ..................45
9.7. Categories for ECG and Vital Sign Outcomes........................................................47
9.8. TIS Calculation in DM............................................................................................48
LIST OF TABLES
Table 1.
Summary of Major Changes in SAP Amendments ................................................7
Table 2.
Details of Approaches to Sensitivity Analyses of Primary Analysis ...................26
Table 3.
Details of Approaches to Sensitivity Analyses of Secondary Analysis ...............27
Table 4.
Definition and Use of Visit Windows in Reporting .............................................39
Table 5.
CDASI Scale.........................................................................................................40
Table 7.
Input Parameters for LANCOVA and ANCOVA Analyses ................................45
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1. VERSION HISTORY
This  Statistical Analysis Plan (SAP) for study C0251002 is based on the protocol dated 
01 July 2020.  
Table 1.
Summary of Major Changes in SAP Amendments
SAP Amendment
Change
Rationale
1
Minor corrections

Pulse is measured in sitting 
position

RR interval is excluded from
CSR/SAP

Serum (correct) replaces 
plasma in PK section

Matches CRF

Matches Protocol  

Corrects the 
language of  the 
earlier version of  
the SAP. 
2

Slight widening of the 
acceptable analysis window 
in Table 4.

Need to incorporate 
all available 
observations   
3

Slight widening of analysis 
window in Table 4 (week 12).

Need to incorporate 
all available 
observations   
4
This SAP amendment supports the 
addition of Stage 2, Amended Stage 
2, and Stage 3 following protocol 
amendment 4.

Section 2.1.2, 2.1.3, 2.1.4: 
Added all objectives for 
newly added stages.

Section 2.2: Updated study 
design to reflect newly added 
stages.

Section 3: Add general 
definitions and conventions 
for endpoints in newly added 
stages.

Align with new 
objectives and 
endpoints of newly 
added stages; 
provide context and 
update of design 
changes.


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SAP Amendment
Change
Rationale

Section 3.2, 3.3, 3.4: Added 
all endpoints for newly added 
stages.

Section 4: Created separate 
subsections to define Full 
Analysis Sets, Per Protocol 
Analysis Sets, Safety 
Analysis Sets, and other 
analysis sets in newly added 
stages.

Section 5.1.2, 5.1.3: Added
hypotheses and decision rules 
for newly added stages. 

Section 6.1.1.1: %CFB 
adding to CDASI-A 
reporting.

Section 6.1.2: Added plots for 
secondary endpoint reporting.

Section 6.1.3.1, 6.1.3.2: 
Added population PK 
modeling description and 
additional PK plots.

Section 6.1.3.4: Clarified that 
post-hoc analyses may occur 
for PROs with established 
MCIDs.

Section 6.2, 6.3: Added all 
statistical analyses for newly 
added stages.

Section 6.6, 6.7: Update 
baseline and safety 
summaries to include newly 
added stages.

Section 7: Clarified that an 
interim analysis previously 
occurred and provided details 

New analysis sets 
required for 
analyses of newly 
added stages.

Clarify that all 
alpha is consumed 
in Stage 1 analyses.

Update reporting 
for Stage 1 
analyses.

Describe reporting 
and analyses for 
newly added stages. 
Provide 
descriptions of new 
PRO endpoints and 
the TIS.


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SAP Amendment
Change
Rationale
for other potential interim 
analyses.

Sections 9.4.5-9.4.9: Added 
descriptions for PROs that 
were included in newly added 
stages.

Section 9.8: Provided 
summary of the TIS 
derivation.
5

Section 3: Reworded some 
descriptions for clarity. In this 
section and throughout the 
SAP, rephrased “CSMs of the 
TIS” to “components of the 
TIS” to emphasize analyses 
will be done on the native 
scale and not the CSM scale. 

Section 4: Updated names of 
analysis sets for clarity.

Sections 6.1.1.2, 6.2.1.3: 
Added sensitivity analysis 
that addresses prohibited 
medication use.

Section 6.3.2.1.1: Added
supportive and sensitivity 
analyses for the TIS.

Section 6.3.2.2: Clarified 
analyses for the components 
of the TIS.

Sections 6.3.2.3, 6.6.4: Added 
that additional plots may be 
provided.

Section 9.1: Updated visit 
windows.

Clarify analyses 
and analysis set 
names.

Update supportive 
and sensitivity 
analyses.

Update visit 
windows.


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2. INTRODUCTION
This SAP provides the detailed methodology for summary and statistical analyses of the data 
collected in study C0251002.  This document may modify the plans outlined in the protocol; 
however, any major modifications of the primary endpoint definition or its analysis will also 
be reflected in a protocol amendment.
2.1. Study Objectives
2.1.1. Study Objectives in Stage 1
2.1.1.1. Primary Objective in Stage 1
•
To evaluate the efficacy of PF-06823859 in adult subjects with moderate to severe 
DM.
2.1.1.2. Secondary Objectives in Stage 1
•
To evaluate the efficacy of PF-06823859 over time.
•
To determine the safety, and tolerability, of PF-06823859.
2.1.1.3. Exploratory Objectives in Stage 1
•
To characterize pharmacokinetics (PK) of PF-06823859.
•
To characterize pharmacodynamics (PD) effects of PF-06823859. 
•
To evaluate the effects of PF-06823859 on patient-reported outcomes (PROs) and 
physician global assessment (PhGA) over time.
•
To evaluate the effects of PF-06823859 on CDASI sub-scores.
 
 
2.1.2. Study Objectives in Stage 2
2.1.2.1. Primary Objectives in Stage 2
•
To estimate the efficacy of PF-06823859 in adult participants with moderate to 
severe DM across two stages.
2.1.2.2. Secondary Objectives in Stage 2
•
To estimate the efficacy of PF-06823859 across two Stages.
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•
To determine the safety, and tolerability, of PF-06823859 across two Stages.
•
To estimate the effects of PF-06823859 on patient-reported outcomes (PROs) and 
physician global assessment (PhGA) over time across the two stages.
•
To estimate the effects of PF-06823859 on CDASI sub-scores across the two stages.
 
 
2.1.3. Study Objectives in Amended Stage 2
2.1.3.1. Primary Objectives in Amended Stage 2
•
To estimate the efficacy of PF-06823859 in adult participants with moderate to 
severe DM across Stage 1 and Stage 2.
2.1.3.2. Secondary Objectives in Amended Stage 2
•
To estimate the efficacy of PF-06823859 over time across Stage 1 and Stage 2.
•
To determine the safety, and tolerability, of PF-06823859 across Stage 1 and Stage 2.
 
•
To estimate the effects of PF-06823859 on the Physician Global Assessment (PhGA, 
VAS) across Stage 1 and Stage 2.
•
To estimate the effects of PF-06823859 on patient-reported outcomes (PROs) over 
time across Stage 1 and Stage 2.
•
To estimate the effects of PF-06823859 on CDASI sub-scores across Stage 1 and 
Stage 2.
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2.1.4. Study Objectives in Stage 3
2.1.4.1. Primary Objectives in Stage 3
•
To evaluate the safety and tolerability of PF-06823859 in adult DM participants with 
moderate to severe active muscle disease.
2.1.4.2. Secondary Objectives in Stage 3
•
To evaluate the efficacy of PF-06823859 over time in adult DM participants with 
moderate active muscle disease.
 
 
•
To estimate the effects of PF-06823859 on the physician global assessment (PhGA, 
VAS) over time.
•
To estimate the effects of PF-06823859 on patient-reported outcomes (PROs) over 
time.
 
 
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2.2. Study Design
Initially, this was a multi-center Phase 2A study planned to be conducted in approximately 
30 adult participants with moderate to severe DM.  Thirty two participants were randomized 
in order to collect data from 24 participants who completed the study.  Each participant was 
to take part in the study for a period of approximately 9 months.  After the 35 day screening 
period, participants who were eligible enrolled into the study and were randomized in a 
blinded manner, 2:1 (Active:Placebo) ratio.  Investigational drug or placebo administration 
took place on Day 1, Week 4, and Week 8 of the study.  Participants then entered a 5-month 
follow-up period. 
For Stage 2, with the addition of 1 lower dose 150 mg arm, this study then became a Phase 2, 
dose-finding double-blind, randomized, placebo-controlled study.  Approximately 
20 additional participants who meet eligibility criteria will be enrolled and randomly 
assigned in a blinded manner to receive PF-06823859 600 mg, 150 mg, or placebo dosed 
every 4 weeks according to a randomization ratio. 5:11:4. Participants will receive study 
drug, (active or placebo) on Day 1, Week 4, and Week 8 of the study and when treatment is 
completed all participants will enter a 5-month follow-up period.
The study was further amended, and Stage 2 became “Amended Stage 2” changing the study 
to a fixed sequence design. In this design participants will be randomized to a treatment 
sequence at Day 1.  The treatment sequence (Active -> Placebo or Placebo ->Active) will 
dictate whether the participant will receive active study drug during Day 1 to Week 12 or 
active study drug during Week 12 to Week 20.  Although dosing is completed at Week 20, 
the treatment period goes through to Week 24.  There is no washout in between the dose 
changes (Day 1 to Week 12 and Week 12 to Week 20) for this design.  Another key feature is 
that this design will allow placebo subjects to receive active treatment at some timepoint 
during the study.  No re-randomization will occur at Week 12.  Participants who start the 
study on active study drug (600 mg or 150 mg) will have a prespecified dose change to 
placebo at Week 12, and participants who are on placebo will have a prespecified dose 
change to active study drug at Week 12.  The placebo participants will receive prespecified 
doses of either 600 mg or 150 mg, in order to maintain equal distribution of these doses.  
There will be no unblinding or interruption of dosing during the treatment period.  Each 
participant will receive 3 consecutive doses of active study drug and 3 consecutive doses of 
placebo during the trial.  The dose change between active and placebo in this fixed sequence 
design will provide each participant 12 weeks of active drug.  The participant, study doctor, 
or sponsor will not know what the participant is assigned to during the treatment period. The 
end of the treatment period is at Week 24, although the last dose is administered at the 
Week 20 visit (Visit 8).  All participants will then enter a 4 month follow-up period (the 
interval between the last dose and the end of the follow-up period is 5 months). 
Participants who entered Stage 2 prior to Protocol Amendment 4 will follow the design and 
SoA of Protocol Amendment 3, which is Stage 2.  Statistical analyses including Stage 2 
endpoints will involve data from the original Stage 2 of Amendment 3 and the Amended 
Stage 2 of Amendment 4 or later, as appropriate.


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In Protocol Amendment 4, an additional DM cohort of 8 to 16 participants with active 
moderate muscle involvement (MMT-8 ≤136/150) will be enrolled.  This cohort is referred to 
as Stage 3.  Participants in this cohort are allowed to have any amount of skin involvement, 
as no specific CDASI score is required.  All participants who meet eligibility criteria for 
(Stage 3) will be randomized to receive either PF-06823859 600 mg active study drug or 
placebo.  This study design is similar to the Amended Stage 2 as all participants will receive 
their dosing assignment at Day 1 in a fixed sequence manner for the duration of the treatment 
period.  The treatment period will consist of 6 dosing’s occurring at Day 1, Week 4, (Visit 4), 
Week 8, (Visit 5), Week 12 (Visit 6), Week 16 (Visit 7), and Week 20, (Visit 8).  Each 
participant will receive 3 consecutive doses of active study drug and 3 consecutive doses of 
placebo.  At Week 12 (Visit 6), participants will be switched to the opposite treatment arm 
from what they were randomly assigned to at Day 1, Week 4 and Week 8.  The  study design 
permits all participants to receive active study drug in a blinded manner.  The dose change 
between active and placebo will provide each participant 12 weeks of active drug.  The end 
of the treatment period is at Week 24, although the last dose is administered at the Week 20 
visit (Visit 8).  All participants will then enter a 4 month follow-up period (the interval 
between the last dose and the end of the follow-up period is 5 months).  
If a participant meets eligibility criteria for both Amended Stage 2 and Stage 3, the 
participant will be enrolled in Stage 3 unless the enrollment maximum for Stage 3 has been 
reached, at which point the participant would enroll in the Amended Stage 2.
The overall duration of the study will be approximately 69 months from first subject first 
visit, (FSFV) to last subject last visit, (LSLV) and will be conducted at approximately 
35-40 investigative sites. Overall, approximately 76 participants will be randomized into this 
study.
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
In Stage 1, Stage 2, and Amended Stage 2, the primary and secondary endpoints assess 
changes in the modified CDASI activity and damage scores.  The details of the calculation of 
these scores are presented in Section 9.2. In Stage 3, the secondary endpoints assess changes 
in the modified CDASI activity and damage scores and changes in the TIS and the
components of the TIS. The details of the calculation of the TIS are presented in Section 9.8.
In each stage, baseline is defined as the measurement at Day 1 (prior to dosing).  Change 
from baseline is defined as the value at a specific visit minus the value from baseline. 
Efficacy endpoint analyses may use data from a single stage or pool data across multiple 
stages. Stage 1 analyses will include Stage 1 data only, and Stage 3 analyses will include 
Stage 3 data only. Pooled analyses of data from Stage 1, Stage 2, and Amended Stage 2 will 
pool data from the first 12 weeks of these stages. For 
 endpoints newly added to 
Amended Stage 2 that were not previously included in Stage 1 or Stage 2, analyses will occur 
among Amended Stage 2 participants only.
Primary analysis of the CDASI activity score in Stage 1, Stage 2, and Amended Stage 2 
include data from baseline to Week 12. Sensitivity and supportive analyses in these stages 
may include data beyond Week 12.
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Secondary analysis of the TIS, components of the TIS, CDASI activity, and CDASI damage 
scores in Stage 3 include data from baseline to Week 12. Sensitivity and supportive analyses 
in these stages may include data beyond Week 12.
3.1. Endpoints in Stage 1
3.1.1. Primary Endpoint in Stage 1
•
Change from baseline in CDASI activity score at Week 12.
3.1.2. Secondary Endpoint(s) in Stage 1
•
Absolute values and change from baseline of CDASI activity and CDASI damage 
scores at all scheduled time points.  Exception: The change from baseline in CDASI 
activity score at Week 12 is a primary endpoint.
•
Incidence of adverse events (AEs), laboratory abnormalities, changes in vital signs, 
and electrocardiogram (ECG) findings.  The extended discussion of these endpoints 
is presented in Section 9.3.
 
•
Absolute values and change from baseline in the values of selected biomarkers (Gene 
signature panel in blood and tissue; Human Myxovirus A (MXA), interferon 
gamma-induced protein 10 (IP-10), IFNbeta, high sensitive C-reactive protein, 
(hsCRP), muscle and bone blood biomarkers, autoantibody concentrations in 
serum/plasma) at all scheduled time points.
•
Absolute values and change from baseline in the values of PROs (the short form 
(SF36) Health Survey, Dermatology and Life Quality Index (DLQI), 5D Itch Scale, 
and physician’s evaluation of disease (PhGA)) at all scheduled time points. The brief 
description of the scales is presented in Section 9.4.
•
Absolute values and change from baseline values of the sub-scores of CDASI activity 
and CDASI damage scores at all scheduled time points.  The description on the scores 
is presented in Section 9.2.
•
 
 
.
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3.2. Endpoints in Stage 2
3.2.1. Primary Endpoint in Stage 2
•
Change from baseline in CDASI activity score at Week 12.
3.2.2. Secondary Endpoints in Stage 2
•
Absolute values and change from baseline of CDASI activity and CDASI damage 
scores at all scheduled times points. (Exception: The change from baseline in CDASI 
activity score at Week 12 is a primary endpoint).
•
Incidence of adverse events (AEs) laboratory abnormalities, changes in vital signs, 
and electrocardiogram (ECG) findings. The extended discussion of these endpoints is 
presented in Section 9.3.
•
Absolute values and change from baseline in the values of selected biomarkers (Gene 
signature panel in blood and tissue; Human Myxovirus A (MXA), interferon 
gamma-induced protein 10 (IP-10), IFNbeta, high sensitive C-reactive protein, 
(hsCRP), muscle and bone blood biomarkers, autoantibody concentrations in 
serum/plasma) at all scheduled time points.
•
Absolute values and change from baseline in the values of PROs (the short form 
(SF36) Health Survey, Dermatology and Life Quality Index (DLQI), 5D Itch Scale, 
and physician’s evaluation of disease (PhGA)) at all scheduled time points. The brief 
description of the scales is presented in Section 9.4.
•
Absolute values and change from baseline values of the sub-scores of CDASI activity 
and CDASI damage scores at all scheduled time points.  The description on the scores 
is presented in Section 9.2.
 
 
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3.3. Endpoints in Amended Stage 2
3.3.1. Primary Endpoint in Amended Stage 2
•
Change from baseline in CDASI activity score at Week 12.
3.3.2. Secondary Endpoints in Amended Stage 2
•
Absolute values and change from baseline of CDASI activity and CDASI damage 
scores at all scheduled time points.  (Exception: The change from baseline in CDASI 
activity score at Week 12 is a primary endpoint).
•
Incidence of adverse events (AEs) laboratory abnormalities, changes in vital signs, 
and electrocardiogram (ECG) findings. The extended discussion of these endpoints 
is presented in Section 9.3.
 
•
Absolute values and change from baseline in the values of selected biomarkers (Gene 
signature panel in blood and tissue; 
 
β
 
 
•
Absolute values and change from baseline in the values of the PhGA, VAS at all 
scheduled time points.
•
Absolute values and change from baseline in the values of PROs including the Patient 
Global Assessment (PtGA), the Health Assessment Questionnaire - Disability Index 
(HAQ-DI), the 5-D Pruritus Scale,
 
, the Short Form (SF-36 v2 
Acute), the Dermatology and Life Quality Index (DLQI) and the European Quality of 
Life Five Dimension, Five Level Scale (EQ-5D-5L) & EQ Visual Analogue Scale 
(EQ-VAS) at all scheduled time points. The brief description of the scales is 
presented in Section 9.4.
•
Absolute values and change from baseline values of the sub-scores of CDASI activity 
and CDASI damage scores at all scheduled time points. The description on the 
scores is presented in Section 9.2.
 
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3.4. Endpoints in Stage 3
3.4.1. Primary Endpoint in Stage 3
•
Incidence of adverse events (AEs) laboratory abnormalities, changes in vital signs, 
and electrocardiogram (ECG) findings. The extended discussion of these endpoints 
is presented in Section 9.3.
3.4.2. Secondary Endpoints in Stage 3
•
Total Improvement Score (TIS) at Week 12 and intermediate scheduled time points. 
The description of the TIS is presented in Section 9.8.
•
Change from baseline in the core Set Measures (CSM) of the TIS including PGA, 
PtGA, MMT, HAQ-DI, muscle enzymes, and extra-muscular activity, (MDAAT).
•
Absolute values and change from baseline of CDASI activity and CDASI damage 
scores at all scheduled time points. The description on the scores is presented in 
Section 9.2.
•
Absolute values and change from baseline in the values of selected biomarkers (Gene 
signature panel in blood; Human Myxovirus A (MXA), interferon gamma-induced 
protein 10 (IP-10), IFNbeta, highly sensitive C-reactive protein, (hsCRP), muscle and 
bone blood biomarkers, autoantibody concentrations in serum/plasma) at all 
scheduled time points.
•
Absolute values and change from baseline in the values of the PhGA, VAS at all 
scheduled time points.
•
Absolute values and change from baseline in the values of PROs including the Patient 
Global Assessment (PtGA), the Health Assessment Questionnaire - Disability Index 
(HAQ-DI), the 5-D Pruritus Scale,
 
 the Functional Assessment of 
Chronic Illness Therapy – Fatigue (FACIT-F), the Short Form (SF-36 v2 Acute), and 
the European Quality of Life Five Dimension, Five Level Scale (EQ-5D-5L) & EQ 
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Visual Analogue Scale (EQ-VAS) at all scheduled time points. The brief description 
of the scales is presented in Section 9.4.
 
 
 
 
3.5. Other Endpoints
Medical history, pregnancy testing, physical examination and recording of concomitant 
medications data will be analyzed according to Pfizer standard practices.
3.6. Baseline Variables
The day 1 measurements will serve as the baseline for clinical reported outcomes (CDASI 
Scores, Physician Global Assesment Score), patient-reported outcomes (SF36, DLQI, 5D 
Itch Scale), medical assessments (skin biopsies, ECG, weight, vital signs), laboratory safety 
measurements
 
 
  Demographics and medical history data will be collected at the 
baseline.
4. ANALYSIS SETS
4.1. Full Analysis Set
Multiple full analysis sets are defined. They are listed briefly here and described in more 
detail in Sections 4.1.1 through 4.1.2.
•
The Full Analysis Set (FAS) includes all subjects who received at least one dose of 
randomized treatment in any study stage.
•
The Full Analysis Set in Stage 1 (FAS1) includes all subjects who received at least 
one dose of randomized treatment in Stage 1.
•
The Full Analysis Set in Stage 2 (FAS2) includes all subjects who received at least 
one dose of randomized treatment in Stage 2.
•
The Full Analysis Set in Amended Stage 2 (FASA2) includes all subjects who 
received at least one dose of randomized treatment in Amended Stage 2.
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
The Full Analysis Set in Stage 1 and Stage 2 (FAS12) includes all subjects who 
received at least one dose of randomized treatment in Stage 1 or Stage 2.

The Pooled Full Analysis Set, skin cohort (PFASS) includes all subjects who received 
at least one dose of randomized treatment in Stage 1, Stage 2, or Amended Stage 2. 

The Full Analysis Set in Stage 3 (FAS3) includes all subjects who received at least 
one dose of randomized treatment in Stage 3.

The Pooled Full Analysis Set, fixed sequence stages (PFASF) includes all subjects 
who received at least one dose of randomized treatment in Amended Stage 2 or 
Stage 3.
4.1.1. Full Analysis Sets in Stage 1, Stage 2, and Amended Stage 2
The FAS1 is defined as all subjects who have received at least one dose of randomized 
treatment in Stage 1.  This is the primary analysis population for the safety and treatment 
compliance in Stage 1.  In the analyses it is assumed that subjects are assigned to the 
randomized treatment regardless of what treatment was received.  Note that Section 9.2 of 
the protocol references a modified intent to treat (mITT) set.  In Stage 1, the mITT set in 
Stage 1 is synonymous with the FAS1 mentioned in this document. 
The FAS2 is defined as all subjects who have received at least one dose of randomized 
treatment in Stage 2.  This is the primary analysis population for the safety and treatment 
compliance in Stage 2.  
The FAS12 is defined as all subjects who have received at least one dose of randomized 
treatment in Stage 1 or Stage 2. The FAS12 may be used for analyses assessing the 
durability of response for subjects in Stage 1 or Stage 2.
The FASA2 is defined as all subjects who have received at least one dose of randomized 
treatment in Amended Stage 2.  This analysis population will be used only for endpoints 
unique to Amended Stage 2 that were not collected in other stages.
The PFASS is defined as all subjects who have received at least one dose of randomized 
treatment in Stage 1, Stage 2, or Amended Stage 2.  This is the primary analysis population 
for the safety and treatment compliance across Stage 1, Stage 2, and Amended Stage 2.  In 
the analyses it is assumed that subjects are assigned to the randomized treatment regardless 
of what treatment was received.  Note that Section 9.2 of the protocol references a mITT set.  
The mITT set for Stage 1, Stage 2, and Amended Stage 2 is synonymous with the PFASS
mentioned in this document. 
4.1.2. Full Analysis Sets in Stage 3
The FAS3 is defined as all subjects who have received at least one dose of randomized 
treatment in Stage 3. This is the primary analysis population for the safety and treatment 
compliance in Stage 3. In the analyses it is assumed that subjects are assigned to the 
randomized treatment regardless of what treatment was received.  Note that Section 9.2 of 


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the protocol references a mITT set. In Stage 3, the mITT set in Stage 3 is synonymous with 
the FAS in Stage 3 mentioned in this document. 
The PFASF is defined as all subjects who have received at least one dose of randomized 
treatment in Amended Stage 2 or Stage 3. The PFASF may be used for analyses assessing 
the durability of response for subjects with baseline CDASI activity score of 14 or greater in 
Amended Stage 2 or Stage 3.
4.2. Per Protocol Analysis Set 
4.2.1. Per Protocol Analysis Set in Stage 1
The Per Protocol Analysis Set in Stage 1 (PPAS1) is a subset of the FAS1 and includes 
subjects who did not have major protocol deviations.  The list of major protocol deviations will
be finalized by the project team prior to un-blinding of the study. The PPAS1 may be used in 
sensitivity analyses.  For evaluation of sensitivity of the primary analysis in Stage 1 we will 
not use data collected after Week 12. 
4.2.2. Per Protocol Analysis Set in Stage 2 and Amended Stage 2
The per protocol analysis set for pooled Stage 1, Stage 2, and Amended Stage 2, skin cohort
(PPASS) is a subset of the PFASS and includes subjects who did not have major protocol 
deviations.  The list of major protocol deviations will be finalized by the project team prior to
un-blinding of the study. The PPASS may be used in sensitivity analyses.  For evaluation of 
sensitivity of the primary analysis we will not use data collected after Week 12. 
4.2.3. Per Protocol Analysis Set in Stage 3
The per protocol analysis set in Stage 3 (PPAS3) is a subset of the FAS3 and includes 
subjects who did not have major protocol deviations.  The list of major protocol deviations will
be finalized by the project team prior to un-blinding of the study. The PPAS3 may be used in 
sensitivity analyses.  For evaluation of sensitivity of the secondary analysis in Stage 3 we 
will not use data collected after the participant receives 12 weeks of active treatment.
4.3. Safety Analysis Set
Multiple safety analysis sets are defined. 

The safety analysis set (SAS) includes all subjects who received at least one dose of 
randomized treatment in any stage.

The safety analysis set in Stage 1 (SAS1) includes all subjects who received at least 
one dose of randomized treatment in Stage 1. 

The safety analysis set in Stage 2 (SAS2) includes all subjects who received at least 
one dose of randomized treatment in Stage 1 or Stage 2.

The safety analysis set in Amended Stage 2 (SASA2) includes all subjects who 
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•
The safety analysis set in Stage 3 (SAS3) includes all subjects who received at least 
one dose of randomized treatment in Stage 3.
Subjects who are not treated will be excluded from the safety analysis.
 
 
 
 
 
 
 
 
 
 
•
In Stage 1, the biomarker analysis population is defined as all enrolled subjects in 
Stage 1 who received at least one dose of PF-06823859 with at least one biomarker 
assessment.
•
For Stage 1, Stage 2, and Amended Stage 2, the biomarker analysis population is 
defined as all enrolled participants in Stage 1, Stage 2 and Amended Stage 2 who 
received at least one dose of PF-06823859 with at least one biomarker assessment.
•
In Stage 3, the biomarker analysis population is defined as all enrolled participants in 
Stage 3 who received at least one dose of PF-06823859 with at least one biomarker 
assessment.
5. GENERAL METHODOLOGY AND CONVENTIONS
5.1. Hypotheses and Decision Rules
5.1.1. Hypotheses and Decision Rules in Stage 1
The primary hypothesis to be tested is that there is no difference between the effects of 
treatment and placebo exposures on the CDASI activity score in Stage 1.
The primary endpoint in Stage 1 is the mean change from baseline in CDASI activity score at 
Week 12.  The placebo-adjusted treatment effect is defined as the difference (mean change 
from baseline at Week 12 in the active treatment group minus the mean change from baseline 
at Week 12 in the placebo group) in the mean change of CDASI activity score from baseline 
at Week 12.  A successful treatment should decrease CDASI activity score and therefore the 
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desired treatment effect is negative.  The value -5 is viewed as the minimal clinically relevant 
value of the treatment effect. 
The treatment is declared efficacious if each of the following conditions is satisfied:

C1: Estimated value of the treatment effect is lower than -5.

C2: An upper limit of 2-sided 90% confidence interval for the treatment effect is 
below zero.
5.1.2. Hypotheses and Decision Rules in Stage 2 and Amended Stage 2
The primary endpoint for Stage 2 and Amended Stage 2 is the change from baseline in 
CDASI activity score at Week 12 and uses data from Stage 1, Stage 2, and Amended Stage 2. 
No p-values will be presented for the comparisons listed in the objectives and endpoints of 
this pooled analysis. The placebo-adjusted treatment effect is defined as the difference 
(mean change from baseline at Week 12 in the active treatment group minus the mean 
change from baseline at Week 12 in the placebo group) in the mean change of CDASI 
activity score from baseline at Week 12. No hypotheses will be tested in the pooled analysis.
5.1.3. Hypotheses and Decision Rules in Stage 3
The primary endpoint in Stage 3 is safety, including incidence of adverse events (AEs) 
laboratory abnormalities, changes in vital signs, and electrocardiogram (ECG) findings.
Major efficacy endpoints, including the TIS, the components of the TIS, and the CDASI 
activity and damage scores, are assessed as secondary endpoints. No hypotheses will be 
tested in Stage 3.
5.2. General Methods 
Pfizer’s standards will be used to describe distributions of outcomes for each of the visits and 
treatment groups in each stage. In addition to that the following statistical methods will be 
used.  To explore the data further and to assess the goodness-of-fit of all statistical models, 
separate SAS datasets and common separated value files will be provided by the clinical 
programmer to the statistician.
5.2.1. Analyses for Continuous Longitudinal Data
5.2.1.1. Longitudinal Analysis of Covariance (LANCOVA) Model
A discussion of this model may be found in Lu (2010).  We will use the following variations 
of the method: LANCOVA-P and LANCOVA-S where letters P and S denote the versions 
that are used for primary (P) and sensitivity (S) analyses.
The LANCOVA-P model uses the change from baseline as an outcome and the baseline 
value as a covariate.  The model assumes visit-independent adjustment of the mean outcome 
for baseline, saturated treatment by time model for the mean and an un-structured within 
subject error covariance matrix.  Treatment and time are considered as factor variables and 
treatment by time is considered as unstructured interaction effect. 


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The LANCOVA-S model also uses the change from baseline as an outcome and the baseline 
value as a covariate.  The model assumes a saturated baseline by time and treatment by time 
fixed effects and an un-structured within subject error covariance.  Treatment and time are
considered as factor variables and baseline by time and treatment by time are considered as 
unstructured interaction effects.  This allows the baseline and treatment effects to vary over 
time. 
Variations of LANCOVA-P and LANCOVA-S models with the covariance matrices that 
have less general structure (eg, compound symmetry) may be considered if there are 
convergence issues with the primary versions of the model.
The analysis will provide an estimate and a two-sided 90% confidence interval for the 
difference (for each of the active doses against placebo) in the expected values of the 
outcome at multiple visits.
The sample SAS code for the LANCOVA calculations is presented in Section 9.6.
5.2.1.2. Conventional ANCOVA Model
The conventional ANCOVA method will use the difference between post-baseline and 
baseline values as an outcome and the baseline value as a covariate and will provide an 
estimate and a two sided 90% confidence interval for the difference (each of the active doses
against placebo) in the expected values of the outcome at each of the individual visits.
The ANCOVA-based estimate of the treatment effect at the particular visit incorporates only 
a visit-specific post-baseline observations of outcome while the LANCOVA-based estimate 
simultaneously estimates treatment effect at all treatment visits using all of the observed data.  
The ANCOVA-based estimate will be used for sensitivity analysis.  A qualitative similarity 
of the LANCOVA and ANCOVA-based estimates of the treatment effect will support the 
robustness of the primary (LANCOVA-based) estimate.
The sample SAS code for the ANCOVA calculations is presented in Section 9.6.
5.3. Methods to Manage Missing Data
•
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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•
For other endpoints, statistical analyses will be based on available data.  Missing data 
will not be imputed. 
6. ANALYSES AND SUMMARIES
6.1. Analyses and Summaries During Stage 1
6.1.1. Primary Endpoint in Stage 1
The primary endpoint is the change from baseline in CDASI activity score at Week 12.
6.1.1.1. Primary Analysis in Stage 1
•
Analysis time point: Week 12.
•
Analysis population: subset of FAS1 that includes baseline observations and 
observations collected at weeks 1-12.  Note that subjects with some missing data are 
included.
•
Analysis methodology: change from baseline will be analyzed using the 
LANCOVA-P model (as described in Section 5.2.1.1). 
•
Supporting objective: Primary Objective.
•
Reporting results (for CDASI activity score change from baseline at Week 12):
•
The sample size, mean, standard deviation, median, minimum and maximum will 
be presented for each treatment arm. 
•
The LS means, 90% confidence interval for the LS means, difference between the 
LS means of treatment groups (active-placebo) and the corresponding 
90% confidence interval for the estimate. These summary statistics will also be 
reported for the percent change from baseline in CDASI activity score at 
Week 12. 
6.1.1.2. Sensitivity Analyses 1-3 in Stage 1
•
The sensitivity analyses will explore sensitivity of the result of the primary analysis to 
the following variatons of the data analysis methods (as described in Section 5.2.1) 
and data sets (as described in Sections 4.1.1, 4.2.1).
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Table 2.
Details of Approaches to Sensitivity Analyses of Primary Analysis
Sensitivity 
Analysis
Data Set
(population)
Included Observations
(Time Window)
Method
1
FAS1
Baseline, weeks 1-12
LANCOVA-S
2
FAS1
Baseline, week 12
ANCOVA
3
PPAS1
Baseline, weeks 1-12
LANCOVA-S

Here FAS1 and PPAS1 denote full and per-protocol data sets defined in
Sections 4.1.1 and 4.2.1.  The reporting results will include the LS means, 
90% confidence interval for the LS means, difference between the LS means of 
treatment groups (active-placebo) and the corresponding 90% confidence interval. 

Note that in the sensitivity analyses (similarly to the primary analysis) we do not use 
data collected after Week 12 visit. 

In addition, the analysis for the CDASI-A in Section 6.1.1.1 may be repeated 
adjusting for subjects meeting protocol discontinuation criteria for use of prohibited 
medications as an intercurrent event (if any). Data from visits occurring after meeting
discontinuation criteria for use of prohibited medications will be censored from this 
analysis.
6.1.2. Secondary Endpoint(s) in Stage 1

Absolute values and change from baseline of CDASI activity and CDASI damage 
scores at all scheduled time points.
In the analyses (both the secondary analysis and corresponding sensitivity analyses) the 
observations collected after Week 12 are included into the modeling.  The main goal of the 
analyses is to produce the estimate and two-sided confidence interval (with 90% coverage) of 
the treatment effect at all scheduled time points (ie, 1, 4, 8, 12, 16, 20, 24, 28 weeks).  In 
addition to that the standard descriptive statistics for each of the two outcomes (CDASI 
activity and CDASI damage score), each of the treatment groups and each visit will be 
presented for absolute values of the scores.  The descriptive statistics will include number of 
observations, mean, standard deviation, median, minimum and maximum values.
6.1.2.1. Analysis of Secondary Endpoints in Stage 1

Analysis time points: 1, 4, 8, 12, 16, 20, 24, 28 weeks.

Analysis population: FAS1.

Analysis methodology: change from baseline will be analyzed using the 
LANCOVA-P model (as described in Section 5.2.1.1). 

Supporting objective: Secondary Objective.

Reporting results (for CDASI scores changes at each visit): 


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•
The sample size, mean, standard deviation, median, minimum and maximum will 
be presented for each treatment arm. 
•
The LS means, 90% confidence interval for the LS means, difference between the 
LS means of treatment groups (active-placebo) and the corresponding 
90% confidence interval for the estimate. Plots of this data will also be presented.
6.1.2.2. Sensitivity Analyses 1-3 in Stage 1
•
The analyses will explore sensitivity of the result of the primary analysis to the 
following variatons of the data analysis methods (as described in Section 5.2.1) and 
data sets (as described in Sections 4.1.1, 4.2.1).
Table 3.
Details of Approaches to Sensitivity Analyses of Secondary Analysis
Sensitivity
Analysis
Data Set
(population)
Included
Observations
Method
1
FAS1
All
LANCOVA-S
2
FAS1
All
ANCOVA
3
PPAS1
All
LANCOVA-S
•
Here FAS1 and PPAS1 denote full and per-protocol data sets defined in 
Sections 4.1.1 and 4.2.1. The reporting results will include the LS means, 
90% confidence interval for the LS means, difference between the LS means of 
treatment groups (active-placebo) and the corresponding 90% confidence interval. 
 
 
 
  
 
 
 
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6.1.3.3. Additional Biomarkers (Gene Signature Panel in Blood and Tissue, Muscle 
Bone and Blood Biomarkers, Autoantibody Concentrations in Serum/Plasma) in 
Stage 1
These analyses will be reported in the additional exploratory analysis report.
6.1.3.4. Patient Reported Outcomes (SF36, DLQI, 5D Itch Scale) and Physician’s 
Evaluation of Disease (PhGA), CDASI Activity and CDASI Damage Subscores in 
Stage 1
•
Analysis population: FAS1.
•
Analysis time points: all visits with samples taken.
•
Analysis methodology: summary statistics.  For SF36(PCS and MCS scores), DLQI, 
5D itch scale and PhGA scores the change from baseline will be also investigated by 
applying the LANCOVA-P model (as described in Section 5.2.1.1). 
•
Supporting objective: Exploratory Objective.
•
Reporting results: 
•
Change from baseline: The sample size, mean, standard deviation, median, 
minimum and maximum by visit.
•
Absolute values: The sample size, mean, standard deviation, median, minimum 
and maximum by visit.
•
For the SF36 (short form Health Survey) observations two summary component 
scores (PCS and MCS) and 8 scale subscores (PF, RP, BP, GH, VT, SF, RE, and MH) 
will be summarized. 
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
For the DLQI (Dermatology and Life Quality Index), 5D Itch Scale and physician’s 
evaluation of disease (PhGA) scores a single score summarizes each of the 
corresponding patient-reported outcomes.

For the CDASI activity score we will analyze the following subscores: total extent 
score (ES), total erythema score (ER), total scaling (SC) and total erosion/ulceration 
scores (EU), Gottorn hands score (GHS), peringual score (PS), and alopecia score 
(AS).

For the damage score we will analyze the following subscores: total poilkiloderma 
score (POLS), total calcinosis score (CALS) and Gotorn’s hands damage score 
(GHDS).
We emphasize that the LANCOVA-P models will only be created for SF36 (PCS and MCS 
scores), DLQI, 5D itch scale and PhGA scores.  Ad-hoc analyses for PROs with minimum 
clinically important differences may be performed.
6.2. Analyses and Summaries During Stage 2 and Amended Stage 2
6.2.1. Primary Endpoint in Stage 2 and Amended Stage 2
The primary endpoint is the change from baseline in CDASI activity score at Week 12.
6.2.1.1. Primary Analysis in Stage 2 and Amended Stage 2
The treatment effect is defined as the difference (between each pooled active treatment group 
and the pooled placebo group across Stage 1, Stage 2, and Amended Stage 2 in the mean 
change of CDASI activity score from baseline at Week 12. The pooled 600 mg treatment 
arm will include data from baseline to Week 12 from participants assigned to the 600 mg in 
Stage 1, the 600 mg arm in Stage 2, and the 600 mg -> placebo arm in Amended Stage 2. 
The pooled 150 mg treatment arm will include data from baseline to Week 12 from 
participants assigned to the 150 mg arm in Stage 2 or the 150 mg -> placebo arm in Amended 
Stage 2. The pooled placebo arm will include data from baseline to Week 12 from 
participants assigned to the placebo arm in Stage 1, the placebo arm in Stage 2, the 
placebo ->150 mg arm in Amended Stage 2, and the placebo ->600 mg arm in Amended 
Stage 2.

Analysis time point: Week 12.

Analysis population: subset of FAS2 that includes baseline observations and 
observations collected at weeks 1-12 for subjects in Stage 1, Stage 2, and Amended 
Stage 2. Note that subjects with missing data are included.

Analysis methodology: change from baseline will be analyzed using the 
LANCOVA-P model (as described in Section 5.2.1.1). 

Supporting objective: Primary Objective. 


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
Reporting results [for CDASI activity score change (between each active treatment 
group and placebo group across Stage 1, Stage 2, and Amended Stage 2) from 
baseline at Week 12]: 

The sample size, mean, standard deviation, median, minimum and maximum will 
be presented for each treatment arm. Results will also be presented by study stage 
for these summary statistics.

The LS means, 90% confidence interval for the LS means, difference between the 
LS means of treatment groups (each active treatment arm - placebo across the two 
stages) and the corresponding 90% confidence interval for the estimate.  No 
p-values will be computed for the analysis in this stage.
6.2.1.2. Secondary Analysis in Stage 2 and Amended Stage 2
Data permitting, the secondary analysis for the primary endpoint in Stage 2 will be the 
PF-06823859 exposure-response analysis of the combined data from Stage 1, Stage 2, and 
Amended Stage 2. The Population Modeling Analysis Plan will describe the evaluation of 
the relationship between PF-06823859 exposures and response at Week 12.  
6.2.1.3. Sensitivity Analyses in Stage 2 and Amended Stage 2
The sensitivity analyses from Stage 1 (Section 6.1.1.2) may be repeated using the pooled data 
from Stage 1, Stage 2, and Amended Stage 2 using the PFASS. For these sensitivity analyses, 
estimates and CIs may be produced. No p-values will be produced.
The analysis for the CDASI-A in Section 6.2.1.1 using PFASS may be repeated adjusting for 
subjects meeting protocol discontinuation criteria for use of prohibited medications as an 
intercurrent event (if any).  Data from visits occurring after meeting discontinuation criteria 
for use of prohibited medications will be censored from this analysis.
6.2.1.4. Supportive Analyses in Stage 2 and Amended Stage 2
Supportive analyses may be reported in Stage 2. For onesupportive analysis, summary 
statistics will be reported by treatment sequence and visit for the participants in the FASA2 
from baseline to Week 28. The sample size, mean, standard deviation, median, minimum 
and maximum will be presented.
6.2.2. Secondary Endpoint(s) in Stage 2 and Amended Stage 2
The analyses and summaries of the secondary endpoints in Stage 2 will be the same as those 
in Stage 1 (Section 6.1.2) except that they will be conducted for the data across Stage 1, 
Stage 2, and Amended Stage 2 and use the appropriate Stage 2 analysis set. No p-values will 
be presented for these analyses.
6.2.3. Exploratory Efficacy Endpoints in Stage 2, and Amended Stage 2
The analyses and summaries of the exploratory efficacy endpoints in Stage 2 will be the 
same as those in Stage 1 (Section 6.1.3) except that they will be conducted for the data across 
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Statistical summaries will stratified by treatment group. No p-values will be presented for 
these analyses.
Percent change from baseline in the CDASI activity score will also be analyzed and reported 
in the same manner as the change from baseline CDASI activity score as described in 
Section 6.2.1.1.
For PROs newly added to Amended Stage 2 that were not collected in Stage 2, including the 
PtGA, HAQ-DI, 
 and EQ-5D-5L & EQ-VAS, descriptive 
statistics will be provided at each visit using the FASA2 and reported by treatment group. 
The reporting results for these PROs will be the same as those in Section 6.1.3.4, with some 
additional details provided below:
•
For the PtGA and EQ-VAS scores, a single score summarizes each of the 
corresponding patient-reported outcomes (see Sections 9.4.5 and 9.4.8).
•
For the 
 each of the three questions will be 
summarized by a single score (see Section 9.4.7).
•
For the EQ-5D-5L, the summed number of checked boxes under each of the five 
sections will be reported (see Section 9.4.8).
•
For the HAQ-DI, a single averaged score summarizes each of the corresponding 
patient-reported outcomes under the eight sections (see Section 9.4.6). In sections of 
the HAQ-DI relating to aids or devices or help from another person, each checkable 
box will be treated as binary data and summarized with proportions and frequency 
counts. A single score summarizes the severity of pain VAS.
6.3. Analyses and Summaries During Stage 3
6.3.1. Primary Endpoint in Stage 3
The primary endpoint in Stage 3 includes the incidence of adverse events (AEs) laboratory 
abnormalities, changes in vital signs, and electrocardiogram (ECG) findings. All safety 
summaries and analyses will be performed as specified in Section 6.7.
6.3.2. Secondary Endpoint(s) in Stage 3
6.3.2.1. Total Improvement Score in Stage 3
•
Analysis population: FAS3.
•
Analysis time points: Week 12 and intermediate scheduled time points.
•
Analysis methodology: The TIS at post baseline visits are scored relative to baseline
and the TIS at baseline is 0 by definition; thus all analyses are performed directly on 
the TIS. The estimates of the treatment effect from baseline to Week 12 will be 
obtained by MMRM where the TIS will be used as a dependent variable.  This model 
uses fixed effects for treatment, time (visit), treatment by time, and a random effect 
for subject, Due to the unknown nature of the longitudinal data, different covariance 
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structures among repeated measures will be examined based on model diagnostics 
starting with the unstructured variance-covariance model. 

Supporting objective: Secondary objective.

Reporting results: The absolute value of the TIS at each post baseline visit will be 
summarized by the following descriptive statistics:

The sample size, mean, standard deviation, median, minimum and maximum will 
be presented for each treatment arm (active and placebo). 

The LS means, 90% confidence interval for the LS means, difference between the 
LS means of treatment groups (active treatment arm - placebo) and the 
corresponding 90% confidence interval for the estimate. Plots of this data will 
also be presented. No p-values will be computed for the analysis in this stage.

The proportion of subjects achieving minimal, moderate, and major responses in 
their TIS score (defined as scores of ≥20, ≥40, and ≥60 in the TIS respectively)
will also be reported by treatment.
6.3.2.1.1. Supportive and Sensitivity Analyses for the TIS in Stage 3
Additional analyses may be performed for the TIS in Stage 3. 

Summary statistics will be reported by treatment sequence and time for the 
participants in the FAS3 from baseline to Week 24. The sample size, mean, standard 
deviation, median, minimum and maximum will be presented.

The analysis for the TIS in Section 6.3.2.1 may be repeated adjusting for subjects 
meeting protocol discontinuation criteria for use of prohibited medications as an 
intercurrent event (if any).  Data from visits occurring after meeting discontinuation 
criteria for use of prohibited medications will be censored from this analysis.

The analysis for the TIS in Section 6.3.2.1 may be repeated using treatment sequence 
as a covariate from baseline to Week 24.

The analysis for the TIS in Section 6.3.2.1 may be repeated using last observation 
carried forward (LOCF) for missing TIS values.
6.3.2.2. Components of the TIS in Stage 3
The absolute values and change from baseline in each of the components of the TIS, 
including the PhGA (from the MDAAT), PtGA, MMT, HAQ-DI, muscle enzymes, and 
extramuscular global assessment, will be summarized by descriptive statistics at each visit, 
including number of observations, mean, standard deviation, median, minimum and 
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Estimates of treatment effect for selected components of the TIS (PhGA, PtGA, 
extramuscular global assessment, HAQ-DI, and MMT-8) will be obtained by LANCOVA in 
the same manner as described in Section 6.1.2 where the change from baseline of a specified 
component will be used as a dependent variable. The absolute values of these five 
components will also be assessed using an MMRM model. Estimates and the confidence 
intervals for treatment effect will be presented for each of these methods. Accompanying 
plots may also be provided.
6.3.2.3. CDASI Activity and CDASI Damage Scores in Stage 3
The absolute values and change from baseline of CDASI activity and damage scores at all 
scheduled time points will be summarized by descriptive statistics, including number of 
observations, mean, standard deviation, median, minimum and maximum values.
The estimates for treatment effect may be obtained by LANCOVA in the same manner as 
described in Section 6.1.2 where the change from baseline of a corresponding score 
(ie, activity or damage score) will be used as a dependent variable. Estimates and the 
confidence intervals for treatment effect will be presented for each of these methods.
Accompanying plots may also be provided.
A supportive analysis that includes subjects with skin disease (baseline CDASI activity score 
of 14 or greater) in Stage 3 (FAS3) may also be performed for the CDASI activity and 
damage score using the models specified in Section 6.1.2. 
6.3.3. Exploratory Efficacy Endpoints in Stage 3
Exploratory efficacy endpoints will be summarized in Stage 3 in the same manner as the 
corresponding endpoints in Stage 1, Stage 2, or Amended Stage 2 using the appropriate 
Stage 3 analysis set (Section 6.1.3; Section 6.2.3). The only newly added PRO to Stage 3 is 
the FACIT-F. The average ranking across all questions of the FACIT-F for each patient will 
be summarized in the same manner as the PhGA (see Sections 6.1.3.4 and 9.4.9). 
 
 
6.5. Subset Analyses 
Subset analysis is not planned.
6.6. Baseline and Other Summaries and Analyses
6.6.1. Baseline Summaries
In (a) Stage 1, (b) Stage 1, Stage 2, and Amended Stage 2, and (c) Stage 3, a breakdown of 
all subjects will be provided by demographic characteristics (age, race, weight, body mass 
index, and height), extent of disease and prior use of conventional therapy in accordance with 
Pfizer data standards. Mean steroid use and duration of disease will also be presented by 
stage. Baseline CDASI (activity and damage) will be summaried descriptively.
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Subject evaluation groups will show end of study subject disposition and will show which 
subjects were analyzed for PK, as well as for safety (adverse events and laboratory data).  
Frequency counts will be supplied for subject discontinuation(s) by treatment.
6.6.2. Study Conduct and Subject Disposition
In (a) Stage 1, (b) Stage 1, Stage 2, and Amended Stage 2, and (c) Stage 3, subject evaluation 
groups will show end of study subject disposition and will show which subjects were 
analyzed in the full analysis set, and as well as for safety, PK and PD.  Frequency counts will 
be supplied for subject discontinuations by treatment. Disposition will also be summarized 
separately for subjects who discontinue.
Data will be reported in accordance with reporting standards.
6.6.3. Study Treatment Exposure
In (a) Stage 1, (b) Stage 1, Stage 2, and Amended Stage 2, and (c) Stage 3, number of the 
doses of active and control treatments will be recorded and summarized by the treatment 
group.
6.6.4. Concomitant Medications and Non-Drug Treatments
All concomitant medication(s) as well as non-drug treatment(s) will be provided in the
listings. These will be listed for both stages and stage will be indicated.  A separate listing 
may be provided for DM-related prior and concomitant medications.  Additional plots may 
be provided that illustrate concomitant medication use prior to and during the study period.
6.7. Safety Summaries and Analyses
The safety will be monitored over the study period that includes treatment and follow-up 
periods in all stages.
6.7.1. Adverse Events
It should be recognized that most studies are not designed to reliably demonstrate a causal
relationship between the use of a pharmaceutical product and an adverse event or a group of
adverse events.  Except for select events in unique situations, studies do not employ formal
adjudication procedures for the purpose of event classification.  As such, safety analysis is
generally considered as an exploratory analysis and its purpose is to generate hypotheses for
further investigation. Separate AE tables will show the data from (a) Stage 1, (b) Stage 1, 
Stage 2, and Amended Stage 2, and (c) Stage 3.
6.7.2. Laboratory Data
Laboratory data will be listed and summarized by treatment in accordance with the sponsor
reporting standards. The laboratory data listing will be listed for all stages and stage will be 
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6.7.3. Vital Signs
Systolic blood pressure, diastolic blood pressure and pulse rate will be listed and tabulated by 
dose group and week with descriptive statistics (N, mean, standard deviation, median, 
minimum and maximum).  Change from baseline (defined as mean pre-dose value collected 
at Week 0) will also be summarized using the same descriptive statistics by dose group and 
week in (a) Stage 1, (b) Stage 1, Stage 2, and Amended Stage 2, and (c) Stage 3.
The numbers of subjects with vital sign outcomes within the specified categories (see 
Section 9.7) will be tabulated by treatment and study week.
6.7.4. Electrocardiogram
The following ECG data will be listed: QT, QTc (Fridericia’s), heart rate, QRS duration, PR 
interval.  QTc based on Fridericia’s correction will be derived.
Baseline and change from baseline for QT, QTcF, heart rate, QRS, PR will be summarized 
using descriptive statistics by treatment and study week in (a) Stage 1, (b) Stage 1, Stage 2, 
and Amended Stage 2, and (c) Stage 3.  For QTcF a classification of absolute values and 
increase from baseline will be used.
The numbers of subjects with ECG outcomes within the specified categories (see 
Section 9.7) and number of subjects with uncorrected QT values ≥500 ms will be 
summarized by treatment and study week.
 
 
 
 
 
 
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6.7.7. Physical Examination
All physical exam data will be provided in the listings.
6.7.8. Other Safety Data
Prior medication(s), non-drug treatment(s), medical history, lab data and physical 
examination will be listed in accordance with the sponsor reporting standards.  Any other 
data that is captured on the study database, will be listed.
7. INTERIM ANALYSES
7.1. Introduction
In Stage 1 of the study, an interim analysis was performed when 32 participants were 
randomized and completed Visit 6 (Week 12). Additional interim analyses during later 
stages of the study may be conducted depending on the enrollment rate. If an additional 
interim analysis is done in the future, an internal review committee (IRC) independent from 
the blinded study team will review efficacy and safety data for business decision planning, if 
applicable. The results of the interim analysis will not be shared with the study team, 
participants, or investigators.
It is expected that in addition to the study team, an unblinded team may review the 
 (ie, any data not explicitly stated as primary or secondary endpoint) and exposure 
data on an ongoing basis. The analyses of the group will not be included into the report 
described in the current SAP.
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8. REFERENCES 
1.
Lu. K. (2010) On efficiency of constrained longitudinal data analysis versus 
longitudinal analysis of covariance. Biometrics; 66: 891–896.
2.
Aggarwal R, Rider LG, Ruperto N, et al. 2016 American college of 
rheumatology/European league against rheumatism criteria for minimal, moderate, and 
major clinical response in adult dermatomyositis and polymyositis: an international 
myositis assessment and clinical studies group/paediatric rheumatology international 
trials organisation collaborative initiative. Arthritis & Rheumatology. 
2017;69(5):898-910.


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9. APPENDICES 
9.1. Definition and Use of Visit Windows in Reporting
The currently assumed assignment of the observations to visits is based on the subject’s 
arrival day.  It assumes that the arrival times for each visit occur within the (-5,7) days time 
window centered around the target day as specified in the schedule of activities.  We will 
check the validity of the assumption by the analysis of the visit specific, distributions of 
actually observed arrivival days at the end of the study before data unblinding and may 
update the assignment rules slightly. 
Table 4.
Definition and Use of Visit Windows in Reporting
Visit Label
Targeted Day
Analysis window
Screening
35 days prior to Day 1
1-35 days prior to Day 1
Baseline
Day 1
(reference day)
Day 1
(reference day)
Week 1
Day 8
Days 3-16
Week 4
Day 29
Days 24-38
Week 8
Day 57
Days 49-64
Week 12
Day 85
Days 71-99
Week 16
Day 113
Days 108-122
Week 20
Day 141
Days 136-155
Week 24
Day 169
Days 163-188
Week 28
Day 197
Days 191-218
Week 32
Day 226
Days 222-236
Week 36
Day 252
Days 245-259
Week 40
Day 280
Days 273-287
If more than one observation from the same subject falls into the same window then the 
association of the observation with the visit will be done after the consultation with the study 
clinician and lead statistician. 


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9.2. CDASI
Table 5.
CDASI Scale
Figure 2 presents the CDASI scale.  The main outcomes of interest are the activity score and 
damage score.


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9.2.1. The Activity Score (AS)
The Activity Score (AS) is calculated as a sum of the contribution from the extent score (ES), 
Gottorn hands score (GHS), peringual score (PS) and allopecia score (AS).
AS = ES+GHS +PS+AS 
The total extent score (ES) is obtained by summing up scores for the total erythema (ER, 
quantifies redness of the skin or mucous membranes), total scaling (SC, quantifies peeling of 
the skin) and total erosion/ulceration (EU, quantifies presence of the deeper wound).
ES = ER+SC+EU
Total erythema (ER), scaling (SC) and erosion/ulceration (EU) scores are calculated as a sum 
of the contributions from 15 individual areas of the body.  The range of the total erytherma 
score is 0-45, the range of the total scaling score is 0-30 and the range of total 
erosion/ulceration is 0-15.  The resulting range of the extent score is 0-90.
Gottorn hands score (GHS) characterizes papules (swellings) on hand and is a sum of the 
papule’s characterization score (range 0-6) and ulceration score (range = 0-1).
Peringual score (PS) characterizes abnormalities around nails and its range is 0-2.  The 
alopecia score (AS) characterizes hair loss and has the range 0-1.
The resulting range of the activity score is 0-100.
9.2.2. Damage Score
The Damage Score (DS) is calculated as a sum of the total poilkiloderma score (POLS), total 
calcinosis score (CALS) and Gotorn’s hands damage score (GHDS).
DS = POLS +CALS+GDHS
The polikiolderma score characterizes specific dispigmentation in the particulal area and 
calcinosis score characterizes calcification of the skin in the particular area.  The total 
polikiolderma score (POLS) and the total calcinosis score (CALS) are summed up over 
15 individual areas in the body and each of them has range 0-15.  The Gotorn’s hands 
damage score (GHDS) has the range 0-2 so that the damage score (DS) has the range 0-32.
In our analysis we will look at the activity score (AS), damage score (DS). 
For the activity score we will analyze the following subscores: total extent score (ES), total 
erythema score (ER), total scaling (SC) and total erosion/ulceration scores (EU), Gottorn 
hands score (GHS), peringual score (PS), and alopecia score (AS).
For the damage score we will analyze the following subscores: total poilkiloderma score 
(POLS), total calcinosis score (CALS) and Gotorn’s hands damage score (GHDS).


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9.3. Additional Information for Safety Endpoints
9.3.1. Adverse Events
An adverse event (AE) is considered treatment emergent relative to a given treatment if:

the event occurs for the first time during the effective duration of treatment and was 
not seen prior to the start of treatment (for example, during the baseline or run-in 
period), or

the event was seen prior to the start of treatment but increased in severity during 
treatment.
9.3.2. Laboratory Data
The description of the laboratory data is given in Section 7.8 of the protocol.
9.3.3. Vital Signs 
Vital signs (blood pressure, pulse, respiratory rates and temperature) will be measured after 
5 minutes of rest as indicated in the Schedule of Activities.  Baseline will be the last 
measurement prior to receiving study treatment.
9.3.4. Electrocardiogram 
Single 12-lead ECGs should be collected at times specified in the Schedule of Activities.
The screening ECG values will serve as each subject’s baseline values.  To ensure safety of 
the subjects, 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 subject’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.
9.4. Patient-Reported Outcomes and physician’s Evaluation of Disease
9.4.1. SF36: The Short Form Health Survey
The SF-36 v.2 (Acute version) is a 36-item generic health status measure.  It measures
8 general health concepts or domains: physical functioning (PF), role physical (RP), bodily
pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE) 
and mental health (MH).  These domains are also summarized as physical and mental
component scores (PCS and MCS).  All domains and summary components are scored such
that a higher score indicates a higher functioning or health level.
9.4.2. DLQI: Dermatology Life Quality Index 
The DLQI is calculated by summing the responses to each of the 10 questions (see 
Appendix 7 of the protocol) resulting in maximum of 30 and minimum of 0.  The higher 
value of the score denotes higher impairment/lower quality of life. 


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9.4.3. 5D Itch Scale
The scores of each of the five domains in the questionary (see Appendix 8 of the Protocol) 
are calculated separately and then summed together to obtain a total 5-D score.  5-D scores 
can potentially range between 5 (no pruritus) and 25 (most severe pruritus). 
Single-item domain scores (duration, degree and direction) are equal to the value indicated 
below the response choice (range 1–5).  The disability domain includes four items that assess 
the impact of itching on daily activities: sleep, leisure/social activities, housework/errands 
and work/school.  The score for the disability domain is calculated by taking the highest 
score on any of the four items.
For the distribution domain, the number of affected body parts is tallied (potential sum 0–16) 
and the sum is sorted into five scoring bins: sum of 0–2 = score of 1, sum of 3–5 = score of 2, 
sum of 6–10 = score of 3, sum of 11–13 = score of 4, and sum of 14–16 = score of 5.
9.4.4. PhGA: Physician Global Assessment 
The score is a subjective assessment of the severity of disease by the physician.  The 
physician uses the visual analog scales and puts a mark on 0-10 cm scale where higher score 
indicates worse status. 
9.4.5. PtGA: Patient Global Assessment
The score is a subjective assessment of the severity of disease by the patient.  The patient
uses a visual analog scales and puts a mark on the scale where higher score indicates worse 
status (see Appendix 13 of the protocol). 
9.4.6. HAQ-DI: Health Assessment Questionnaire and Disease Index
The HAQ-DI contains eight sections (including dressing & grooming, arising, eating, 
walking, hygiene, grip, reach, and activities). Each section has multiple questions that the 
participant can use to rank their functionality (see Appendix 12 of the protocol). For each 
participant, the average ranking will be reported for each of the eight sections. 
The HAQ-DI also contains sections where the participant can indicate use of aids or devices 
or help from another person from a list of choices. 
The HAQ-DI also includes a VAS that the participant can use to indicate the severity of their 
pain, where a higher score indicates more pain.
 
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9.4.8. EQ-5D-5L & EQ-VAS
The EQ-5D-5L contains five sections, including mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression (see Appendix 10 of the protocol). Each of the five 
sections will be summarized by the number of checked boxes under their respective headers.
The EQ-VAS ranges from 0 to 100, where 100 is the best (ie, most healthful) score.
9.4.9. FACIT-F
The FACIT-F contains 13 questions with ranked scores (see Appendix 11 of the protocol). 
Each patient’s average ranked score will be used in reporting.
 
 
 
 
  
 
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9.6. Examples of SAS Code for the LANCOVA and ANCOVA Analyses
Create data set ds where for each subject and each visit the following information is stored in 
the row of the data set.
Table 7.
Input Parameters for LANCOVA and ANCOVA Analyses
Id
Subject’s id
Cfb
Change from baseline 
Time
time of interest (treated as a class variable).  
Only the post-baseline visits are included
Trt
Treatment group (stored as a class variable, 
trt=”Active” denotes active treatment and 
“Control” denotes control treatment)
Base
Baseline observation of the outcome
The analysis will be implemented as follows.  In all of the LANCOVA and ANCOVA 
analyses we use the reference baseline value XXX (see below) which is the mean of the 
baseline values for all participants.
%let basemean=XXX; 


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LANCOVA-P 
proc mixed data=ds ;
           class          id trt (ref=”Control”) time (ref=”2”);
           model        cfb = base time trt  time*trt / ddfm=kr;
           repeated     time /subject= id type= un;
           lsmeans    visit*trt / pdiff at base = &basemean alpha=0.10 cl;
           ods output diffs= dlancovaP  lsmeans= dlancovaMP;
run;
data dlancovaP;
  set dlancovaP;
  if( (trt="Active" & _trt="Control") & (time=_time));
run;
The resulting estimates of the visit-dependent difference in means of cfb (active-control 
treatments) and means of cfb for active and control groups are stored in the dlancovaP and 
dlancovaMP data sets. 
LANCOVA-S 
proc mixed data=ds ;
           class          id trt (ref=”Control”)  time (ref=”2”);
           model       cfb = base time trt  time*trt  time*base / ddfm=kr;
           repeated     time /subject= id type= un;
           lsmeans      visit*trt / pdiff at base= &basemean alpha=0.10 cl;
           ods output   diffs= dlancovaS  lsmeans= dlancovaMS;
run;
data  dlancovaS;
  set dlancovaS;
  if( (trt="Active" & _trt="Control") & (time=_time));
run;
The only difference between the LANCOVA-S and LANCOVA-P analyses is the addition of 
the time*base term to the model.
The resulting estimates of the visit-dependent difference in means of cfb (active-control 
treatments) and means of cfb for active and control groups are stored in the dlancovaS and 
dlancovaMS data sets. 


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ANCOVA
Create data set ds as described in the Table 7 and sort it by visit.  The analysis will be 
implemented as follows
proc mixed data=ds ;
           by          visit;
           class     id trt (ref=”Control”) visit;
           model    cbaseline = trt baseline /ddfm=kr;
           lsmeans trt  / at baseline = &basemean  alpha=0.10 cl pdiff;
           ods output   diffs= dancovaS  lsmeans= dancovaMS;
run;
The resulting estimates of the visit-dependent difference in means of cfb (active-control 
treatments) and means of cfb for active and control groups are stored in the dancovaS and 
dancovaMS data sets. 
9.7. Categories for ECG and Vital Sign Outcomes
The following Pfizer’s standard will be used. For the sitting measurements of pulse rate the 
categories for the supine pulse rate ( min <40 bpm and max >120 bpm) will be used.


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9.8. TIS Calculation in DM
The total improvement score is the sum of all 6 improvement scores associated with the 
change in each core set measure.  A total improvement score of ≥20 represents minimal 
improvement, a score of ≥40 represents moderate improvement, and a score of 
≥60 represents major improvement.2