Clinical trial NCT04092452
Conditions: Acne Inversa
Sponsor: Pfizer
Start date: 2019-12-02; Completion date: 2022-01-10
Enrollment: 194 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a study with 3 kinase inhibitors (PF 06650833, PF 06700841 and PF 06826647) in participants with moderate to severe HS. The study will have a maximum duration of approximately 26 weeks. This includes an up to 6-week Screening Period, a 16 week Dosing Period and a 4 week Follow up Period.

Detailed description:

Arms: arm 1: PF-06650833 arm 2: PF-6700841 arm 3: PF-06826647 arm 4: placebo
Interventions: intervention 1: PF-06650833 intervention 2: PF-06700841 intervention 3: PF-06826647 intervention 4: Placebo
Intervention descriptions: intervention 1: 400 mg QD intervention 2: 45 mg QD intervention 3: 400 mg QD intervention 4: placebo

Protocol documents:
Prot_000.pdf: 
PF-06650833, PF-06700841, PF-06826647 
Protocol C2501007
Final Protocol Amendment 1, 28 January 2020
PFIZER CONFIDENTIAL 
Page 1
A PHASE 2A, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED, 16-WEEK STUDY EVALUATING THE SAFETY AND 
EFFICACY OF PF-06650833, PF-06700841, AND PF-06826647 IN ADULTS WITH 
MODERATE TO SEVERE HIDRADENITIS SUPPURATIVA
Investigational Product Number:
PF-06650833, PF-06700841, PF-06826647
Investigational Product Name:
Not Applicable (N/A)
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trials Database 
(EudraCT) Number:
Not Applicable (N/A)
Protocol Number:
C2501007
Phase:
2a
Short Title: A 16-Week Study to Evaluate the Safety and Efficacy of PF-06650833, PF-06700841, and 
PF-06826647 in Adults With Hidradenitis Suppurativa
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information in 
confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer must be 
promptly notified.
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Final Protocol Amendment 1, 28 January 2020
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Protocol Amendment Summary of Changes Table
Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 1
28 January 2020
•
Schedule of Activities, Section 3 
Objectives, Estimands, and Endpoints, 
and Section 8.1 Efficacy Assessments, 
added International Hidradenitis 
Suppurativa Severity Score System 
(IHS4). 
Rationale: IHS4 added to measure 
treatment effect. 
 
 
 
 
 
 
 
 
 
 
•
Schedule of Activities, PK collection 
window added.
Rationale: PK collection window added 
for clarity. 
•
Schedule of Activities, Section 5.2
Exclusion Criteria, and Appendix 2 
Clinical Laboratory Tests, Urine 
myoglobin testing added.
Rationale: Urine myoglobin testing 
added to screening and reflex testing
for CK >3 X ULN to ensure participant
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safety.
•
Schedule of Activities and Section 8.10 
Patient Reported Outcome Measures, 
added footnote for PROs.
Rationales: details added to provide
clarity.
•
Schedule of Activities, Section 8.2.7 
Suicidal Ideation and Behavior Risk 
Monitoring, Appendix 11 CSSRS, 
CSSRS will be performed at post-base 
line visits. 
Rationale: CSSRS added to post dose 
visits to ensure suicidal ideation and 
behavior will be evaluated during the
study.
•
Schedule of Activities, and Appendix 2 
Clinical Laboratory Tests, Urine 
analysis will be performed at central 
laboratory. 
Rationale: Urine analysis will be 
performed at central laboratory. Details 
added to provide clarity. 
•
Section 3 Objectives, Estimands, and 
Endpoints, added new efficacy 
endpoints. 
Rationale: new secondary 
 
 efficacy endpoints added to 
measure treatment effect by comparing 
of PF-06650833, PF-06700841, and 
PF-06826647 vs placebo.
•
Section 3 Objectives, Estimands, and 
Endpoints,
 
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Final Protocol Amendment 1, 28 January 2020
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•
Section 5.1 Inclusion Criteria, inclusion 
criterion #6 has been merged with #4.
Rationale: requirements for the 
antibiotic therapy has been merged to 
provide clarity.  
•
Section 5.1 Inclusion Criteria, inclusion 
criterion #5 added below text: 
Anti-TNF naïve; or Has initiated only 
one anti-TNF treatment including 
participants with inadequate response 
to the anti-TNF; Note: participants who 
initiated more than one anti-TNF 
treatments are not eligible.
Rationale: details added to provide 
clarity.  Anti-TNF naïve subjects are 
allowable. 
•
Section 5.1 Inclusion Criteria and 
Section 5.3.4 Antiseptic therapy,
allowable antiseptic washes are not 
limited.
Rationale: language for allowable 
antiseptic washes are provided for 
flexibility.
•
Section 5.1 Inclusion Criteria, added 
definition for inadequate response of 
oral antibiotic. 
Rationale: added details for clarity.
•
Section 5.2 Exclusion Criteria, added 
following exclusions: History of 
recurrent (≥2) venous thrombosis or 
any arterial thromboembolism or
known blood clotting disorders.
Rationale: Subjects will be fully 
evaluated prior to study entry to ensure 
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safety.
•
Section 5.2 Exclusion Criteria,
exclusion criterion for hemoglobin has 
been revised from 11 to 9 g/dL. 
Rationale: there is no safety related 
effects on hemoglobin, the hemoglobin 
exclusion criterion was adjusted for HS 
population.
 
Rationale: details modified to provide 
clarity. More information will be 
provided in a separate manual. 
•
Section 9.1 Estimands and Statistical 
Hypotheses, some text deleted.
Rationale: details will be provided in 
the statistical analysis plan.
 
Rationale: details will be provided in 
the internal review committee charter.
•
Appendix 8 Guideline for Safety 
Monitoring and Discontinuation, 
retesting window has been updated to 
1 week; added CK >3X ULN to 
monitoring criteria; hemoglobin
criterion has been updated from 
10 g/dL to 8 g/dL. CSSRS evaluation 
was added to discontinuation criterion. 
Rationale: retesting window updated to 
provide flexibility. CK >3X ULN will 
be re-tested to ensure safety. 
hemoglobin criterion was updated for 
HS population. CSSRS assessments 
will be performed during the study to 
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ensure safety.

Appendix 10 eGFR calculation: added
formula for cystatin C based eGFR. 
Rationale: formula added to provide 
clarity. 

Appendix 10.4.4 Contraception 
Methods: added barrier method for 
female subjects randomized to receive 
PF-06650833/matching placebo who 
use implantable progestogen-only 
hormone contraception.
Rationale: barrier method is added due 
to potential drug-drug interaction effect
between PF-06650833 and 
progestogen. 

Appendix 10.4.4 Contraception 
Methods: added restriction that all 
contraceptives containing ethinyl 
estradiol, being a CYP 1A2 inhibitor, 
are prohibited in female participants
randomized to receive 
PF-06826647/matching placebo.
Rationale: ethinyl estradiol is 
prohibited for female subjects 
randomized to receive 
PF-06826647/placebo due to potential 
drug-drug interaction effect. 
Minor administrative changes and sentence 
revisions made throughout the document.
Original protocol
16 August 2019
Not applicable (N/A)
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities  and institutional review boards (IRBs)/ethics 
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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................12
1. PROTOCOL SUMMARY...................................................................................................13
1.1. Synopsis ..................................................................................................................13
1.2. Schema ....................................................................................................................20
1.3. Schedule of Activities (SoA)...................................................................................21
2. INTRODUCTION ...............................................................................................................26
2.1. Study Rationale .......................................................................................................28
2.2. Background .............................................................................................................28
2.2.2. Nonclinical Safety of PF-06650833 ...........................................................28
2.2.5. Nonclinical Pharmacokinetics and Metabolism of PF-06700841 ..............33
2.2.6. Nonclinical Safety of PF-06700841 ...........................................................33
2.2.7. Clinical Safety of PF-06700841 .................................................................34
2.2.8. Clinical Pharmacology of PF-06700841 ....................................................38
2.2.10. Nonclinical Safety of PF-06826647 .........................................................40
2.2.11. Clinical Safety of PF-06826647 ...............................................................41
2.3. Benefit/Risk Assessment.........................................................................................42
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS ...........................................................43
4. STUDY DESIGN.................................................................................................................48
4.1. Overall Design.........................................................................................................48
4.2. Scientific Rationale for Study Design.....................................................................49
4.3. Justification for Dose ..............................................................................................49
4.3.1. PF-06650833...............................................................................................49
4.3.2. PF-06700841...............................................................................................50
4.3.3. PF-06826647...............................................................................................51
4.4. End of Study Definition ..........................................................................................52
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5. STUDY POPULATION......................................................................................................52
5.1. Inclusion Criteria.....................................................................................................52
5.2. Exclusion Criteria....................................................................................................54
5.3. Lifestyle Considerations..........................................................................................58
5.3.1. Contraception..............................................................................................58
5.3.2. Vaccination.................................................................................................58
5.3.3. Dietary Supplements...................................................................................58
5.3.4. Antiseptic Therapy......................................................................................59
5.3.5. Other Lifestyle Requirements.....................................................................59
5.4. Screen Failures ........................................................................................................59
6. STUDY INTERVENTION..................................................................................................60
6.1. Study Intervention(s) Administered........................................................................60
6.1.1. Administration............................................................................................60
6.2. Preparation/Handling/Storage/Accountability ........................................................61
6.2.1. Preparation and Dispensing........................................................................62
6.3. Measures to Minimize Bias: Randomization and Blinding.....................................62
6.3.1. Allocation to Investigational Product .........................................................63
6.3.2. Breaking the Blind......................................................................................63
6.4. Study Intervention Compliance...............................................................................63
6.5. Concomitant Therapy..............................................................................................64
6.5.1. Permitted Concomitant Medications ..........................................................64
6.5.1.1. Wound Care...............................................................................65
6.5.1.2. Antibiotic Therapy ....................................................................65
6.5.1.3. Analgesic Therapy.....................................................................65
6.5.2. Prohibited Medications and Treatments .....................................................66
6.5.3. Rescue Medicine.........................................................................................66
6.6. Dose Modification...................................................................................................66
6.7. Intervention After the End of the Study..................................................................66
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL...........................................................................66
7.1. Discontinuation of Study Intervention ....................................................................66
7.2. Participant Discontinuation/Withdrawal From the Study.......................................67


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7.3. Lost to Follow-up....................................................................................................68
8. STUDY ASSESSMENTS AND PROCEDURES...............................................................68
8.1. Efficacy Assessments..............................................................................................69
8.1.1. Hidradenitis Suppurativa Clinical Response (HiSCR)...............................69
8.1.1.1. Lesion Counts............................................................................70
8.1.2. Hurley Staging............................................................................................70
8.1.4. Erythema Assessment.................................................................................71
8.1.5. International Hidradenitis Suppurativa Severity Score System (IHS4 
Score)...............................................................................................................71
8.1.6. Rater Qualifications....................................................................................71
8.2. Safety Assessments .................................................................................................72
8.2.1. Assessments at Screening Only..................................................................72
8.2.1.1. Tuberculosis Testing .................................................................72
8.2.1.2. Chest Radiograph ......................................................................73
8.2.1.3. Medical History.........................................................................73
8.2.2. Physical Examinations (Full Physical and Brief Physical).........................73
8.2.2.1. HS Lesion Photography (at selected sites only)........................74
8.2.2.2. Height and Weight ....................................................................74
8.2.3. Vital Signs ..................................................................................................74
8.2.4. Electrocardiograms.....................................................................................75
8.2.5. Clinical Safety Laboratory Assessments ....................................................76
8.2.5.1. Creatinine, Cystatin C, and Estimates of Glomerular 
Filtration Rate....................................................................................76
8.2.6. Herpetiform Rash Surveillance...................................................................77
8.2.7. Suicidal Ideation and Behavior Risk Monitoring.......................................77
8.2.7.1. Columbia Suicide Severity Rating Scale ..................................77
8.2.8. Pregnancy Testing ......................................................................................77
8.3. Adverse Events and Serious Adverse Events..........................................................78
8.3.1. Time Period and Frequency for Collecting AE and SAE Information.......78
8.3.1.1. Reporting SAEs to Pfizer Safety...............................................79
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF...................79
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8.3.2. Method of Detecting AEs and SAEs ..........................................................79
8.3.3. Follow-up of AEs and SAEs.......................................................................79
8.3.4. Regulatory Reporting Requirements for SAEs...........................................79
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational 
Exposure ..........................................................................................................80
8.3.5.1. Exposure During Pregnancy......................................................80
8.3.5.2. Exposure During Breastfeeding ................................................80
8.3.5.3. Occupational Exposure .............................................................80
8.3.6. Medication Errors .......................................................................................81
8.4. Treatment of Overdose............................................................................................81
8.5. Pharmacokinetics ....................................................................................................82
8.5.1. Plasma for Analysis of PF-06650833, PF-06700841 and PF-
06826647..........................................................................................................82
8.9. Health Economics ...................................................................................................86
8.10. Patient Reported Outcome Measures ....................................................................86
8.10.1. HS Symptom Items...................................................................................86
8.10.2. PGA Skin Pain Numeric Rating Scale (NRS) Items ................................86
8.10.3. Dermatology Life Quality Index (DLQI) .................................................87
9. STATISTICAL CONSIDERATIONS ................................................................................88
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9.1. Estimands and Statistical Hypotheses.....................................................................88
9.1.1. Estimands....................................................................................................88
9.2. Sample Size Determination.....................................................................................89
9.3. Populations for Analysis .........................................................................................89
9.4. Statistical Analyses .................................................................................................90
9.4.1. Efficacy Analyses .......................................................................................90
9.4.2. Safety Analyses ..........................................................................................91
9.4.2.1. Electrocardiogram Analyses......................................................91
9.4.3. Other Analyses............................................................................................92
9.4.3.1. Analysis of Pharmacokinetic (PK) Endpoints...........................92
9.4.3.2. Patient Reported Outcome Analyses.........................................92
9.4.3.3. PK
 Unblinding Plan ............................................................92
9.5. Interim Analyses .....................................................................................................93
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS..........................................................................................................94
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations...............94
10.1.1. Regulatory and Ethical Considerations ....................................................94
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP.........................................................................94
10.1.2. Financial Disclosure .................................................................................95
10.1.3. Informed Consent Process ........................................................................95
10.1.4. Data Protection .........................................................................................96
10.1.5. Dissemination of Clinical Study Data ......................................................96
10.1.6. Data Quality Assurance ............................................................................98
10.1.7. Source Documents....................................................................................99
10.1.8. Study and Site Closure..............................................................................99
10.1.9. Publication Policy...................................................................................100
10.1.10. Sponsor’s Qualified Medical Personnel ...............................................101
10.2. Appendix 2: Clinical Laboratory Tests ...............................................................102
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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ....................................................................103
10.3.1. Definition of AE .....................................................................................103
10.3.2. Definition of SAE...................................................................................104
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs.....................105
10.3.4. Reporting of SAEs..................................................................................108
10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information..............................................................................................................110
10.4.1. Male Participant Reproductive Inclusion Criteria..................................110
10.4.2. Female Participant Reproductive Inclusion Criteria...............................110
10.4.3. Woman of Childbearing Potential (WOCBP) ........................................111
10.4.4. Contraception Methods...........................................................................112
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments ......116
10.7. Appendix 7: ECG Findings of Potential Clinical Concern .................................118
10.8. Appendix 8: Guidelines for Safety Monitoring and Discontinuation .................120
10.9. Appendix 9: Prohibited Concomitant Medications.............................................123
10.10. Appendix 10: eGFR Calculations .....................................................................127
10.11. Appendix 11: Columbia Suicide Severity Rating Scale (C-SSRS)19................128
10.12. Appendix 12: Abbreviations .............................................................................132
11. REFERENCES ................................................................................................................138
LIST OF TABLES
Table 1.
Protocol-Required Safety Laboratory Assessments ...............................102
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1. PROTOCOL SUMMARY 
1.1. Synopsis 
Short Title: A 16-Week Study to Evaluate the Safety and Efficacy of PF-06650833, 
PF-06700841 and PF-06826647 in Adults With Hidradenitis Suppurativa.
Rationale
This multicenter, Phase 2a, randomized, double-blind, placebo controlled study is being 
conducted to provide data on safety, tolerability, pharmacokinetics (PK), and efficacy of 
PF-06650833, PF-06700841, and PF-06826647 in adults with moderate to severe hidradenitis 
suppurativa (HS). In addition, the study is intended to provide additional information for 
determining the future clinical development of janus kinase (JAK) inhibitors and/or IL-1 
receptor associated kinase 4 (IRAK4) in HS.
Objectives, Estimands, and Endpoints
Objectives
Endpoints
Estimands
Primary: 
Primary:
Primary: 
To evaluate the efficacy of 
PF-06650833, PF-06700841, 
and PF-06826647 vs placebo 
in participants with HS as 
assessed by HiSCR.
Percentage of participants with 
HiSCR response* at Week 16.
This estimand uses a composite 
estimand theory (ICH E9 addendum) 
and is intended to provide a 
population level estimate of the 
treatment effect of the IP on a binary 
endpoint regardless of participant 
compliance with the IP dosing.
Population-level summary: difference 
between treated and placebo in 
proportion of participants with HiSCR 
response at Week 16.
Secondary: 
Secondary:
Secondary: 
To evaluate the efficacy of 
PF-06650833, PF-06700841, 
and PF-06826647 vs placebo 
in participants with HS at 
Week 16 and over time.
Percentage of participants with
HiSCR response* at Weeks 1, 2, 4, 
6, 8, and 12.
Percentage of participants with a 
total abscess and inflammatory 
nodule (AN) count of 0 or 1; 0, 1, 
or 2 at Week 16.
This estimand is intended to provide a 
population level estimate of the 
treatment effect of the IP on a binary 
endpoint regardless of participant
compliance with the IP dosing.
Population-level summary: difference
between treated and placebo in 
proportion of participants with HiSCR 
response at Weeks 1, 2, 4, 6, 8 and 12, 
respectively; difference between 
treated and placebo in proportion of 
participants with a total AN count of 
0 or 1, or 0, 1 or 2, respectively at 


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Percent change from baseline 
(CFB) in AN count at Weeks 1, 2, 
4, 6, 8, 12 and 16.
Week 16.
This estimand is intended to provide a 
population level estimate of the 
treatment effect of the IP on a 
continuous endpoint regardless of 
participant compliance with the IP
dosing. 
Population-level summary: difference 
between treated and placebo change 
from baseline in AN count at 
Weeks 1, 2, 4, 6, 8, 12 and 16.
To evaluate the efficacy of 
PF-06650833, PF-06700841, 
and PF-06826647 vs placebo 
on International Hidradenitis 
Suppurativa Severity Score 
System (IHS4).
Absolute score and percent CFB in 
IHS4 at Weeks 1, 2, 4, 6, 8, 12 and
16.
This estimand is intended to provide a 
population level estimate of the 
treatment effect of the IP on a 
continuous endpoint regardless of 
participant compliance with the IP 
dosing.
Population-level summary: difference 
between treated and placebo in 
absolute score and change from 
baseline on IHS4 at Weeks 1, 2, 4, 6, 
8, 12 and 16.
To evaluate the effects of 
PF-06650833, PF-06700841, 
and PF-06826647 vs placebo 
on HS flare.
Proportion of participants who 
experience an HS flare, defined as 
at least a 25% increase in AN count 
with a minimum increase of 
2 relative to Baseline, at 
Weeks 4, 8, 12 and 16.
The estimand is intended to provide a 
population level estimate of the 
treatment effect of the IP on a binary
endpoint regardless of participant 
compliance with IP dosing.
Population-level summary: difference 
between treated and placebo in 
proportion of participants experience 
flare at Weeks 4, 8, 12 and 16.
To evaluate the efficacy of 
PF-06650833, PF-06700841, 
and PF-06826647 vs placebo 
on pain and pain reduction 
over time in participants with 
HS.
Percentage of participants with 
≥30% reduction and ≥1-unit
reduction from baseline in 
PGA-Skin Pain numeric rating 
scale (NRS30) – at worst and on 
average, respectively, amongst
participants with baseline NRS ≥3, 
at Weeks 1, 2, 4, 6, 8, 12 and 16.
Percent CFB in NRS, at worst and 
on average respectively, in 
participants who have baseline 
NRS ≥3, at Weeks 1, 2, 4, 6, 8, 12 
and 16.
This estimand is intended to provide a
population level estimate of the 
treatment effect of the IP on a binary 
endpoint regardless of participant 
compliance with the IP dosing.
Population-level summary: difference 
between treated and placebo in 
proportion of participants with 
≥30% reduction and ≥1-unit reduction 
from baseline in PGA-Skin Pain NRS 
(NRS30), at worst and on average, 
respectively, amongst participants 
with baseline NRS ≥3, at Weeks 1, 2, 
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CFB in NRS, at worst and on 
average respectively, at Weeks 1, 
2, 4, 6, 8, 12 and 16.
This estimand is intended to provide a 
population level estimate of the 
treatment effect of the IP on a 
continuous endpoint regardless of 
participant compliance with the IP 
dosing.
Population-level summary: difference 
between treated and placebo percent 
change from baseline in NRS, at worst 
and on average respectively, in 
participants who have baseline 
NRS ≥3, at Weeks 1, 2, 4, 6, 8, 12 and 
16. Difference between treated and 
placebo change from baseline in NRS, 
at worst and on average respectively, 
at Weeks 1, 2, 4, 6, 8, 12 and 16.
To evaluate the efficacy of 
PF-06650833, PF-06700841, 
and PF-06826647 vs placebo 
on erythema.  
Proportion of participants 
achieving erythema score of 1 or 
0 in all affected anatomic regions 
among participants who have an 
erythema score of 2 or more in at 
least 1 anatomic region at 
baseline.
The estimand is intended to provide a 
population level estimate of the 
treatment effect of the IP on a binary 
endpoint regardless of participant 
compliance with IP dosing.
Population-level summary: difference 
between treated and placebo in 
proportion of participants achieving 
erythema score of 1 or 0 in all affected 
anatomic regions among participants 
who have erythema score of 2 or more 
in at least 1 anatomic region at 
baseline.
To assess the safety and 
tolerability of PF-06650833, 
PF-06700841, and 
PF-06826647 vs placebo in 
participants with HS.
Incidence of TEAEs (AEs and 
SAEs), significant changes in vital 
signs, clinical laboratory 
abnormalities, and ECG.
There is no defined estimand for these 
endpoints and they will be analyzed 
using Pfizer data standards as 
applicable.
To evaluate the effects of
PF-06650833, PF-06700841, 
and PF-06826647 vs placebo 
on patient centered outcomes 
in participants with HS.
Absolute score and CFB at time 
points specified in the SoA in HS 
Symptom Items and Dermatology 
Life Quality Index (DLQI) total 
score. 
Proportion of participants 
achieving a DLQI=0 or 1.
These endpoints will be analyzed 
descriptively and with respect to an 
estimand. 
To evaluate the PK of 
PF-06650833, PF-06700841, 
and PF-6826647 vs placebo in 
participants with HS.
Summary of plasma concentration 
of PF-06700841, PF-06826647 
and PF-06650833.
There is no defined estimand for these 
endpoints and they will be analyzed 
using Pfizer data standards as 
applicable.


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*HiSCR requires:
•
At least a 50% reduction in the total AN count relative to baseline; and
•
No increase in abscess count; and
•
No increase in draining fistula count.
For all endpoints, baseline is defined as the result closest prior to dosing on Day 1.
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Overall Design
This is a Phase 2a, randomized, double-blind, placebo-controlled, parallel group, multicenter 
platform study with 3 kinase inhibitors (PF-06650833, PF-06700841 and PF-06826647) in 
participants with moderate to severe HS.  The study will have a maximum duration of 
approximately 26 weeks. This includes an up to 6-week Screening Period, a 16-week Dosing 
Period and a 4-week Follow-up Period.  The study will not be blinded across the 
PF-06650833, PF-06700841 and PF-06826647 treatment arms, but will be 
placebo-controlled double-blinded within each investigational product (IP) treatment arm.  
Following the screening period, participants who meet eligibility criteria at the baseline visit, 
will be randomly assigned to receive PF-06650833 or matching placebo in a 3:1 ratio, or
PF-06700841 or matching placebo in a 3:1 ratio, or PF-06826647 or matching placebo in a 
3:1 ratio.  One oral dose level of each PF-06650833 (400 mg QD), PF-06700841 (45 mg QD) 
and PF-06826647 (400 mg QD) or matching placebo will be investigated.  No more than 
30% of enrolled participants will be inadequate anti-tumor necrosis factor (TNF) responders.  
Participants will be stratified according to whether they are an inadequate anti-TNF 
responder or not. 
Additionally, no more than 20% of enrolled participants may enter the study on a background 
of concomitant oral antibiotic therapy for treatment of HS; the dosing regimen (dose and 
frequency) must have been stable for at least 8 weeks (56 days) prior to the baseline (Day 1) 
visit and must remain stable throughout study participation.  Participants will be stratified 
according to whether they are on a background of concomitant antibiotic therapy or not.  
Biopsies of unaffected areas and lesional area biopsies will be collected from participants at 
selected sites; it is expected that approximately 60 participants across these selected sites will
have biopsies collected.  
Number of Participants
The study will enroll a total of approximately 192 participants (expected to provide 
approximately 156 completers).  The study will be conducted globally at approximately 
60 study sites.  
Intervention Groups and Duration
Following the screening period, participants who meet eligibility criteria at the baseline visit, 
will be randomly assigned to receive PF-06650833 (400 mg QD) or matching placebo in a 
3:1 ratio, PF-06700841 (45 mg QD) or matching placebo in a 3:1 ratio, or PF-06826647 
(400 mg QD) or matching placebo in a 3:1 ratio.


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Intervention Name
PF-06650833
PF-06700841
PF-06826647
ARM Name
PF-06650833 400 mg
Active and Placebo
PF-06700841 45 mg
Active and Placebo
PF-06826647 400 mg
Active and Placebo
Dose Formulation
Tablet
Tablet
Tablet
Unit Dose Strength(s)
200 mg Active
Placebo
25 mg, 5 mg Active
Placebo
100 mg Active
Placebo
Dosage Level(s)
400 mg QD
45 mg QD
400 mg QD
Route of
Administration
Oral
Oral
Oral
Packaging and 
Labeling
 
 
 
 
 
 
 
  
 
Current/Former 
Name(s) or Alias(es)
IRAK4
TYK2/JAK1
TYK2
 
 
  
  
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.
The primary estimand will be the population treatment effect on proportion of participants 
with hidradenitis suppurativa clinical response (HiSCR) at Week 16 for the active treatment 
group relative to placebo without regard to IP compliance.  
Hidradenitis suppurativa clinical response, the primary endpoint used, is defined as: 
•
At least a 50% reduction in the total abscess and inflammatory nodule (AN) count 
relative to baseline; and
•
No increase in abscess count; and
•
No increase in draining fistula count.
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Final Protocol Amendment 1, 28 January 2020
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Sample size calculation is based on the primary endpoint of HiSCR response at 16 weeks.  A 
total of approximately 192 participants will be randomized in 3 active treatment groups 
(48/arm) and 3 placebo groups (16/arm) to have 39 completers for each active treatment arm, 
assuming a 15% dropout rate and the active treatment arm HiSCR response rate of 60% and
placebo HiSCR rate of 30%.  Statistical comparisons will be made between each of the active 
treatment arms against the 3 placebo groups pooled together. With one-sided family-wise 
error rate of 0.1 with a Bonferroni correction (0.033 after Bonferroni adjustment for 
3 comparisons), this sample size will provide approximately 80% power.  No statistical
comparisons will be done between active treatment arms.
1.2. Schema


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Final Protocol Amendment 1, 28 January 2020
PFIZER CONFIDENTIAL 
Page 21
1.3. Schedule of Activities (SoA)
The SoA table provides an overview of the protocol visits and procedures.  Refer to the STUDY ASSESSMENTS AND 
PROCEDURES section of the protocol for detailed information on each procedure and assessment required for compliance with the 
protocol. 
The investigator may schedule visits (unplanned visits) in addition to those listed in the SoA table, in order to conduct evaluations or 
assessments required to protect the well-being of the participant.
Study Procedure
Screening
Baseline
Investigational Treatment Period
Follow-
Up (EOS)
Early 
Terminationb
Visit Identifier
1
2
3
4
5
6
7
8
9
10
Week
-6 to -1
Day 1
1
2
4
6
8
12
16
20
ET
Study Daya
-42 to -1
1
8
15
29
43
57
85
113
141
ET
Visit Window (Days)
N/A
±1
±1
±2
±2
±2
±2
±2
±3
Enrollment Procedures
Informed consent
X
Medical history & demography
X
X
Eligibility assessment
X
X
Medication History
X
X
Randomization
X
Clinical Assessments
Full Physical Exam
X
X
X
X
Brief Physical Exam
X
X
X
X
X
X
X
Vital signsc
X
X
X
X
X
X
X
X
X
X
X
ECGd
X
Xd
X
Xd
X
Xd
X
Height/Weighte
X
X
X
Chest radiographf
X
C-SSRSg
X
X
X
Laboratory Assessments
Hematology/Blood chemistry (including 
eGFR)
X
X
X
X
X
X
X
X
X
X
X
Urine myoglobinv
X
Serum cystatin C
X
X
X
X
X
X
X
X
X
X
Lipid panelh (fasting) 
X
X
X
Urinalysis (to be processed at central lab)i
X
X
X
X
X
X
X
X
X
X
X
FSHj
X


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Final Protocol Amendment 1, 28 January 2020
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Page 22
Study Procedure
Screening
Baseline
Investigational Treatment Period
Follow-
Up (EOS)
Early 
Terminationb
Visit Identifier
1
2
3
4
5
6
7
8
9
10
Week
-6 to -1
Day 1
1
2
4
6
8
12
16
20
ET
Study Daya
-42 to -1
1
8
15
29
43
57
85
113
141
ET
Visit Window (Days)
N/A
±1
±1
±2
±2
±2
±2
±2
±3
Serum β-HCGk
X
Urine β-HCGl (done at site)
X
X
X
X
X
X
X
X
X
X
HIV serology (per local regulations)
X
HBsAg, HBcAb, and HCVAb (Hep B and 
Hep C reflex testing)m
X
Tuberculosis test
X
Urine drug screening
X
Pharmacokinetics (PK)
PK pre-dose
X
X
X
X
X
X
X
X
PK 0.5, 1, 2, 4 hours post dose
Xw
PK sample
Xw
Banked Biospecimens and Pharmacodynamics (PD)
 
Study Treatment
IP dispensingo
X
X
X
X
IP accountability
X
X
X
X
X
X
X
X
Clinical Assessments of HS
Hurley Stage
X
X
X
X
X
Lesion Countsp
X
X
X
X
X
X
X
X
X
X
Abscess Count
X
X
X
X
X
X
X
X
X
X
Inflammatory Nodule Count
X
X
X
X
X
X
X
X
X
X
Fistula Count
X
X
X
X
X
X
X
X
X
X
Erythema Assessmentsq
X
X
X
X
X
X
X
X
X
X
IHS4 Score
X
X
X
X
X
X
X
X
X
X
Patient Reported Outcomes (PROs)r
Dispense eDiary device and instructions 
on use
X
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Final Protocol Amendment 1, 28 January 2020
PFIZER CONFIDENTIAL 
Page 23
Study Procedure
Screening
Baseline
Investigational Treatment Period
Follow-
Up (EOS)
Early 
Terminationb
Visit Identifier
1
2
3
4
5
6
7
8
9
10
Week
-6 to -1
Day 1
1
2
4
6
8
12
16
20
ET
Study Daya
-42 to -1
1
8
15
29
43
57
85
113
141
ET
Visit Window (Days)
N/A
±1
±1
±2
±2
±2
±2
±2
±3
Patient Global Assessment
of Skin Pain (Numeric
Rating Scale)s
X
→
→
→
→
→
→
→
→
X
X
HS Symptom Itemss
X
→
→
→
→
→
→
→
→
X
X
DLQI
X
X
X
X
X
X
X
Other
 
 
Monitoring
Contraception Checku
X
X
X
X
X
X
X
X
X
X
X
Prior/Concomitant Treatment(s)
X
→
→
→
→
→
→
→
→
→
X
AE monitoring
X
→
→
→
→
→
→
→
→
→
X
Abbreviations: AE= adverse event; C-SSRS= Columbia Suicide Severity Rating Scale; EOS = end of study; 
; 
DLQI= Dermatology Life Quality Index; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; 
;
FSH= follicle stimulating hormone; β-HCG= human chorionic gonadotropin; HBsAg = hepatitis B surface antigen; HBcAb = hepatitis B core antibody; 
HCVAb = hepatitis C virus antibody; HIV= human immunodeficiency virus; IHS4 = International Hidradenitis Suppurativa Severity Score System; 
IP = Investigational Product; PE= physical exam; 
; 
PK = pharmacokinetic; PRO = patient reported outcome; 
 
VAS = visual analog scale; WOCBP= women of child-bearing potential; →= daily assessment.
a.
Days relative to Day 1.
b.
Participants who prematurely withdraw during Investigational Treatment Period should return for an Early Termination (ET) visit and enter into Follow-up 
with their EOS Visit occurring approximately 4 weeks after their ET Visit.
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Protocol C2501007
Final Protocol Amendment 1, 28 January 2020
PFIZER CONFIDENTIAL 
Page 24
c.
Vital signs consist of blood pressure, pulse rate, and temperature and should be performed before laboratory blood collection and after 5 minutes rest while 
supine.  Participants should not use nicotine containing products or ingest caffeine 30 minutes prior to blood pressure and pulse rate measurements. 
d.
12-lead ECG should be performed after the participant has rested quietly for at least 10 minutes in a supine position and before laboratory blood collection
(except for the pose dose ECG). On Weeks 8 and 16 single ECGs will be collected prior to dosing and also at 2 hours (with a ±15 minutes window) post 
dose. Refer to Section 8.2.4 for details.
e.
Height only measured at Screening; height and weight will be measured without shoes.
f.
Chest X-ray or other appropriate chest diagnostic imaging (ie, CT or MRI) may be performed within 12 weeks prior to Day 1. 
g.
Use C-SSRS “Lifetime” version at Screening. Participants who have recent or active suicidal ideation or behaviors will be excluded from study entry. Use 
C-SSRS “post base line visits” version for Week 8 and 16 Visits.
h.
Participants must be fasting (water only) for at least 8 hours prior to visits, when lipid panel is being assessed.
i.
Collect urine sample for central laboratory urinalysis and urine microscopy at Screening and pre-dose at Baseline. At postdose visits: urine microscopy is 
indicated if the urinalysis is positive for blood, nitrite, leukocyte esterase and/or protein, or there is clinical suspicion of urinary tract infection, or decrease in 
renal function; urine culture is performed if urinalysis is positive for nitrite and/or leukocyte esterase, or if otherwise clinically indicated.
j.
To be done in females 60 years or older and who are amenorrheic for at least 12 consecutive months. 
k.
Required for WOCBP at Screening.
l.
Required for WOCBP prior to dosing at baseline and at all subsequent visits.  To be conducted at the site.  Pregnancy tests (serum or urine) may also be 
repeated more frequently as per request of IRBs/ECs or if required by local regulations. 
m. Reflex-testing (if necessary) consists of: participants at Screening who are HBsAg negative but HBcAb positive should be reflex-tested for HBsAb, if 
HBsAb is positive, may enroll; if HBsAb is negative, they will be screen-failed; participants at Screening who are positive for HCV Ab will be reflex-tested 
for HCV RNA and, if HCV RNA is negative, may enroll; if HCV RNA is positive, they will be screen-failed.
 
o.
Participants should take blinded study medication daily during the Investigational Treatment Period; however, on study visit days, participants are instructed 
to refrain from dosing at home, and are to take the dose in the clinic. 
p.
Refer to Section 8.1.1.1 for details of measurements.  
q.
At every visit, for each affected anatomic region, the investigator will assess the overall degree of erythema using a four-point ordinal scale ranging 
between 0 and 3.  
r.
Effort should be made to complete all PRO questionnaires before any other assessments (except that PGA Skin Pain NRS and HS Symptoms will be 
completed daily at home).  PGA Skin Pain NRS and HS Symptoms will be completed as a daily diary from Day -7 prior to Baseline and through Week 16 at 
home, and at site at the FU visit and the ET visit (if applicable).  At site visits participants will complete PROs in the following order:
 
DLQI, 
.  At all other times not associated with site visits, participants will complete PROs in the following order: PGA Skin Pain NRS and 
HS Symptom Items.
s.
PGA Skin Pain NRS and HS Symptoms Items will be completed daily from Day -7 throughout Week 16 at home. Both will be completed at the site at the 
follow-up visit and at the early termination visit (if applicable).
C
C
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Protocol C2501007
Final Protocol Amendment 1, 28 January 2020
PFIZER CONFIDENTIAL 
Page 25
u.
To confirm that contraception, if assigned, is used consistently and correctly.
v.
Urine myoglobin will be measured at Screening and in case of CK >3 x ULN during the study.
w.
PK collection windows are defined as follows (if applicable): ±15 minutes for 0.5 hour post dose; +30 minutes for 1 hour post dose; ±30 minutes for 2 and 
4 hours post dose. Blood sample for PK will be collected at early termination visit for subjects who discontinue early from the Treatment Period only if the
most recent dose taken prior to ET visit was within 48 hours.
C
C


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Final Protocol Amendment 1, 28 January 2020
PFIZER CONFIDENTIAL 
Page 26
2. INTRODUCTION
Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease 
that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine 
gland-bearing areas of the body.1 HS presents a variable clinical course. One of the main 
features of the disease is the intertriginous occurrence, although, other areas of skin may also 
be affected. The affected areas are in decreasing order of frequency: inguinal, axillary, 
perineal and perianal as well as the submammary and/or intermammary fold in women,
buttocks, mons pubis, scalp, area behind the ears and eyelids. 
The prevalence of self-reported disease is about 1% in Western Europe. The average interval 
from the onset of symptoms to diagnosis is 7.2 years. Women are affected 2 to 5 times as 
frequently as men, and the disease may be more common in blacks than in whites. Disease 
severity ranges from mild (localized lesions) to severe (multiple areas of widely dispersed 
lesions, including interconnected sinus tracts and hypertrophic scars). Pain, drainage, and 
range-of motion limitations from scarring can decrease the quality of life.2,3
Pain is a prominent feature of HS, which is reflected in the recently defined set of core 
outcomes to be assessed in future trials.4,5  The majority of patients rated their pain on a 
Numerical Rating Scale-11 (NRS-11) ranging from 4/10 - 10/10 and described it at various 
times as hot, burning, pressure stretching, cutting, sharp, taut, splitting, gnawing, pressing 
sore, throbbing, and aching.6
The pathophysiology of HS remains incompletely defined. Numerous inflammatory 
mediators including tumor necrosis factor (TNF)-, interleukin (IL)-17, IL-32 and IL-36 
subtypes have been implicated in the disease. However, there is an incomplete 
understanding of the source and triggers of these mediators and how they sustain the chronic 
inflammation that characterizes this disease.7
The severity of HS is classified in stages according to Hurley definition:  

Hurley Stage I: Abscess formation, single or multiple, without sinus tracts and 
cicatrization.

Hurley Stage II: Recurrent abscesses with tract formation and cicatrization, single or
multiple, widely separated lesions.

Hurley Stage III: Diffuse or near-diffuse involvement, or multiple interconnected
tracts and abscesses across the entire area.
Stage I disease is most common (68% of patients), while stage II occurs in 28% of patients, 
and 4% of HS patients have stage III.1


PF-06650833, PF-06700841, PF-06826647 
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Page 27
The European S1 HS guideline suggests that the disease should be treated based on its 
individual subjective impact and objective severity. Locally recurring lesions can be treated 
by classical surgery or light amplification by stimulated emission of radiation (LASER)
techniques, whereas medical treatment either as monotherapy or in combination with radical
surgery is more appropriate for widely spread lesions. Medical therapy may include 
antibiotics (clindamycin plus rifampicin, tetracyclines), acitretin and biologics (adalimumab,
infliximab). Adjuvant measurements, such as pain management, treatment of 
superinfections, weight loss and tobacco abstinence have to be considered.1
Currently adalimumab is the only approved medical treatment for moderate to severe HS. It 
is based on two similarly designed (PIONEER I and PIONEER II), Phase 3 multicenter trials 
of adalimumab for HS.3 A total of 307 patients were enrolled in PIONEER I, and 326 were 
enrolled in PIONEER II. Clinical response rates [hidradenitis suppurativa clinical response 
(HiSCR)]: defined as at least a 50% reduction from baseline in the abscess and 
inflammatory-nodule count, with no increase in abscess or draining-fistula counts] at
Week 12 were significantly higher for the groups receiving adalimumab weekly than for the 
placebo groups: 41.8% versus 26.0% in PIONEER I (P = 0.003) and 58.9% versus 27.6% in 
PIONEER II (P<0.001). Patients receiving adalimumab had significantly greater 
improvement than the placebo groups in rank-ordered secondary outcomes (lesions, pain, and 
the modified Sartorius score for disease severity) at Week 12 in PIONEER II only.3 The 
main difference between the study designs is that in PIONEER I, patients receiving oral 
antibiotic agents for HS were required to stop treatment for at least 28 days before baseline; 
in PIONEER II, patients were allowed to continue treatment with antibiotics (tetracycline 
class) in stable doses. 
Thus, a significant number of patients (~40%) with moderate to severe HS did not respond to 
treatment with adalimumab, and therefore there is still an unmet need for an effective, safe, 
and well tolerated treatment in patients with moderate to severe HS.
The objectives of the current study are to evaluate the efficacy, safety and tolerability of 
PF-06650833, an IL-1 receptor associated kinase 4 (IRAK4) inhibitor, PF-06700841, a dual 
inhibitor of human tyrosine kinase 2 (TYK2) and Janus kinase 1 (JAK1), and PF-06826647,
a potent TYK2 inhibitor, in patients with moderate to severe HS. Since the pathophysiology 
of HS is not defined completely, it is uncertain which of these three disease targets and 
pathways would be of more relevance for the treatment of patients with HS. Therefore, the 
additional objective of this study is to compare the efficacy of PF-06650833, PF-06700841,
and PF-06826647 with the goal to select one of these inhibitors for further clinical 
development.
PF-06650833 is currently being investigated in rheumatoid arthritis and will be investigated 
in HS.
PF-06700841 is currently being investigated in patients with plaque psoriasis (PsO), alopecia 
areata (AA), ulcerative colitis, Crohn’s disease, vitiligo, and will be investigated in HS.


PF-06650833, PF-06700841, PF-06826647 
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Final Protocol Amendment 1, 28 January 2020
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Page 28
PF-06826647 is being investigated in participants with plaque PsO and will be investigated 
in HS.  
2.1. Study Rationale 
This multicenter, Phase 2a, randomized, double-blind, placebo controlled study is being 
conducted to provide data on safety, tolerability, pharmacokinetics (PK), and efficacy of 
PF-06650833, PF-06700841, and PF-06826647 in adults with moderate to severe HS. In 
addition, the study is intended to provide additional information for determining the future 
clinical development of JAK inhibitors and/or IRAK4 in HS.
2.2. Background 
The following sections summarize available in vitro and in vivo human disposition and 
drug-drug interaction profiling for PF-06650833, PF-06650833, PF-06700841 and
PF-06826647 as well as the available clinical safety and pharmacology of these
investigational products.  Further details of can be found in the individual Investigator 
Brochures (IB).
 
 
 
 
 
 
 
2.2.2. Nonclinical Safety of PF-06650833
Nonclinical toxicity studies with PF-06650833 were conducted using a sprayed dried 
dispersion (SDD) or nanomilled formulation.  Since exposures with the SDD formulation 
were higher than those observed with the same dose using the nanomilled formulation, 
toxicity findings are presented in terms of exposure, instead of dose. In safety pharmacology 
studies, PF-06650833-related increases in heart rate and decreases in blood pressure (BP)
were observed in telemetered rats and dogs [at maximum observed concentration (Cmax)
≥358 ng/mL and area under the curve at 24 hours (AUC24) ≥1540 ng•h/mL].  Although the 
hERG IC50 was >100 μM (36,100 ng/mL), small (+6 to +11 msec) prolongations of the QTc 
interval was observed in the 24-day cardiovascular (CV) study in telemetered dogs (at 
Cmax ≥742 ng/mL and AUC24 ≥8550 ng•h/mL).
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PF-06650833 was evaluated in single-dose and exploratory toxicity studies in rats (7 or 
14 days) and dogs (14 days) using both the SDD and nanomilled formulations, and was 
evaluated Good Laboratory Practice (GLP) toxicity studies up to 26 weeks duration in rats 
and up to 39 weeks duration in dogs, using the nanomilled formulation. In these studies, the 
renal system, heart, skeletal muscle, liver, and the gastrointestinal (GI) tract were identified 
as PF-06650833-related target organs.  
PF-06650833-related and adverse, mild to severe obstructive nephropathy occurred in the 
3-month study in rats (at Cmax ≥2910 ng/mL and AUC24 ≥18,300 ng•h/mL), that was still 
observed at the end of the 1-month recovery period in female rats.  However, obstructive 
nephropathy was not observed at any dose tested in the 26-week study in rats (at Cmax
≤3360 ng/mL and AUC24 ≤34,400 ng•h/mL).  Urine sediment crystals (determined to be 
PF-06650833 or its metabolites) were observed in rats at Cmax ≥1080 ng/mL and AUC24
≥5920 ng•h/mL.  Following 8-week to 1-month recovery phases in the 3-month and 26-week 
studies, respectively, no crystals in urine sediment were observed.  At very high exposures, 
PF-06650833-related pale kidney, renal tubular dilatation, and pelvic inflammation was 
observed in exploratory studies in rats (at Cmax = 7640 ng/mL and AUC24 = 33,500 ng•h/mL) 
and congestion of the medulla secondary to PF-06650833-related toxicity was observed in 
dogs (at Cmax ≥7460 ng/mL and AUC24 ≥35,100 ng•h/mL). 
The no observed adverse effect level (NOAEL) for PF-06650833 when administered by oral 
gavage for 26 weeks in rats or 39 weeks in dogs was 150 mg/kg/day in female rats 
(Cmax=3360 ng/mL and AUC24=34,400 ng•h/mL), 300 mg/kg/day in male rats 
(Cmax=1780 ng/mL and AUC24=15,800 ng•h/mL), and 60 mg/kg/day (30 mg/kg twice daily 
(BID), 7 hours apart) in dogs (Cmax=1710 ng/mL and AUC24=17,200 ng•h/mL). 
PF-06650833 was negative for mutagenicity in bacterial reverse mutation assays.  
PF-06650833 did not induce micronuclei in vivo, in polychromatic erythrocytes in peripheral 
blood of rats, at any dose tested.  PF-06650833 absorbs in the Ultra Violet A (UVA) range 
but was not phototoxic in an in vivo assay.
In the fertility and early embryonic development study in rats, there were no PF-06650833 
related effects on male or female reproductive and early embryonic toxicity; therefore the 
NOAEL was 1000 mg/kg/day (mean plasma concentrations of 2257 and 3457 ng/mL for 
males and females, respectively), the highest dose tested.  In the embryo-fetal developmental 
(EFD) study in rats, PF-06650833-related fetal skeletal malformations and variations 
occurred at Cmax 5020 ng/mL and AUC24 42,600 ng•h/mL.  The maternal NOAEL in rats was 
1000 mg/kg/day and the developmental NOAEL in rats was Cmax=3560 ng/mL and 
AUC24=20,000 ng•h/mL (100 mg/kg/day).  There was no maternal or developmental toxicity 
in the EFD study in rabbits, therefore the maternal and developmental NOAEL was 
1000 mg/kg/day (Cmax=2030 ng/mL and AUC24=25,600 ng•h/mL), the highest dose tested. 
Further details on the nonclinical safety program of PF-06650833 are provided in the current 
PF-06650833 IB.


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More detailed information on the clinical PK with PF-06650833 can be found in the current 
PF-06650833 IB.
2.2.5. Nonclinical Pharmacokinetics and Metabolism of PF-06700841
In vitro and in vivo metabolite profiling indicated that the primary clearance mechanisms for 
PF-06700841 were through CYP-mediated oxidation. In vitro studies using human 
hepatocytes indicated greater than 88% of the PF-06700841 metabolism observed was 
attributed to CYP450, with CYP3A4 identified as the major contributor (~62%). In vitro 
studies indicated that PF-06700841 showed a low risk of inhibiting the major drug 
metabolizing CYP or UGT enzymes, as well as a low risk of significant induction of 
CYP3A4, 2B6, or 1A2.  PF-06700841 was shown to be a substrate for MDR1, but not 
BCRP, OATP1B1, or OATP1B3.  PF-06700841 showed a low risk of inhibition of bile salt 
export pump (BSEP), OAT1, OAT3, OATP1B1, OATP1B3.  However, PF-06700841 
showed potential to inhibit BCRP, MDR1, OCT1, OCT2, MATE1, and MATE2K.  
Clinically, PF-06700841 was shown to increase serum creatinine (SCr) levels (OCT2 
substrate), but not cystatin C.
2.2.6. Nonclinical Safety of PF-06700841
No adverse findings were observed in oral repeat-dose toxicity studies with PF-06700841 in 
rats and monkeys up to 6 and 9 months in duration, respectively.  PF-06700841-related, 
non-adverse, target organs identified include the immune and hematolymphopoietic systems 
(thymus, spleen, lymph nodes, and bone marrow), cardiovascular system (BP, heart rate, 
corrected Q wave interval [QTc]), GI tract (body weight and weight gain effects), and 
adrenal gland (vacuolation).  The findings in the thymus, spleen, lymph nodes, and bone 
marrow are consistent with the pharmacological activity of PF-06700841.  The NOAELs in 
the 6-and 9-month toxicity studies were 45 mg/kg/day in rats (unbound Cmax of 8280 ng/mL 
and AUC24 of 69,700 ng•h/mL) and 20 mg/kg/day in monkeys (unbound Cmax of 2260 ng/mL 
and AUC24 of 10,700 ng•h/mL).  Adverse findings in the central nervous system (decreased 
activity, mortality, prostration, convulsions) were observed at high systemic exposures in 
pregnant, but not in non-pregnant rabbits. 
In oral EFD studies in rats and rabbits, adverse PF-06700841-related developmental effects 
occurred in rats only (lower embryo-fetal viability and mean fetal body weights, fetal skeletal 
malformations, external malformations).  The developmental NOAEL in rabbits was
1 mg/kg/day (unbound Cmax of 174 ng/mL and AUC24 of 608 ng•h/mL). 
The developmental NOAEL in rats was not established and is <2 mg/kg/day (unbound Cmax
of 482 ng/mL and AUC24 of 2240 ng•h/mL), the lowest dose tested.  No effects on female 
reproductive organs, as assessed by histopathologic examination, were noted in either the rat 
or monkey repeat-dose toxicity studies.  
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PF-06700841 is not mutagenic in bacterial reverse mutation assays.  Although PF-06700841 
was positive for micronuclei formation in vitro (through an aneugenic mechanism), it did not 
induce micronuclei in vivo in rats at 55 mg/kg/day (unbound Cmax=7730 ng/mL and 
AUC24=88,300 ng•h/mL), the highest dose tested in the 1-month oral toxicity study. No 
evidence of PF-06700841-related phototoxicity in the skin or eyes of pigmented rats in a 
3-day oral phototoxicity study was observed up to the highest dose tested of 100 mg/kg/day, 
demonstrating that PF-06700841 was not a phototoxicant, in vivo.
Further details of the nonclinical safety program of PF-06700841 are provided in the current 
PF-06700841 IB.
2.2.7. Clinical Safety of PF-06700841
The first in human (FIH) study was a Phase 1, randomized, double-blind, third party open, 
placebo-controlled, single and multiple dose escalation, parallel group study in healthy adult 
participants and participants with plaque PsO, with a relative bioavailability (BA) and food 
effect assessment of a tablet formulation of PF-06700841 in healthy adult participants.  In the 
completed FIH study (B7931001), 41 healthy volunteers were exposed to single doses and 
26 of the 41 participants received multiple daily doses of PF-06700841 over 10 days; a small 
cohort of plaque PsO patients (n=21) were treated QD with PF-06700841 for 28 days at 
30 mg and 100 mg doses.
An additional healthy volunteer cohort was included to support the evaluation of the relative 
BA of a tablet formulation of PF-06700841, and assessment of a high fat meal on tablet BA.  
Twelve healthy participants participated in this BA assessment, and received single doses of 
open label PF-06700841 in a 3-way cross over design (PF-06700841 tablet fasted, 
PF-06700841 solution/suspension fasted, and PF-06700841 tablet under fed conditions).  
PF-06700841 was generally safe and well tolerated in the Phase 1 clinical study B7931001.
A Phase 1 study to determine the absorption, distribution, metabolism, and excretion 
(ADME) of PF-06700841 (B7931014) in healthy males is ongoing. 
The most commonly reported all causality TEAEs across active participants in both single 
ascending dose (SAD) and multiple ascending dose (MAD) cohorts were increased blood 
creatinine, and decreased neutrophil count. In the SAD period, 1 participant in the 
PF-06700841 100 mg group had SCr values meeting the criteria for high levels 
[>1.3 X upper limit of normal (ULN)].  In the MAD period, 4 participants (1, 2, and 
1 participants in the PF-06700841 10 mg QD, 100 mg QD, and 50 mg BID groups, 
respectively) had SCr values meeting the criteria for high levels.  No participants in the PsO 
period had SCr values meeting the criteria for high levels. In the SAD period, 3 participants 
(1 participant each in the PF-06700841 1 mg, 200 mg, and placebo group) had abnormal low 
neutrophil counts (<0.8 X LLN).  In the MAD period, 14 participants (1, 3, 3, 5, and 
2 participants in the PF-06700841 10 mg QD, 100 mg QD, 50 mg BID, 175 mg QD, and 
placebo group, respectively) had abnormal low neutrophil counts.  In the PsO period, 
6 participants (1 and 5 participants in the PF-06700841 30 mg and 100 mg QD groups, 
respectively) had abnormal low neutrophil counts.  All laboratory abnormalities reported as 


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AEs were mild in severity, except for one case of neutropenia which was reported as 
moderate in severity (Grade 3 neutropenia).  No neutrophil counts reached or fell below 
500 cells/mm3 during the study.
The most commonly reported all causality TEAEs across active participants in the PsO 
cohorts treated with either 30 mg or 100 mg PF-06700841 were blood creatinine increased 
and neutrophil count decreased.
An AE of herpes zoster occurred in a single participant with PsO after completing 28-day 
treatment with PF-06700841 at the 100 mg QD dose level.  The participant had a 
non-disseminated, herpetiform rash on the upper left back and left arm that was reported to 
have presented on Study Day 30 (2 days after the last dose of PF-06700841).  The AE was 
mild in severity and was treated with acyclovir and Vicodin by the investigator.
In the BA cohort, the reported AEs were nausea, contusion, and headache, each of which was 
experienced by 1 participant.  All TEAEs were mild in severity.
Oral administration of PF-06700841 at multiple doses of 100 mg QD was well-tolerated and 
generally safe in healthy Japanese participants investigated in study B7931009.  There were 
no deaths, SAEs, severe AEs, discontinuations due to AEs, or dose reductions or temporary 
discontinuations due to AEs during this study.
Overall, 3 TEAEs were reported by 1 participant following placebo treatment, including 
palpitations, abdominal pain and insomnia.  Among these AEs, palpitations and insomnia 
were considered treatment-related.  Seven (7) TEAEs were reported by 3 participants 
following oral administration of PF-06700841 100 mg, including flatulence, fatigue, viral 
upper respiratory tract infection, headache, somnolence, nocturia and haematoma.  Among 
these AEs; flatulence, headache, somnolence and nocturia were considered treatment-related 
by the investigator.  One (1) AE of abdominal pain in the placebo treatment group was 
moderate and the others were considered mild in severity.
There were no clinically significant findings observed in laboratory parameters, vital signs, 
ECG parameters, and physical examinations.
PF-06700841 was administered to 6 healthy Japanese participants in the Phase 1 study 
B7931009 at a daily dose of 100 mg.  PF-06700841 demonstrated acceptable safety and 
tolerability in healthy Japanese participants investigated in study B7931009, in which 
multiple doses of 100 mg QD or placebo was administered for 10 days.  There were no 
deaths, SAEs, severe AEs, discontinuations due to AEs, or dose reductions or temporary 
discontinuations due to AEs during this study.  All AEs were mild or moderate in severity.  
An AE of palpitations was observed in a placebo participant during the treatment period.  
There were no clinically significant findings observed in laboratory parameters, vital signs, 
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In study B7931019, a definitive QT study for PF-06700841 in healthy participants, each 
participant received single oral doses of PF-06700841 200 mg, placebo and moxifloxacin 
400 mg in a 3-way crossover design.  Treatment assignments to PF-06700841 and placebo 
were blinded to participants and investigator but moxifloxacin treatment was unblinded.  In 
total, 33 participants were enrolled with 32 completed all 3 treatments.  Overall, 
PF-06700841 200 mg and moxifloxacin 400 mg were safe and well tolerated with no deaths, 
SAEs, severe AEs or discontinuation due to AEs. A total of 24 TEAEs (all causalities) were 
reported in 15 participants after PF-06700841 treatment.  There were 11 and 12 TEAEs 
reported in 10 and 8 participants after moxifloxacin and placebo treatment respectively.  All 
AEs were mild to moderate in severity.  Despite QTc increases observed after single doses of 
PF-06700841 200 mg and moxifloxacin 400 mg, there were no clinically significant findings 
in ECG categorical analyses including no changes in corrected QT (Fridericia method) 
(QTcF >60) msec or an absolute value >500 msec.  
PF-06700841 was also investigated in patients with plaque PsO (B7931004).  This study was 
a Phase 2a, randomized, double-blind, placebo-controlled, parallel group, multicenter study 
in adult participants with moderate to severe plaque PsO.  The first part of the study, 
following a screening period (up to 6 weeks), was a 4-week induction period with 
double-blind daily treatment.  At the end of Week 4, all participants switched to their 
predefined double-blind maintenance treatment regimen for Week 5 through Week 12.  A 
total of 212 PsO participants were randomized and received at least one dose of study 
treatment.  The randomization ratio was 7:1, active:placebo.
During the first 4 weeks of the treatment period, participants received 1 of the 3 treatments
orally, either 30 mg QD or 60 mg QD of PF-06700841, or matching placebo.  During the 
8-week maintenance portion of the treatment period (Weeks 5 through 12), participants 
received 1 of the 4 treatments, either PF-06700841 10 mg, or 30 mg QD, or a 100 mg once 
weekly (QW) regimen of PF-06700841, or matching placebo.  Maintenance dose level and 
regimen were assigned at the initial time of randomization into the study.  All participants, 
regardless of assigned regimen (ie, QD or QW) received blinded QD tablets throughout the 
study treatment period to maintain the study blind.
The proportion of participants with all-causality TEAEs was comparable across all treatment 
groups but numerically higher in the active treatment groups (64.0% to 76.7%) than the 
placebo group (56.5%).  The majority of participants in all the treatment groups experienced 
mild or moderate all-causality TEAEs, and only 11 (5.2%) out of 212 participants 
experienced severe all-causality TEAEs.  Overall, there were no dose-dependent increases in 
the all-causality TEAEs.
A total of 13 participants discontinued from the study due to TEAEs. One participant in the 
60 mg QD to placebo group discontinued the investigational product treatment, but remained 
in the study.  There were 5 participants with dose reduced or temporarily discontinued due to 
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One post-therapy death occurred due to gunshot wound after the participant was discontinued 
from the study due to noncompliance with investigational product, which was considered 
unrelated to the study treatment by the investigator.  
Five participants experienced a total of 6 SAEs during the study; 3 of the SAEs were 
considered to be related to investigational product by the investigator, of which 2 SAEs 
(pneumonia and sepsis) reported by 1 participant in the 60 mg QD to 100 mg QW group 
were considered not related to investigational product by the sponsor.  The participant had 
1 dose of PF-06700841 60 mg on Day 1 and had 2 SAEs of pneumonia and sepsis on Day 2 
before dosing and was permanently discontinued from study due to the SAE of pneumonia.  
One participant in the 30 to 10 mg group was found to have a positive urine human chorionic 
gonadotropin test at the Week 6 (Day 42) visit after which confirmation with serum 
pregnancy test led to permanent discontinuation from study on Day 53.  On Day 165, an 
obstetrical ultrasound demonstrated a right-sided cleft lip with a gap of 10 millimeters in the 
fetus, with no definite cleft palate.  The Day 176 obstetrical ultrasound confirmed presence of 
cleft lip in the fetus, with all other findings appearing within normal limits.  This event of 
fetal cleft lip was unexpected in the single reference safety document for the investigational 
product and was assessed as related per sponsor.  
No participants experienced herpes zoster during the study.  Six participants experienced 
AEs of herpes simplex; 5 were mild in severity and 1 was a moderate AE of herpes simplex 
reported by 1 participant in the 60 mg QD to 100 mg QW group during the induction period.
One participant in the 30 mg QD to 100 mg QW group was reported to have an AE of 
squamous cell carcinoma of the skin on Day 2.  The AE was mild and not related to the 
investigational product as evaluated by the investigator, and resolved on Day 57.  
Serious infections (pneumonia and sepsis) were reported for 1 participant in the 60 mg QD to 
100 mg QW group.  The participant only had 1 dose of PF-06700841 60 mg on Day 1 and 
the serious infections (pneumonia and sepsis) occurred on Day 2 before dosing.  
There were no clinically meaningful observable dose dependent neutropenia, lymphopenia, 
thrombocytopenia, and anemia among the active treatment groups, except for 1 SAE of 
anemia reported by 1 participant in the 60 to 10 mg QD group.  The same participant had 
pre-existing kidney dysfunction (chronic kidney disease Stage 3), and increased SCr and
serum Cystatin-C values (1.3 mg/dL [reference range: 0.4 to 1.2 mg/dL], 1.72 mg/L 
[reference range: 0.53 to 0.95 mg/L], respectively) at screening.  During the study, the 
participant developed a moderate AE of acute kidney dysfunction and concomitant 
≥30% decreases from baseline in SCr based and serum Cystatin-C based eGFR, which were
considered as individual clinically significant laboratory abnormalities.  
No participants met the laboratory test discontinuation criteria (laboratory test abnormalities 
confirmed through re-testing within 48 hours) during study treatment.  There was no 
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There were no clinical meaningful findings in vital signs, ECG, and suicidal behavior or 
ideation during the study.
PF-06700841 is currently being investigated in patients with PsO (B7931023, topical), 
alopecia areata (B7931005), atopic dermatitis (B7931022, topical), ulcerative colitis 
(B7981005), psoriatic arthritis (B7931030), systemic lupus erythematosus (B7931028) and 
Crohn’s disease (B7981007). All Phase 2b studies are ongoing and blinded.
Further details on the clinical safety information with PF-06700841 are provided in the IB.
2.2.8. Clinical Pharmacology of PF-06700841
Following single oral PF-06700841 doses, peak plasma concentrations generally occurred at 
or before 1 hour for doses of 1 mg-200 mg.  In general, both AUCinf and Cmax appeared to 
increase proportionally with dose from 1 mg-100 mg; there appeared to be a trend toward 
more than proportional increase from 100 mg-200 mg.  Mean t½ was 3.8-7.5 hours with a 
trend towards longer t½ at the higher doses, probably due to concentrations remaining above 
the lower limit of quantification (LLOQ) for a longer time as the dose increased.  
On Day 10 of multiple-dose administration, PF-06700841 was absorbed rapidly with median 
Tmax at or before 1.5 hours postdose across the entire range of doses from a total daily dose of 
10 mg up to 175 mg.  Plasma Cmax and AUCtau both appeared to increase proportionally with 
dose from 10 mg QD to 100 mg QD with a trend towards greater than proportional increase 
from 100 mg to 175 mg QD.  As would be expected, dose normalized Cmax for 50 mg BID is 
slightly higher than that for 100 mg QD while dose normalized AUCtau is consistent between 
the two dosing regimens.  Mean terminal t½ ranged from 4.9 to 10.7 hours.  Steady state 
generally appeared to have been reached by Day 8 of QD or BID dosing.  Urinary recovery 
of PF-06700841 was low, with less than 16% of the dose recovered unchanged.
Following multiple-dose administration in participants with PsO, PF-06700841 was absorbed 
rapidly with median Tmax of 1 to 2 hours post dose.  Mean terminal t½ was 16 hours in the 
30 mg group and 6 hours in the 100 mg group.  The mean t½ value in the 30 mg group
included a reported t½ value of 87.5 hours for one participant with an anomalous data point at 
216 hours postdose.  All other participants in the dose group had concentrations below the 
LLOQ after 24 hours and t½ values of 6.48 hours or less.  
Relative BA of 100 mg PF-06700841 tablets compared to 100 mg oral suspension was 
96.18% for AUCinf and 94.28% for Cmax.  Both of the 90% CIs for the ratio were within the 
80%-125% equivalence interval.  When the 100 mg tablets were administered under fed 
conditions, Tmax was delayed with a median value of 4.0 hours, compared to 0.5 hours under 
fasted conditions.  For 100 mg tablets fed versus fasted, the ratio (90% CI) of adjusted 
geometric means for AUCinf and Cmax was 82.33% (73.45%, 92.29%) and 64.25% 
(55.98%, 73.75%), respectively.  The results indicate that PF-06700841 can be administered 
with or without food.


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Following single oral dose of PF-06700841 100 mg under fasted conditions in Japanese 
participants (B7931009), absorption was rapid with a median Tmax of 1 hour and a range of 
0.5-2 hours on Day 1. Geometric mean AUCinf was 8725 ng•hr/mL and Cmax was
1035 ng/mL. Mean terminal t½ was 5.7 hours based on a 24-hour sampling.
On Day 10 following multiple oral dosing, median Tmax was 0.76 hours with a range of 
0.5-4.0 hours. Both AUCtau and Cmax increased slightly compared to Day 1, with geometric 
mean values of 9888 ng•hr/mL and 1114 ng/mL, respectively. Mean terminal t½ was 
8.9 hours. Steady-state generally appeared to have been achieved by Day 6. Urinary 
recovery of PF-06700841 was low, with less than 16% of the dose recovered unchanged.
Following a single dose of 200 mg PF-06700841 in B7931019, the maximum 
placebo-corrected QTcF change from baseline was observed at 3 hours post-dose with mean 
of 14.6 ms and 90% confidence interval (CI) of (12.4, 16.8 ms). In addition, the maximum 
mean change in QTcF observed following administration of 400 mg moxifloxacin was 
13.8 ms (90% CI: 11.6, 16.0 ms), suggesting a good sensitivity in this QT study. 
Per protocol, concentration-QTcF analysis was pre-defined as the primary analysis to 
determine PF-06700841 effects on QT prolongation at relevant clinical doses. The results 
described here are considered as preliminary data as the Clinical Study Report is being 
drafted.
The relationship between PF-06700841 concentration and QTcF change from baseline was 
best and adequately described by Emax model, in which the maximum QTcF change (Emax) 
was estimated to be 15.7 ms (90% CI: 13.2, 18.2 ms). The QTcF change observed at 200 mg
PF-06700841 appeared to reach maximum effect. Based on concentration-QT model, the 
estimated mean change in QTcF at steady-state Cmax of 45 mg QD was 7.7 ms (90%CI: 6.5, 
9.1 ms). This suggested that no clinically significant QT effect expected following
PF-06700841 treatment up to 45 mg QD as the upper bound of two-sided 90% CI is less than 
10 ms threshold. Following PF-06700841 60 mg QD, the highest clinical dose being tested 
in Phase 2/2b studies, the mean QTcF change at expected Cmax were 8.8 ms (90%CI: 7.7, 
10.2 ms) with the upper bound slightly exceeding 10 ms.  
B7931004 study was recently completed and clinical study report is ongoing.  In study 
B7931004, PF-06700841 plasma concentrations were collected pre-dose at each visit from 
the baseline visit, and for Weeks 1, 2, 4, 6, 8, 10, and 12; at ~0.5 hours post-dose for the 
Week 2, 4, 6, 8, 10, and 12 visits, and at 1, 2, and 4 hours (±30 min) post-dose for the 
Week 4 and Week 12 visits.
Plasma concentrations of PF-06700841 observed were as expected based on PK in healthy 
participants.


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2.2.10. Nonclinical Safety of PF-06826647
No adverse findings were observed in oral repeat dose toxicity studies with PF-06826647 in
rats and monkeys up to 6 and 9 months in duration, respectively.  Test article related, 
nonadverse, target organs identified include the immune and hemolymphatic systems 
(thymus, spleen, lymph nodes, bone marrow, erythron, and leukon), liver (increased 
transaminases), and bone (increased trabecular thickness).  The findings in the immune and 
hemolymphatic systems are consistent with the pharmacological activity of PF-06826647.  In 
the 6-month toxicity study in rats, the NOAEL was 500 mg/kg/day [250 mg/kg twice daily 
(BID)] with unbound maximum concentration Cmax of 1680 ng/mL, and unbound 
AUC24 (area under the curve 24 hours) of 16,600 ng•h/mL.  In the 9-month toxicity study in 
monkeys, the NOAEL was 220 mg/kg/day with unbound Cmax of 663 ng/mL and unbound 
AUC24 of 8130 ng•h/mL, respectively.  
In an EFD study in rabbits, adverse PF-06826647-related embryolethality due to higher 
incidence of late resorptions resulting in higher postimplantation loss and lower number of 
live fetuses was observed at 500 mg/kg/day (unbound Cmax of 1290 ng/mL and AUC24 of 
17,300 ng•h/mL).  The developmental NOAEL in rats was 500 mg/kg/day (unbound Cmax of 
1850 ng/mL and AUC24 of 19,600 ng•h/mL), and in rabbits was 150 mg/kg/day (unbound 
Cmax of 864 ng/mL and AUC24 of 9930 ng•h/mL).  
PF-06826647 was not mutagenic in bacterial reverse mutation assays.  Although 
PF-06826647 was positive for micronuclei formation in vitro (through an aneugenic 
mechanism), it did not induce micronuclei in vivo in rats at 500 mg/kg/day (250 mg/kg BID) 
(unbound Cmax of 2110 ng/mL and AUC24 of 24,100 ng•h/mL), the highest dose tested in the 
1-month study.  No evidence of PF-06826647 related phototoxicity in the skin or eyes of 
pigmented rats in a 3-day phototoxicity study was observed up to the highest dose tested of 
500 mg/kg/day (250 mg/kg/BID), demonstrating that PF-06826647 was not a phototoxicant, 
in vivo.
Further details of the nonclinical safety program of PF-06826647 are provided in the current 
IB.
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2.2.11. Clinical Safety of PF-06826647
As of 19 October 2018, the clinical development program for PF-06826647 was comprised 
of an ongoing placebo-controlled Phase 1 study (C2501001).  In this study, six SAD cohorts 
and five MAD cohorts in healthy participants have been completed, with 54 healthy adult 
participants randomized and treated with PF-06826647 or placebo; an ongoing study is 
evaluating a cohort of 6 healthy Japanese participants receiving 400 mg QD, along with
2 cohorts of participants with moderate to severe plaque PsO receiving 400 mg or 
100 mg QD of PF-06826647 or placebo.  PsO participants receiving active treatment with 
PF-06826647 (100 mg or 400 mg QD for 28 days) had clinically meaningful decreases in 
disease activity as measured by Psoriasis Area and Severity Index (PASI), the defined 
primary endpoint.
Preliminary safety, efficacy, and pharmacodynamic (PD) results from this study support 
further development of PF-06826647 in plaque PsO.  The Phase 1 study (C2501001) 
demonstrated an acceptable safety and PK profile at single doses of PF-06826647 ranging 
from 3 mg to 1600 mg in the SAD portion and ten-day doses from 10 mg to 1200 mg daily in 
the MAD portion of the study.  Dose escalation stopping rules were not triggered.  There 
were no clinically meaningful findings in vital signs, ECGs, or potential Hy’s Law cases 
reported during this study.  In addition, there have been no serious AEs (including death) or 
suspected, unexpected, serious adverse reactions (SUSARs) reported.  Based on preliminary 
review of treatment group data, all reported TEAEs have been of mild intensity.
Further details on the clinical safety information with PF-06826647 are provided in the IB.
 
 
 
 
 
 
  
 
 
 
 
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2.3. Benefit/Risk Assessment
Currently, adalimumab is the only approved medical treatment for moderate to severe HS.  
However, a significant number of patients (~40%) with moderate to severe HS, did not 
respond to treatment with adalimumab.  
As described in Section 2 (Introduction), the pathophysiology of HS remains incompletely 
defined, and numerous inflammatory mediators have been implicated in the disease.  
PF-06650833 is a highly selective, small molecule inhibitor of IRAK4.  IRAK4 is a key node 
in the signal transduction of many tool-like receptors (TLR)- induced pro-inflammatory 
pathways.  
PF-06650833 has been evaluated in multiple Phase 1 studies in healthy participants, and in a 
Phase 2, dose-ranging, 12-week study in participants with moderate to severe rheumatoid 
arthritis (RA).  PF-06650833 appears to be generally safe and effective up to 400 mg 
administered QD for 12 weeks in participants with RA (Study B7921005, Section 2.2.3).  
PF-06700841 is a dual TYK2/JAK1 inhibitor.  Based on its cytokine inhibition profile, 
PF-06700841 is expected to target the T-helper (TH)17 pathway directly by inhibiting TYK2 
and indirectly by inhibiting JAK1.
PF-06700841 has been evaluated in multiple Phase 1 studies and in participants with plaque 
psoriasis.  PF-06700841 is currently being investigated in participants with psoriasis, 
alopecia areata, atopic dermatitis, ulcerative colitis, and Crohn’s disease.  The overall safety 
profile to date with PF-06700841 has been acceptable with doses up to 60 mg QD for 
4 weeks and 30 mg QD for up to 20 weeks in completed studies (Section 2.2.7).
PF-06826647 is a potent TYK2 inhibitor.  Based on its cytokine inhibition profile, 
PF-06826647 is expected to target the TH1 and TH17 pathways, and Types I and II 
interferon signaling, directly by inhibiting TYK2, and to provide therapeutic benefit in the 
treatment of inflammatory conditions driven by TH1/TH17 and interferon immune 
responses.
PF-06826647 has been evaluated in a Phase 1 study (C2501001) in healthy participants and 
in two cohorts of participants with moderate to severe plaque psoriasis.  A second study in 
participants with moderate to severe plaque psoriasis is ongoing.  PF-06826647 appears to be 
safe up to 1600 mg administered as a single dose, and 1200 mg as multiple doses (up to 
4 weeks).  
For this current study, the dose rationale for PF-06650833, PF-06700841 and PF-06826647
are detailed in Section 4.3.


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Overall, the safety profile observed to date for PF-06650833, PF-06700841 and 
PF-06826647 appears to be acceptable at the respective oral dosages (ie, 400 mg QD, 
45 mg QD and 400 mg QD) to be evaluated in this study. The potential benefits of 
PF-06650833, PF-06700841 and PF-06826647 is expected to outweigh the potential risks for 
participants with moderate to severe HS.
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of PF-06650833, PF-06700841 and PF-06826647 may be found in the 
respective IBs, which are the single reference safety documents (SRSD) for this study. 
3. OBJECTIVES, ESTIMANDS, AND ENDPOINTS
Objectives
Endpoints
Estimands
Primary: 
Primary:
Primary: 
To evaluate the efficacy of 
PF-06650833, PF-06700841, and 
PF-06826647 vs placebo in 
participants with HS as assessed by 
HiSCR.
Percentage of participants with 
HiSCR response* at Week 16.
This estimand uses a composite 
estimand theory (ICH E9 
addendum) and is intended to 
provide a population level 
estimate of the treatment effect 
of the IP on a binary endpoint 
regardless of participant 
compliance with the IP dosing.
Population-level summary: 
difference between treated and 
placebo in proportion of 
participants with HiSCR 
response at Week 16.
Secondary: 
Secondary:
Secondary: 
To evaluate the efficacy of 
PF-06650833, PF-06700841, and 
PF-06826647 vs placebo in 
participants with HS at Week 16 
and over time.
Percentage of participants with HiSCR 
response* at Weeks 1, 2, 4, 6, 8, and 
12.
Percentage of participants with a total 
abscess and inflammatory nodule 
(AN) count of 0 or 1; 0, 1, or 2 at 
Week 16.
This estimand is intended to 
provide a population level 
estimate of the treatment effect 
of the IP on a binary endpoint 
regardless of participant 
compliance with the IP dosing.
Population-level summary: 
difference between treated and 
placebo in proportion of 
participants with HiSCR 
response at Weeks 1, 2, 4, 6, 8 
and 12, respectively; difference 
between treated and placebo in 
proportion of participants with 
a total AN count of 0 or 1, or 0, 
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Percent change from baseline (CFB)
in AN count at Weeks 1, 2, 4, 6, 8, 12 
and 16.
This estimand is intended to 
provide a population level 
estimate of the treatment effect 
of the IP on a continuous 
endpoint regardless of 
participant compliance with the
IP dosing. 
Population-level summary: 
difference between treated and 
placebo change from baseline 
in AN count at Weeks 1, 2, 4, 
6, 8, 12 and 16.
To evaluate the efficacy of 
PF-06650833, PF-06700841, and 
PF-06826647 vs placebo on 
International Hidradenitis 
Suppurativa Severity Score System
(IHS4).
Absolute score and percent CFB in 
IHS4 at Weeks 1, 2, 4, 6, 8, 12 and 16.
This estimand is intended to 
provide a population level 
estimate of the treatment effect 
of the IP on a continuous 
endpoint regardless of 
participant compliance with the
IP dosing.
Population-level summary: 
difference between treated and 
placebo in absolute score and 
change from baseline on IHS4 
at Weeks 1, 2, 4, 6, 8, 12 and
16.
To evaluate the effects of 
PF-06650833, PF-06700841, and
PF-06826647 vs placebo on HS
flare.
Proportion of participants who 
experience an HS flare, defined as at 
least a 25% increase in AN count with 
a minimum increase of 2 relative to 
Baseline, at Weeks 4, 8, 12 and 16.
The estimand is intended to 
provide a population level 
estimate of the treatment effect 
of the IP on a binary endpoint 
regardless of participant 
compliance with IP dosing.
Population-level summary: 
difference between treated and 
placebo in proportion of 
participants experience flare at 
Weeks 4, 8, 12 and 16.
To evaluate the efficacy of 
PF-06650833, PF-06700841, and 
PF-06826647 vs placebo on pain
and pain reduction over time in 
participants with HS.
Percentage of participants with 
≥30% reduction and ≥1-unit
reduction from baseline in PGA-Skin 
Pain numeric rating scale (NRS30) –
at worst and on average, 
respectively, amongst participants
with baseline NRS ≥3, at Weeks 1, 2, 
4, 6, 8, 12 and 16.
Percent CFB in NRS, at worst and on 
average respectively, in participants 
who have baseline NRS ≥3, at 
Weeks 1, 2, 4, 6, 8, 12 and 16.
This estimand is intended to 
provide a population level 
estimate of the treatment effect 
of the IP on a binary endpoint
regardless of participant 
compliance with the IP dosing.
Population-level summary: 
difference between treated and 
placebo in proportion of 
participants with ≥30% 
reduction and ≥1-unit reduction 
from baseline in PGA-Skin 
Pain NRS (NRS30), at worst 


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CFB in NRS, at worst and on 
average respectively, at Weeks 1, 2, 
4, 6, 8, 12 and 16.
and on average, respectively, 
amongst participants with 
baseline NRS ≥3, at Weeks 1, 
2, 4, 6, 8, 12 and 16.
This estimand is intended to 
provide a population level 
estimate of the treatment effect 
of the IP on a continuous 
endpoint regardless of 
participant compliance with the 
IP dosing.
Population-level summary: 
difference between treated and 
placebo percent change from 
baseline in NRS, at worst and 
on average respectively, in 
participants who have baseline 
NRS ≥3, at Weeks 1, 2, 4, 6, 8, 
12 and 16. Difference between 
treated and placebo change 
from baseline in NRS, at worst 
and on average respectively, at 
Weeks 1, 2, 4, 6, 8, 12 and 16.
To evaluate the efficacy of 
PF-06650833, PF-06700841, and 
PF-06826647 vs placebo on 
erythema.  
Proportion of participants achieving 
erythema score of 1 or 0 in all 
affected anatomic regions among 
participants who have an erythema 
score of 2 or more in at least 1
anatomic region at baseline.
The estimand is intended to 
provide a population level 
estimate of the treatment effect 
of the IP on a binary endpoint 
regardless of participant 
compliance with IP dosing.
Population-level summary: 
difference between treated and 
placebo in proportion of 
participants achieving erythema 
score of 1 or 0 in all affected 
anatomic regions among
participants who have erythema 
score of 2 or more in at least 
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To assess the safety and 
tolerability of PF-06650833, 
PF-06700841, and PF-06826647
vs placebo in participants with HS.
Incidence of TEAEs (AEs and 
SAEs), significant changes in vital 
signs, clinical laboratory 
abnormalities, and ECG.
There is no defined estimand 
for these endpoints and they 
will be analyzed using Pfizer 
data standards as applicable.
To evaluate the effects of 
PF-06650833, PF-06700841, and 
PF-06826647 vs placebo on patient 
centered outcomes in participants 
with HS.
Absolute score and CFB at time 
points specified in the SoA in HS 
Symptom Items and Dermatology 
Life Quality Index (DLQI) total 
score. 
Proportion of participants achieving 
a DLQI=0 or 1.
These endpoints will be 
analyzed descriptively and with 
respect to an estimand. 
To evaluate the PK of 
PF-06650833, PF-06700841, and 
PF-06826647 vs placebo in 
participants with HS.
Summary of plasma concentration of 
PF-06700841, PF-06826647 and 
PF-06650833.
There is no defined estimand 
for these endpoints and they 
will be analyzed using Pfizer 
data standards as applicable.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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*HiSCR requires:
•
At least a 50% reduction in the total AN count relative to baseline; and
•
No increase in abscess count; and
•
No increase in draining fistula count.
For all endpoints, baseline is defined as the result closest prior to dosing on Day 1.
4. STUDY DESIGN
4.1. Overall Design
This is a Phase 2a, randomized, double-blind, placebo-controlled, parallel group, multicenter 
platform study with 3 kinase inhibitors (PF-06650833, PF-06700841 and PF-06826647) in 
participants with moderate to severe HS.  The study will have a maximum duration of 
approximately 26 weeks. This includes an up-to-6-week Screening Period, a 16-week 
Dosing Period and a 4-week Follow-up Period.  The study will enroll a total of 
approximately 192 participants (expected to provide approximately 156 completers).  The 
study will be conducted globally at approximately 60 study sites. The study will not be 
blinded across the PF-06650833, PF-06700841 and PF-06826647 treatment arms, but will be 
placebo-controlled double-blinded within each IP treatment arm.  
Following the screening period, participants who meet eligibility criteria at the baseline visit, 
will be randomly assigned to receive PF-06650833 or matching placebo in a 3:1 ratio, or
PF-06700841 or matching placebo in a 3:1 ratio, or PF-06826647 or matching placebo in a 
3:1 ratio.  One oral dose level of each PF-06650833 (400 mg QD), PF-06700841 (45 mg QD) 
and PF-06826647 (400 mg QD) or matching placebo will be investigated.  For analysis,
placebo groups will be combined to yield final IP:placebo ratio of 1:1:1:1 for each IP and 
placebo.  No more than 30% of enrolled participants will be inadequate anti-TNF responders.  
Participants will be stratified according to whether they are an inadequate anti-TNF 
responder or not. Additionally, no more than 20% of enrolled participants may enter the 
study on a background of concomitant oral antibiotic therapy for treatment of HS; the dosing 
regimen (dose and frequency) must have been stable for at least 8 weeks (56 days) prior to 
the baseline (Day 1) visit and must remain stable throughout study participation.  Antibiotics 
taken on an “as needed” (PRN) basis are not considered a stable dose. Participants will be 
stratified according to whether they are on a background of concomitant antibiotic therapy or 
not.  Further details are described in Section 6.5.1.2.
Biopsies of unaffected areas and lesional area biopsies will be collected according to the SoA
at selected sites; it is expected that approximately 60 participants across these selected sites 
will have biopsies collected.  Further details are described in Section 8.8.3 and the lab 
manual.
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4.2. Scientific Rationale for Study Design
This study is being conducted to provide data on efficacy, safety, tolerability and PK of 
PF-06650833, PF-06700841 and PF-06826647 in the oral treatment of moderate to severe 
HS.  The chronic toxicology package for each asset supports the planned study treatment 
duration of 16 weeks.  
The treatment duration of 16 weeks in this study should allow adequate assessment of the 
primary endpoint of HiSCR in patients with moderate to severe HS. Prior placebo-controlled
study with adalimumab on background treatment with antibiotics (PIONEER II) in patients 
with moderate to severe HS showed HiSCR response rate at Week 12 of 58.9% as compared 
to a placebo response rate of 27.6% (P<0.001).3 The additional 4 weeks treatment period 
should provide a more robust efficacy and safety data for the current study, and enable a 
clear decision of selecting the IP for further clinical development. 
Since PF-06826647 is metabolized primarily by CYP1A2, CYP3A4 and CYP2D6, the strong 
and moderate inducers and inhibitors of these drug metabolizing enzymes are prohibited.  
Dofetilide being a multidrug and toxin extrusion (MATE) substrate is also prohibited because 
PF-06826647 is a MATE2K substrate and can potentially increase exposure.
 
 
 
Patient reported outcomes (PROs) will evaluate changes in HS symptoms and health-related 
quality of life (QoL).  These utility scores will be further utilized for development of an early 
cost-effectiveness model.
 
 
4.3. Justification for Dose
4.3.1. PF-06650833
PF-06650833 was tested as an orally administered extemporaneously prepared IR 
formulation in doses up to 1000 mg QID for up to 14 days in healthy participants without a 
dose-limiting adverse effect being demonstrated.  
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Therefore, based on accumulated available clinical and comprehensive nonclinical toxicity 
data package for PF-06650833, a 400 mg MR QD dose is expected to be safe and 
well-tolerated while providing the best opportunity to maximize efficacy.
4.3.2. PF-06700841
In this Phase 2a study, a single dose of 45 mg of PF-06700841 will be administered once a 
day (QD) for 16 weeks in comparison to placebo.  This dose was selected based on the safety 
and efficacy observed to date with PF-06700841 in healthy participants (B7931001) and 
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participants with active PsO (B7931001 and B7931004) and AA with more than 50% hair 
loss (B7931005). The overall safety profile to date with PF-06700841 has been acceptable 
with doses up to 60 mg QD for 4 weeks and 30 mg QD for up to 20 weeks in completed 
studies. Ongoing studies in inflammatory bowel disease (IBD) are assessing the 60 mg QD 
dose for up to 12 weeks, and an extended period at 30 mg QD for up to 52 weeks.
Based on the preliminary population PK analysis with combined data from studies B7931001
in healthy participants and B7931004 in patients with moderate to severe PsO, the expected
median steady state exposures (AUC24) following 45 mg QD is 2030 ng.h/mL, in a patient 
population. As a result, the exposure of PF-06700841 (AUC24) at 45 mg QD in this study are 
expected to be 56x and 8.6x below the AUC24 at the NOAELs observed in the 6-month rat 
(45 mg/kg/day) and 9-month monkey (20 mg/kg/day) studies, respectively. The 
pharmacological activity of PF-06700841 was assessed by reduction of hsCRP in patients 
with moderate to severe PsO (B7931004). In study B7931004, the median reduction (percent 
change from baseline) of hsCRP observed at Week 4 were approximately 61% and 76% with 
PF-06700841 30 and 60 mg QD treatment, respectively. Study B7931004 also showed that 
PF-06700841 reached maximal effect on hsCRP within approximately 2 weeks after start of 
treatment and remained constant throughout the 12-week treatment period. The median 
hsCRP reduction with PF-06700841 45 mg daily dose up to 16 weeks would expect to be 
between 61% to 76% in patients with HS.
4.3.3. PF-06826647
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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The Phase 1 study (C2501001) demonstrated an acceptable safety profile at single doses of 
PF-06826647 ranging from 3 mg to 1600 mg in the single ascending portion and ten-day 
doses from 10 mg to 1200 mg daily in the multiple ascending portion of the study.  Dose
escalation stopping rules were not triggered. There were no clinically meaningful findings in 
vital signs, ECGs, or potential Hy’s Law cases reported during this study.  In addition, there 
were no serious AEs (including death) or suspected, unexpected, serious adverse reactions 
(SUSARs) reported.  All reported TEAEs were of mild intensity.
 
 
4.4. End of Study Definition
A participant is considered to have completed the study if he/she has completed all phases of 
the study including the follow-up visit, shown in the SoA.
The end of the study is defined as the date of the last visit by the last participant in the study 
across all sites globally.
5. STUDY POPULATION
This study can fulfill its objectives only if appropriate participants are enrolled.  The 
following eligibility criteria are designed to select participants for whom participation in the 
study is considered appropriate.  All relevant medical and nonmedical conditions should be 
taken into consideration when deciding whether a particular participant is suitable for this 
protocol.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted.
5.1. Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
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Age and Sex:
1. Male or female participants between the ages of 18 (or the minimum country-specific 
age of consent if >18) and 75 years, inclusive, at Visit 1 (Screening).

Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female 
(Section 10.4.2) participants.
Type of Participant and Disease Characteristics:
2. Participants with a diagnosis (or recognizable symptoms consistent with a diagnosis) 
of moderate to severe HS for at least one year (365 days) prior to Visit 1 (screening).
3. HS lesions (Hurley Stage II-III) present in at least two distinct anatomic areas (eg, left 
and right axilla; or left axilla and left inguino-crural fold).
4. Inadequate response to at least a 4-week (28 day) treatment with an oral antibiotic for 
the treatment of HS, or for whom oral antibiotic treatments are otherwise medically 
inadvisable (eg, because of important side effects or safety risks).
Note: Enrollment of participants on a background of concomitant oral antibiotic 
therapy for treatment of HS will be limited to ≤20% of total participant population.  
The dosing regimen (dose and frequency) of concomitant oral antibiotic therapy must 
have been stable for at least 8 weeks (56 days) prior to the baseline (Day 1) visit and 
must remain stable throughout study participation.
5. Anti-TNF naïve; or
Has initiated only one anti-TNF treatment including participants with inadequate 
response to the anti-TNF; 
Note: participants who initiated more than one anti-TNF treatments are not eligible.
Enrollment of participants with inadequate response to one anti-TNF will be limited 
to ≤30% of total participant population.
Inadequate response to one TNF-inhibiting biologic agent administered in accordance 
with its labeling recommendations.  The TNF-inhibiting biologic could have been 
discontinued due to its being deemed inadequately effective and/or not tolerated as 
defined, for the purpose of this study, by the Investigator’s and participant’s opinions 
that the participant did not experience adequate benefit from the anti-TNF plus the 
presence of sufficient residual disease activity to meet the entry criteria.  The 
anti-TNF biologic could also have been discontinued due to lack of continued access.  
The anti-TNF s should have been discontinued for a minimum of the washout period 
defined as follows (biosimilars of the below agents should be considered the same as 
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
adalimumab (Humira®): 6 weeks.

infliximab (Remicade®), golimumab (Simponi®): 10 weeks.

certolizumab pegol (Cimzia®): 12 weeks.
6. Participant must agree to daily use (and through follow-up) to one of the 
non-prescription topical antiseptics on their HS lesions such as: chlorhexidine 
gluconate, benzoyl peroxide, pyrithione zinc, or dilute bleach in bathwater. 
7. Total AN of ≥4 at baseline; and a draining fistula count of ≤20 at baseline.
8. Participants who are willing and able to comply with all scheduled visits, treatment 
plan, laboratory tests, lifestyle considerations, and other study procedures.
Body Mass Index and Weight:
9. Body Mass Index (BMI) ≥17.5 kg/m2 and body weight ≥40 kg.
Informed Consent:
10. Capable of giving signed informed consent as described in Appendix 1, which
includes compliance with the requirements and restrictions listed in the informed 
consent document (ICD) and in this protocol.
5.2. Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Evidence of other active skin disease or condition (eg, bacterial, fungal, or viral 
infection) at the time of screening or baseline visit that would interfere with the 
evaluation of HS.
2. Any psychiatric condition including recent (within the past year) or active suicidal 
ideation or behavior that meets any of the following criteria at screening:

Suicidal ideation associated with actual intent and a method or plan in the past 
year: “Yes” answers on items 4 or 5 of the Columbia suicide severity rating scale 
(C-SSRS) (See Section 8.2.7).

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.

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3. Have any condition possibly affecting oral drug absorption, eg, gastrectomy, 
clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery 
such as gastric bypass.  Procedures such as gastric banding, that simply divide the 
stomach into separate chambers, are NOT exclusionary.
4. Have current or recent (within the past year) history of severe, progressive, or 
uncontrolled renal, hepatic, hematological, GI, metabolic, endocrine, pulmonary, 
cardiovascular, or neurological disease.
5. Have acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) 
or any history of significant cerebrovascular disease within 24 weeks of screening.
6. 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 disease.
7. History of recurrent (≥2) venous thrombosis or any arterial thromboembolism or
known blood clotting disorders.
8. History (single episode) of multidermatomal herpes zoster or disseminated herpes 
simplex, or a recurrent (more than one episode of) localized, 1-2 dermatomal herpes 
zoster.
9. History of infection (not including infection symptoms resulting from HS) requiring 
hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically 
significant by the investigator within 3 months (90 days) prior to first dose of IP or a 
history of infection requiring oral antimicrobial therapy within 2 weeks prior to the 
first dose of IP.
10. Infected with Mycobacterium tuberculosis (TB) (See Section 8.2.1.1).
11. Have known immunodeficiency disorder or a first-degree relative with a hereditary 
immunodeficiency.
12. Have any malignancies or history of malignancies with the exception of adequately 
treated or excised non-metastatic basal cell or squamous cell cancer of the skin or 
cervical carcinoma in situ.
13. Have undergone significant trauma or major surgery within 1 month (30 days) prior 
to screening or plan to undergo surgery during the treatment period.
14. 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 IP administration or may 
interfere with the interpretation of study results and, in the judgment of the 
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Prior/Concomitant Therapy:
Refer to Section 6.5 and Appendix 9 for details regarding prohibited prior/concomitant 
medications.
15. Participant requires, or is expected to require, opioid analgesics for any reason.
16. Participant received prescription topical therapies for the treatment of HS within 
14 days prior to the baseline (Day 1) visit. 
17. Receipt of systemic therapies for HS including non-biologics with potential 
therapeutic impact for HS less than 28 days or within 5 half-lives (if known), 
whichever is longer, prior to the baseline (Day 1) visit (other than permitted 
antibiotics).  
Prior/Concurrent Clinical Study Experience:
18. Previous administration with an investigational drug within 30 days (or as determined 
by the local requirement) or 5 half-lives preceding the first dose of IP used in this 
study (whichever is longer). 
Diagnostic Assessments:
19. Screening 12-lead ECG that demonstrates clinically significant abnormalities 
requiring treatment (eg, acute myocardial infarction, serious tachy- or 
brady-arrhythmias) or that are indicative of serious underlying heart disease 
(eg, cardiomyopathy, major congenital heart disease, low voltage in all leads, 
Wolff-Parkinson-White syndrome) and other clinically relevant abnormalities which
may affect participant safety or interpretation of study results.  Specifically, 
participants with screening Fredericia corrected QT interval (QTcF) 
>450 milliseconds (msec) should be excluded.  
If QTcF exceeds 450 msec, the ECG should be repeated 2 more times and the average 
of the 3 QTcF should be used to determine the participant’s eligibility. 
20. A history of additional risk factors for torsade de pointes (TdP) (eg, heart failure 
[New York Heart Association status of Class III or IV], hypokalemia, family history 
of Long QT Syndrome).
21. Infected with human immunodeficiency virus (HIV), hepatitis B or hepatitis C
viruses.

Participants who are hepatitis C virus (HCV) antibody (Ab) positive require 
further testing with HCV ribonucleic acid (RNA) polymerase chain reaction 
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
Participants who are hepatitis B surface antigen (HBsAg) positive are not eligible 
for the study.

Participants who are HBsAg negative and hepatitis B core antibody (HBcAb)
positive should be reflex tested for hepatitis B surface antibody (HBsAb) and if 
HBsAb is positive, may be enrolled in the study; if HBsAb is negative, the 
participant is not eligible for the study.
22. Participants with ANY of the following abnormalities in clinical laboratory tests at 
screening, as assessed by the study-specific laboratory and confirmed by a single 
repeat, if deemed necessary:

Hemoglobin 9.0 g/dL or hematocrit 30% (0.30 v/v).

Absolute lymphocyte count (ALC) 1.0 x 109/L (1000/mm3).

Absolute neutrophil count (ANC) 1.5 x 109/L (1500/mm3).

Platelet count 100 x 109/L (100,000/mm3).

eGFR 60 mL/min/1.73 m2 using SCr or cystatin C based calculation (See 
Section 8.2.5.1).

AST or ALT ≥1.5 times the upper limit of normal (ULN).

Total bilirubin ≥1.5 time the ULN (for participants with a history of Gilbert’s 
syndrome: direct bilirubin ULN).

Creatinine kinase (CK) 3 times the ULN and positive urine myoglobin.

Positive urine drug screen.

In the opinion of the investigator or sponsor, any uncontrolled clinically 
significant laboratory abnormality that would affect interpretation of study data or 
the participant’s participation in the study.
Other Exclusions:
23. History of alcohol or substance abuse, unless in full remission for greater than 
6 months prior to Day 1.
24. Donation of blood in excess of 500 mL within 8 weeks prior to Day 1.
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26. 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 
Pfizer employees, including their family members, directly involved in the conduct of 
the study.
5.3. Lifestyle Considerations
5.3.1. Contraception
The investigator or his or her designee, in consultation with the participant, will confirm that 
the participant has selected an appropriate method of contraception for the individual 
participant and his or her partner(s) from the permitted list of contraception methods (see 
Appendix 4 Section 10.4.4) and will confirm that the participant has been instructed in its 
consistent and correct use.  At time points indicated in the SoA, the investigator or designee 
will inform the participant of the need to use highly effective contraception consistently and 
correctly and document the conversation and the participant’s affirmation in the participant’s 
chart (participants need to affirm their consistent and correct use of at least 1 of the selected 
methods of contraception).  In addition, the investigator or designee will instruct the 
participant to call immediately if the selected contraception method is discontinued or if 
pregnancy is known or suspected in the participant or partner.
5.3.2. Vaccination
Vaccination with live virus, attenuated live virus, or any live viral components is prohibited 
within the 6 weeks prior to Day 1, during the study, and until the last follow-up visit.  
Similarly, current routine household contact with individuals who have been vaccinated with 
live vaccine components should be avoided during this same period.  This is due to the 
potential for virus to be shed in bodily fluids (including stool) following vaccination with live 
component vaccines, leading to a potential risk that the virus may be transmitted.
Such vaccines include: FluMist® (intranasal influenza vaccine), attenuated rotavirus vaccine, 
varicella (chickenpox) vaccine, attenuated typhoid fever vaccine, oral polio vaccine, measles, 
mumps, rubella (MMR) vaccine and vaccinia (smallpox) vaccine.
5.3.3. Dietary Supplements
For the purposes of this protocol, dietary supplements are defined as vitamins, minerals, 
purified food substances, and herbals with pharmaceutical properties.  Vitamins, minerals 
and purified food substances are allowed in amounts not known to be associated with adverse 
effects (such as hypervitaminosis).
Herbals supplements are only allowed on a case by case basis; please contact the Sponsor.  
Herbals eg, St. John’s Wort that are known to have an effect on drug metabolism must be 
discontinued at least 4 weeks or 5 half-lives (whichever is longer) before Day 1.
Participants should not consume grapefruit or grapefruit juice or citrus fruits eg, Seville 
oranges, pomelos within 7 days prior to Day 1 and until collection of the final PK blood 
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5.3.4. Antiseptic Therapy
Participants are required to use an over-the-counter daily antiseptic wash on their HS lesions
such as chlorhexidine gluconate, benzoyl peroxide, pyrithione zinc, or dilute bleach in 
bathwater.
5.3.5. Other Lifestyle Requirements
Participants are required to comply with fasting requirements (water only) for at least 8 hours 
prior to the study visits where fasting laboratory assessments are performed as indicated in 
the SoA.  Participants should abstain from strenuous exercise (eg, heavy lifting, weight 
training, calisthenics, and aerobics) for at least 48 hours prior to each blood collection for 
clinical laboratory tests.  Walking at a normal pace is permitted.  Use of nicotine containing 
products or ingestion of caffeine (eg, tea, coffee, some soft drinks/colas/energy drinks and 
power bars) is prohibited during the 30 minutes prior to BP and pulse (heart) rate 
measurements.
On study visit days, participants should be instructed to refrain from taking their dose of IP at 
home.  Dosing of IP will be administered while at the study site.  Prescribed permitted 
concomitant medication may be administered, as needed, prior to the study visit, if it can be 
administered with water only.  Prescribed permitted concomitant medications that must be 
taken with food or after meals should not be taken until after the visit procedures have been 
completed.  Participants should be instructed to contact the study site if there are any changes 
or additions to concomitant medications.
Participants may shower or bath prior to attending study visits; however moisturizing should 
be avoided.
5.4. Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to IP. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any SAE.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once if they fail screening due to transitory conditions. Re-screened participants 
will be re-consented.  All screening assessments must be repeated during re-screening, with
the exception of chest radiograph, HIV, Hepatitis and TB testing, provided re-screening is 
done within 3 months of screening. Rescreened participants should be assigned a new
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6. STUDY INTERVENTION
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to 
the study protocol.
For the purposes of this protocol, the term IP may be used synonymously with study 
intervention.
6.1. Study Intervention(s) Administered
Intervention Name
PF-06650833
PF-06700841
PF-06826647
ARM Name
PF-06650833 400 mg
Active and Placebo
PF-06700841 45 mg
Active and Placebo
PF-06826647 400 mg
Active and Placebo
Type
Drug
Drug
Drug
Dose Formulation
Tablet
Tablet
Tablet
Unit Dose Strength(s)
200 mg Active
Placebo
25 mg, 5 mg Active
Placebo
100 mg Active
Placebo
Dosage Level(s)
400 mg QD
45 mg QD
400 mg QD
Route of 
Administration
Oral
Oral
Oral
Investigational 
Medicinal Product 
(IMP) and 
Noninvestigational 
Medicinal Product 
(NIMP)
IMP
IMP
IMP
Sourcing
Provided centrally by the 
sponsor.  Refer to IP
Manual.
Provided centrally by the 
sponsor.  Refer to IP
Manual.
Provided centrally by the 
sponsor.  Refer to IP
Manual.
Packaging and 
Labeling
 
 
 
IP will be blinded within 
the intervention only; 
ie, blinded to active or 
placebo only.  Blinding 
will not occur across the 
asset line.
 
 
 
 
IP will be blinded within 
the intervention only; 
ie, blinded to active or 
placebo only.  Blinding 
will not occur across the 
asset line.
 
  
 
IP will be blinded within 
the intervention only; 
ie, blinded to active or 
placebo only.  Blinding 
will not occur across the 
asset line.
Current/Former 
Name(s) or Alias(es)
IRAK4
TYK2/JAK1
TYK2
6.1.1. Administration
Participants will be provided dosing instructions.
Sites will be trained on how participants should take tablets at home through an 
investigational product (IP) manual and/or other vehicle(s).  Sites are responsible for 
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communicating this information to participants; and site staff should review the dosing 
instructions with participants at every study visit.
A temporary hold on dosing of the IP during the study for an individual participant for up to 
a maximum of 7 consecutive days is allowed once from Day 1 to Day 113, if the principal 
investigator (PI) deems it necessary because of infections (eg, upper respiratory infection, 
urinary tract infection), GI disorders (eg, diarrhea, nausea, vomiting) or hematological 
abnormalities.  Any temporary hold on dosing of the IP during the study should be recorded 
in the case report form (CRF).
Participants will swallow the IP whole with ambient temperature water to a total volume of 
approximately 240 mL, and will not manipulate or chew the medication prior to swallowing.  
It is recommended that PF-06650833/matching placebo and PF-06700841/matching placebo 
be taken while fasting; PF-06826647/matching placebo must be taken with food.  On IP 
dispensing study visit days, participants are to be instructed to refrain from dosing at home, 
and are to take the dose in the clinic from their current blister card/wallet or bottle.
If a dose is missed and the interval to the next dose is less than 8 hours, the missed dose 
should not be administered.
6.2. Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study interventions received and any 
discrepancies are reported and resolved before use of the study intervention, as 
applicable for temperature-monitored shipments. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions must be stored in a secure, environmentally controlled, and monitored 
(manual or automated recording) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized site staff.  At a 
minimum, daily minimum and maximum temperatures for all site storage locations 
must be documented and available upon request.  Data for nonworking days must 
indicate the minimum and maximum temperature since previously documented for all 
site storage locations upon return to business.
3. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records). All study 
interventions will be accounted for using an IP accountability form/record.  The 
participant will be asked to bring all dispensed IP
 
 to the clinic at every visit.  Detailed drug 
accountability records will be maintained by study staff for each participant. 
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4. Further guidance and information for the final disposition of unused study 
interventions are provided in the IP manual.
5. Any storage conditions stated in the SRSD will be superseded by the storage 
conditions stated on the product label. 
6. Study interventions should be stored in their original containers and in accordance 
with the labels. 
7. Site staff will instruct participants on the proper storage requirements for take-home 
study intervention. 
8. Any excursions from the study intervention label storage conditions should be 
reported to Pfizer upon discovery along with any actions taken. The site should 
actively pursue options for returning the study intervention to the storage conditions 
described in the labeling, as soon as possible. Once an excursion is identified, the 
study intervention must be quarantined and not used until Pfizer provides permission 
to use the study intervention.  It will not be considered a protocol deviation if Pfizer 
approves the use of the study intervention after the temperature excursion.  Use of the 
study intervention prior to Pfizer approval will be considered a protocol deviation. 
Specific details regarding the definition of an excursion and information the site 
should report for each excursion will be provided to the site in the IP manual.
9. The sponsor or designee will provide guidance on the destruction of unused study 
intervention (eg, at the site).  If destruction is authorized to take place at the 
investigator site, the investigator must ensure that the materials are destroyed in 
compliance with applicable environmental regulations, institutional policy, and any 
special instructions provided by Pfizer, and all destruction must be adequately 
documented.
Additional details about accountability, storage, destruction, and excursion reporting can be 
found in the IP manual.
6.2.1. Preparation and Dispensing
The IP will be dispensed using an IRT drug management system at each IP dispensing visit 
per the SoA.  A qualified staff member will dispense the IP
 
provided, in quantities appropriate for the study visit 
schedule.  The participant/caregiver should be instructed to maintain the product 
 
provided throughout the course of dosing and return 
 
to the site at the next IP dispensing study visit.
6.3. Measures to Minimize Bias: Randomization and Blinding
Allocation to treatment will occur via an Interactive Response Technology (IRT) system.  
The system will be programmed with blind-breaking instructions.  Refer to Section 6.3.2 for 
further details.
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One oral dose level of each PF-06650833 (400 mg QD), PF-06700841 (45 mg QD) and 
PF-06826647 (400 mg QD) plus matching placebo in a 3:1 ratio will be investigated.  For 
analysis, placebo groups will be combined to yield final IP:placebo ratio of 1:1:1:1 for each 
IP and placebo.
6.3.1. Allocation to Investigational Product
Allocation of participants to treatment groups will proceed through the use of an IRT system 
(interactive Web-based response [IWR]).  The site personnel (study coordinator or specified 
designee) 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 site personnel will then be provided with a treatment assignment, randomization number, 
and dispensable unit (DU) or container number when IP is being supplied via the IRT 
system.  The IRT system will provide a confirmation report containing the participant
number, randomization number, and DU or container number assigned.  The confirmation 
report must be stored in the site’s files. 
Investigational product will be dispensed at the study visits summarized in the SoA.
Returned IP must not be redispensed to the participants.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded 
IP records at the site(s) to verify that randomization/dispensing has been done accurately.
6.3.2. Breaking the Blind 
The IRT will be programmed with blind-breaking instructions. In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a participant’s 
treatment assignment is warranted. Participant safety must always be the first consideration
in making such a determination. If the investigator decides that unblinding is warranted, the 
investigator should make every effort to contact the sponsor prior to unblinding a 
participant’s treatment assignment unless this could delay further management of the 
participant. If a participant’s treatment assignment is unblinded, the sponsor must be notified 
within 24 hours after breaking the blind. The date and reason that the blind was broken must 
be recorded in the source documentation and CRF.
The study-specific IRT reference manual and IP manual will provide the contact information 
and further details on the use of the IRT system.
6.4. Study Intervention Compliance
The participant will take the IP at home (except on study visits); compliance will be captured
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Participant compliance with IP will be assessed at each visit.  At non-dispensing visits, sites 
should assess the 
 for compliance however the 
 should 
remain in the possession of the participant.  Participants will be instructed to bring all 
dispensed IP supplies in the original packaging (used as well as unused) to every study visit.
Non-compliance is defined as less than 80% or more than 120% of IP dosing as directed by 
the dosing instructions.  The investigator and the sponsor have the discretion to withdraw any 
participant from the study for reasons of non-compliance with the dosing regimen.  
Investigators should indicate on the appropriate CRF page noncompliance with study 
intervention and provide an explanation. Inventory control of all IPs must be rigorously 
maintained throughout the duration of the study until all medication has been accounted for 
and/or returned to the sponsor.  Any discrepancies noted between drug dispensing records 
and the drug inventory must be reported to the sponsor.
6.5. Concomitant Therapy
Medications that are taken in the Screening period (after informed consent is obtained and 
before the first dose of IP) will be documented as prior medications.  Medications taken after 
the first dose of IP has been administered will be documented as concomitant medications.  
All concomitant medications taken during the study must be recorded in study records with 
indication, daily dose, route of administration and start and stop dates of administration.  
Participants will be queried about concomitant medication (including topical medications and 
treatments, over-the-counter and prescription medications and treatments, and vaccinations) 
at each study visit.  Any new concomitant medications or dose changes to current 
concomitant medications should be evaluated for potential new or worsening AEs.
The start date, stop date, route of administration and indication for all therapies will be 
recorded on the CRF.
6.5.1. Permitted Concomitant Medications
A participant who is receiving a permitted concomitant medication for any reason must be on 
a locally-approved medication and dose for the treated indication, and this must be 
documented in the CRF.  Participants are not allowed any other investigational drugs or 
treatments during the study. 
Participants should refrain from starting new or changing doses of permitted prescription
or non-prescription drugs, vitamins, and dietary supplements within 7 days or 5 half-lives 
(whichever is longer) prior to Day 1 and prior to study visits throughout the study, unless 
otherwise noted below.
Participants should report any changes to permitted medications during the study to the study 
site as soon as they occur.  Medication changes must be documented in the participant’s 
record and CRF.
Participants may be administered medications necessary for the treatment of concomitant 
medical disorders as deemed necessary by the treating physician.  Following Day 1, addition 
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of concomitant medications or any change in the dosage should be limited to those 
considered medically essential.
For the purposes of this protocol, dietary supplements are defined as vitamins, minerals, and 
purified food substances with pharmaceutical properties.  Vitamins, minerals and purified 
food substances are allowed in amounts not known to be associated with adverse effects 
(such as hypervitaminosis).
A participant who is receiving metformin as concomitant medication must allow at least two 
hours to elapse after taking the metformin before taking the IP.
Hormonal contraceptives that meet the requirements of this study are allowed to be used in 
participants who are women of childbearing potential (WOCBP) (see Appendix 4).
6.5.1.1. Wound Care
Concomitant use of wound care dressings on HS wounds is permitted; however, options are 
limited to alginates, cydrocolloids, and hydrogels. 
6.5.1.2. Antibiotic Therapy
Participants may enter the study on a background of permitted concomitant oral antibiotic 
therapy for treatment of HS provided the dosing regimen (dose and frequency) has been 
stable for at least 8 weeks (56 days) prior to the baseline (Day 1) visit.  The dosing regimen 
must remain stable throughout study participation.  Antibiotics taken on a PRN basis are not 
considered a stable dose. 
Permitted oral concomitant antibiotics include:

Doxycycline (at a dose of up to 100 mg po BID);

Minocycline (at a dose of up to 100 mg po BID).
If another baseline oral concomitant antibiotic for HS is medically necessitated, the 
Sponsor’s Medical Monitor must be contacted for approval.  Participants should not 
initiate/change background antibiotic therapy once entered into the study.
6.5.1.3. Analgesic Therapy
If a participant is on a stable dose of non-opioid analgesic, the participant may continue the 
analgesic, provided the dose is stable for 14 days prior to the baseline (Day 1) visit and is 
anticipated to remain stable throughout study participation.  
If a participant’s pain worsens after baseline, they may initiate analgesic therapy at any time 
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Permitted analgesics are limited to:

Nonsteroidal anti-inflammatory drugs (NSAIDs) (at a dose of up to 3200 mg/day).

Acetaminophen (at a dose of up 4 g/day).
Dose adjustments of NSAIDs or acetaminophen, and use of these analgesics on an PRN basis 
up to the maximum permitted dose and frequency are allowed.
Note: Analgesics should not be administered within 4 to 6 hours prior to study assessments.
Opioid analgesics (including tramadol and any products that may contain tramadol, eg, cough 
suppressants) are prohibited.
6.5.2. Prohibited Medications and Treatments
Participants will abstain from all concomitant medications as described in Section 5.2 and 
Appendix 9.
Participants should be instructed at each visit to contact the study site investigator promptly if 
there are any intended changes or additions to concomitant medications. 
Please see Section 5.3.2 and Section 5.3.3 for restrictions regarding vaccinations and herbal 
supplements.  
6.5.3. Rescue Medicine
There is no rescue therapy to reverse the AEs observed with PF-06650833, PF-06700841 and 
PF-06826647; standard medical supportive care must be provided to manage the AEs. 
Participants requiring rescue medication will be discontinued from IP dosing and will enter 
the Follow-up Period.  
6.6. Dose Modification
No dose adjustment is allowed during the study.
6.7. Intervention After the End of the Study
No intervention will be provided to study participants at the end of the study.
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1. Discontinuation of Study Intervention
For participants who discontinue early, the Early Termination (ET) visit assessments will be 
performed.  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 
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clinically relevant abnormalities or AEs have resolved, returned to a baseline state, or are 
deemed clinically stable.
For Guidelines for Monitoring and Discontinuations refer to Appendix 8.
In rare instances, it may be necessary for a participant to permanently discontinue the IP.  Per 
the study estimands, if IP is permanently discontinued, the participant will proceed to Early 
Termination per SoA.  The site will inform the Sponsor if the criteria for permanent 
discontinuation of the IP defined in Appendix 8 are triggered.
Any participant meeting discontinuation criteria must have the procedures scheduled for ET 
Visit performed on the last day the subject takes the investigational product or as soon as 
possible thereafter and enter into Follow-up with their end of study (EOS) visit occurring 
approximately 4 weeks after their ET Visit. 
See the SoA for data to be collected at the time of intervention discontinuation and follow-up
and for any further evaluations that need to be completed.
7.2. Participant Discontinuation/Withdrawal From the Study
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, 
or administrative reasons.
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted. See the SoA for assessments to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
The early discontinuation visit applies only to participants who are randomized and then are 
prematurely withdrawn from the study.  Participants should be questioned regarding their 
reason for withdrawal.  The participant will be permanently discontinued both from the study 
intervention and from the study at that time.
If a participant withdraws from the study, he/she may request destruction of any remaining 
samples, but data already generated from the samples will continue to be available, and may 
be used to protect the integrity of existing analyses.  The investigator must document any 
such requests in the site study records.
If the participant withdraws from the study and also withdraws consent (see below) 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.
When a participant withdraws from the study because of an SAE, the SAE must be recorded 
on the CRF and reported on the Clinical Trial (CT) SAE Report.


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Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s 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 IP or also from study procedures and/or 
posttreatment 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.
7.3. Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study;

Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record;

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole is handled as part of Appendix 1.
8. STUDY ASSESSMENTS AND PROCEDURES
The investigator (or an appropriate delegate at the investigator site) must obtain a signed and 
dated ICD before performing any study-specific procedures.  


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Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed.
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct.
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. All screening labs are assessed by the study-specific 
laboratory and confirmed by a single repeat, if deemed necessary. The investigator will 
maintain a screening log to record details of all participants screened and to confirm 
eligibility or record reasons for screening failure, as applicable.
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances outside the control of the investigator that may make it unfeasible to perform 
the test.  In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the participant.  When a protocol-required test cannot be performed, the 
investigator will document the reason for the missed test and any corrective and preventive 
actions that he or she has taken to ensure that required processes are adhered to as soon as 
possible.  The study team must be informed of these incidents in a timely manner.
For samples being collected and shipped, detailed collection, processing, storage, and 
shipment instructions and contact information will be provided to the investigator site prior 
to initiation of the study.
The total blood sampling volume for individual participants in this study does not exceed 
550 mL during any period of 60 consecutive days.  The actual collection times of blood 
sampling may change.  Additional blood samples may be taken for safety assessments at 
times specified by Pfizer, provided the total volume taken during the study does not exceed 
550 mL during any period of 60 consecutive days.
8.1. Efficacy Assessments
8.1.1. Hidradenitis Suppurativa Clinical Response (HiSCR)
Hidradenitis suppurativa clinical response, the primary endpoint used, is defined as: 

At least a 50% reduction in the total AN count relative to baseline, and

No increase in abscess count, and

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8.1.1.1. Lesion Counts
The number of inflammatory and non-inflammatory nodules, abscesses, draining and 
non-draining fistulas, and hypertrophic scars, as well as the physical location (right/left 
axilla, right/left inframammary, intermammary, right/left buttock, right/left inguino-crural
fold, perianal, perineal, other) will be assessed according to the SoA.
8.1.1.1.1. Abscess Count
Number of abscesses (fluctuant, with or without drainage, tender or painful) will be counted 
in each of the regions as defined above.
8.1.1.1.2. Inflammatory Nodule Count
Number of inflammatory nodules (tender, erythematous, pyogenic granuloma lesion) will be 
counted in each of the regions as defined above.
8.1.1.1.3. Fistula Count
Number of fistula (sinus tracts, with communications to skin surface, draining purulent fluid) 
will be counted in each of the regions as defined above.
8.1.2. Hurley Staging
Hurley staging is defined as follows:
•
Stage I: Abscess formation, single or multiple, without sinus tracts and cicatrization 
(scarring).
•
Stage II: One or more widely separated recurrent abscesses with tract formation and 
cicatrization (scars).
•
Stage III: Multiple interconnected tracts and abscesses across the entire area, with 
diffuse or near diffuse involvement. 
Hurley staging will be performed according to the SoA.
 
 
 
 
 
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8.1.4. Erythema Assessment
The overall degree of erythema will be assessed for each anatomic region affected by HS 
using a four-point ordinal scale ranging between 0 (no redness), 1 (faint but discernible pink 
coloration), 2 (moderate red coloration), or 3 (very red or bright red coloration).  
8.1.5. International Hidradenitis Suppurativa Severity Score System (IHS4 Score) 
The IHS4 score is calculated by the number of nodules, the number of abscesses, and the 
number of draining tunnels. IHS4 score will be calculated according to the SoA.
IHS4 score = (number of nodules × 1) + (number of abscesses × 2) + {number of draining 
tunnels (fistulae/sinuses) × 4}.20
8.1.6. Rater Qualifications 
For specific rating assessments, only qualified raters will be allowed to evaluate and/or rate 
participants in this study.  The minimum qualifications a rater must meet for each study 
rating assessment will be outlined in the Rater Assessment Manual provided to each 
participating site.  The level of experience with the target population (or equivalent), specific 
scale experience (or equivalent), and certification required (if applicable) will be listed and 
used to determine whether a rater is approved for a given assessment. Proposed raters who 
do not meet specific criteria but who may be qualified based on unique circumstances may be 
individually reviewed by the study clinical team to determine whether or not a waiver may be 
issued.  The rater must become certified to perform selected study assessments before he or 
she can participate in the conduct of the study. For specifically defined assessments, rater 
training and standardization exercises may be conducted, and written and signed 
documentation will be provided by the site for each rater’s certification.  In return, each site 
will be provided written and signed documentation outlining each rater’s certification for 
specific study assessments.  Recertification may be required at periodic intervals during the 
study.  The raters who administer specific study assessments will be documented in a 
centralized location and all site staff who administer ratings will be verified in the site study 
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documentation during the conduct of the study.  Every effort should be made to ensure 
consistency in evaluations; therefore, the same rater should evaluate the same study 
participants throughout the trial.
8.2. Safety Assessments
Planned time points for all safety assessments are provided in the SoA.  Unscheduled clinical
laboratory measurements may be obtained at any time during the study to assess any 
perceived safety concerns.
8.2.1. Assessments at Screening Only
8.2.1.1. Tuberculosis Testing
Participants will be screened for infection with TB either using Interferon Gamma Release 
Assay (IGRA) test or Mantoux/Purified Protein Derivative (PPD) tuberculin skin test.  This 
will be performed at Screening.
It is recommended that participants with a history of Bacille Calmette Guérin (BCG) 
vaccination be tested with the IGRA test since the Mantoux/PPD tuberculin skin test may be 
positive due to vaccination.
8.2.1.1.1. Interferon Gamma Release Assay Tuberculin Test
The following are acceptable IGRA assays: QuantiFERON®-TB Gold test (QFT-G), 
QuantiFERON®-TB Gold Plus (QFT-plus) and T-SPOT® TB test.  Site personnel should 
follow the processing and analyses steps based on the assay chosen. 
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 
pulmonary or infectious disease specialist that determines low risk of infection 
(ie, participant would be acceptable for immunosuppressant (eg, anti-TNF) treatment without 
additional action).
Participants who test positive for QFT-G/QFT-plus test, but in the opinion of the PI are at 
low risk of TB infection may be referred to pulmonary or infectious disease specialist for 
consultation and potential IGRA test repeated once.  Participants will be eligible if the repeat 
test is negative before the randomization.
8.2.1.1.2. Mantoux/Purified Protein Derivative (PPD) Tuberculin Skin Test
Participants can be TB screened using the Mantoux/PPD Tuberculin Skin Test.  
Mantoux/PPD testing can also be performed if there are indeterminate QFT-G test results.  
Participants must have a Mantoux/PPD tuberculin skin test administered and then evaluated 


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by a health care professional 48 to 72 hours later.  A positive Mantoux/PPD tuberculin skin
test is exclusionary.
8.2.1.2. Chest Radiograph
Participants must have chest radiograph taken at Screening and read by a radiologist.  
Documentation of the official reading must be located and available in the source 
documentation.
If chest radiograph has been taken within 12 weeks prior to Day 1 and read by a radiologist 
as normal, this does not have to be repeated at screening, provided documentation is 
available. 
Chest radiograph may include chest x-ray (posterior-anterior and lateral views are 
recommended, however local guidelines should be followed) or other appropriate diagnostic 
image (ie, computed tomography [CT] or magnetic resonance imaging [MRI]).  Participants 
with evidence of currently active TB, general infections, heart failure or malignancy will be 
excluded.  Participants with changes suggestive of untreated latent or active TB infection 
may be enrolled after consultation with a pulmonary or infectious disease specialist who 
determines a low risk of infection.
8.2.1.3. Medical History
Investigators should make all reasonable efforts to obtain an accurate and complete medical
history and history of prior medication use (at least two years) when evaluating whether a 
participant is eligible for the study.  The following will be collected at Screening and 
reviewed at baseline: complete medical history (at least two years), HS disease history 
(including disease duration and prior treatments) and alcohol and tobacco use history (at least 
two years).
History of alcohol and tobacco use, current smoking status and average alcohol consumption 
will be collected in units.  A unit of alcohol contains 12 g of pure alcohol, an amount 
equivalent to that contained in 5 oz/150 mL (a glass) of wine, 12 oz/360 mL of beer, or 
1.5 oz/45 mL of 90 proof of spirits. 
If the status of a participant’s medical history is in doubt or information pertaining to a 
critical variable is conflicting, every reasonable step to secure proper documentation of 
correct medical status should be attempted.  Documentation of the medical and medication 
histories over the protocol defined time periods should be available for sponsor review 
during the source data verification process.  Questions about prior medications or eligibility 
should be directed to the Sponsor.
8.2.2. Physical Examinations (Full Physical and Brief Physical)
Full physical examinations must be performed by a qualified healthcare professional per 
local guidelines. A full physical examination will include assessments of the general 
appearance, skin, head, eyes, ears, nose, throat, cardiovascular, respiratory, GI, and 


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neurological systems.  Investigators should pay special attention to clinical signs related to 
previous serious illnesses. 
A brief physical examination will include assessments of the skin, heart, lung, abdomen, and 
body systems with any symptoms reported by the study participants. 
Any clinically significant changes from the most recent physical examination should be 
recorded as AEs.  Investigators should pay special attention to clinical signs related to 
previous serious illnesses.
Full and brief physical exams will be performed as specified in the SoA.
8.2.2.1. HS Lesion Photography (at selected sites only)
HS lesion photography is optional, may be available only at selected study sites and will be 
performed at time points specified in the SoA.  HS lesion photography will be a photographic 
documentation of representative lesion(s) and will be performed using a digital camera 
approved by the Sponsor or delegate.  Both an overview and regional lesion photo may be 
taken.  The procedure will be described in a separate manual that will be provided prior to 
first participant first dose.  All images acquired must be saved by the site until the conclusion 
of the study.
Photographic images are primarily taken for documentation and publication.  They may be 
reviewed and evaluated by a central review facility and/or the Sponsor.  This central image 
review will not be a medical review of the study participant and no incidental findings will be 
shared with the investigator, other site staff, or the study participant. Review of these skin 
areas captured in the photographic images for any potential safety or tolerability concerns 
will be done by the site staff during the visit.
8.2.2.2. Height and Weight
It is recommended that weight be measured in kilograms (kg) and that height be measured in 
centimeters (cm).  Height and weight will be measured to one decimal place.
For measuring weight, a scale with appropriate range and resolution should be used and must 
be placed on a stable, flat surface.  Participants should remove shoes, bulky layers of 
clothing, and jackets so that only light clothing remains.
8.2.3. Vital Signs
Temperature (Oral, Tympanic, Axillary or Temporal), pulse rate and BP will be assessed.  It 
is preferred that body temperature be collected using the same method for the same
participant throughout the study.  Axillary temperature assessments should be avoided in 
cases where the axillary region is affected by HS.
BP and pulse rate measurements will be assessed with a completely automated device in a 
supine position.  Manual techniques will be used only if an automated device is not available.  


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It is preferred that the same arm (preferably the dominant arm) be used throughout the study.  
BP and pulse rate measurements should be preceded by at least 5 minutes of rest.
8.2.4. Electrocardiograms
Standard 12-Lead ECGs should be collected at times specified in the SoA section of this
protocol using an ECG machine that automatically calculates the heart rate and measures PR, 
QT, and QTc intervals and QRS complex.  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 collections (except for the post dose ECG). ECGs will be read and interpreted 
centrally, however to ensure safety of the participants, a qualified individual (investigator or 
sub-investigator) at the investigative site will perform the initial ECG read and make
comparisons to baseline measurements. 
On Day 1 Visit, triplicate ECGs will be obtained, and the average of the triplicate ECG 
measurements will serve as the participant’s baseline value.  If the Day 1 ECG is missing,
then the screening ECG will serve as baseline value. On Weeks 8 and 16 single ECGs will 
be collected prior to dosing and also at 2 hours (with a ±15 minutes window) post dose.
A paper or digital copy of the ECG should be filed in the participant’s chart and must be 
available to the sponsor upon request.  Any clinically significant changes will be recorded as 
AEs and evaluated further, as clinically warranted.  In some cases, it may be appropriate to 
repeat abnormal ECGs to rule out improper lead placement as contributing to the ECG 
abnormality.
If a postdose QTc interval remains ≥30 msec from the baseline and is >450 msec; or b) an 
absolute QTc value is ≥500 msec for any scheduled ECG for greater than 4 hours (or sooner,
at the discretion of the investigator), or QTc intervals get progressively longer, the participant
should undergo continuous ECG monitoring.  A cardiologist should be consulted if QTc 
intervals do not return to less than the criterion listed above after 8 hours of monitoring (or 
sooner, at the discretion of the investigator). Participants with QTc prolongation ≥30 msec 
from the baseline and >450 msec; or b) an absolute QTc value is ≥500 msec for any 
scheduled ECG for greater than 4 hours should discontinue treatment as described in 
Appendix 8.  
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality.  It is important that leads be placed in the 
same positions each time in order to achieve precise ECG recordings.  If a machine-read QTc 
value is prolonged, as defined above, repeat measurements may not be necessary if a 
qualified medical provider’s interpretation determines that the QTc values are in the 
acceptable range.
ECG values of potential clinical concern are listed in Appendix 7.


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8.2.5. Clinical Safety Laboratory Assessments
See Appendix 2 for the list of clinical safety laboratory tests to be performed and the SoA for 
the timing and frequency.
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. 
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 28 days after the last dose of study intervention should be 
repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or medical monitor.
If such values do not return to normal/baseline within a period of time judged reasonable by
the investigator, the etiology should be identified, and the sponsor notified.
All protocol-required laboratory assessments, as defined in Appendix 2, must be conducted
in accordance with the laboratory manual and the SoA.
If laboratory values from non-protocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the investigator (eg, SAE or AE or dose modification), then the 
results must be recorded in the CRF.
8.2.5.1. Creatinine, Cystatin C, and Estimates of Glomerular Filtration Rate
Serum creatinine (Scr) is the best known standard test for monitoring renal function.  
However, SCr based eGFR may be affected by factors other than renal function, including 
chronic and acute illness.  Serum cystatin C is a test that can be used either as an adjunct to 
or a replacement for SCr.  The most reliable estimates of glomerular filtration rate (GFR) use 
both test results.8
Serum cystatin C is a low molecular weight protein that is used as an alternative to SCr for 
monitoring of renal function.  It seems to correlate more closely with GFR than SCr 
concentration and may be a more sensitive detector of early renal dysfunction.9,10 While use 
of cystatin C has been limited, its independence of demographic factors (eg, race) has made it 
an interesting means of determining changes in renal function in clinical settings and it is 
included in the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines.  
Estimated GFR may be calculated via the 2012 Chronic Kidney Disease Epidemiology 
Collaboration (CKD-EPI) creatinine, cystatin C, or creatinine-Cystatin C equations.11
Serum creatinine will be measured as part of serum chemistry at times specified in the SoA
section of the protocol.  Creatinine elevations above the ULN will be followed until 
resolution or baseline.  Serum creatinine based eGFR will be calculated.  Serum cystatin C 


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will be measured, and cystatin C based eGFR will be calculated at corresponding times per 
SoA.
In this study, the eGFR will be calculated using the 2 sets of equations developed by the 
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI),12 which utilize SCr and 
serum Cystatin C (S Cystatin C) respectively12 (See Appendix 10).
8.2.6. Herpetiform Rash Surveillance
For any occurrence of a suspected herpetiform rash (eg, herpes zoster and herpes simplex), 
specimens for viral deoxyribonucleic acid (DNA) analysis will be obtained: A swab of the 
affected area will be collected for confirmation; a blood sample for viral surveillance will be 
collected for the analysis of viral load. Details for these collections will be provided in the 
laboratory manual.
8.2.7. Suicidal Ideation and Behavior Risk Monitoring
Participants meeting exclusionary criteria (See Section 5.2) for suicidal ideation/behavior 
will be excluded from study participation.  It is recommended the participant’s primary care 
physician (PCP) is informed if this exclusion criterion is met, and the participant referred to a 
mental health professional, either by the PCP or the investigator according to their usual 
practice.
8.2.7.1. Columbia Suicide Severity Rating Scale
The C-SSRS is a validated tool to evaluate suicidal ideation and behavior13 (See 
Appendix 11).  It is administered by the investigator or site staff who have been trained to 
administer the scale.  “Lifetime” version will be used at screening. “Post-baseline” version 
will be used at Week 8 and 16 visits. 
At Screening Visit, if there are “yes” answers on items 4, 5 or on any question in the suicidal 
behavior section of the C-SSRS, the subject will not be included in the study. 
At any post-baseline visits, if there are “yes” answers on items 4, 5 or on any question in the 
suicidal behavior section of the C-SSRS, the subject will be discontinued from the IP and 
referred to a mental health professional for appropriate evaluation and treatment.  If the 
subject cannot be seen by a mental health professional within 24 hours, then the subject 
should be sent to a local emergency room for psychiatric assessment.
8.2.8. Pregnancy Testing 
Pregnancy tests may be urine or serum tests, but must have a sensitivity of at least 
25 mIU/mL.  Pregnancy tests will be performed in WOCBP at the times listed in the SoA.  
Following a negative pregnancy test result at screening, appropriate contraception must be 
commenced, and a second negative pregnancy test result will be required at the baseline visit 
prior the participant’s receiving the IP.  Pregnancy tests will also be done whenever 
1 menstrual cycle is missed during the active treatment period (or when potential pregnancy 
is otherwise suspected) and at the end of the study.  Pregnancy tests may also be repeated if 


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requested by institutional review boards (IRBs)/ethics committees (ECs) or if required by 
local regulations.  If a urine test cannot be confirmed as negative (eg, an ambiguous result), a 
serum pregnancy test is required.  In such cases, the participant must be excluded if the 
serum pregnancy result is positive.
8.3. Adverse Events and Serious Adverse Events
The definitions of an AE and an SAE can be found in Appendix 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible to pursue 
and obtain adequate information both to determine the outcome and to assess whether it 
meets the criteria for classification as an SAE or that caused the participant to discontinue the 
study intervention (see Section 7). 
In addition, the investigator may be requested by Pfizer Safety to obtain specific follow-up 
information in an expedited fashion.
8.3.1. Time Period and Frequency for Collecting AE and SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each participant begins from the time the participant provides informed consent, 
which is obtained before the participant’s participation in the study (ie, before undergoing 
any study-related procedure and/or receiving IP), through and including a minimum of 
28 calendar days after the last administration of the IP.
For participants who are screen failures, the active collection period ends when screen failure 
status is determined.
Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded on the Medical History/Current Medical Conditions 
section of the CRF, not the AE section.
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.
Investigators are not obligated to actively seek AEs or SAEs after conclusion of the study
participation.  However, if the investigator learns of any SAE, including a death, at any time 
after a participant has been discharged from the study, and he/she considers the event to be
reasonably related to the study intervention or study participation, the investigator must 
promptly notify the sponsor.


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8.3.1.1. 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 immediately and under no circumstance should this 
exceed 24 hours, as indicated in Appendix 3. The investigator will submit any updated SAE 
data to the sponsor within 24 hours of it being available.
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 IP must be 
reported to Pfizer Safety.
8.3.1.2. Recording Nonserious AEs and SAEs on the CRF
During the active collection period, both nonserious AEs and SAEs are recorded on the CRF.
8.3.2. Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs.  Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3. Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. For each event, the investigator must pursue and 
obtain adequate information until resolution, stabilization, the event is otherwise explained, 
or the participant is lost to follow-up (as defined in Section 7.3).
In general, follow-up information will include a description of the event in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of 
possible causality.  Any information relevant to the event, such as concomitant medications 
and illnesses, must be provided.  In the case of a participant death, a summary of available 
autopsy findings must be submitted as soon as possible to Pfizer Safety. 
Further information on follow-up procedures is given in Appendix 3.
8.3.4. Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a 
study intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation.  The 
sponsor will comply with country-specific regulatory requirements relating to safety 


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reporting to the regulatory authority, institutional review boards (IRBs)/ethics committees 
(ECs), and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will review 
and then file it along with the investigator’s brochure and will notify the IRB/EC, if 
appropriate according to local requirements.
8.3.5. Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
Exposure to the IP under study during pregnancy or breastfeeding and occupational exposure 
are reportable to Pfizer Safety within 24 hours of investigator awareness.
8.3.5.1. Exposure During Pregnancy
Details of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected after the start of study intervention and until 28 days after the 
last dose of IP.
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 4.
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs.
8.3.5.2. 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.
8.3.5.3. 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.
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 


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information is not recorded on a CRF; however, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file.
8.3.6. Medication Errors
Medication errors may result from the administration or consumption of the IP by the wrong 
participant, or at the wrong time, or at the wrong dosage strength.
Exposures to the IP under study may occur in clinical trial settings, such as medication 
errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE Report 
Form to Pfizer Safety Within 
24 Hours of Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an SAE
Medication errors include:

Medication errors involving participant exposure to the IP;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the study participant.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified 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 nonserious, 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.
8.4. Treatment of Overdose
For this study, any dose of PF-06650833, PF-06700841 or PF-06826647 greater than the 
randomized daily dose within a 24-hour time period will be considered an overdose.
Sponsor does not recommend specific treatment for an overdose.
In the event of an overdose, the investigator should:


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1. Contact the medical monitor immediately.
2. Closely monitor the participant for any AEs/SAEs and laboratory abnormalities until 
the assigned IP can no longer be detected systemically (at least 3 days).
3. Obtain a blood sample for PK analysis within 3 days from the date of the last dose of 
study intervention if requested by the medical monitor (determined on a case-by-case 
basis).
4. Document the quantity of the excess dose as well as the duration of the overdose in 
the CRF.
5. Overdose is reportable to Safety only when associated with an SAE.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.
8.5. Pharmacokinetics 
8.5.1. Plasma for Analysis of PF-06650833, PF-06700841 and PF-06826647
During all study periods, blood samples will be collected into appropriately labeled tubes 
containing K2EDTA at times specified in the SoA section of the protocol for measurement of 
PF-06650833 and metabolites, PF-06700841 and PF-06826647.
Blood will be collected at the time points identified in the SoA section of the protocol.  All 
efforts will be made to obtain the PK samples at the exact nominal time relative to dosing.  
The date and exact time of the sample collection is to be noted on the source document and 
data collection tool (eg, CRF).  Samples obtained outside the windows specified in the SoA
will be considered a protocol deviation.
•
Further details regarding the collection, processing, storage and shipping of the blood 
samples will be provided in the lab manual.
•
Samples will be analyzed using a validated analytical method in compliance with 
Pfizer standard operating procedures. 
 
 
The PK samples must be processed and shipped as indicated in the instructions provided to 
the investigator site to maintain sample integrity.  Any deviations from the PK sample 
handling procedure (eg, sample collection and processing steps, interim storage or shipping 
conditions), including any actions taken, must be documented and reported to the sponsor.  
On a case-by-case basis, the sponsor may make a determination as to whether sample 
integrity has been compromised.
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Drug concentration information that may unblind the study will not be reported to 
investigator sites or blinded personnel.
 
 
 
 
 
 
 
 
 
 
 
 
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8.9. Health Economics
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study.
8.10. Patient Reported Outcome Measures
Every effort should be made for the participant to complete all patient reported outcome 
(PRO) questionnaires before any other assessments.  All PROs should be completed in the
following order: patient’s global assessment (PGA) of Skin Pain NRS and HS Symptoms 
will be completed as a daily diary from baseline Day -7 through Week 16 at home.  At
Follow-up (FU) visit and ET visit (if applicable), PGA of Skin Pain NRS and HS Symptoms 
will be completed at site. At site visits, participants will complete PROs in the following 
order: Dermatology Life Quality Index (DLQI), 
.  The amount of time required for a participant to 
complete the PRO questionnaires is approximately 15 minutes (depending on the visit and 
associated PROs).
Once participants meet all eligibility criteria, they will be provided a handheld device 
(provided by the sponsor) for the PGA Skin Pain NRS and HS Symptom Items.  All other 
PROs will be completed on site prior to other study procedures.  All PROs are to be 
completed as per the time points defined in the SoA.
Delegated site staff will oversee the use of electronic Patient Reported Outcomes (ePRO) 
devices.  At screening, sites should emphasize the importance  of completing the diary every 
day and ensure that the patient does not have any questions about the device or assessment 
completion schedule. Completion of PROs will be monitored for adherence.  Delegated site 
staff will review adherence to all applicable PROs with participants at each visit and counsel 
as appropriate.  If a participant has repeated non-adherence, the participant should be 
retrained on use of the device.  Less than 80% ePRO compliance will be reported as protocol 
deviation. 
8.10.1. HS Symptom Items
The HS symptoms items are 5 single items that will assess patient self-reported symptoms 
related to HS. The participants are asked to rate each symptom on a 0 to 10 numerical rating 
scale, with 0 indicating no symptom experience and 10 indicating the worst possible 
symptom.  The symptoms assessed include: pain, tenderness, swelling, tiredness, and bother 
of lesion appearance.
Participants should complete the HS Symptoms Items according to the SoA.
8.10.2. PGA Skin Pain Numeric Rating Scale (NRS) Items
The PGA of Skin Pain NRS will be used to assess the worst skin pain and the average skin 
pain due to HS. Ratings for the 2 items range from 0 (no skin pain) to 10 (skin pain as bad as 
you can imagine). The assessments will be completed on a daily diary by participants before 
they went to bed (except for FU Visit and ET visit) and responded to the items based on a 
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recall period of the "last 24 hours." The PGA of Skin Pain NRS will also be completed at site 
at FU visit and ET visit (if applicable).
Participants should complete the PGA Skin Pain NRS Items according to the SoA. The last 
7 assessments prior to the date of first dose of investigational product will be averaged and 
serve as the participant’s baseline.
8.10.3. Dermatology Life Quality Index (DLQI)
The DLQI is a general dermatology questionnaire that consists of 10 items that assess patient 
health-related quality of life (daily activities, personal relationships, symptoms and feelings, 
leisure, work and school, and treatment) over the last week.14 The DLQI is a 
psychometrically valid and reliable instrument that has been translated into several 
languages, and the DLQI total scores and been shown to be responsive to change.
Participants should complete the DLQI according to the SoA.
 
 
 
 
 
 
 
 
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9. STATISTICAL CONSIDERATIONS
Detailed methodology for summary and statistical analyses of the data collected in this study 
is outlined here and further detailed in a 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.
9.1. Estimands and Statistical Hypotheses
9.1.1. Estimands
The primary estimand will be the population treatment effect on proportion of participants 
with HiSCR response at Week 16 for the active treatment group relative to placebo without 
regard to IP compliance.  
Hidradenitis suppurativa clinical response, the primary endpoint used, is defined as: 
•
At least a 50% reduction in the total AN count relative to baseline; and
•
No increase in abscess count; and
•
No increase in draining fistula count.
The population-based treatment effect will be the differences in the proportion of participants 
with HiSCR response at Week 16 in each active treatment arm compared to the combined
placebo group. 
The binary secondary estimand will be the population treatment effect on the proportion of
participants with a total abscess and AN count of 0 or 1 at Week 16, for active treatment 
group relative to placebo group without regard to compliance with IP.  The population-based
treatment effect will be the differences in the proportions of success in each treatment arm 
compared to the combined placebo.  
The continuous secondary estimand will be the population treatment effect on the continuous 
endpoint for NRS. The population level summary is the difference between treated and 
placebo in percent change from baseline in NRS at worst in participants who have baseline 
NRS ≥3, at Week 16. Intercurrent event for the continuous secondary estimand: withdrawal
and all other events leading to missing data will be imputed in the active treatment arms 
using a jump to control method using the distribution of the placebo group (ie, missing data 
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in active treatment participants will be imputed from the distribution of matching placebo 
participants). Inadequate compliance participants data will be used as is.
All other secondary binary clinical endpoints, using various definitions and at different time 
points, will be analyzed using the primary estimand and binary secondary estimand, while all 
other secondary continuous clinical endpoints, using various definitions and at different time 
points, will be analyzed by comparing the scores of the active treatment group with the 
placebo group, as in the continuous secondary estimand. 
 
 
 Details of these analyses will be presented in the 
SAP.
9.2. Sample Size Determination
Sample size calculation is based on the primary endpoint of HiSCR response at 16 weeks.  A 
total of approximately 192 participants will be randomized in 3 active treatment groups 
(48/arm) and their matching placebo groups (16/arm) to have 39 completers for each active 
treatment arm, assuming a 15% dropout rate and the active treatment arm HiSCR response 
rate of 60% and placebo HiSCR rate of 30% (approximated based on the PIONEER 1 and II 
studies).3  Statistical comparisons will be made between each of the active treatment arms 
against the 3 placebo groups pooled together. With one-sided family-wise error rate of 0.1 
with a Bonferroni correction (0.033 after Bonferroni adjustment for 3 comparisons), this 
sample size will provide approximately 80% power.  No statistical comparisons will be done 
between active treatment arms. 
9.3. Populations for Analysis
For purposes of analysis, the following populations are defined:
Population
Description
Full Analysis Set (FAS)
All participants randomized and receiving at least one dose of IP.
Per-protocol analysis set 
(PPAS)
All participants randomized and receiving at least one dose of IP, with both
baseline and Week 16 primary efficacy data, and without protocol 
deviations that were thought to impact the efficacy evaluation during the 
treatment period.  All protocol deviations will be reviewed and assessed by 
the study team prior to database release.  
Safety
All participants randomly assigned to IP and who take at least 1 dose of IP.
Participants will be analyzed according to the product they actually 
received.
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Defined Population for 
Analysis
Description
PK concentration set
All enrolled participants who take at least one dose of active 
PF-06700841, PF-06826647 or PF-06650833 and in whom at 
least one concentration value is reported.
PD Analysis set
All enrolled participants who take at least one dose of 
PF-06700841, PF-06826647 or PF-06650833 and in whom at 
least one value of PD parameter of interest is reported.
9.4. Statistical Analyses
The SAP will be developed and finalized before database lock and will describe the 
participant populations to be included in the analyses, and procedures for accounting for 
missing, unused, and spurious data, and any sensitivity analyses, subgroup analyses.  This 
section is a summary of the planned statistical analyses of the primary and secondary 
endpoints.
9.4.1. Efficacy Analyses
Endpoint
Statistical Analysis Methods
Primary

The primary efficacy endpoint is the HiSCR response at Week 16.  The 
HiSCR response data comparing active treatment group and placebo 
group will be analyzed using the Cochran Mantel Hanzel (CMH) test, 
adjusting for the stratification factor of prior anti-TNF failure status and 
concomitant use of antibiotics status.  Treatment differences in HiSCR 
response and the corresponding 2-sided 80% confidence intervals 
adjusting for the stratification factor will be computed using the 
methods proposed by Cochran with the minimum risk weights proposed 
by Mehrotra and Railkar.  More details and sensitivity analyses will be 
documented in the SAP.  The population for the primary analysis will be 
based on the FAS.  Sensitivity analysis will be performed using the 
PPAS.  All missing values will be imputed as non-response to treatment. 
Secondary

The binary secondary efficacy endpoint of proportion of participants 
with a total AN count of 0 or 1 at Week 16, will be analyzed similar to 
the primary efficacy endpoint using CMH test comparing the treatment 
differences adjusting for the two stratification factors.  Point estimates
and confidence intervals will be provided similarly as well.  Other 
binary secondary efficacy endpoints, using various definitions and at 
different time points, will be analyzed similarly.

The continuous secondary efficacy endpoint of change from baseline
NRS at worst at Week 16 will be analyzed using analysis of covariance 
(ANCOVA) model which will include terms for treatment group, the 
stratification factors (if there are sufficient number of subjects in each 
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model), and the baseline NRS. Other continuous secondary efficacy 
endpoints, using various definitions and at different time points, will be 
analyzed similarly.
•
Population for the secondary efficacy endpoints will be full analysis set 
(FAS). Sensitivity analysis using PPAS might be performed.
 
 
9.4.2. Safety Analyses
All safety analyses will be performed on the safety population.
Endpoint
Statistical Analysis Methods
Primary
Not applicable.  The primary endpoint is an efficacy endpoint.
Secondary
The safety data will be summarized in accordance with Pfizer Data 
Standards.  All participants who receive IP (safety population) will be 
included in the safety analyses.  All safety data will be summarized 
descriptively through appropriate data tabulations, descriptive statistics, 
categorical summaries, and graphical presentations.  Safety endpoints for the 
study include:
•
TEAEs and SAEs;
•
Withdrawals from treatment due to AEs;
•
Safety laboratory tests (eg, hematology [including coagulation 
panel], chemistry and lipid profiles);
•
Vital signs.
CFB in laboratory data and vital signs will be additionally summarized.  
Participant listings will also be produced for these safety endpoints.
 
9.4.2.1. Electrocardiogram Analyses
Changes from baseline for the ECG parameters QT interval, heart rate, QTc interval, PR 
interval, and QRS complex will be summarized by treatment and time.
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The number (%) of participants with maximum postdose QTc values and maximum increases
from baseline in the following categories will be tabulated by treatment: 
Safety QTc Assessment
Degree of Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450-480
>480-500
>500
Increase from baseline
30-60
>60
In addition, the number of participants with uncorrected QT values >500 msec will be 
summarized.
9.4.3. Other Analyses 
9.4.3.1. Analysis of Pharmacokinetic (PK) Endpoints
The PK concentration population is defined as all enrolled participants who received at least
one dose of PF-06700841, PF-06826647 or PF-06650833 and in whom at least one 
concentration value is reported. PK concentrations will be summarized and presented with 
descriptive statistics. Population PK modeling may be performed with the concentration data 
from this study alone or combined with data from other studies. In addition, a relationship 
between exposures and efficacy/safety endpoints may be evaluated using population PK/PD 
approach. Any population analyses conducted will not be part of the clinical study report 
(CSR) and may be reported separately.
9.4.3.2. Patient Reported Outcome Analyses
The full analysis set (FAS) will be used for these analyses.  PRO endpoints will be 
summarized descriptively.  
Continuous PRO endpoints including CFB in HS symptom Items and CFB in DLQI score, 
will be analyzed using mixed models to compare the difference of active treatments with 
placebo participants.  Missing data due to any cause including censoring due to initiation of 
prohibited medication will be imputed using the corresponding placebo arm, missing data in 
a placebo arm will be imputed using data from the placebo arm assuming data are missing at 
random (MAR).
9.4.3.3. PK
 Unblinding Plan
If needed, a PK
 unblinding plan approved by the clinical lead, clinical pharmacology lead
and statistical lead will be in place to describe the procedures to be employed in safeguarding
the study blind for members of the study team. These procedures will be in accordance with
applicable Pfizer standard operating procedures (SOPs) for releasing randomization codes 
and breaking the study blind.  Under this plan a group of statisticians, PK
 data provider, 
PK
analyst and PK
support would be unblinded in order to initiate the building of 
statistical models of the PK, dose/response as well as exposure/response analysis models and 
conduct associated simulations. The aim of this work would be to facilitate a fuller 
interpretation of the study upon completion (at appropriate interim milestone). This group 
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will not serve on the study team during the period of early unblinding. The unblinding may 
occur after the last participant has been randomized. The details of the procedures will be 
described in the PK
 Unblinding Plan for Modelling and Simulation for this study which 
will be finalized prior to the start of the PK
 unblinding.
9.5. Interim Analyses
An interim analysis may be performed to assess efficacy and safety. Interim analysis results 
may be used for internal business decisions regarding future study planning.  Before any 
interim analysis is initiated, the details of the objectives, decision criteria, dissemination plan,
and method of maintaining the study blind as per Pfizer’s SOPs will be documented and 
approved in an interim analysis plan.  The results will only be distributed to a select list of 
individuals who are not part of the study team, and will be involved in the internal decision-
making process in order to protect the integrity of the study.  This list of individuals will be 
provided in the interim analysis plan.  The results of the interim analysis will not enable 
individuals directly involved in running the study (such as investigators) to identify treatment 
assignments for individual participants remaining in the study.  There are no plans to stop the 
study early for success as a result of any interim analysis.
 
 
  
 
 
 
  
 
 
 
  
 
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10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1.1. Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines;

Applicable International Council for Harmonisation (ICH) Good Clinical Practice 
(GCP) guidelines;

Applicable laws and regulations, including applicable privacy laws.
The protocol, protocol amendments, ICD, investigator’s brochure (IB), and other relevant 
documents (eg, advertisements) must be reviewed and approved by the sponsor and 
submitted to an IRB/EC by the investigator and reviewed and approved by the IRB/EC 
before the study is initiated.
Any amendments to the protocol will require IRB/EC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
The investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/EC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/EC;

Notifying the IRB/EC of SAEs or other significant safety findings as required by 
IRB/EC procedures;

Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/EC, 
European regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations.
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the IP, Pfizer 
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In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study participants against any immediate hazard, and 
of any serious breaches of this protocol or of ICH GCP that the investigator becomes aware 
of.
10.1.2. Financial Disclosure
Investigators and sub investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study.
10.1.3. Informed Consent Process
The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions regarding the 
study.
Participants must be informed that their participation is voluntary. Participants or their 
legally authorized representative will be required to sign a statement of informed consent that 
meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance 
Portability and Accountability Act (HIPAA) requirements, where applicable, and the IRB/EC 
or study center.
The investigator must ensure that each study participant is fully informed about the nature 
and objectives of the study, the sharing of data related to the study, and possible risks 
associated with participation, including the risks associated with the processing of the 
participant’s personal data. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/EC members, and by inspectors from regulatory authorities.
The investigator further must ensure that each study participant is fully informed about his or 
her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data.
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained.
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Participants must be reconsented to the most current version of the ICD(s) during their 
participation in the study.
A copy of the ICD(s) must be provided to the participant or the participant’s legally
authorized representative.
Participants who are rescreened are required to sign a new ICD.
 
 
 
 
 
10.1.4. Data Protection
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of participant data.
Participants’ personal data will be stored at the study site in encrypted electronic and/or paper
form and will be password protected or secured in a locked room to ensure that only 
authorized study staff have access.  The study site will implement appropriate technical and 
organizational measures to ensure that the personal data can be recovered in the event of 
disaster.  In the event of a potential personal data breach, the study site shall be responsible 
for determining whether a personal data breach has in fact occurred and, if so, providing 
breach notifications as required by law.
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, participants will be assigned a single, participant-specific numerical code.
Any participant records or data sets that are transferred to the sponsor will contain the 
numerical code; participant names will not be transferred. All other identifiable data 
transferred to the sponsor will be identified by this single, participant-specific code. The 
study site will maintain a confidential list of participants who participated in the study, 
linking each participant’s numerical code to his or her actual identity. In case of data 
transfer, the sponsor will protect the confidentiality of participants’ personal data consistent 
with the clinical study agreement and applicable privacy laws.
10.1.5. Dissemination of Clinical Study Data
Pfizer fulfills its commitment to publicly disclose clinical study results through posting the
results of studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable local laws/regulations.  In addition, Pfizer reports study results outside of the 
requirements of local laws/regulations pursuant to its standard operating procedures (SOPs).
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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 patients) that evaluate the safety and/or efficacy of a 
product, regardless of the geographical location in which the study is conducted.  US Basic 
Results are generally 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 (CSR synopses in which any data that could be used 
to identify individual participants have been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
Documents within marketing authorization packages/submissions
Pfizer complies with the European Union Policy 0070, the proactive publication of clinical 
data to the European Medicines Agency (EMA) website.  Clinical data, under Phase 1 of this 
policy, includes clinical overviews, clinical summaries, CSRs, and appendices containing the 
protocol and protocol amendments, sample CRFs, and statistical methods.  Clinical data,
under Phase 2 of this policy, includes the publishing of individual participant data.  
Policy 0070 applies to new marketing authorization applications submitted via the 
centralized procedure since 01 January 2015 and applications for line extensions and for new 
indications submitted via the centralized procedure since 01 July 2015.


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Data Sharing
Pfizer provides researchers secure access to patient-level data or full CSRs for the purposes 
of “bona-fide scientific research” that contribute to the scientific understanding of the 
disease, target, or compound class. Pfizer will make available data from these trials 
24 months after study completion.  Patient-level data will be anonymized in accordance with 
applicable privacy laws and regulations.  CSRs will have personally identifiable information 
redacted.
Data requests are considered from qualified researchers with the appropriate competencies to 
perform the proposed analyses. Research teams must include a biostatistician. Data will not 
be provided to applicants with significant conflicts of interest, including individuals 
requesting access for commercial/competitive or legal purposes.
10.1.6. Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must ensure that the CRFs are securely stored at the study site in encrypted 
electronic and/or paper form and are password protected or secured in a locked room to 
prevent access by unauthorized third parties.
The investigator must permit study-related monitoring, audits, IRB/EC review, and 
regulatory agency inspections and provide direct access to source data documents.  This 
verification may also occur after study completion.  It is important that the investigator(s) 
and their relevant personnel are available during the monitoring visits and possible audits or 
inspections and that sufficient time is devoted to the process.
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities, and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring), are provided in the 
monitoring plan.
The sponsor or designee is responsible for the data management of this study, including 
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Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICDs, pertaining to the conduct of this study must
be retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 
the retention period without the written approval of the sponsor. No records may be
transferred to another location or party without written notification to the sponsor. The 
investigator must ensure that the records continue to be stored securely for as long as they are 
maintained.
When participant data are to be deleted, the investigator will ensure that all copies of such
data are promptly and irrevocably deleted from all systems.
The investigator(s) will notify the sponsor or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with the sponsor or its agents to prepare the investigator site for the inspection and will allow 
the sponsor or its agent, whenever feasible, to be present during the inspection.  The 
investigator site and investigator will promptly resolve any discrepancies that are identified 
between the study data and the participant's medical records.  The investigator will promptly 
provide copies of the inspection findings to the sponsor or its agent.  Before response 
submission to the regulatory authorities, the investigator will provide the sponsor or its 
agents with an opportunity to review and comment on responses to any such findings.
10.1.7. Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator site.
Data reported on the CRF or entered in the electronic CRF (eCRF) that are transcribed from 
source documents must be consistent with the source documents or the discrepancies must be 
explained. The investigator may need to request previous medical records or transfer 
records, depending on the study. Also, current medical records must be available.
Definition of what constitutes source data can be found in the study monitoring plan (SMP).
10.1.8. Study and Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon 
study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed.


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The investigator may initiate study-site closure at any time upon notification to the contract 
research organization (CRO) if requested to do so by the responsible IRB/EC or if such 
termination is required to protect the health of study participants.
Reasons for the early closure of a study site by the sponsor may include but are not limited 
to:

Failure of the investigator to comply with the protocol, the requirements of the 
IRB/EC or local health authorities, the sponsor's procedures, or GCP guidelines;

Inadequate recruitment of participants by the investigator;

Discontinuation of further study intervention development.
Study termination is also provided for in the clinical study agreement.  If there is any conflict 
between the contract and this protocol, the contract will control as to termination rights.
10.1.9. Publication Policy
The results of this study may be published or presented at scientific meetings by the 
investigator after publication of the overall study results or 1 year after end of the study (or 
study termination), whichever comes first. 
The investigator agrees to refer to the primary publication in any subsequent publications 
such as secondary manuscripts, and submits all manuscripts or abstracts to the sponsor 
30 days before submission. This allows the sponsor to protect proprietary information and to
provide comments and the investigator will, on request, remove any previously undisclosed 
confidential information before disclosure, except for any study- or Pfizer 
intervention-related information necessary for the appropriate scientific presentation or
understanding of the study results.
For all publications relating to the study, the investigator will comply with recognized ethical 
standards concerning publications and authorship, including those established by the 
International Committee of Medical Journal Editors.
The sponsor will comply with the requirements for publication of the overall study results 
covering all investigator sites.  In accordance with standard editorial and ethical practice, the 
sponsor will support publication of multicenter studies only in their entirety and not as 
individual site data.  In this case, a coordinating investigator will be designated by mutual 
agreement.
Authorship of publications for the overall study results will be determined by mutual 
agreement and in line with International Committee of Medical Journal Editors authorship 
requirements. 
If publication is addressed in the clinical study agreement, the publication policy set out in 
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10.1.10. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the study team on demand (SToD) 
system.  
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 IP identifiers, participant 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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10.2. Appendix 2: Clinical Laboratory Tests
The following safety laboratory tests will be performed at times defined in the SoA section of 
this protocol.  Additional laboratory results may be reported on these samples as a result of 
the method of analysis or the type of analyzer used by the clinical laboratory; or as derived 
from calculated values.  These additional tests would not require additional collection of
blood.  Unscheduled clinical laboratory measurements may be obtained at any time during 
the study to assess any perceived safety concerns.
Table 1.
Protocol-Required Safety Laboratory Assessments
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
MCV
MCH
MCHC
MPV
Platelet count
WBC count
Total neutrophils 
(Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes (Abs)
BUN/urea, creatinine
and Cystatin C
Glucose
Calcium
Sodium
Potassium
Chloride
Total CO2 (bicarbonate)
AST, ALT
Total bilirubin
Alkaline phosphatase
Uric acid
Albumin
Total protein
CK
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopy and/or 
urine culturea
At screening only:
FSHb
Urine drug screening
Pregnancy test (-hCG)c
Hepatitis B surface antigen
(HBsAg)
Hepatitis B core antibody
(HBcAb)
HepB reflex (HBsAbd), if 
applicable
Hepatitis C antibody
Hepatitis C RNA, if 
applicable
HIVUrine myoglobine
Abbreviations: Abs = absolute; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
-hCG = beta-human chorionic gonadotropin; BUN = blood urea nitrogen; CO2 = carbon dioxide; 
FSH = follicle-stimulating hormone; HBcAb = hepatitis B core antibody; HBsAg = hepatitis B 
surface antigen; HBsAb = hepatitis B surface antibody; MCH = mean corpuscular hemoglobin; 
MCHC = mean corpuscular hemoglobin concentration; MCV = mean corpuscular volume;
MPV = mean platelet volume; qual = qualitative; RBC = red blood cell; WBC = white blood cell.
a.
Collect urine sample for central laboratory urinalysis and urine microscopy at Screening and
pre-dose at Baseline. At postdose visits: urine microscopy is indicated if the urinalysis is
positive for blood, nitrite, leukocyte esterase and/or protein, or there is clinical suspicion of 
urinary tract infection, or decrease in renal function; urine culture is performed if urinalysis is 
positive for nitrite and/or leukocyte esterase, or if otherwise clinically indicated.
b.
For confirmation of postmenopausal status only.
c.
Local urine testing will be standard for the protocol unless serum testing is required by local 
regulation or institutional review board/ethics committee (IRB/EC).  Serum or urine -hCG for 
female participants of childbearing potential.
d.
HepB reflex testing only if HBsAg negative but HBcAb positive at Screening,
e.
At Screening and in case of CK >3 x ULN.
Investigators must document their review of each laboratory safety report.


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10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
10.3.1. Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or not 
considered related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (ie, not related to progression of 
underlying disease).

Exacerbation of a chronic or intermittent preexisting condition including either an
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of
sequelae.

“Lack of efficacy” or “failure of expected pharmacological action” per se will not 
be reported as an AE or SAE.  Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting 
from lack of efficacy will be reported as an AE or SAE if they fulfill the definition 
of an AE or SAE.


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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.
10.3.2. Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (eg, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting.  Complications that occur during hospitalization are AEs.  If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious.


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Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d. Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive treatment
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse.
10.3.3. Recording/Reporting and Follow-up of AEs and/or SAEs
AE and SAE Recording/Reporting
The table below summarizes the requirements for recording AEs on the CRF and for 
reporting serious AEs on the Clinical Trial (CT) SAE Report Form to Pfizer Safety.  These 
requirements are delineated for 3 types of events: (1) SAEs; (2) nonserious AEs; and 
(3) exposure to the IP under study during pregnancy or breastfeeding, and occupational 
exposure. 
It should be noted that the CT SAE Report Form for reporting of SAE information is not 
the same as the AE page of the CRF. When the same data are collected, the forms must be 
completed in a consistent manner.  AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE 
Report Form for reporting of SAE information.


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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
Nonserious AE
All
None
Exposure to the IP under 
study during pregnancy
or breastfeeding, and 
occupational exposure
None
All (and exposure during 
pregnancy [EDP]
supplemental form for 
EDP)  

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic 
reports) related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to Pfizer Safety in lieu of completion of the CT SAE Report 
Form/AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are 
requested by Pfizer Safety. In this case, all participant identifiers, with the 
exception of the participant number, will be redacted on the copies of the medical 
records before submission to Pfizer Safety.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 

Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with an SAE.  Severe is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe.


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
An event is defined as “serious” when it meets at least 1 of the predefined 
outcomes as described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the investigator’s brochure (IB) and/or product 
information, for marketed products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has
minimal information to include in the initial report to the sponsor. However, it is 
very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to the sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

If the investigator does not know whether or not the IP caused the event, then the 
event will be handled as “related to IP” for reporting purposes, as defined by the 
sponsor. In addition, if the investigator determines that an SAE is associated with 
study procedures, the investigator must record this causal relationship in the source 
documents and CRF, and report such an assessment in the dedicated section of the 
CT SAE Report Form and in accordance with the SAE reporting requirements.


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Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
sponsor to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other healthcare professionals.

If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide Pfizer Safety with a copy of any 
postmortem findings including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to the sponsor within 24 hours 
of receipt of the information.
10.3.4. Reporting of SAEs
SAE Reporting to Pfizer Safety via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE to Pfizer Safety will be the electronic 
data collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as the data
become available.

After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see 
next section) or to Pfizer Safety by telephone.
SAE Reporting to Pfizer Safety via CT SAE Report Form

Facsimile transmission of the CT SAE Report Form is the preferred method to 
transmit this information to Pfizer Safety.

In circumstances when the facsimile is not working, notification by telephone is 
acceptable with a copy of the CT SAE Report Form sent by overnight mail or 


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courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the CT SAE Report Form pages within the designated reporting 
time frames.


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10.4. Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information
10.4.1. Male Participant Reproductive Inclusion Criteria
Male participants are eligible to participate if they agree to the following requirements during 
the intervention period and for at least 28 days after the last dose of study intervention, which 
corresponds to the time needed to eliminate study intervention(s) plus an additional 90 days 
(a spermatogenesis cycle): 

Refrain from donating sperm.
PLUS either:

Be abstinent from heterosexual or homosexual intercourse 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 when engaging in any activity that allows for 
passage of ejaculate to another person.

Use of an additional highly effective contraceptive method with a failure rate of 
<1% per year as described below in Section 10.4.4 for a female partner of 
childbearing potential.
10.4.2. Female Participant Reproductive Inclusion Criteria
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at 
least 1 of the following conditions applies:

Is not a WOCBP (see definitions below in Section 10.4.3).
OR

Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), (preferably) with low user dependency, as described below 
during the intervention period and for at least 28 days after the last dose of study 
intervention, which corresponds to the time needed to eliminate any study 
intervention(s).  The investigator should evaluate the effectiveness of the 
contraceptive method in relationship to the first dose of study intervention.
OR


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
Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), with high user dependency, as described below during the 
intervention period and for at least 28 days after the last dose of study intervention,
which corresponds to the time needed to eliminate any study intervention(s).  In 
addition, a second effective method of contraception, as described below, must be 
used (except for sexual abstinence).  The investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose of study 
intervention.
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy. 
10.4.3. Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before the first dose of study intervention, additional evaluation should be 
considered.
Women in the following categories are not considered WOCBP:
1. Premenopausal female with 1 of the following:

Documented hysterectomy;

Documented bilateral salpingectomy;

Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than 
the above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion 
should be applied to determining study entry.
Note: Documentation for any of the above categories can come from the site 
personnel’s review of the participant’s medical records, medical examination, or 
medical history interview.  The method of documentation should be recorded in the 
participant’s medical record for the study.
2. Postmenopausal female:

A postmenopausal state is defined as age 60 years or older or no menses for 
12 months without an alternative medical cause. 


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
A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormone replacement therapy (HRT). 

Females on HRT and whose menopausal status is in doubt will be required to 
use one of the nonestrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study.  Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment.
10.4.4. Contraception Methods
Highly Effective Methods That Have Low User Dependency
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.§
2. Intrauterine device (IUD).
3. Intrauterine hormone-releasing system (IUS).
4. Bilateral tubal occlusion or bilateral tubal ligation.
5. Vasectomized partner.

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.
§ Use of implantable progestogen-only hormone contraception associated with inhibition of ovulation with an 
effective barrier method (as described below) is required for female participants randomized to receive 
PF-06650833/matching placebo.
Highly Effective Methods That Are User Dependent 
One of the following effective barrier methods must be used in addition to the highly 
effective methods listed below that are user dependent except for sexual abstinence:

Male or female condom with or without spermicide;

Cervical cap, diaphragm, or sponge with spermicide;

A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods).


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1. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:§

oral;

intravaginal;

transdermal;

injectable.
2. Progestogen-only hormone contraception associated with inhibition of ovulation:

oral;

injectable.
3. 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.
§ All contraceptives containing ethinyl estradiol, being a CYP 1A2 inhibitor, are prohibited in female 
participants randomized to receive PF-06826647/matching placebo. Refer to Appendix 10.9.
Collection of Pregnancy Information
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 IP; or the female 
becomes or is found to be pregnant after discontinuing and/or being exposed to the 
IP;

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 
IP prior to or around the time of conception and/or is exposed during his partner’s 
pregnancy.


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If a participant or participant’s partner becomes or is found to be pregnant during the 
participant’s treatment with the IP, 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, a 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 
integrity of the neonate can be assessed at the time of birth.  In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless 
preprocedure test findings are conclusive for a congenital anomaly and the findings are 
reported).
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 IP. 
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.


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CCI


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10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-up Assessments 
Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt 
are termed “adaptors.” In some participants, transaminase elevations are a harbinger of a 
more serious potential outcome.  These participants fail to adapt and therefore are 
"susceptible" to progressive and serious liver injury, commonly referred to as drug-induced 
liver injury (DILI).  Participants who experience a transaminase elevation above 3 x ULN 
should be monitored more frequently to determine if they are an “adaptor” or are 
“susceptible.”
In the majority of DILI cases, elevations in AST and/or 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 laboratory sample).  In rare instances, by the time TBili elevations 
are detected, AST/ALT values might have decreased. This occurrence is still regarded as a
potential DILI.  Therefore, abnormal elevations in either AST OR ALT in addition to TBili 
that meet the criteria outlined below are considered potential DILI (assessed per Hy’s law 
criteria) cases and should always be considered important medical events, even before all 
other possible causes of liver injury have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the 
participant’s individual baseline values and underlying conditions.  Participants who present 
with the following laboratory abnormalities should be evaluated further as potential DILI 
(Hy’s law) cases to definitively determine the etiology of the abnormal laboratory values:

Participants with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value
<2 × ULN or not available.

For participants with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches 
>3 × ULN (whichever is smaller).


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Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.  
The participant should return to the investigator site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history, and physical assessment.  
In addition to repeating measurements of AST and ALT and TBili for suspected cases of 
Hy’s law, additional 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, and alkaline phosphatase.  Consideration should also 
be given to drawing a separate tube of clotted blood and an anticoagulated tube of blood for
further testing, as needed, for further contemporaneous analyses at the time of the recognized 
initial abnormalities to determine etiology.  A detailed history, including relevant 
information, such as review of ethanol, acetaminophen (either by itself or as a coformulated 
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) and collection of 
serum sample for acetaminophen drug and/or protein adduct levels may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no 
other reason for the 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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10.7. Appendix 7: ECG Findings of Potential Clinical Concern
ECG Findings That May Qualify as Adverse Events (AEs)

Marked sinus bradycardia (rate <40 bpm) lasting minutes.

New PR interval prolongation >280 msec.

New prolongation of QTcF to >480 msec (absolute) or by ≥60 msec from baseline.

New-onset atrial flutter or fibrillation, with controlled ventricular response rate:
ie, rate <120 bpm.

New-onset type I second-degree (Wenckebach) AV block of >30 seconds’ duration.

Frequent premature ventricular complexes (PVCs), triplets, or short intervals 
(<30 seconds) of consecutive ventricular complexes.
ECG Findings That May Qualify as Serious Adverse Events (SAEs)

QTcF prolongation >500 msec.

New ST-T changes suggestive of myocardial ischemia.

New-onset left bundle branch block (QRS >120 msec).

New-onset right bundle branch block (QRS >120 msec).

Symptomatic bradycardia.

Asystole:

In awake, symptom-free patients in sinus rhythm, with documented periods of 
asystole ≥3.0 seconds or any escape rate <40 bpm, or with an escape rhythm 
that is below the AV node; 

In awake, symptom-free patients with atrial fibrillation and bradycardia with 
1 or more pauses of at least 5 seconds or longer; 

Atrial flutter or fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.

Sustained supraventricular tachycardia (rate >120 bpm) (“sustained” = short
duration with relevant symptoms or lasting >1 minute).

Ventricular rhythms >30 seconds’ duration, including idioventricular rhythm (rate 
<40 bpm), accelerated idioventricular rhythm (40< x <100), and 


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monomorphic/polymorphic ventricular tachycardia >100 bpm (such as torsades 
de pointes).

Type II second-degree (Mobitz II) AV block.

Complete (third-degree) heart block.
ECG Findings That Qualify as Serious Adverse Events

Change in pattern suggestive of new myocardial infarction.

Sustained ventricular tachyarrhythmias (>30 seconds’ duration).

Second- or third-degree AV block requiring pacemaker placement.

Asystolic pauses requiring pacemaker placement.

Atrial flutter or fibrillation with rapid ventricular response requiring cardioversion.

Ventricular fibrillation/flutter.

At the discretion of the investigator, any arrhythmia classified as an adverse 
experience.
The enumerated list of major events of potential clinical concern are recommended as “alerts” or 
notifications from the core ECG laboratory to the investigator and Pfizer study team, and not to be 
considered as all-inclusive of what to be reported as AEs/SAEs.


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10.8. Appendix 8: Guidelines for Safety Monitoring and Discontinuation
These guidelines for participant safety monitoring and discontinuation are to be applied to all 
participants in the study.  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
The following laboratory abnormalities require re-testing within 1 week (ideally within 
48 hours):

Neutrophil counts <1000 neutrophils/mm3;

Lymphocyte counts <500 lymphocytes/mm3;

Platelet counts <50,000 platelets/mm3;

Any single AST and/or ALT elevation 3 times the ULN (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 ULN 
increases in ALT, AST need confirmation on separate blood draw before undertaking 
thorough evaluation for liver injury); note: re-testing for AST and/or ALT is expected 
to be completed within 48 hours;

Any single hemoglobin value <8.0 g/dL or one that drops 2 gm/dL below baseline;

For women of child-bearing potential with any positive urine beta-human chorionic 
gonadotrophin (-hCG) test, the participant will have investigational product
interrupted and a serum sample submitted to the central laboratory for -hCG testing;

CK >3 x ULN (this also triggers urine myoglobin).
Discontinuation
Potential Cases of Decreased eGFR 

If an individual participant demonstrates CONCOMITANT SCr-based AND serum 
Cystatin C-based eGFR decline of ≥30% (See Section 8.2.5.1) compared to the 
participant’s baseline eGFR, then the participant should not be further dosed and 
adequate, immediate, supportive measures including immediate evaluation by a 
nephrologist (preferably within 24 hours) with appropriate management and treatment 
as clinically indicated.  Results should be repeated as indicated by the nephrologist or 


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weekly at a minimum until the eGFR returns to baseline ±15%, or the renal 
parameters are deemed to be stable by the nephrologist and/or the investigator.

If the participant cannot be seen by a nephrologist within 24 hours (as described 
above), then the participant should be sent to a local emergency room for evaluation 
and treatment as clinically indicated.

Follow-up evaluations should include laboratory tests, detailed history, and physical 
assessment.  In addition to repeating SCr and serum cystatin C, laboratory tests 
should also include: serum blood urea nitrogen (BUN), serum creatine kinase (CK), 
serum electrolytes (including at a minimum potassium, sodium, 
phosphate/phosphorus, calcium), in addition to urine dipstick, urine microscopic 
examination, and urinary indices.  All cases confirmed on repeat testing as meeting 
the laboratory criteria for acute kidney injury, with no other cause(s) of laboratory 
abnormalities identified should be considered as potential cases of drug-induced 
kidney injury irrespective of availability of all the results of the investigations 
performed to determine etiology of the abnormal SCr.

All relevant test results will be forwarded to Sponsor Medical Monitor for review 
immediately upon receipt by the PI.
Adverse Events
The sponsor’s Clinical team should be consulted as soon as possible and participants may 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 AE;

Other serious or severe AEs, at the discretion of the investigator or sponsor;

Participants triggering criteria for suicidal ideation and behavior as described in 
Section 8.2.7.
All of the following laboratory abnormalities require discontinuation if they are confirmed 
(confirmation through re-testing should occur within one week [ideally within 48 hours]): 

Two sequential absolute neutrophil counts <1.0 x 109/L (<1000/mm3);

Two sequential hemoglobin values <8.0 g/dL; <4.96 mmol/L; <80 g/L;

Two sequential platelet counts <50 x 109/L (<50,000/mm3);

Two sequential lymphocyte counts <500/mm3; <0.5x109/L;


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
Two sequential AST or ALT elevation ≥3 times the ULN with at least one total 
bilirubin value ≥1.5 times the upper limit of normal;a note: re-testing for AST and/or 
ALT is expected to be completed within 48 hours:

Two sequential AST or ALT elevation ≥3 times the ULN 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

Pregnancy confirmed by serum -hCG testing.  Sponsor Clinician or Sponsor 
Medical Monitor should be notified immediately;

Participants with QTc prolongation ≥30 msec from the baseline and >450 msec; 
or b) an absolute QTc value is ≥500 msec for any scheduled ECG for greater than 
4 hours.
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.
C-SSRS Assessment

At any post-baseline visits, if there are “yes” answers on items 4, 5 or on any 
behavioral question of the C-SSRS, the subject will be discontinued from the IP and 
referred to a mental health professional for appropriate evaluation and treatment.  If 
the subject cannot be seen by a mental health professional within 24 hours, then the 
subject should be sent to a local emergency room for psychiatric assessment.


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10.9. Appendix 9: Prohibited Concomitant Medications
This is not an all-inclusive list.  Study personnel should stay current and consult with their 
pharmacy to exclude all concomitant medications that fall into the categories in the table 
below. 
CYP1A2, CYP3A  and 
CYP2D6 Inhibitors
CYP1A2, CYP3A4, 
Inducers
OCT2/MATE 
substrates
CYP1A2
CYP1A2
Dofetilide
Ciprofloxacin
Carbamazepine
Clinafloxacin
Efavirenz 
diethyl-dithiocarbamate  
Phenytoin
Enoxacin
Rifampin
Etintidine
Ritonavir
Fluvoxamine
BCRP Inhibitors
Idrocilamide
Cyclosporine
Methoxsalen
Elacridar (FG120918)
Mexiletine
Eltrombopag
Oltipraz
Gefitinib
Oral contraceptives (only 
those containing ethinyl 
estradiol)
BCRP Substrates 
Phenylpropanolamine
Rosuvastatin
Pipemidic acid
P-gp substrates with 
narrow TI:
Propafenone
Digoxin
Propranolol
Rofecoxib
Troleandomycin
Vemurafenib
Zafirlukast
CYP2D6
Buproprion
Cinacalcet
Dacomitinib
Dronedarone
Duloxetine
Eliglustat
Fluoxetine
Mirabegron
Moclobemide
Paroxetine
Quinidine


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CYP1A2, CYP3A  and 
CYP2D6 Inhibitors
CYP1A2, CYP3A4, 
Inducers
OCT2/MATE 
substrates
Rolapitant
Telithromycin
Terbinafine
Tipranavir
CYP 3A4
CYP3A4
Avasimibe
Amiodarone
Barbiturates
Amprenavir
Bosentan 
Aprepitant
Carbamazepine 
Atazanavir
Efavirenz 
Boceprevir
Enzalutamide
Casopitant
Etravirine
Cimetidine
Genistein
Ciprofloxacin
Lersivirine 
Clarithromycin
Lopinavir
Cobicistat
Mitotane
Conivaptan
Modafinil
Crizotinib
Nafcillin
Cyclosporine
Phenobarbital
Danoprevir
Phenytoin
Darunavir
Rifabutin
Delavirdine
Rifampin
Diltiazem
Ritonavir
Dronedarone
Semagacestat
Elvitegravir
St. John’s Wort
Erythromycin
Talviraline
Faldaprevir
Teriflunomide
Fluconazole
Thioridazine
Gestodene
Troglitazone
Grapefruit Juice***, 
marmalade
Idelalisib
Imatinib
Indinavir
Isavuconazole
Itraconazole
Ketoconazole
Lopinavir
Mibefradil
Mifepristone (RU486)
Nefazodone


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CYP1A2, CYP3A  and 
CYP2D6 Inhibitors
CYP1A2, CYP3A4, 
Inducers
OCT2/MATE 
substrates
Nelfinavir
Netupitant
Nilotinib
Norfloxacin
Norfluoxetine
Posaconazole
Ritonavir
Saquinavir
Schisandra sphenanthera
Telaprevir
Telithromycin
Tipranavir
Tofisopam
Troleandomycin
Verapamil
Viekira pak
Voriconazole
All prohibited drugs that are CYP3A inhibitors require at least a 7 day or 5 half-lives (whichever is 
longer) prior to the first dose of study drug.  Note: Amiodarone requires discontinuation at least 290 days 
(~5 half-lives, half-life averages ~58 days) prior to the first dose of IP.
All prohibited drugs that are CYP3A inducers require at least a 28 day or 5 half-lives (whichever is 
longer) prior to the first dose of IP.
***It is recommended that subjects avoid consumption of grapefruit juice exceeding 8 ounces (~240 mL) 
total in a day while in the study.
In a situation where appropriate medical care of a subject requires the use of a prohibited CYP3A 
inhibitor or inducer:
Moderate to potent inhibitors and inducers of CYP3A are not permitted in the study EXCEPT in 
emergency situations requiring no more than one day of administration.  Note: Amiodarone and 
mitotane are not permitted for any duration due to their long half-lives.  Topical (including skin or 
mucous membranes) application of antimicrobial and antifungal medications is permitted.
Concomitant Medications to be Used with Caution 
BCRP Substrates (Use with caution)*
Pibrentasvir 
Glecaprevir
*As per their respective labels, the concentration of these compounds may increase when co-administered 
with BCRP inhibitors (eg, PF-06650833, PF-06700841).


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From: https://www.ptcommunity.com/system/files/pdf/ptj4207473.pdf


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10.10. Appendix 10: eGFR Calculations
The estimated GFR (eGFR) will be calculated using the 2 sets of equations developed by the 
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), which utilize serum 
creatinine (SCr) and serum Cystatin C respectively.
CKD-EPI2009Scr
If female and SCr is 0.7 mg/dL:

GFR (mL/min/1.73 m2) = 144 x (SCr/0.7) – 0.329 x 0.993age (x 1.159, if black).
If female and SCr is >0.7 mg/dL:

GFR (mL/min/1.73 m2) = 144 x (SCr/0.7) – 1.209 x 0.993age (x 1.159, if black).
If male and SCr is 0.9 mg/dL:

GFR (mL/min/1.73 m2) = 141 x (SCr/0.9) – 0.411 x 0.993age (x 1.159, if black).
If male and SCr is >0.9 mg/dL:

GFR (mL/min/1.73 m2) = 141 x (SCr/0.9) – 1.209 x 0.993age (x 1.159, if black).
CKD-EPI2012cys
If female and Scys is 0.8 mg/dL:

GFR (mL/min/1.73 m2) = 133 x (Scys/0.8) – 0.499 x 0.996age x 0.932.
If female and Scys is >0.8 mg/dL:

GFR (mL/min/1.73 m2) = 133 x (Scys/0.8) –1.328 x 0.996age x 0.932.
If male and Scys is 0.8 mg/dL:

GFR (mL/min/1.73 m2) = 133 x (Scys/0.8) – 0.499 x 0.996age.
If female and Scys is >0.8 mg/dL:

GFR (mL/min/1.73 m2) = 133 x (Scys/0.8) –1.328 x 0.996age.


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10.11. Appendix 11: Columbia Suicide Severity Rating Scale (C-SSRS)19
C-SSRS for Screening Visit 


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C-SSRS for post-baseline visits


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10.12. Appendix 12: Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Abbreviation
Term
AA
alopecia areata
Abs
absolute
ACPA+
anti-anticitrullinated protein antibody positive 
ADME
absorption, distribution, metabolism, and excretion
AE
adverse event
ALC
absolute lymphocyte count
ALT
alanine aminotransferase
AN
abscess and inflammatory nodule
ANC
absolute neutrophil count
AST
aspartate aminotransferase
AUC
area under the curve
AUC24
area under the curve at 24 hours
AUCinf
area under the curve time zero to infinity
AV
atrioventricular
BA
bioavailability
BBS
Biospecimen Banking System
BCG
Bacille Calmette Guérin
BCRP
breast cancer resistance protein
-hCG
beta-human chorionic gonadotropin
BID
twice daily
BMI
body mass index
BP
blood pressure
bpm
beats per minute
BSEP
bile salt export pump
BUN
blood urea nitrogen
Cav,ss
average amount at steady state
CFB
change from baseline
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatinine kinase
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
CL/F
apparent clearance 
Cmax
maximum observed concentration
Cmin
minimum observed concentration
CO2
carbon dioxide (bicarbonate)
CONSORT
Consolidated Standards of Reporting Trials
CRF
case report form
CrI
credible interval


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Abbreviation
Term
CRO
contract research organization
CSR
clinical study report
C-SSRS
Columbia Suicide Severity Rating Scale
CT
clinical trial
CTCAE
Common Terminology Criteria for Adverse Events
CTMS
clinical trial management system
CV
cardiovascular
CYP
cytochrome P450
DCT
data collection tool
DILI
drug-induced liver injury
DLQI
Dermatology Life Quality Index
dn
dose normalized
DNA
deoxyribonucleic acid
DU
dispensable unit
EBV
Epstein-Barr virus
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDP
exposure during pregnancy
EFD
embryofetal developmental
eGFR
estimated glomerular filtration rate
EMA
European Medicines Agency
EOS
End of Study
EPO
epogen
ePRO
electronic patient reported outcomes
ET
early termination
EU
European Union
EudraCT
European Clinical Trials Database
FAS
full analysis set
FIH
first in human
FSH
follicle-stimulating hormone
fu
fraction of drug unbound in plasma
GCP
Good Clinical Practice
GFR
glomerular filtration rate
GGT
gamma-glutamyl transferase
GI
gastrointestinal
GLP
Good Laboratory Practice
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
CCI
CCI
CCI


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Abbreviation
Term
HBsAg 
hepatitis B surface antigen
HCVAb
hepatitis C virus antibody
HIPAA
Health Insurance Portability and Accountability Act
HiSCR
hidradenitis suppurativa clinical response
HIV
human immunodeficiency virus
HRQoL
health-related Qaulity of Life
HRT
hormone replacement therapy
HS
hidradenitis suppurativa
IB
investigator’s brochure
IBD
inflammatory bowel disease
IC
inhibitory concentration
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IFN
interferon
IGRA
Interferon Gamma Release Assay
IHS4
International Hidradenitis Suppurativa Severity Score System
IL
interleukin
IMP
investigational medicinal product
IND
investigational new drug application
INR
international normalized ratio
IP
investigational product
IP manual
investigational product manual
IR
immediate release
IRAK4
IL -1 receptor associated kinase 4
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
IWR
interactive Web-based response
JAK1
Janus Kinase 1
KDIGO
Kidney Disease: Improving Global Outcomes
LASER
light amplification by stimulated emission of radiation
LBBB
left bundle branch block
LFT
liver function test
LLOQ
lower limit of quantification 
MAD
multiple ascending dose
MAR
missing at random
MATE
multidrug and toxin extrusion transporter
MCH
mean corpuscular hemoglobin
CCI


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Abbreviation
Term
MCHC
mean corpuscular hemoglobin concentration
MCS
mental component scores
MCV
mean corpuscular volume
MDR1
multidrug resistant protein 1
MMR
Measles Mumps Rubella
MPV
mean platelet volume
MR
modified release
MRI
magnetic resonance imaging
MRP
multidrug resistance-associated protein
msec
millisecond
MTX
methotrexate
N/A
not applicable
NIMP
noninvestigational medicinal product
NOAEL
no-observed-adverse-effect level
NRS
numeric rating scale
NRS-11
Numerical Rating Scale-11
NSAIDs
nonsteroidal anti-inflammatory drugs
NTCP
sodium/taurocholate co-transporting polypeptide
OAT
organic anion transporter 
OATP
organic anion transporting polypeptide 
OCT
organic cation transporter
PASI
Psoriasis Area and Severity Index 
PBMC
peripheral blood mononuclear cell
PCD
primary completion date
PCP
primary care physician
PCR
polymerase chain reaction
PCS
physical component score
PD
pharmacodynamic(s)
PE
physical exam
PGA
Patient’s Global Assessment
PI
principal investigator
PK
pharmacokinetic(s)
PPAS
per protocol analysis set
PPD
Purified Protein Derivative
PRN
as needed
PRO
patient reported outcome
PsO
psoriasis
PT
prothrombin time
PVC
premature ventricular contraction/complex
CCI
CCI
CCI


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Abbreviation
Term
QD
once daily
QID
four times a day
QoL
quality of life
QFT-plus
QuantiFERON®-TB Gold Plus (QFT-plus)
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
QW
once weekly
qual
qualitative
RA
rheumatoid arthritis
RBC
red blood cell
RNA
ribonucleic acid
SAD
single ascending dose
SAE
serious adverse event
SAP
statistical analysis plan
SCr
serum creatinine
SDAI
simplified disease activity index
SDD
sprayed dried dispersion 
SMP
study monitoring plan
SoA
schedule of activities
SOC
system organ class
SOP
standard operating procedure
SRSD
single reference safety document
SSID
screening number
SToD
study team on demand
SUSAR
suspected unexpected serious adverse reaction
T1/2
half-life
TB
tuberculosis
TBili
total bilirubin
TBNK
lymphocyte subsets (T cells, B cells, and NK cells)
TdP
torsade de pointes
TEAEs
treatment emergent adverse events
TH
T-helper
TID
three time a day
TLR
tool-like receptor
Tmax
time to maximal concentration
TNF
tumor necrosis factor
TYK2
tyrosine kinase 2
UGT
5’-diphospho-glucuronosyltransferase
ULN
upper limit of normal
US
United States
UVA
Ultra violet A
C
CI


PF-06650833, PF-06700841, PF-06826647 
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Abbreviation
Term
VAS
visual analog scale
VTE
venous thromboembolic events
Vz/F
volume of distribution
WBC
white blood cell
WOCBP
woman of childbearing potential


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11. REFERENCES
1.
Zouboulis, C., del Marmol, V., Mrowietz, U., Prens, E., Tzellos, T. and Jemec, G. 
(2015). Hidradenitis Suppurativa/Acne Inversa: Criteria for Diagnosis, Severity 
Assessment, Classification and Disease Evaluation. Dermatology, 231(2), pp.184-190.
2.
Jemec GB. Clinical Practice. Hidradenitis suppurativa. N Eng J Med 2012; 366: 158-64.
3.
Kimball, A., Okun, M., Williams, D., Gottlieb, A., Papp, K., Zouboulis, C., Armstrong, 
A., Kerdel, F., Gold, M., Forman, S., Korman, N., Giamarellos-Bourboulis, E., 
Crowley, J., Lynde, C., Reguiai, Z., Prens, E., Alwawi, E., Mostafa, N., Pinsky, B., 
Sundaram, M., Gu, Y., Carlson, D. and Jemec, G. (2016). Two Phase 3 Trials of 
Adalimumab for Hidradenitis Suppurativa. New England Journal of Medicine, 375(5), 
pp.422-434. 
4.
Nielsen, R., Lindsø Andersen, P., Sigsgaard, V., Riis, P. and Jemec, G. (2019). Pain 
perception in patients with Hidradenitis Suppurativa. British Journal of Dermatology. 
5.
Thorlacius, L., Ingram, J., Villumsen, B., Esmann, S., Kirby, J., Gottlieb, A., Merola, J., 
Dellavalle, R., Nielsen, S., Christensen, R., Garg, A. and Jemec, G. (2018). A core 
domain set for hidradenitis suppurativa trial outcomes: an international Delphi process. 
British Journal of Dermatology, 179(3), pp.642-650. 
6.
Smith, H., Chao, J. and Teitelbaum, J. (2010). Painful Hidradenitis Suppurativa. The 
Clinical Journal of Pain, 26(5), pp.435-444. 
7.
Frew, J. (2019). Commentary: Hidradenitis Suppurativa: A Systematic Review
Integrating Inflammatory Pathways Into a Cohesive Pathogenic Model. Frontiers in 
Immunology, 10. 
8.
Hoek, F. J., F. A. W. Kemperman and R. T. Krediet (2003). "A comparison between 
cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of
glomerular filtration rate." Nephrology Dialysis Transplantation 18(10): 2024-2031.
9.
Dharnidharka, V. R., C. Kwon and G. Stevens (2002). "Serum cystatin C is superior to 
serum creatinine as a marker of kidney function: A meta-analysis." American Journal of
Kidney Diseases 40(2): 221-226.
10.
Newman, D. J., H. Thakkar, R. G. Edwards, M. Wilkie, T. White, A. O. Grubb and C.
P. Price (1995). "Serum cystatin C measured by automated immunoassay: A more 
sensitive marker of changes in GFR than serum creatinine." Kidney International 47(1): 
312-318.
11.
Inker , L. A., C. H. Schmid , H. Tighiouart , J. H. Eckfeldt , H. I. Feldman , T. Greene ,
J. W. Kusek , J. Manzi , F. Van Lente , Y. L. Zhang , J. Coresh and A. S. Levey (2012). 
"Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C." New 
England Journal of Medicine 367(1): 20-29.


PF-06650833, PF-06700841, PF-06826647 
Protocol C2501007
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12.
Zhu, Y. et al. Comparisons between the 2012 new CKD-EPI (Chronic Kidney Disease 
Epidemiology Collaboration) equations and other four approved equations. PloS one 9, 
e84688, doi:10.1371/journal.pone.0084688 (2014).
13.
Posner, K. et al. The Columbia-Suicide Severity Rating Scale: initial validity and 
internal consistency findings from three multisite studies with adolescents and adults. 
The American journal of psychiatry 168, 1266-1277, 
doi:10.1176/appi.ajp.2011.10111704 (2011).
14.
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) – a simple practical 
measure for routine clinical use. Clin Exp Dermatol 1994; 19(3):210-6.
 
 
 
19.
Posner, K., M. A. Oquendo, M. Gould, B. Stanley and M. Davies (2007). "Columbia 
Classification Algorithm of Suicide Assessment (C-CASA): Classification of Suicidal 
Events in the FDA’s Pediatric Suicidal Risk Analysis of Antidepressants." The 
American journal of psychiatry 164(7): 1035-1043.
20.
Zouboulis, C. C., et al. (2017). "Development and validation of the International 
Hidradenitis Suppurativa Severity Score System (IHS4), a novel dynamic scoring 
system to assess HS severity." British Journal of Dermatology 177(5): 1401-1409.
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SAP_001.pdf: 
Protocol C2501007 (PF-06650833, PF-06700841, PF-06826647) Statistical Analysis Plan
PFIZER CONFIDENTIAL 
Page 1
Protocol C2501007
A PHASE 2A, MULTICENTER, RANDOMIZED, DOUBLE-BLIND,
PLACEBO-CONTROLLED, 16-WEEK STUDY EVALUATING THE SAFETY AND
EFFICACY OF PF-06650833, PF-06700841, AND PF-06826647 IN ADULTS WITH
MODERATE TO SEVERE HIDRADENITIS SUPPURATIVA
Statistical Analysis Plan 
(SAP)
Version:
3
Date:
03 Nov 2021


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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................5
LIST OF FIGURES ...................................................................................................................5
APPENDICES ...........................................................................................................................5
1. VERSION HISTORY............................................................................................................7
2. INTRODUCTION .................................................................................................................7
2.1. Study Objectives, Endpoints, and Estimands............................................................8
2.1.1. Primary Estimand .......................................................................................12
2.1.2. Secondary Estimands..................................................................................13
2.1.3. Additional Estimands..................................................................................13
2.2. Study Design ...........................................................................................................14
2.2.1. Design Overview ........................................................................................14
2.2.2. Number of Participants...............................................................................15
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS ................................................................................................................15
3.1. Primary Efficacy Endpoint......................................................................................15
3.2. Secondary Efficacy Endpoints ................................................................................15
3.2.1. Binary Endpoints ........................................................................................15
3.2.2. Continuous Endpoints.................................................................................16
3.4. Pharmacokinetic (PK) Endpoint..............................................................................17
3.5. Patient Reported Outcome Endpoints .....................................................................17
3.7. Safety Endpoints .....................................................................................................18
3.7.1. Adverse Events...........................................................................................18
3.7.2. Laboratory Data..........................................................................................19
3.7.3. Vital Signs ..................................................................................................20
3.7.4. Electrocardiograms.....................................................................................20
3.7.5. Physical Examinations................................................................................20
3.8. Baseline Variables...................................................................................................20
4. ANALYSIS SETS ...............................................................................................................22
5. GENERAL METHODOLOGY AND CONVENTIONS....................................................23
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5.1. Hypotheses and Decision Rules ..............................................................................23
5.2. General Methods .....................................................................................................24
5.2.1. Cochran-Mantel-Haenszel (CMH) Method with Minimum Risk 
(MR) Weighting Strategy ................................................................................24
5.2.2. ANCOVA Model........................................................................................24
5.2.3. MMRM Model............................................................................................24
5.3. Methods to Manage Missing Data ..........................................................................24
5.3.1. Binary Data.................................................................................................24
5.3.2. Continuous Data .........................................................................................25
5.3.3. PK 
 Data..............................................................................25
5.3.4. Missing Dates .............................................................................................26
5.3.5. NRS Missing Data......................................................................................26
6. ANALYSES AND SUMMARIES ......................................................................................26
6.1. Primary Efficacy Analysis ......................................................................................26
6.1.1. Percentage of Participants Achieving HiSCR Response at Week 16.........26
6.1.1.1. Main Analysis ...........................................................................26
6.1.1.2. Sensitivity Analysis...................................................................27
6.1.1.3. Supplementary Analysis............................................................27
6.2. Secondary Efficacy Analysis ..................................................................................27
6.2.1. Percentage of Participants with HiSCR Response at Weeks 1, 2, 4, 6, 
8, and 12...........................................................................................................27
6.2.1.1. Main Analysis ...........................................................................27
6.2.1.2. Sensitivity Analysis...................................................................28
6.2.2. Percent CFB in AN Count at Weeks 1, 2, 4, 6, 8, 12 and 16......................28
6.2.2.1. Main Analysis ...........................................................................28
6.2.2.2. Sensitivity Analysis...................................................................29
6.2.3. Percentage of Participants with a Total AN Count of 0 or 1; 0, 1, or 2 
at Week 16 .......................................................................................................29
6.2.4. Percentage of Participants with ≥30% Reduction and ≥1-unit 
Reduction from Baseline in PGA Skin Pain Numeric Rating Scale 
(NRS30) – at Worst and on Average, Respectively, amongst 
Participants with Baseline NRS ≥3, at Weeks 1, 2, 4, 6, 8, 12 and 16 ............29
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6.2.5. Percent CFB in NRS30, at Worst and On Average Respectively, in 
Participants who have Baseline NRS ≥3, at Weeks 1, 2, 4, 6, 8, 12 and 
16......................................................................................................................30
6.2.6. CFB in NRS, at Worst and On Average Respectively, at Weeks 1, 2, 
4, 6, 8, 12 and 16..............................................................................................31
6.2.7. Proportion of Participants Achieving Erythema Score of 1 or 0 in All 
Affected Anatomic Regions among Participants who have an Erythema 
Score of 2 or More in at least 1 Anatomic Region at Baseline........................31
6.2.8. Absolute Score and Percent CFB in International Hidradenitis 
Suppurativa Severity Score System (IHS4) at Weeks 1, 2, 4, 6, 8, 12 and 
16......................................................................................................................32
6.2.9. Proportion of Participants who Experience an HS Flare at Weeks 4, 
8, 12 and 16......................................................................................................32
 
 
6.4. Analysis of Pharmacokinetic Endpoints .................................................................35
6.5. Analysis of Patient Reported Outcome Endpoints..................................................35
6.5.1. Absolute Score and CFB in HS Symptom Items and Dermatology 
Life Quality Index (DLQI) Total Score at Scheduled Time............................35
6.5.2. Proportion of Participants Achieving a DLQI=0 or 1 ................................36
 
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6.7. Safety Summaries and Analyses .............................................................................38
6.7.1. Adverse Events...........................................................................................38
6.7.2. Laboratory Data..........................................................................................39
6.7.3. Vital Signs including Weight......................................................................39
6.7.4. Electrocardiograms.....................................................................................39
6.7.5. Physical Examination .................................................................................40
6.8. Subset Analyses.......................................................................................................40
6.9. Baseline and Other Summaries and Analyses.........................................................40
6.9.1. Baseline Summaries....................................................................................40
6.9.2. Study Conduct and Participant Disposition................................................40
6.9.3. Study Treatment Exposure .........................................................................41
6.9.4. Concomitant Medications and Nondrug Treatments..................................41
7. INTERIM ANALYSES.......................................................................................................41
8. REFERENCES ....................................................................................................................42
9. APPENDICES .....................................................................................................................43
LIST OF TABLES
Table 1. Summary of Changes...................................................................................................7
Table 2. Study Objectives and Endpoints.................................................................................8
LIST OF FIGURES
Figure 1. Study Design Schema...............................................................................................14
APPENDICES
Appendix 1. Definition and Use of Visit Windows in Reporting............................................43
Appendix 2. Definition of AE, SAE and TEAE ......................................................................43
Appendix 3. SAS Code for Imputation of Continuous Endpoint ............................................47
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Appendix 4. SAS Code for CMH Test with MR Weighting Strategy Adjusted by 
Stratification Factors.................................................................................48
Appendix 5. SAS Code for Hochberg P-value ........................................................................49
Appendix 6. SAS Code for the Confidence Interval of a Binomial Proportion (Blyth 
Still Casella)..............................................................................................50
Appendix 7. List of Abbreviations...........................................................................................51


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1. VERSION HISTORY
This Statistical Analysis Plan (SAP) for study C2501007 is based on the protocol 
(Amendment 1) dated 28 January 2020.
Table 1. Summary of Changes
Version/
Date
Associated Protocol 
Amendment
Rationale
Specific Changes
1
07Feb2020
Not Applicable
Not Applicable
Not Applicable
2
24May2020
C2501007 Protocol 
Amendment 1
Adjust or supplement 
the planned statistical 
analysis due to 
COVID-19

Section 2.1, section 3.8, section 5.3 and 
section 6, details were added regarding 
missing data due to COVID-19.

Section 3.7 and 6.7, additional listings and 
safety anslysis were added for COVID-19. 

Section 6.9.1, analysis for comparison between
before and after TYK2 coming into study were 
removed. 
3
03Nov2021
C2501007 Protocol 
Amendment 1
To be consistent with 
protocol

Section 2.1, estimands were changed to E1, E2 
and E3.

Sections 3.2, 3.3 and 3.5, detailed definition of 
endpoints were added according to protocol.

Sections 5.2.1, 6.2, 6.3 and 6.5, CIs for non-
primary endpoints were updated to 90% CI, 
adjusted p-values were used only for primary 
endpoint, and was changed from Bonferroni to 
Hochberg correction.

Section 5.3.2, baseline value was added into 
the MMRM model as an independent variable.

Section 5.3.2, PROC MI was added for 
continuous endpoint.

Sections 5.3.5, 6.2.3, 6.2.4 and 6.2.5 multiple 
imputation with Bayesian model were added 
for NRS missing data.

Sections 6.2, 6.3 and 6.5, same types of 
analysis were merged.

Section 6.8, number of draing/non-draing 
fistula at baseline was added.

Appendix, example SAS codes were added.
2. INTRODUCTION
This statistical analysis plan (SAP) provides the detailed methodology for summary and 
statistical analyses of the data collected in Study C2501007. 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.


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2.1. Study Objectives, Endpoints, and Estimands
The objectives of the current study are to evaluate the efficacy, safety and tolerability of 
PF-06650833, an IL-1 receptor associated kinase 4 (IRAK4) inhibitor, PF-06700841, a dual 
inhibitor of human tyrosine kinase 2 (TYK2) and Janus kinase 1 (JAK1), and PF-06826647, 
a potent TYK2 inhibitor, in patients with moderate to severe hidradenitis suppurativa (HS).  
Since the pathophysiology of HS is not defined completely, it is uncertain which of these 
three disease targets and pathways would be of more relevance for the treatment of patients 
with HS.  Therefore, the additional objective of this study is to compare the efficacy of 
PF-06650833, PF-06700841, and PF-06826647 with the goal to select one of these 
inhibitors for further clinical development. The detailed study objectives and corresponding 
endpoints are provided in the Table 2.
Table 2. Study Objectives and Endpoints
Objectives
Endpoints
Estimands
Primary: 
Primary:
Primary: 
To evaluate the efficacy of 
PF-06650833, PF-06700841, 
and PF-06826647 vs placebo 
in participants with HS as 
assessed by HiSCR.
Percentage of participants with 
HiSCR response* at Week 16.
This estimand uses a composite 
estimand theory (ICH E9 addendum) 
and is intended to provide a 
population level estimate of the 
treatment effect of the IP on a binary 
endpoint regardless of participant 
compliance with the IP dosing.
Population-level summary: difference 
between treated and placebo in 
proportion of participants with HiSCR 
response at Week 16.
Secondary: 
Secondary:
Secondary: 
To evaluate the efficacy of 
PF-06650833, PF-06700841, 
and PF-06826647 vs placebo 
in participants with HS at 
Week 16 and over time.
Percentage of participants with 
HiSCR response* at Weeks 1, 2, 4, 
6, 8, and 12.
Percentage of participants with a 
total abscess and inflammatory 
nodule (AN) count of 0 or 1; 0, 1, 
or 2 at Week 16.
Percent change from baseline 
(CFB) in AN count at Weeks 1, 2, 4, 
6, 8, 12 and 16.
This estimand is intended to provide a 
population level estimate of the 
treatment effect of the IP on a binary 
endpoint regardless of participant 
compliance with the IP dosing.
Population-level summary: difference 
between treated and placebo in 
proportion of participants with HiSCR 
response at Weeks 1, 2, 4, 6, 8 and 12, 
respectively; difference between 
treated and placebo in proportion of 
participants with a total AN count of 
0 or 1, or 0, 1 or 2, respectively at 
Week 16.
This estimand is intended to provide a 
population level estimate of the 
treatment effect of the IP on a 
continuous endpoint regardless of 


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Table 2. Study Objectives and Endpoints
Objectives
Endpoints
Estimands
participant compliance with the IP 
dosing. 
Population-level summary: difference 
between treated and placebo change 
from baseline in AN count at Weeks 1, 
2, 4, 6, 8, 12 and 16.
To evaluate the efficacy of 
PF-06650833, PF-06700841, 
and PF-06826647 vs placebo 
on International Hidradenitis 
Suppurativa Severity Score 
System (IHS4).
Absolute score and percent CFB in 
IHS4 at Weeks 1, 2, 4, 6, 8, 12 and 
16.
This estimand is intended to provide a 
population level estimate of the 
treatment effect of the IP on a 
continuous endpoint regardless of 
participant compliance with the IP 
dosing.
Population-level summary: difference 
between treated and placebo in 
absolute score and change from 
baseline on IHS4 at Weeks 1, 2, 4, 6, 
8, 12 and 16.
To evaluate the effects of 
PF-06650833, PF-06700841, 
and PF-06826647 vs placebo 
on HS flare.
Proportion of participants who 
experience an HS flare, defined as 
at least a 25% increase in AN count 
with a minimum increase of 2 
relative to Baseline, at Weeks 4, 8, 
12 and 16.
The estimand is intended to provide a 
population level estimate of the 
treatment effect of the IP on a binary 
endpoint regardless of participant 
compliance with IP dosing.
Population-level summary: difference 
between treated and placebo in 
proportion of participants experience 
flare at Weeks 4, 8, 12 and 16.
To evaluate the efficacy of 
PF-06650833, PF-06700841, 
and PF-06826647 vs placebo 
on pain and pain reduction 
over time in participants with 
HS.
Percentage of participants with 
≥30% reduction and ≥1-unit 
reduction from baseline in 
PGA-Skin Pain numeric rating 
scale (NRS30) – at worst and on 
average, respectively, amongst 
participants with baseline NRS ≥3, 
at Weeks 1, 2, 4, 6, 8, 12 and 16.
Percent CFB in NRS, at worst and 
on average respectively, in 
participants who have baseline 
NRS ≥3, at Weeks 1, 2, 4, 6, 8, 12 
and 16.
CFB in NRS, at worst and on 
average respectively, at Weeks 1, 
2, 4, 6, 8, 12 and 16.
This estimand is intended to provide a 
population level estimate of the 
treatment effect of the IP on a binary 
endpoint regardless of participant 
compliance with the IP dosing.
Population-level summary: difference 
between treated and placebo in 
proportion of participants with 
≥30% reduction and ≥1-unit reduction 
from baseline in PGA-Skin Pain NRS 
(NRS30), at worst and on average, 
respectively, amongst participants 
with baseline NRS ≥3, at Weeks 1, 2, 
4, 6, 8, 12 and 16.
This estimand is intended to provide a 
population level estimate of the 
treatment effect of the IP on a 
continuous endpoint regardless of 
participant compliance with the IP 
dosing.
Population-level summary: difference 
between treated and placebo percent 


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Table 2. Study Objectives and Endpoints
Objectives
Endpoints
Estimands
change from baseline in NRS, at worst 
and on average respectively, in 
participants who have baseline NRS ≥3, 
at Weeks 1, 2, 4, 6, 8, 12 and 16.  
Difference between treated and placebo 
change from baseline in NRS, at worst 
and on average respectively, at Weeks 1, 
2, 4, 6, 8, 12 and 16.
To evaluate the efficacy of 
PF-06650833, PF-06700841, 
and PF-06826647 vs placebo 
on erythema.  
Proportion of participants 
achieving erythema score of 1 or 0 
in all affected anatomic regions 
among participants who have an 
erythema score of 2 or more in at 
least 1 anatomic region at 
baseline.
The estimand is intended to provide a 
population level estimate of the 
treatment effect of the IP on a binary 
endpoint regardless of participant 
compliance with IP dosing.
Population-level summary: difference 
between treated and placebo in 
proportion of participants achieving 
erythema score of 1 or 0 in all affected 
anatomic regions among participants 
who have erythema score of 2 or more 
in at least 1 anatomic region at 
baseline.
To assess the safety and 
tolerability of PF-06650833, 
PF-06700841, and 
PF-06826647 vs placebo in 
participants with HS.
Incidence of TEAEs (AEs and 
SAEs), significant changes in vital 
signs, clinical laboratory 
abnormalities, and ECG.
There is no defined estimand for these 
endpoints and they will be analyzed 
using Pfizer data standards as 
applicable.
To evaluate the effects of 
PF-06650833, PF-06700841, 
and PF-06826647 vs placebo 
on patient centered outcomes 
in participants with HS.
Absolute score and CFB at time 
points specified in the SoA in HS 
Symptom Items and Dermatology 
Life Quality Index (DLQI) total 
score. 
Proportion of participants 
achieving a DLQI=0 or 1.
These endpoints will be analyzed 
descriptively and with respect to an 
estimand. 
To evaluate the PK of 
PF-06650833, PF-06700841, 
and PF-6826647 vs placebo in 
participants with HS.
Summary of plasma concentration 
of PF-06700841, PF-06826647 
and PF-06650833.
There is no defined estimand for these 
endpoints and they will be analyzed 
using Pfizer data standards as 
applicable.
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 2. Study Objectives and Endpoints
Objectives
Endpoints
Estimands
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 2. Study Objectives and Endpoints
Objectives
Endpoints
Estimands
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
*HiSCR requires:
•
At least a 50% reduction in the total AN count relative to baseline; and
•
No increase in abscess count; and
•
No increase in draining fistula count.
For all endpoints, baseline is defined as the result closest prior to dosing on Day 1.
2.1.1. Primary Estimand
The primary estimand E1 is intended to provide a population level of treated arm versus 
placebo arm on a binary endpoint.  It includes the following 4 attributes:
•
Population: Participants with moderate to severe HS, as defined by the inclusion and 
exclusion criteria.
•
Variable: The proportion of participants achieving HiSCR response at Week 16.
•
Non-pandemic related Intercurrent Events: Withdrawal and all other events leading to 
missing data will be treated as non-responders.
•
COVID-19 pandemic related Intercurrent Events: The subjects who intermittently 
miss the visit due to COVID-19 will be excluded from the analysis for that visit. The 
subjects who discountinues treatment or withdraws from the study due to COVID-19 
will be excluded from the analysis after the treatment discountinuation visit or study 
withdraw visit. 
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
Population-level summary: The mean difference in proportions of HiSCR responders 
between treated and placebo arms.
2.1.2. Secondary Estimands
The secondary estimand E2 is intended to provide a population level of treated arm versus 
placebo arm on a continuous endpoint. It includes the following 4 attributes:

Population: Participants with moderate to severe HS, as defined by the inclusion and 
exclusion criteria.

Variable: Percent CFB in AN count at Weeks 1, 2, 4, 6, 8, 12 and 16.

Non-pandemic related Intercurrent Events: Withdrawal and all other events leading to 
missing data will be imputed in the active treatment arms using a jump to control 
method using the distribution of the placebo group (ie, missing data in active 
treatment participants will be imputed from the distribution of matching placebo 
participants). Missing data in a placebo arm will be imputed using data from the 
placebo arm assuming data are MAR.

COVID-19 pandemic related Intercurrent Events: The subjects who miss visit, 
discountinues treatment, or withdraw from the study at or prior to Week 16 due to 
COVID-19 will not be excluded from the analysis. The missing data due to 
COVID-19 are assumed to be missing completely at random (MCAR).

Population level summary: The mean difference in percent CFB in AN count between 
treated and placebo arms. 
2.1.3. Additional Estimands
The estimand E3 is intended to provide a population level of treated arm versus placebo arm 
on time-to-event endpoint. It includes the following 4 attributes:

Population: Participants with moderate to severe HS as defined by the inclusion and 
exclusion criteria.

Viariable: Time to first flare, calculated from the first dose to the day that a flare is 
first observed.

Non-pandemic related Intercurrent Events: Withdrawal subjects will be censored at 
the last available visit. Any other reason cause the missing value before first flare and 
prior the last visit will be censored. 

COVID-19 pandemic related Intercurrent Events: Subject who are observed to 
comply with treatment for at least 12 weeks will be included in the analysis. Missing 
values will be censored at the last available visit; Subjects who do not meet 12-week 
minimally acceptable level of drug compliance will be excluded from the analysis.  


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
Population-level summary: Hazard ratio of flare between treatment and placebo.
2.2. Study Design
2.2.1. Design Overview
This is a Phase 2a, randomized, double-blind, placebo-controlled, parallel group, 
multicenter platform study with 3 kinase inhibitors (PF-06650833, PF-06700841 and 
PF-06826647) in participants with moderate to severe HS.  The study will have a maximum 
duration of approximately 26 weeks.  This includes an up to 6-week Screening Period, a 
16-week Dosing Period and a 4-week Follow-up Period.  The study will not be blinded 
across the PF-06650833, PF-06700841 and PF-06826647 treatment arms, but will be 
placebo-controlled double-blinded within each investigational product (IP) treatment arm.  
Following the screening period, participants who meet eligibility criteria at the baseline 
visit, will be randomly assigned to receive 1 of 6 treatments.  One oral dose level of each 
PF-06650833 (400 mg QD), PF-06700841 (45 mg QD) and PF-06826647 (400 mg QD) or 
matching placebo in a 3:1 ratio will be investigated.  No more than 30% of enrolled 
participants will be inadequate anti-tumor necrosis factor (TNF) responders.  Participants 
will be stratified according to whether they are an inadequate anti-TNF responder or not. 
The Figure 1 illustrates a schematic display of the study design. 
Additionally, no more than 20% of enrolled participants may enter the study on a 
background of concomitant oral antibiotic therapy for treatment of HS; the dosing regimen 
(dose and frequency) must have been stable for at least 8 weeks (56 days) prior to the 
baseline (Day 1) visit and must remain stable throughout study participation. Participants 
will be stratified according to whether they are on a background of concomitant antibiotic 
therapy or not.  
Figure 1. Study Design Schema


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2.2.2. Number of Participants 
The study will enroll a total of approximately 192 participants (expected to provide 
approximately 156 completers).  The study will be conducted globally at approximately 
60 study sites.  
Sample size calculation is based on the primary endpoint of HiSCR response at 16 weeks.  A 
total of approximately 192 participants will be randomized in 3 active treatment groups 
(48/arm) and 3 placebo groups (16/arm) to have 39 completers for each active treatment 
arm, assuming a 15% dropout rate and the active treatment arm HiSCR response rate of 
60% and placebo HiSCR rate of 30%.  Statistical comparisons will be made between each of 
the active treatment arms against the 3 placebo groups pooled together.  With one sided 
family wise error rate of 0.1 with a Bonferroni correction (0.033 after Bonferroni adjustment 
for 3 comparisons), this sample size will provide approximately 80% power.  No statistical 
comparisons will be done between active treatment arms.
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
3.1. Primary Efficacy Endpoint
The primary efficacy endpoint is the percentage of participants with HiSCR response at 
Week 16. The HiSCR response is defined as:

At least a 50% reduction in the total abscess and inflammatory nodule (AN) count 
relative to baseline; and

No increase in abscess count; and

No increase in draining fistula count.
3.2. Secondary Efficacy Endpoints
3.2.1. Binary Endpoints
Secondary binary endpoints are: 

Percentage of participants with HiSCR response at Weeks 1, 2, 4, 6, 8, and 12.

Percentage of participants with a total AN count of 0 or 1; 0, 1, or 2 at Week 16.

Proportion of participants who experience an HS flare at Weeks 4, 8, 12 and 16. A 
flare is defined as at least a 25% increase in AN count with a minimum increase of 
2 relative to Baseline.


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•
Percentage of participants with ≥30% reduction and ≥1-unit reduction from baseline 
in PGA Skin Pain numeric rating scale (NRS30) – at worst and on average, 
respectively, amongst participants with baseline NRS ≥3, at Weeks 1, 2, 4, 6, 8, 
12 and 16. The PGA of Skin Pain NRS will be used to assess the worst skin pain and 
the average skin pain due to HS. Ratings for the 2 items range from 0 to 10. last 
7 assessments prior to the date of first dose of investigational product will be 
averaged and serve as the participant’s baseline (See Protocol Section 8.10.2).
•
Proportion of participants achieving erythema score of 1 or 0 in all affected anatomic 
regions among participants who have an erythema score of 2 or more in at least 
1 anatomic region at baseline. The overall degree of erythema will be assessed for 
each anatomic region affected by HS using a four-point ordinal scale ranging between 
0 (no redness), 1 (faint but discernible pink coloration), 2 (moderate red coloration), 
or 3 (very red or bright red coloration).
3.2.2. Continuous Endpoints
Secondary continuous endpoints are:
•
Percent CFB in AN count at Weeks 1, 2, 4, 6, 8, 12 and 16.
•
Percent CFB in NRS30, at worst and on average respectively, in participants who 
have baseline NRS ≥3, at Weeks 1, 2, 4, 6, 8, 12 and 16.
•
CFB in NRS, at worst and on average respectively, at Weeks 1, 2, 4, 6, 8, 12 and 16.
•
Absolute score and percent CFB in International Hidradenitis Suppurativa Severity 
Score System (IHS4) at Weeks 1, 2, 4, 6, 8, 12 and 16. The IHS4 score is calculated 
by the number of nodules, the number of abscesses, and the number of draining 
tunnels. IHS4 score will be calculated according to the SoA as below:
IHS4 score = (number of nodules × 1) + (number of abscesses × 2) + {number of 
draining tunnels (fistulae/sinuses) × 4}
 
 
 
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3.4. Pharmacokinetic (PK) Endpoint
Pharmacokinetics (PK) endpoint includes the summary of plasma concentration of 
PF-06700841, PF-06826647 and PF-06650833.
3.5. Patient Reported Outcome Endpoints
The PGA skin pain NRS endpoints are the patient reported outcomes and key secondary 
endpoints which are described in the Section 3.2. Other PRO endpoints include:
•
Absolute score and CFB in HS Symptom Items and Dermatology Life Quality Index 
(DLQI) total score at scheduled time. The HS symptoms items are 5 single items that 
will assess patient self-reported symptoms related to HS. The participants are asked 
to rate each symptom on a 0 to 10 numerical rating scale. The DLQI is a general 
dermatology questionnaire that consists of 10 items that assess patient health-related 
quality of life over the last week.
•
Proportion of participants achieving a DLQI=0 or 1.
 
 
 
 
 
 
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3.7. Safety Endpoints
Safety endpoints will be assessed by the spontaneous reporting of TEAEs (AEs and SAEs), 
significant changes in vital signs, clinical laboratory abnormalities, and ECG and clinical 
laboratory results in all subjects who receive at least one dose of the investigational product. 
Unscheduled clinical laboratory measurements may be obtained at any time during the study 
to assess any perceived safety concerns.
The COVID-19-related AEs may be summarized separately for subjects who becomes 
infected with the COVID-19 virus. The trial participants who missed safety assessment, 
discontinue treatment, or withdraw from the study due to COVID-19 will be considered as 
protocol deviations and will be documented. A separate listing of participants who are
affected by COVID-19 study disruptions will be provided. The summary analysis maybe 
conducted to compare the rate of observed AEs in participants with COVID-19 in the active 
treatment arm to those in the control arm of the study.
3.7.1. Adverse Events
The AE endpoints will be assessed by the spontaneous reporting of:
•
TEAEs (AEs and SAEs);
•
Withdrawals from treatment due to AEs.
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The definition and events meeting the definition of AE, SAE and TEAE is described in 
Appendix 2. The events will be classified as drug-related if the AE is classified as possibly, 
probably, or definitely related to study drug. 
In additional to standard safety displays (Section 6.7.1), a 3-tier approach will be considered 
 to summarize AEs, SAEs and TEAEs. Under this approach, AEs are classified 
into 1 of 3 tiers. Different analyses will be performed for different tiers (see Section 6.7.1).
Tier 1 events: These are prespecified events of clinical importance and are maintained in a 
list in the product’s Safety Review Plan.
Tier 2 events: These are events that are not tier 1 but are “common.” A Medical Dictionary 
for Regulatory Activities (MedDRA) preferred term (PT) is defined as a Tier 2 event if there 
are at least 5% in any treatment group.
Tier 3 events: These are events that are neither Tier 1 nor Tier 2 events.
3.7.2. Laboratory Data
The safety endpoints will be assessed by the significant changes in clinical laboratory 
abnormalities. A list of safety laboratory test parameters is shown in the following: 
Protocol-Required Safety Laboratory Assessments (to be update according to protocol 
amend)
Hematology
Chemistry
Urinalysis
Other
Hemoglobin
Hematocrit
RBC count
MCV
MCH
MCHC
MPV
Platelet count
WBC count
Total neutrophils 
(Abs)
Eosinophils (Abs)
Monocytes (Abs)
Basophils (Abs)
Lymphocytes (Abs)
BUN/urea, creatinine 
and Cystatin C
Glucose
Calcium
Sodium
Potassium
Chloride
Total 
CO2 (bicarbonate)
AST, ALT
Total bilirubin
Alkaline phosphatase
Uric acid
Albumin
Total protein
CK
pH
Glucose (qual)
Protein (qual)
Blood (qual)
Ketones
Nitrites
Leukocyte esterase
Urobilinogen
Urine bilirubin
Microscopy and/or 
urine culturea
At screening only:
FSHb
Urine drug screening
Pregnancy test (β-hCG)c
Hepatitis B surface antigen 
(HBsAg)
Hepatitis B core antibody (HBcAb)
HepB reflex (HbsAbd), if 
applicable
Hepatitis C antibody
Hepatitis C RNA, if applicable
HIVUrine myoglobine
Abbreviations: Abs = absolute; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
β-hCG = beta-human chorionic gonadotropin; BUN = blood urea nitrogen; CO2 = carbon dioxide; 
FSH = follicle-stimulating hormone; MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin 
concentration; MCV = mean corpuscular volume; MPV = mean platelet volume; qual = qualitative; RBC = red blood 
cell; WBC = white blood cell. 
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a.
Collect pre-dose urine sample for central laboratory urinalysis and urine microscopy at Screening and Baseline. At 
postdose visits: urine microscopy is indicated if the urinalysis is positive for blood, nitrite, leukocyte esterase and/or 
protein, or there is clinical suspicion of urinary tract infection, or decrease in renal function; urine culture is 
performed if urinalysis is positive for nitrite and/or leukocyte esterase, or if otherwise clinically indicated.
b.
For confirmation of postmenopausal status only.
c.
Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
institutional review board/ethics committee (IRB/EC).  Serum or urine -hCG for female participants of 
childbearing potential.
d.
HepB reflex testing only if HBsAg negative but HBcAb positive at Screening.
e.
At Screening and in case of CK >3 x ULN.
Additional laboratory results may be reported on these samples as a result of the method of
analysis or the type of analyzer used by the clinical laboratory; or as derived from calculated 
values.  
3.7.3. Vital Signs
The safety endpoints will be assessed by the significant changes in vital signs. The vital 
signs will be measured including temperature (Oral, Tympanic, Axillary or Temporal), pulse 
rate (beats/min), blood pressure (mmHg). 
3.7.4. Electrocardiograms 
The safety endpoints will be assessed by the significant changes in ECG. The average of the 
triplicate ECG measurements collected pre dose on Day 1 will serve as each participant’s 
baseline QTc value. Summary of analysis results is described in the Section 6.7.4.
Safety QTc Assessment
Degree of Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450-480
>480-500
>500
Increase from baseline
30-60
>60
3.7.5. Physical Examinations
A full physical examination will include assessments of the general appearance, skin, head, 
eyes, ears, nose, throat, cardiovascular, respiratory, GI, and neurological systems.  
A brief physical examination will include assessments of the skin, heart, lung, abdomen, and 
body systems with any symptoms reported by the study participants. 
3.8. Baseline Variables
The following baseline variables will be summarized for each treatment group. Details of 
summary analyses are described in Section 6.9.1.
In addition, the summary of baseline variables will be performed for subjects who 
discontinue treatment or withdraw from study caused by COVID-19 pandemic.


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Demographic characteristics:
•
Baseline age (<18, 18-44, 45-75, ≥75; and continuous in years);
•
Gender (female vs. male);
•
Race (white, black, Asian, other);
•
Baseline body weight (<40, 40-100, >100 kg; and continuous in kg);
•
Baseline height (cm);
•
Baseline Body Mass Index (<17.5, 17.5 to <25, 25 to <30, 30 to <40, and ≥40 kg/m2);
•
Screening smoking status (never smoked, ex-smoker, smoker);
•
Alcohol use (yes, no).
Baseline disease characteristics: 
•
Prior anti-TNF treatment (yes vs. no);
•
Concomitant use of antibiotics treatment (yes vs. no);
•
Hurley stages (II vs. III);
•
Total AN Counts;
•
Draining fistula count;
•
Modified Sartorius score;
•
Patient global assessment of skin pain NRS;
•
DLQI;
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For all endpoints except height and weight, baseline is defined as the result closest prior to 
dosing on Day 1. The baseline for height/weight and BMI are measurements at screening 
visit. For ECG, the average of the triplicate ECG measurements will serve as the participant’s 
baseline value. If the Day 1 ECG is missing, then the screening ECG will serve as baseline 
value screening. Also for PGA Skin Pain NRS Items, the last 7 assessments prior to the date 
of first dose of investigational product will be averaged and serve as the participant’s 
baseline. The baseline data measured at Day 1 are:
•
Medical history & demography, medication history, Height/Weight.
•
Vital signs, ECG. 
•
Hurley stage, abscess count, inflammatory nodule count, fistula count, erythema 
assessments, modified Sartorius scale.
•
Patient global assessment of skin pain NRS, HS symptom items,
 
DLQI, 
•
 
 
The stratification factors are in the following and will be summarized by treatment groups:
•
Prior treatment with anti-TNF (yes or no),
•
Concomitant use of antibiotic therapy (yes or no).
4. ANALYSIS SETS
Data for all participants will be assessed to determine if participants meet the criteria for 
inclusion in each analysis population prior to unblinding and releasing the database and 
classifications will be documented per standard operating procedures.
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Population
Description
Full Analysis Set (FAS)
All participants randomized and receiving at least one dose of 
IP.
Per-protocol analysis set 
(PPAS)
All participants randomized and receiving at least one dose of 
IP, with both baseline and Week 16 primary efficacy data, and 
without protocol deviations that were thought to impact the 
efficacy evaluation during the treatment period.  All protocol 
deviations will be reviewed and assessed by the study team 
prior to database release.  
Safety
All participants randomly assigned to IP and who take at least 
1 dose of IP.  Participants will be analyzed according to the 
product they actually received.
PK concentration set
All enrolled participants who take at least one dose of active 
PF-06700841, PF-06826647 or PF-06650833 and in whom at 
least one concentration value is reported.
 
Two additional analysis sets are defined in the following for endpoints corresponding to the 
pain reduction and erythema score: 
The analysis set for pain reduction endpoints is the subset of FAS which defined as all 
participants randomized and receiving at least one dose of IP and with NRS ≥3 at baseline. 
The analysis set for erythema endpoint is the subset of FAS which defined as all participants 
randomized and receiving at least one dose of IP, and have erythema score of 2 or more in at 
least 1 anatomic region at baseline. 
5. GENERAL METHODOLOGY AND CONVENTIONS
The final analysis will be performed after all study participants completed treatment and 
follow-up period, and the CSR will be issued after then.
5.1. Hypotheses and Decision Rules
The null hypothesis for primary efficacy analysis is that the percentage of participants 
achieving HiSCR response at Week 16 is the same for the active treatment (PF-06650833, 
PF-06700841 or PF-06826647) and placebo. 
The Hochberg correction method is used to control the overall familywise error rate of 
0.1 for multiple comparison. The treatment will be considered superior to control if the 
difference is statistically significant at the overall 1-sided 0.1 level. No statistical 
comparisons will be performed between active treatment arms. 
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5.2. General Methods
5.2.1. Cochran-Mantel-Haenszel (CMH) Method with Minimum Risk (MR) Weighting 
Strategy
The treatment difference in proportions will be computed using the Cochran Mantel Hanzel 
(CMH) test with Minimum Risk (MR) weighting strategy,1 adjusting for the stratification 
factor of prior anti-TNF failure status and concomitant use of antibiotics status. The 
treatment differences in proportions will be presented. Their corresponding 2-sided 80% CI 
and 90% CI will be estimated using the MR weighting strategy proposed by Mehrotra and 
Railkar (2000).1 In Primary efficacy analysis, the Hochberg adjusted one-sided p-values2 for 
pairwise comparison between each active treatment and placebo will be presented. In 
secondary efficacy 
 analysis, the p-values will not be adjusted. The summary 
statistics including N, frequency will be tabulated as well.
5.2.2. ANCOVA Model
For continuous data, the N, frequency, mean, standard deviation, median, minimum, and 
maximum will be presented. Graphics may be used to present the data – specific details will 
be outlined in the study List of Table (LOT). The analysis of covariance (ANCOVA) model 
will be implemented for statistical testing, which includes terms of treatment group, the 
stratification factors (if there are sufficient number of subjects in each stratum, otherwise the 
stratification factors will be dropped from the model), and the baseline value as the 
independent variable. P-values will not be adjusted in secondary and explortary analysis.
5.2.3. MMRM Model
In addition, the mixed effect model repeated measurement (MMRM) model with an 
unstructured covariance matrix will be used for patient reported outcome analysis, which 
includes the fixed effects of treatment, visit, treatment-by-visit interaction and baseline value, 
along with patient as a random effect. P-values will not be adjusted in secondary and 
explortary analysis.
5.3. Methods to Manage Missing Data
In general, for descriptive statistics missing values will not be imputed. In addition, for safety 
endpoints missing values will not be imputed.  Other methods for handling missing values 
are discussed below.
5.3.1. Binary Data 
Withdrawal and all other events, except for COVID-19, leading to missing data will be 
treated as non-responders. 
The subjects who intermittently miss the visit due to COVID-19 will be excluded from the 
analysis for that visit. The subjects who discountinues treatment or withdraws from the study 
due to COVID-19 will be excluded from the analysis after the treatment discountinuation 
visit or study withdraw visit. The intercurrent events should be considered COVID-19 
pandemic-related if they occur as a result of pandemic-related factors and are not attributed 
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to other non-pandemic related reasons, eg, treatment discountinuation due to lack of efficacy 
or a toxicity. For individual instances where efficacy endpoints are not collected related to 
COVID-19, the reasons for failing to obtain the efficacy assessment will be documented and 
provided in the listing, including participant’s COVID-19 infection condition, study 
treatment accessibility, and participant’s concomitant treatment for COVID-19 in case of 
infection. 
Participants with inadequate compliance will be handled case by case, based on the later 
discussion with clinician and the team.  
5.3.2. Continuous Data
Withdrawal and all other events, except for COVID-19, leading to missing data will be 
imputed using a control-based imputation method. PROC MI will first be called and a 
control-based method (implemented with the MNAR (Missing Not At Random) option) will 
impute missing placebo observations under the assumption data are missing at random 
(MAR) and impute missing treatment observations assuming they are similar to 
corresponding placebo patients. Imputation will use the full conditional specification (FCS) 
method, the imputed data for the placebo arm will be combined for the analysis.
When using MMRM analysis, only observed data will be used and missing data will not be 
imputed.
The subjects who intermittently miss the visit due to COVID-19 will be excluded from the 
analysis for that visit. The subjects who discountinues treatment or withdraws from the study 
due to COVID-19 will be excluded from the analysis after the treatment discountinuation 
visit or study withdraw visit. The intercurrent events should be considered COVID-19 
pandemic-related if they occur as a result of pandemic-related factors and are not attributed 
to other non-pandemic related reasons, eg, treatment discountinuation due to lack of efficacy 
or a toxicity. For individual instances where efficacy endpoints are not collected related to 
COVID-19, the reasons for failing to obtain the efficacy assessment will be documented and 
provided in the listing, including participant’s COVID-19 infection condition, study 
treatment accessibility, and participant’s concomitant treatment for COVID-19 in case of 
infection. 
Participants with inadequate compliance will be handled case by case, based on the later 
discussion with clinician and the the team.  
5.3.3. PK
 Data
In summary statistics for pharmacokinetic, concentration values below the lower limit of 
quantification (LLOQ) will be set to zero.
 
  The LLOQ for various PK 
 concentrations will be noted in all 
tables and listings.
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If a concentration value is not collected or cannot be analyzed due to sample quality issues, it 
will be considered as missing data and will not be imputed. If actual sampling time is 
missing, the protocol-stated nominal time will be used.
5.3.4. Missing Dates
In compliance with Pfizer standards, if the day of the month is missing for any date used in a 
calculation, the 1st of the month will be used to replace the missing date unless the 
calculation results in a negative time duration (eg, date of resolution cannot be prior to date 
of onset; if replacing resolution date with the 1st of the month results in a negative duration, 
the resolution date will be set to the onset date).  Pfizer standards are similarly used if both 
month and day are missing (January 1 unless negative time duration).  
If the start date is missing for an AE, the AE is considered to be treatment emergent unless 
the collection date is prior to the treatment start date.
5.3.5. NRS Missing Data
Daily NRS data will be multiply imputed (MI) for any subjects with one or more missing 
daily scores for use in the analysis of endpoints in NRS, at worst and on average, 
respectively.  Daily data will be imputed using a hierarchical Bayesian model with separate 
trends for each treatment arm modeled flexibly with a B-spline basis, a random subject effect 
and a first order autoregressive structure for temporal correlation. Separate models will be 
fitted for average and worst pain. The posterior predictive distribution (PPD) from this 
model will be used to impute missing pain scores and create 100 imputed datasets.  The 
imputed daily scores will then be averaged over appropriate time periods for the analysis 
defined on weekly scores (see Section 3.2). 
Participants with missing baseline data in NRS will be excluded from the analysis.
6. ANALYSES AND SUMMARIES
6.1. Primary Efficacy Analysis
6.1.1. Percentage of Participants Achieving HiSCR Response at Week 16.
6.1.1.1. Main Analysis

Estimand strategy: Primary estimand E1 (Section 2.1.1).

Analysis set: Full Analysis Set (Section 4).

Analysis methodology: The number and percentage of participants with HiSCR 
response at Week 16 will be presented. The HiSCR response rate comparing 
treatment and placebo groups will be analyzed using the CMH test with MR 
weighting strategy (Section 5.2.1). Adjusted p-values for multiplicity using 
Hochberg correction2 will be presented for each comparison.


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
Intercurrent events and missing data: handling of missing data is described in
Section 5.3.1. 

Rate (%) differences in HiSCR responders and the corresponding 2-sided 80% and 
90% confidence intervals will be presented.

The number and percent of HiSCR responders will be presented for each treatment 
group at Week 16.

The number and percent of HiSCR responders will be presented for each treatment 
group by stratification factor at Week 16.

A plot of number and percent of HiSCR responders for each treatment group at 
Week 16 will be presented. 80% and 90% CI will be calucated using 
Blyth-Still-Casella method.

Plot of differences between active treatment and placebo adjusted by the stratification 
factor with 80% and 90% CIs will be presented. 

The number of missed or unusable assessments during COVID-19 pandemic and the 
reason of pandemic-related missing data will be summarized for primary endpoint.
6.1.1.2. Sensitivity Analysis
The main analysis will be repeated by using the per-protocol analysis set (PPAS) as defined 
in Section 4. Rate differences may also be analyzed using the method of Chan and Zhang 
(1999) in PROC FREQ using the PPAS and the FAS.
Sensitivity analysis may be performed excluding subject, who had used anitibiotic/analgesic 
during the study due to Adeverse events/topical treatment due to Adverse Events.
Handling of missing data and intercurrent event will be same as main analysis. 
6.1.1.3. Supplementary Analysis
Main analysis will be repeated where both non-pandemic and pandemic-related missing 
response assessment are imputed as non-responder. 
6.2. Secondary Efficacy Analysis
6.2.1. Percentage of Participants with HiSCR Response at Weeks 1, 2, 4, 6, 8, and 12 
6.2.1.1. Main Analysis

Estimand strategy: Primary estimand E1 (Section 2.1.1).

Analysis set: Full Analysis Set (Section 4).


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
Analysis methodology: The number and percentage of participants with HiSCR 
response at Weeks 1, 2, 4, 6, 8, and 12 will be presented. The HiSCR response rate 
comparing treatment and placebo groups at Week 8 and 12 will be analyzed using 
CMH test with MR weighting strategy (Section 5.2.1), but no hypothesis test will be 
performed to compare the treatment against the pooled placebo group at any earlier 
time point. P-values will not be adjusted for secondary endpoints.

Intercurrent events and missing data: handling of missing data is described in
Section 5.3.1. 

Rate (%) differences in HiSCR responders and the corresponding 2-sided 90% 
confidence intervals will be presented. 

The number and percent of HiSCR responders will be presented for each treatment 
group.

The number and percent of HiSCR responders will be presented for each treatment 
group by stratification factor.  

A plot of number and percent of HiSCR responders for each treatment group will be 
presented. 90% CI will be calucated using Blyth-Still-Casella method.

Plot of differences between active treatment and placebo adjusted by the stratification 
factor with 90% CIs over time will be presented.
6.2.1.2. Sensitivity Analysis
The main analysis will be repeated by using the per-protocol analysis set (PPAS) as defined 
in Section 4. Rate differences may also be analyzed using the method of Chan and Zhang 
(1999) in PROC FREQ using the PPAS and the FAS.
6.2.2. Percent CFB in AN Count at Weeks 1, 2, 4, 6, 8, 12 and 16
6.2.2.1. Main Analysis

Estimand strategy: Secondary estimand E2 (Section 2.1.2).

Analysis set: Full Analysis Set (Section 4).

Analysis methodology: Percent CFB in AN count at Weeks 1, 2, 4, 6, 8, 12 and 
16 will be presented. To compare the treatment and placebo groups at Week 8, 
Week 12 and Week 16, respectively, the ANCOVA model will be fitted which 
includes terms of treatment group, the stratification factors (if there are sufficient 
number of subjects in each stratum), and the baseline value as the independent 
variable, and with the observed (or imputed) percent CFB in AN count at Week 8, 
Week 12 and Week 16 as the dependent variable, but no hypothesis test will be 
performed to compare the treatment against the pooled placebo group at any earlier 


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time point. Treatment comparisons will be performed for the treatment difference in 
least square means. The non-adjusted p-values for treatment comparison will be 
presented. 

Intercurrent events and missing data: handling of missing data is described in
Section 5.3.2. 

The least-square means by treatment group and visit, the treatment pairwise 
differences with their corresponding 90% confidence limits will be displayed.

The N, mean, standard deviation, median, minimum, and maximum will be presented 
for percent CFB in AN count by treatment group and time. 

Plot of CFB in AN count by treatment group and time will be presented. 

Plot of differences between active treatment and placebo comparison with 90% CIs 
will be presented. 
6.2.2.2. Sensitivity Analysis

The MMRM (Section 5.2.3) will be fitted to compare the difference of active 
treatments with placebo participants using all data. The model will include the fixed 
effects of treatment, visit, treatment-by-visit interaction and baseline value, along 
with patient as a random effect. The p-values of comparisons between treatment 
groups to placebo will be calculated. 

Intercurrent events and missing data: Observed data (see Section 5.3.2).
6.2.3. Percentage of Participants with a Total AN Count of 0 or 1; 0, 1, or 2 at Week 16
Same as Section 6.1.1.
6.2.4. Percentage of Participants with ≥30% Reduction and ≥1-unit Reduction from 
Baseline in PGA Skin Pain Numeric Rating Scale (NRS30) – at Worst and on Average, 
Respectively, amongst Participants with Baseline NRS ≥3, at Weeks 1, 2, 4, 6, 8, 12 and 
16

Estimand strategy: Primary estimand E1 (Section 2.1.1).

Analysis set: Full Analysis Set with baseline NRS ≥3 (Section 4).

Analysis methodology: The number and percentage of participants with ≥30% 
reduction and ≥1-unit reduction from baseline in PGA Skin Pain NRS30 will be 
presented. The rate comparing treatment and placebo groups at each visit will be 
analyzed using CMH test with MR weighting strategy (Section 5.2.1) between each 
of active treatment group and placebo. The analysis will be repeated for each 


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imputed dataset and the results combined using Rubin’s rules. P-values will not be 
adjusted for secondary endpoints.

Intercurrent events and missing data: handling of missing data is described in
Section 5.3.5. 

Rate (%) differences and the corresponding 2-sided 90% confidence intervals will be 
presented.  

The number and percent of responders will be presented for each treatment group.

The number and percent of responders will be presented for each treatment group by 
stratification factors.  

A plot of number and percent of responders for each treatment group will be 
presented. 

Plot of differences between active treatment and placebo with 90% CIs will be 
presented.
6.2.5. Percent CFB in NRS30, at Worst and On Average Respectively, in Participants 
who have Baseline NRS ≥3, at Weeks 1, 2, 4, 6, 8, 12 and 16

Estimand strategy: Secondary estimand E2 (Section 2.1.2).

Analysis set: Full Analysis Set with baseline NRS ≥3 (Section 4).

Analysis methodology: Percent CFB in NRS30, at worst and on average respectively, 
at Weeks 1, 2, 4, 6, 8, 12 and 16 will be presented. To compare the treatment and 
placebo groups at each visit, at worst and on average respectively, the ANCOVA 
model will be fitted which includes terms of treatment group, the stratification factors 
(if there are sufficient number of subjects in each stratum), and the baseline value as 
the independent variable, and with the percent CFB in NRS30 at each visit as the 
dependent variable (computed from observed and imputed daily scores as needed). 
Treatment comparisons will be performed for the treatment difference in least square 
means. The analysis will be repeated for each imputed dataset and the results 
combined using Rubin’s rules. The non-adjusted p-values for treatment comparison
will be presented. 

Intercurrent events and missing data: handling of missing data is described in
Section 5.3.5. 

The least-square means by treatment group and visit, the treatment pairwise 
differences with their corresponding 90% confidence limits will be displayed.


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
The N, mean, standard deviation, median, minimum, and maximum will be presented 
for percent CFB in NRS, at worst and on average respectively, by treatment group 
and time. 

Plot of percent CFB in NRS, at worst and on average respectively, by treatment group
and time will be presented. 

Plot of differences between active treatment and placebo comparison with 90% CIs 
will be presented. 
6.2.6. CFB in NRS, at Worst and On Average Respectively, at Weeks 1, 2, 4, 6, 8, 12 and 
16 

Estimand strategy: Secondary estimand E2 (Section 2.1.2).

Analysis set: Full Analysis Set (Section 4).

Analysis methodology: Same as Section 6.2.5.
6.2.7. Proportion of Participants Achieving Erythema Score of 1 or 0 in All Affected 
Anatomic Regions among Participants who have an Erythema Score of 2 or More in at 
least 1 Anatomic Region at Baseline

Estimand strategy: Primary estimand E1 (Section 2.1.1).

Analysis set: Full Analysis Set with an erythema score of 2 or more in at least 
1 anatomic region at baseline (Section 4).

Analysis methodology: The number and percentage of participants achieving 
erythema response will be presented. The rate comparing treatment and placebo 
groups at Week 8, Week 12 and Week 16 will be analyzed using CMH test with MR 
weighting strategy (Section 5.2.1) between each of active treatment group and 
placebo. P-values will not be adjusted for secondary endpoints.

Intercurrent events and missing data: handling of missing data is described in
Section 5.3.1 and Section 2.1.1. 

Rate (%) differences and the corresponding 2-sided 90% confidence intervals will be 
presented.  

The number and percent of responders will be presented for each treatment group.

The number and percent of responders will be presented for each treatment group by 
stratification factors.  

A plot of number and percent of responders for each treatment group will be 
presented. 


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
Plot of differences between active treatment and placebo with 90% CIs will be 
presented.
6.2.8. Absolute Score and Percent CFB in International Hidradenitis Suppurativa 
Severity Score System (IHS4) at Weeks 1, 2, 4, 6, 8, 12 and 16

Estimand strategy: Secondary estimand E2 (Section 2.1.2).

Analysis set: Full Analysis Set (Section 4).

Analysis methodology: Absolute score and percent CFB in IHS4 at Weeks 1, 2, 4, 6, 
8, 12 and 16 will be presented.  To compare the treatment and placebo groups at
Week 8, Week 12 and Week 16, the ANCOVA model will be fitted which includes 
terms of treatment group, the stratification factors (if there are sufficient number of 
subjects in each stratum), and the baseline value as the independent variable, and with 
the observed (or imputed) absolute score or percent CFB in IHS4 as the dependent 
variable. Treatment comparisons will be performed for the treatment difference in 
least square means. The non-adjusted p-values for treatment comparison will be 
presented.

Intercurrent events and missing data: handling of missing data is described in
Section 5.3.2. 

The least-square means by treatment group and visit, the treatment pairwise 
differences with their corresponding 90% confidence limits will be displayed.

The N, mean, standard deviation, median, minimum, and maximum will be presented 
for absolute score and percent CFB in IHS4 by treatment group and time. 

Plot of absolute score and percent CFB in IHS4 by treatment group and time will be 
presented. 

Plot of differences between active treatment and placebo comparison with 90% CIs 
will be presented.
6.2.9. Proportion of Participants who Experience an HS Flare at Weeks 4, 8, 12 and 16

Estimand strategy: Primary estimand E1 (Section 2.1.1). 

Analysis set: Full Analysis Set (Section 4).

Analysis methodology: The number and percentage of participants who experience an 
HS flare at Weeks 4, 8, 12 and 16 will be presented for each treatment group by time. 
The rate comparing treatment and placebo groups at Week 8, Week 12 and Week 16 
will be analyzed respectively, using CMH test with MR weighting strategy
(Section 5.2.1) between each of active treatment group and placebo. P-values will not 
be adjusted for secondary endpoints.


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•
Intercurrent events and missing data: missing data in HS flare will no be imputed. 
•
Rate (%) differences and the corresponding 2-sided 90% confidence intervals will be 
presented.  
•
The number and percent of responders will be presented for each treatment group.
•
The number and percent of responders will be presented for each treatment group by 
stratification factors.  
•
A plot of number and percent of responders for each treatment group will be 
presented. 
•
Plot of differences between active treatment and placebo with 90% CIs will be 
presented.
 
 
 
 
 
 
  
 
 
 
 
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6.4. Analysis of Pharmacokinetic Endpoints
The PK analysis will be performed on the PK concentration population which defined as all 
enrolled participants who received at least one dose of PF-06700841, PF-06826647 or 
PF-06650833 and in whom at least one concentration value is reported.  
•
Analysis set: PK Concentration Set.
•
Analysis methodology: PK concentrations will be summarized and presented with 
descriptive statistics by treatment group and visit. Population PK modeling may be 
performed with the concentration data from this study alone or combined with data 
from other studies. In addition, a relationship between exposures and efficacy/safety 
endpoints may be evaluated using population PK/PD approach. Any population 
analyses conducted will not be part of the clinical study report (CSR) and may be 
reported separately.
•
Intercurrent events and missing data: the missing data will not be imputed. The 
subjects who miss visit due to COVID-19 will be excluded from the analysis for that 
visit. The subjects who discountinues treatment or withdraws from the study due to 
COVID-19 will be excluded from the analysis after the treatment discountinuation 
visit or study withdraw visit. The value below limit of quantification are discussed in
Section 5.3.3.
6.5. Analysis of Patient Reported Outcome Endpoints
6.5.1. Absolute Score and CFB in HS Symptom Items and Dermatology Life Quality 
Index (DLQI) Total Score at Scheduled Time
•
Estimand strategy: Secondary estimand E2 (Section 2.1.2).
•
Analysis set: Full Analysis Set (Section 4).
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•
Analysis methodology: Absolute and CFB score in HS Symptom Items and 
Dermatology Life Quality Index (DLQI) total score for each treatment group will be 
presented descriptively by visit. The MMRM (Section 5.2.3) will be used to compare 
the difference of active treatments with placebo participants at each visit. The model 
will include the fixed effects of treatment, visit, treatment-by-visit interaction and 
baseline value, along with patient as a random effect
•
Intercurrent events and missing data: Observed data. 
•
The N, mean, standard deviation, median, minimum, and maximum will be presented 
for absolute and CFB score, by treatment group and visit.
•
Mean (SE) plot of absolute and CFB score will be presented by treatment group.
6.5.2. Proportion of Participants Achieving a DLQI=0 or 1
•
Estimand strategy: Primary estimand E1 (Section 2.1.1).
•
Analysis set: Full Analysis Set (Section 4).
•
Analysis methodology: The number and percentage of participants achieving 
DLQI = 0 and 1 will be presented, respectively. The rate comparing each active 
treatment and placebo at each visit will be analyzed using CMH test with MR 
weighting strategy (Section 5.2.1). P-values will not be adjusted for secondary 
endpoints.
•
Intercurrent events and missing data: handling of missing data is described in
Section 5.3.1. 
•
Rate (%) differences and the corresponding 2-sided 90% confidence intervals will be 
presented.  
•
The number and percent of responders will be presented for each treatment group.
•
The number and percent of responders will be presented for each treatment group by 
stratification factors.  
•
A plot of number and percent of responders for each treatment group will be 
presented. 
•
Plot of differences between active treatment and placebo with 90% CIs will be 
presented.
 
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6.7. Safety Summaries and Analyses
All safety analyses will be performed on the safety population and summarized in accordance 
with Pfizer Data Standards.
All clinical AEs, SAEs, TEAEs, withdrawal due to AEs, ECGs, vital signs and safety 
laboratory data will be reviewed and summarized on an ongoing basis during the study to 
evaluate the safety of participants. The COVID-19-related AEs will be summarized 
according to Section 3.7. 
Safety data will be summarized descriptively through appropriate data tabulations, 
descriptive statistics, categorical summaries, and graphical presentations, where appropriate.
Categorical outcomes (eg, AEs) will be summarized by subject counts and percentage. 
Continuous outcome (eg, blood pressure, pulse rate, etc.) will be summarized using N, mean, 
median, standard deviation, etc. Change from baseline (CFB) in laboratory data, and vital 
signs will also be summarized. Participant listings will be produced for the safety endpoints 
accordingly.
6.7.1. Adverse Events
Generally, the TEAEs (AEs and SAEs) will be summarized for each treatment group and 
overall total. A summary of the number and percentage of patients reporting TEAEs and 
number of TEAE events will be presented overall, as well as for study drug-related TEAEs. 
The TEAEs leading to study drug interruption and withdrawal will be summarized overall, as 
well as for drug-related TEAEs. The incidence of TEAEs normalized for duration of 
exposure will be presented. 
In addition, the AEs, SAEs, TEAEs will be analyzed based on 3-tier approach
(Section 3.7.1). The analyses of AEs under the 3-tier approach are considered 
.
The following descriptions are for the analyses of AEs under the 3-tier approach:
•
Analysis Method: The risk differences and 95% confidence intervals are provided for 
comparing each active treatment dose versus placebo.
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•
There will be no adjustment for multiple comparisons or stratification factors in the 
analyses.
•
Output: For Tier 1 and Tier 2 event outputs, footnotes will be included to provide 
proper interpretation of nominal p-values (Tier 1 events) and 95% confidence 
intervals (Tier 1 and Tier 2 events) for pairwise treatment differences in percentage of 
participants with events.
•
For tier-3 events, observed event counts and proportions will be summarized.
•
The output will be arranged in descending tier order and the descending point 
estimate the risk differences.
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 
analysis and its purpose is to generate hypotheses for 
further investigation. The 3-tier approach facilitates this 
 analysis.
6.7.2. Laboratory Data
Unscheduled clinical labs may be obtained at any time during the study to assess any 
perceived safety concerns at the investigator’s discretion. Laboratory data will be listed and 
summarized in accordance with the Pfizer reporting standards.
6.7.3. Vital Signs including Weight
Vital signs (systolic blood pressure, diastolic blood pressure pulse, pulse rates and 
temperature) will be measured after 5 minutes of rest as indicated in the Schedule of 
Activities. 
The actual outcome and CFB value will be summarized at baseline and over time by 
treatment in accordance with the Pfizer reporting standards.
6.7.4. Electrocardiograms
The actual value and changes from baseline for the ECG parameters QT interval, heart rate, 
QTc interval, PR interval, and QRS complex will be summarized by treatment and time.
The number (%) of participants with maximum post dose QTc values and maximum 
increases from baseline in the following categories will be tabulated by treatment: 
Safety QTc Assessment
Degree of Prolongation
Mild (msec)
Moderate (msec)
Severe (msec)
Absolute value
>450-480
>480-500
>500
Increase from baseline
30-60
>60
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In addition, the number of participants with uncorrected QT values >500 msec will be 
summarized.
6.7.5. Physical Examination
Full and brief physical exams will be summarized separately in accordance with the Pfizer 
reporting standards.
6.8. Subset Analyses
The proportion of participants achieving HiSCR response at Week 16 will be summarized for 
the subsets below. The summary statistics will be presented. 

Gender (male vs. female),

Race (white, black, or other), 

BMI (below or above median of observed data),

Prior anti-TNF treatment (yes vs. no),

Antibiotics treatment (yes vs. no),

Hurley stages (II vs. III),

Median disease duration (below or above median of observed data),

AN Counts (below or above median of observed data),

Number of draing/non-draing fistula at baseline (below or above median of observed 
data),

Modified Sartorius score (below or above median of observed data),

Surgical intervention/drainage required (yes vs. no).
6.9. Baseline and Other Summaries and Analyses
6.9.1. Baseline Summaries
Demographics and baseline disease characteristics defined in Section 3.8 will be summarized 
by treatment group according to Pfizer standards. 
6.9.2. Study Conduct and Participant Disposition
Subjects evaluation, disposition, discontinuation will be summarized according to Pfizer 
standards. 


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6.9.3. Study Treatment Exposure
A summary of compliance and the number of doses received as well as the median total dose 
by visit and treatment group will be provided. 
The exposure to study drug will be summarized by total number of applications, the total 
number of days of dosing, the number and the proportion of participants who are compliant 
with the dosing regimen. 
6.9.4. Concomitant Medications and Nondrug Treatments
Prior drug and non-drug treatment, concomitant drug and non-drug treatment will be 
summarized according to Pfizer standard. 
7. INTERIM ANALYSES
An interim analysis may be performed to assess efficacy and safety.  Details of the interim 
analysis will be described in the Interim Analysis Plan. Interim analysis results may be used 
for internal business decisions regarding future study planning.  Before any interim analysis 
is initiated, the details of the objectives, decision criteria, dissemination plan, and method of 
maintaining the study blind as per Pfizer’s SOPs will be documented and approved in an 
interim analysis plan.  The results will only be distributed to a select list of individuals who 
are not part of the study team and will be involved in the internal decision-making process in 
order to protect the integrity of the study.  This list of individuals will be provided in the 
interim analysis plan.  The results of the interim analysis will not enable individuals directly 
involved in running the study (such as investigators) to identify treatment assignments for 
individual participants remaining in the study. There are no prospective plans to stop the 
study early for success as a result of any interim analysis.


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8. REFERENCES
1.
Mehrotra, Devan V., and Radha Railkar. "Minimum risk weights for comparing 
treatments in stratified binomial trials." Statistics in medicine 19.6 (2000): 811-825.
2.
Yosef Hochberg. "A sharper Bonferroni procedure for multiple tests of significance."
Biometrika 75.4 (1988): 800–802.


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9. APPENDICES
Appendix 1. Definition and Use of Visit Windows in Reporting
Visit Label
Target Day
Start Day
End Day
Screening
NA
Day -42
Day -1
Baseline
Day 1
Day -1
Day 1
Week 1
Day 8
Day 2
Day 11
Week 2
Day 15
Day 12
Day 21
Week 4
Day 29
Day 22
Day 35
Week 6
Day 43
Day 36
Day 49
Week 8
Day 57
Day 50
Day 71
Week 12
Day 85
Day 72
Day 99
Week 16
Day 113
Day 100
Day 127
Week 20
Day 141
Day 128
Day 154
Appendix 2. Definition of AE, SAE and TEAE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study 
participant, temporally associated with the use of study intervention, whether or 
not considered related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (eg, ECG, radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (ie, not 
related to progression of underlying disease).

Exacerbation of a chronic or intermittent preexisting condition including either 
an increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration 
even though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.


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
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication.  Overdose per se will not be reported 
as an AE/SAE unless it is an intentional overdose taken with possible 
suicidal/self-harming intent.  Such overdoses should be reported regardless of 
sequelae.

“Lack of efficacy” or “failure of expected pharmacological action” per se will 
not be reported as an AE or SAE.  Such instances will be captured in the efficacy 
assessments.  However, the signs, symptoms, and/or clinical sequelae resulting 
from lack of efficacy will be reported as an AE or SAE if they fulfill the 
definition of an AE or SAE.
Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by 
the investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms 
of the disease/disorder being studied, unless more severe than expected for the 
participant’s condition.

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) 
present or detected at the start of the study that do not worsen.
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (ego, hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
An SAE is defined as any untoward medical occurrence that, at any dose:
a. Results in death
b. Is life-threatening


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The term “life-threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event.  It does not refer to an event that 
hypothetically might have caused death if it were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting.  Complications that occur during hospitalization are AEs.  If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious.  When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious.
Hospitalization for elective treatment of a preexisting condition that did not worsen from 
baseline is not considered an AE.
d. Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition.  These events 
should usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse.


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The treatment-emergent AEs (TEAE) are considered as an adverse event that started during 
the effective duration of treatment. All events that start on or after the first dosing day and 
time/start time, if collected, but before the last dose plus the lag time will be flagged as 
TEAEs.  


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Appendix 3. SAS Code for Imputation of Continuous Endpoint
proc sort;
by avisitn trtpn;
run;
proc mi data=mock_all2 seed=1007 nimpute=100 out=outimp minimum=0 
maximum=&maxscore.;
by avisitn;
class trtpn;
MONOTONE regpmm(aval=base /details k=5);
mnar model(aval/modelobs=(trtpn='1') );
var base aval;
run;


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Appendix 4. SAS Code for CMH Test with MR Weighting Strategy Adjusted by 
Stratification Factors
PROC FREQ DATA=XXX; 
By visit;
TABLE stratum*TREATMENT*RESP/ COMMONRISKDIFF(CL=MR Correct=NO 
TEST=MR PRINTWTS) alpha=0.1 ;
Output out= XXXX;
RUN;


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Appendix 5. SAS Code for Hochberg P-value
data analysis ;
       set rawpval ;
       p = treatment ; 
       raw_p=pvalue; 
proc sort ; 
       by visit ;
run;
proc multtest inpvalues=analysis out=adjpval hoc;
       by visit ;
run;


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Appendix 6. SAS Code for the Confidence Interval of a Binomial Proportion (Blyth Still 
Casella) 
PROC BINOMIAL DATA=<DATASET> ALPHA=<value>;
BI/BS;
OU <RESPONSE VARIABLE>;
RUN;


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Appendix 7. List of Abbreviations
The following is a list of abbreviations that may be used in the SAP.
Abbreviation
Term
AA
alopecia areata
Abs
absolute
ACPA+
anti-anticitrullinated protein antibody positive 
ADME
absorption, distribution, metabolism, and excretion
AE
adverse event
ALC
absolute lymphocyte count
ALT
alanine aminotransferase
AN
abscess and inflammatory nodule
ANC
absolute neutrophil count
AST
aspartate aminotransferase
AUC
area under the curve
AUC24
area under the curve at 24 hours
AUCinf
area under the curve time zero to infinity
AV
atrioventricular
BA
bioavailability
BCG
Bacille Calmette Guérin
BCRP
breast cancer resistance protein
β-hCG
beta-human chorionic gonadotropin
BID
twice daily
BMI
body mass index
BP
blood pressure
bpm
beats per minute
BSEP
bile salt export pump
BUN
blood urea nitrogen
Cav,ss
average amount at steady state
CFB
change from baseline
CFR
Code of Federal Regulations
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatinine kinase
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
CL/F
apparent clearance 
Cmax
maximum observed concentration
Cmin
minimum observed concentration
CO2
carbon dioxide (bicarbonate)
CONSORT
Consolidated Standards of Reporting Trials
CRF
case report form
CrI
credible interval
CCI


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Abbreviation
Term
CRO
contract research organization
CSR
clinical study report
C-SSRS
Columbia Suicide Severity Rating Scale
CT
clinical trial
CTCAE
Common Terminology Criteria for Adverse Events
CTMS
clinical trial management system
CV
cardiovascular
CYP
cytochrome P450
DCT
data collection tool
DILI
drug-induced liver injury
DLQI
Dermatology Life Quality Index
dn
dose normalized
DNA
deoxyribonucleic acid
DU
dispensable unit
EBV
Epstein-Barr virus
EC
ethics committee
ECG
electrocardiogram
eCRF
electronic case report form
EDP
exposure during pregnancy
EFD
embryofetal developmental
eGFR
estimated glomerular filtration rate
EMA
European Medicines Agency
EPO
epogen
ePRO
electronic patient reported outcomes
ET
early termination
EU
European Union
EudraCT
European Clinical Trials Database
FAS
full analysis set
FIH
first in human
FSH
follicle-stimulating hormone
fu
fraction of drug unbound in plasma
GCP
Good Clinical Practice
GFR
glomerular filtration rate
GGT
gamma-glutamyl transferase
GI
gastrointestinal
GLP
Good Laboratory Practice
HBcAb
hepatitis B core antibody
HbsAb
hepatitis B surface antibody
HbsAg 
hepatitis B surface antigen
CCI
CCI
CCI


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Abbreviation
Term
HCVAb
hepatitis C virus antibody
HIPAA
Health Insurance Portability and Accountability Act
HiSCR
hidradenitis suppurativa clinical response
HIV
human immunodeficiency virus
HRQoL
health-related 53uality of Life
HRT
hormone replacement therapy
HS
hidradenitis suppurativa
IB
investigator’s brochure
IBD
inflammatory bowel disease
IC
inhibitory concentration
ICD
informed consent document
ICH
International Council for Harmonisation
ID
identification
IFN
interferon
IGRA
Interferon Gamma Release Assay
IL
interleukin
IMP
investigational medicinal product
IND
investigational new drug application
INR
international normalized ratio
IP
investigational product
IP manual
investigational product manual
IR
immediate release
IRAK4
IL -1 receptor associated kinase 4
IRB
institutional review board
IRC
internal review committee
IRT
interactive response technology
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
IWR
interactive Web-based response
JAK1
Janus Kinase 1
KDIGO
Kidney Disease: Improving Global Outcomes
LASER
light amplification by stimulated emission of radiation
LBBB
left bundle branch block
LFT
liver function test
LLOQ
lower limit of quantification 
MAD
multiple ascending dose
MAR
missing at random
MATE
multidrug and toxin extrusion transporter
MCH
mean corpuscular hemoglobin
MCHC
mean corpuscular hemoglobin concentration
MCS
mental component scores
CCI


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Abbreviation
Term
MCV
mean corpuscular volume
MDR1
multidrug resistant protein 1
MMR
Measles Mumps Rubella
MPV
mean platelet volume
MR
Minimum Risk
MRI
magnetic resonance imaging
MRP
multidrug resistance-associated protein
msec
millisecond
MTX
methotrexate
N/A
not applicable
NIMP
noninvestigational medicinal product
NOAEL
no-observed-adverse-effect level
NRS
numeric rating scale
NRS-11
Numerical Rating Scale-11
NSAIDs
nonsteroidal anti-inflammatory drugs
NTCP
sodium/taurocholate co-transporting polypeptide
OAT
organic anion transporter 
OATP
organic anion transporting polypeptide 
OCT
organic cation transporter
PASI
Psoriasis Area and Severity Index 
PBMC
peripheral blood mononuclear cell
PCD
primary completion date
PCP
primary care physician
PCR
polymerase chain reaction
PCS
physical component score
PD
pharmacodynamic(s)
PE
physical exam
PGA
Patient’s Global Assessment
PI
principal investigator
PK
pharmacokinetic(s)
PPAS 
per protocol analysis set
PPD
Purified Protein Derivative
PRN
as needed
PRO
patient reported outcome
PsO
psoriasis
PT
prothrombin time
PVC
premature ventricular contraction/complex
QD
once daily
QID
four times a day
CCI
CCI
CCI


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Abbreviation
Term
QoL
quality of life
QTc
corrected QT
QTcF
corrected QT (Fridericia method)
QW
once weekly
qual
qualitative
RA
rheumatoid arthritis
RBC
red blood cell
RNA
ribonucleic acid
SAD
single ascending dose
SAE
serious adverse event
SAP
statistical analysis plan
SCr
serum creatinine
SDAI
simplified disease activity index
SDD
sprayed dried dispersion 
SMP
study monitoring plan
SoA
schedule of activities
SOC
system organ class
SOP
standard operating procedure
SRSD
single reference safety document
SSID
screening number
SToD
study team on demand
SUSAR
suspected unexpected serious adverse reaction
T1/2
half-life
TB
tuberculosis
TBili
total bilirubin
TdP
torsade de pointes
TEAEs
treatment emergent adverse events
TID
three time a day
TLR
tool-like receptor
Tmax
time to maximal concentration
TNF
tumor necrosis factor
TYK2
tyrosine kinase 2
UGT
5’-diphospho-glucuronosyltransferase
ULN
upper limit of normal
US
United States
UVA
Ultra violet A
VTE
venous thromboembolic events
Vz/F
volume of distribution
C
CI
CCI
CC
I
CCI


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Abbreviation
Term
WBC
white blood cell
WOCBP
woman of childbearing potential