Clinical trial NCT03077412
Conditions: Fistulizing Crohn's Disease
Sponsor: Gilead Sciences
Start date: 2017-04-06; Completion date: 2021-02-17
Enrollment: 57 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the efficacy of filgotinib as compared to placebo in establishing combined fistula response at Week 24. Participants will have the option to enter a separate Long-Term Extension (LTE) study (GS-US-419-3896; NCT02914600) if they meet eligibility requirements.

Detailed description:

Arms: arm 1: Filgotinib 200 mg + placebo to match filgotinib 100 mg for 24 weeks arm 2: Filgotinib 100 mg + placebo to match filgotinib 200 mg for 24 weeks arm 3: Placebo to match filgotinib 200 mg + placebo to match filgotinib 100 mg for 24 weeks
Interventions: intervention 1: Filgotinib intervention 2: Placebo to match filgotinib
Intervention descriptions: intervention 1: Tablet(s) administered orally once daily intervention 2: Tablet(s) administered orally once daily

Protocol documents:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL
Study Title:
A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study 
Evaluating the Efficacy and Safety of Filgotinib in the Treatment of 
Perianal Fistulizing Crohn’s Disease
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404, USA
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
129646
2016-003153-15
NCT03077412
Indication:
Fistulizing Crohn’s Disease 
Protocol ID:
GS-US-419-4016
Contact Information:
The medical monitor name and contact information will be 
provided on the Key Study Team Contact List.
Protocol Version/Date:
Original:
12 September 2016
Amendment 1:
06 January 2017
Amendment 1.1:
28 February 2017
Amendment 2:
26 June 2017
Amendment 3:
11 October 2018
Amendment 4:
11 April 2019
Amendment 5:
04 February 2020
CONFIDENTIALITY STATEMENT
The information contained in this document, particularly unpublished data, is the property or 
under control of Gilead Sciences, Inc., and is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable 
Institutional Review Board or Independent Ethics Committee. The information is only to be 
used by you in connection with authorized clinical studies of the investigational drug 
described in the protocol. You will not disclose any of the information to others without 
written authorization from Gilead Sciences, Inc., except to the extent necessary to obtain 
informed consent from those persons to whom the drug may be administered.
(fJ' GILEAU Galapagos 


Filgotinib 
GS-US-419-4016 
Gilead Sciences, Inc 
Final 
Amendment5 
TABLE OF CONTENTS 
TABLE OF CONTENTS .............................................................................................................................................. 2 
LIST OF IN-TEXT TABLES ........................................................................................................................................ 5 
LIST OF IN-TEXT FIGURES ...................................................................................................................................... 5 
PROTOCOL SYNOPSIS .............................................................................................................................................. 6 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS .................................................................... 16 
DEFINITION OF TERMS .......................................................................................................................................... 20 
1. 
INTRODUCTION .............................................................................................................................................. 21 
1.1. 
Background ............................................................................................................................................ 21 
1.2. 
Filgotinib (GS-6034) .............................................................................................................................. 23 
1.2.1. 
General Infonnation ............................................................................................................. 23 
1.2.2. 
Preclinical Phannacology and Toxicology ........................................................................... 24 
1.2.3. 
Clinical Trials ofFilgotinib .................................................................................................. 26 
1.3. 
Rationale for This Study ........................................................................................................................ 27 
1.4. 
Rationale for Dose .................................................................................................................................. 28 
1.5. 
Risk/Benefit Assessment for the Study .................................................................................................. 29 
1.6. 
Compliance ............................................................................................................................................ 30 
2. 
OBJECTIVES ..................................................................................................................................................... 31 
3. 
STUDY DESIGN ................................................................................................................................................ 32 
3.1. 
3.2. 
3.3. 
3.4. 
3.5. 
3.6. 
3.7. 
3.8. 
3.9. 
3.10. -
Endpoints ............................................................................................................................................... 32 
Study Design .......................................................................................................................................... 32 
Study Treatments ................................................................................................................................... 34 
Duration ofTreatment ............................................................................................................................ 35 
Criteria for Study Drng Intenuption or Discontinuation ........................................................................ 35 
3 .5 .1. 
Study Thug Intem1ption Considerations ............................................................................... 35 
3.5.2. 
Study Thug Discontinuation Considerations ........................................................................ 35 
Luminal Disease Activity - Non-Response Criteria ............................................................................... 38 
Perianal Fistulizing Disease Activity - Non-Response Criteria ............................................................. 38 
Luminal Disease Activity - Disease Worsening Criteria ........................................................................ 3 8 
End ofStudy ........................................................................................................................................... 39 
Post Stud Care ...................................................................................................................................... 39 
4. 
SUBJECT POPULATION .................................................................................................................................. 41 
4.1. 
Number of Subjects and Subject Selection ............................................................................................ 41 
4.2. 
Inclusion Criteria .................................................................................................................................... 41 
4.3. 
Exclusion Criteria ................................................................................................................................... 45 
5. 
INVESTIGATIONAL MEDICINAL PRODUCTS .......................................................................................... .48 
5.1. 
Rando1nization, Blinding and Treatment Codes .................................................................................... 48 
5.1.1. 
Procedures for Breaking Treatment Codes .......................................................................... .48 
5.1.2. 
Blinding ................................................................................................................................ 48 
5.2. 
Description and Handling ofFilgotinib and Placebo to Match (PTM) Filgotinib .................................. 49 
5.2.1. 
Foimulation .......................................................................................................................... 49 
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5.2.2. 
Packaging and Labeling ....................................................................................................... 49 
5.2.3. 
Storage and Handling ........................................................................................................... 49 
5.3. 
Dosage and Administrntion of Study Dmg ............................................................................................ 50 
5.4. 
Prior and Concomitant Medication ........................................................................................................ 50 
5.4.1. 
Allowed Concomitant Medication ....................................................................................... 51 
5.4.2. 
Prohibited Concomitant Medication ..................................................................................... 52 
5.5. 
Co1ticosteroid Tapering .......................................................................................................................... 53 
5.6. 
Vaccine Guidelines ................................................................................................................................ 53 
5.7. 
Accountability for Study D1ug ............................................................................................................... 54 
5.7.1. 
Investigational Medicinal Product Retuin or Disposal. ....................................................... 54 
6. 
STUDY PROCEDURES .................................................................................................................................... 55 
6.1. 
6.2. 
6.4. 
6.5. 
6.6. 
6.7. 
6.8 . .. 
6.11. 
-
6.13. 
6.14. 
Subject Enrollment and Treatment Assignment ..................................................................................... 55 
Se. uence of Assessments at Stud Visits .............................................................................................. 55 
Flexible Sig1noidoscopy ......................................................................................................................... 56 
Magnetic Resonance Imaging ................................................................................................................ 57 
Perianal Assessment ............................................................................................................................... 57 
Perianal Disease Activi 
Index ............................................................................................................. 58 
Sa ety ..................................................................................................................................................... 59 
6.11. 1. 
Clinical Laborato1y Evaluations ........................................................................................... 59 
6.11.2. 
Repeat Screening Assessments ............................................................................................. 60 
6.11.3. 
Pregnancy Testing (for females of childbearing potential only) .......................................... 61 
6.11.4. 
Vital Signs ............................................................................................................................ 61 
6.11.5. 
Physical Examination ........................................................................................................... 61 
12-lead Electi·ocardio . ·run ................................................................................................... 61 
Post-Treatinent Assessments .................................................................................................................. 62 
Early Tennination Assessments ............................................................................................................. 62 
7. 
ADVERSE EVENTS AND TOXICITY MANAGEMENT ............................................................................... 64 
7 .1. 
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events ................................. 64 
7. 1.1. 
Adverse Events ..................................................................................................................... 64 
7.1.2. 
Serious Adverse Events ........................................................................................................ 64 
7 .2. 
Assessment of Adverse Events and Serious Adverse Events ................................................................. 65 
7.2.1. 
Assessment of Causality for Study Drngs and Procedw-es ................................................... 65 
7.2.2. 
Assess1nent of Severity ........................................................................................................ 66 
7.3. 
Investigator Requirements and Instiuctions for Repo1ting Adverse Events and Serious 
Adverse Events to Gilead ....................................................................................................................... 66 
7 .3.1. 
Adverse Events ..................................................................................................................... 66 
7 .3.2. 
Serious Adverse Events ........................................................................................................ 66 
7 .4. 
Gilead Repo1ting Requirements ............................................................................................................. 68 
7.5. 
Clinical Laborato1y Abnonnalities and Other Abnonnal Assessments as Adverse Events or 
Serious Adverse Events .......................................................................................................................... 68 
7.6. 
Toxicity Management ............................................................................................................................ 68 
7.6.1. 
Grades 1 and 2 Laborat01y Abnonnality or Clinical Event... ............................................... 69 
7.6.2. 
Grade 3 Laborato1y Abno1mality or Clinical Event.. ........................................................... 69 
CONFIDENTIAL 
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7.6.3.
Grade 4 Laboratory Abnormality or Clinical Event.............................................................69
7.7.
Special Situations Reports......................................................................................................................69
7.7.1.
Definitions of Special Situations..........................................................................................69
7.7.2.
Instructions for Reporting Special Situations.......................................................................70
8.
STATISTICAL CONSIDERATIONS................................................................................................................73
8.1.
Analysis Objectives and Endpoints........................................................................................................73
8.1.1.
Analysis Objectives..............................................................................................................73
8.1.2.
Primary Endpoint .................................................................................................................74
8.1.3.
Secondary Endpoints............................................................................................................74
8.2.
Analysis Conventions.............................................................................................................................75
8.2.1.
Analysis Sets ........................................................................................................................75
8.3.
Data Handling Conventions ...................................................................................................................75
8.4.
Demographic Data and Baseline Characteristics ...................................................................................76
8.5.
Efficacy Analysis ...................................................................................................................................76
8.5.1.
Primary Analysis..................................................................................................................76
8.5.2.
Secondary Analyses .............................................................................................................76
8.6.
Safety Analysis.......................................................................................................................................76
8.6.1.
Extent of Exposure...............................................................................................................77
8.6.2.
Adverse Events.....................................................................................................................77
8.6.3.
Laboratory Evaluations ........................................................................................................77
8.6.4.
Other Safety Evaluations......................................................................................................77
8.6.5.
Pharmacokinetic Analysis ....................................................................................................78
8.8.
Sample Size............................................................................................................................................78
8.9.
Data Monitoring Committee ..................................................................................................................79
8.10.
Cardiovascular Safety Endpoint Adjudication Committee (CVEAC) ...................................................80
9.
RESPONSIBILITIES..........................................................................................................................................81
9.1.
Investigator Responsibilities ..................................................................................................................81
9.1.1.
Good Clinical Practice..........................................................................................................81
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval...........................................................................................................81
9.1.3.
Informed Consent.................................................................................................................81
9.1.4.
Confidentiality......................................................................................................................82
9.1.5.
Study Files and Retention of Records ..................................................................................82
9.1.6.
Case Report Forms...............................................................................................................83
9.1.7.
Investigational Medicinal Product Accountability and Return.............................................84
9.1.8.
Inspections............................................................................................................................84
9.1.9.
Protocol Compliance............................................................................................................84
9.2.
Sponsor Responsibilities ........................................................................................................................85
9.2.1.
Protocol Modifications.........................................................................................................85
9.2.2.
Study Report and Publications .............................................................................................85
9.3.
Joint Investigator/Sponsor Responsibilities ...........................................................................................85
9.3.1.
Payment Reporting...............................................................................................................85
9.3.2.
Access to Information for Monitoring..................................................................................86
9.3.3.
Access to Information for Auditing or Inspections ..............................................................86
9.3.4.
Study Discontinuation..........................................................................................................86
10.
REFERENCES ...................................................................................................................................................87
11.
APPENDICES ....................................................................................................................................................90
CCI
CCI
CCI
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Filgotinib 
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Gilead Sciences, Inc 
Appendix 1. 
Appendix 2. ... 
A 
endix 5. 
Appen ix 8. 
Appendix 9. 
Appendix 10. 
Table 5-1. 
Table 7-1. 
Table 8-1. 
Figw-e 3-1. 
CONFIDENTIAL 
Final 
Amendment5 
Investigator Signature Page .................................................................................................... 91 
Study Procedw·es Table .......................................................................................................... 92 
Mana ement of Clinical and Laborato1 Adverse Events ...................................................... 95 
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements ................................................................................................. IO I 
Clinical Laborat01y Assessment Table ................................................................................. 104 
LIST OF IN-TEXT TABLES 
Prohibited Concomitant Medication ....................................................................................... 52 
Grading of Adverse Event Severity ........................................................................................ 66 
Combined Fistula Response Rates (90% CI) .......................................................................... 78 
LIST OF IN-TEXT FIGURES 
Study Design Schematic ......................................................................................................... 33 
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Gilead Sciences, Inc 
Study Title: 
IND Number: 
EudraCT Number: 
Clinical Trials.gov 
Identifier: 
Study Centers 
Planned: 
Objectives: 
CONFIDENTIAL 
PROTOCOL SYNOPSIS 
Gilead Sciences, Inc. 
333 Lakeside Drive 
Foster City, CA 94404, USA 
Final 
Amendment5 
A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study 
Evaluating the Efficacy and Safety ofFilgotinib in the Treatment of 
Perianal Fistulizing Crohn's Disease 
129646 
2016-003153-15 
NCT03077412 
Approximately 60 centers across North America and Em-ope 
The primaiy objective of this study is: 
• 
To evaluate the efficacy of filgotinib as compared to placebo in 
establishing combined fistula response at Week 24 
The secondaiy objectives of this study ai·e: 
• 
To evaluate the efficacy of filgotinib as compai·ed to placebo in 
establishing combined fistula remission at Week 24 
• 
To assess the time to clinical fistula response 
• 
To assess the time to clinical fistula remission 
• 
To evaluate the efficacy of filgotinib as compared to placebo in 
establishing proctitis remission at Week 24, in subjects that had 
moderately to severely active proctitis at baseline 
• 
To evaluate the safety and tolerability of filgotinib 
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Filgotinib 
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Gilead Sciences, Inc 
Study Design: 
CONFIDENTIAL 
I 
I 
I 
I 
I 
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Amendment5 
This is a Phase 2, randomized, double-blind, placebo-controlled study 
to evaluate the efficacy and safety of filgotinib in treating subjects 
with perianal fistulizing Crohn's disease (CD). Approximately 
75 subjects aged 18 to 75 years with perianal fistulizing CD will be 
randomized to 1 of 3 ti·eatment groups in a 2:2: 1 ratio. 
g 
Week 10 
FIL 200 mg 
I 
(n•30) 
. : . 
Non-responclln"« 
m••ttngdl~ 
wors.,.;ng entltl,-
FIL = filgotinib; PBO = placebo; mg = milligram. 
Week 24 (1 'erdpoml) 
I 
* 
Non-responders (luminal disease) are defined as subjects who either had a baseline 
CDAI score:::: 220 and never achieve a:::: 70-point CDAI reduction from baseline at any 
point up to and including Week IO OR had a baseline CDAI score < 220 and have an 
increase in CDAI of:::: 100 points from baseline, with CDAI :::: 220 at Week IO. Non-
responders (perianal fistulizing disease) are defined as subjects who meet the following 
criteria for PDAI symptom subscores : "Discharge" subscore of>I and:::: I-point 
increase from baseline at Week 6 and Week IO OR "Pain/restriction of activities" 
subscore of> I and:::: I-point increase from baseline at Week 6 and Week IO 
""" Disease worsening is defined as an increase in CDAI of:::: 100 points from the Week IO 
value with CDAI score:::: 220 points at 2 consecutive visits 
0
• Subjects who are non-responders, meeting disease worsening criteria, or complete the 
study at Week 24, will have the option to enter a separate LTE study, if eligible. 
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Treatment group 1 (n=30): filgotinib 200 mg and placebo-to-match 
(PTM) filgotinib 100 mg, once daily
Treatment group 2 (n=30): filgotinib 100 mg and PTM filgotinib 
200 mg, once daily
Treatment group 3 (n=15): PTM filgotinib 200 mg and PTM 
filgotinib 100 mg, once daily
Note: United States (US) males who have not failed at least 2 prior 
biologic therapies (any tumor necrosis factor-alpha [TNFα
antagonist and vedolizumab) will be randomized in a 2:1 ratio to 
either filgotinib 100 mg or matching placebo.
For the purposes of this protocol, US males who have failed at least 
one prior TNF antagonist and present with actively draining perianal 
fistulae despite concomitantly taking vedolizumab at Day 1 will be 
considered as dual refractory patients. This assessment is based on 
recently published data from a subgroup analysis of the GEMINI-2 
study, showing a beneficial effect of vedolizumab treatment for 
patients that were randomized with actively draining perianal fistulae 
at baseline {Feagan 2018}.
Treatment assignments will be stratified by:

Anatomy of draining perianal fistulae at screening determined by
MRI (simple versus complex)

Receiving vedolizumab therapy concomitantly at Day 1
(Yes or No)

Presence of moderately to severely active proctitis (Yes or No)
This study includes:

Screening (Day -30 to -1)

Randomization (Day 1)

Blinded treatment (Day 1 to Week 24)
Efficacy assessment: At Week 24, physical examination (PE),
flexible sigmoidoscopy to assess presence of proctitis, and
MRI of the pelvis to assess fistula response
Subjects who complete all procedures per protocol, including
the MRI at Week 24, may be offered the option to continue
into a separate Long Term Extension (LTE) study
(GS-US-419-3896), if deemed appropriate by the investigator
Subjects who are non-responders at Week 10 (see Section 3.6
OR Section 3.7) or who meet disease worsening criteria
(see Section 8) after Week 10 will have the option to enter the
LTE study, if eligible.


Filgotinib 
GS-US-419-4016 
Gilead Sciences, Inc 
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CONFIDENTIAL 
• 
Post Treatment (PTx) safety assessments 
Final 
Amendment5 
All subjects completing this study will be offered the option to 
continue study drng in a blinded fashion in the LTE study, 
if eligible 
Subjects who are eligible and opt to paiiicipate in the LTE 
study can continue into the L TE study without PTx safety 
assessments 
Subjects who opt out of the LTE study will return to clinic 
30 days after the last dose of study drng for PTx safety 
assessments 
Subjects who are non-responders or meet disease-worsening 
criteria at or after Week 10 will complete MRI and flexible 
sigmoidoscopy prior to study discontinuation or entiy into the 
LTE study 
Non-responders for luminal disease activity ai·e subjects who either 
had a baseline CDAI score 
220 and never achieve a ~ 70-point 
CDAI reduction from baseline at any point up to and including Week 
10 OR had a baseline CDAI score < 220 and have an increase in 
CDAI of~ 100 points from baseline, with CDAI 
220 at Week 10. 
Non-responders (perianal fistulizing disease) ai·e defined as subjects 
who meet the following criteria for PDAI symptom subscores: 
"Discharge" subscore of> 1 and ~ I point increase from baseline at 
Week 6 and Week 10 OR "Pain/resti·iction of activities" subscore 
of > 1 and ~ I-point increase from baseline at Week 6 and Week 10. 
Disease worsening is defined as an increase in CDAI of~ 100 points 
from the Week 10 value with CDAI 220 at 2 consecutive visits. 
Steroid tapering must begin at Week 10 for subjects who are 
considered responders. 
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Gilead Sciences, Inc 
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Filgotinib 
GS-US-419-4016 
Gilead Sciences, Inc 
Test Product, Dose, 
and Mode of 
Administration: 
Reference Therapy, 
Dose, and Mode of 
Administration: 
Criteria for 
Evaluation: 
Safety: 
CONFIDENTIAL 
Filgotinib 200 mg oral tablet, once daily 
Filgotinib 100 mg oral tablet, once daily 
PTM filgotinib 200 mg oral tablet, once daily 
PTM filgotinib 100 mg oral tablet, once daily 
Final 
Amendment5 
Assessment of AEs and concomitant medications will continue 
throughout the duration of the study. Safety evaluations include 
documentation of AEs, PE ( complete, symptom-driven, and perianal), 
vital signs, and clinical laborato1y evaluations (hematology, 
chemistiy, urinalysis). An ECG will be perfo1med at screening and at 
Week 10 or ET if the subject te1minates prior to Week 10. 
A data monitoring committee (DMC) will meet twice to evaluate all 
available safety data of the study. The initial meeting will occur after 
approximately 20% of the planned total number of subjects reaches 
Week 10 in the study. Following this, the next meeting will occur 
after approximately 50% of the subjects reach Week 10. Additionally, 
the DMC members may request an unscheduled review of the study 
data based on a concern for subject safety. 
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Gilead Sciences, Inc 
Efficacy: 
-
Final 
Amendment5 
Efficacy will be evaluated by combined fistula response (reduction 
of~l from baseline in the number of draining external perianal fistula 
openings that were present at baseline and absence of fluid 
collection > 1cm on MRI pelvis) at Week 24. 
After a minimum of 35 subjects (estimated to be 7 from placebo 
group and 14 from each filgotinib treatment group based on 
randomization ratio) are emolled and complete Week 10 visit or 
discontinue from the study, an interim futility analysis will be 
conducted to evaluate efficacy improvement in fistulizing disease. 
The summaiy statistics to evaluate erianal fistula closure of external 
openings, and 
improvement w1 
e generate an prov1 e to t e DMC. 
will make a recommendation to either continue the study without 
modification or recommend that the study be halted due to lack of 
efficacy based on the totality of data available at the time of the 
interim analysis. 
Statistical Methods: 
The primaiy analysis set for efficacy analyses will be the Full 
Analysis Set (FAS), which includes all randomized subjects who 
received at least one dose of study dmg. 
CONFIDENTIAL 
The primaiy efficacy endpoint is the propo1iion of subjects 
establishing combined fistula response at Week 24. 
Secondaiy efficacy endpoints include: 
• 
Propo1iion of subjects establishing combined fistula remission at 
Week24 
• 
Time to clinical fistula response 
• 
Time to clinical fistula remission 
• 
Propo1iion of subjects achieving proctitis remission at Week 24, 
in subjects that had moderately to severely active proctitis at 
baseline 
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Gilead Sciences, Inc
Amendment 5
CONFIDENTIAL
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For the primary efficacy endpoint, the number and proportion of 
subjects establishing combined fistula response at Week 24 for each 
treatment group will be summary zed with a corresponding 90% 
exact confidence interval (CI) based on the binomial distribution 
(Clopper-Pearson method). The difference in proportions between 
each filgotinib dose group and the placebo group will be presented, 
along with the associated 90% CI.
Subjects who do not have sufficient measurements to determine 
efficacy endpoints will be considered failures (ie, non-responder 
imputation [NRI]). No formal hypothesis testing will be performed.
All time-to-event endpoints will be analyzed using the Kaplan-Meier 
method. The stratified Cox proportional hazards model will be used 
to estimate the hazard ratio with the corresponding 90% CI.
Safety will be evaluated by assessment of clinical laboratory tests, 
PEs, vital signs measurements at various time points during the study, 
and by the documentation of AEs. All safety data collected on or after 
the first dose of study drug administration (Day 1) up to 30 days after 
permanent discontinuation of study drug will be summarized by 
treatment group according to the study drug received.
A total of approximately 75 subjects are planned to be randomized 
(2:2:1 ratio); 30 subjects to each of the filgotinib dose groups and 
15 subjects to the placebo group. This sample size is considered 
adequate to assess the safety, tolerability, and efficacy of filgotinib in 
a descriptive manner.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


Filgotinib
GS-US-419-4016
Final
Gilead Sciences, Inc
Amendment 5
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GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
C
degrees Celsius
F
degrees Fahrenheit
5-ASA
5-aminosalicylate
6-MP
6-mercaptopurine
ADL 
Activities of Daily Living
AE
adverse event
ALT
alanine aminotransferase
ANC
absolute neutrophil count
ANOVA
analysis of variance
AST
aspartate aminotransferase
AUC
area under the plasma/serum/peripheral blood mononuclear cell concentration, drug 
versus time curve
BAP
Biomarker Analysis Plan
BLQ
below the limit of quantitation
BMI
body mass index
CC&G
Cockcroft-Gault
C. diff
Clostridium difficile
CD
Crohn’s disease
CDAI
Crohn’s Disease Activity Index
CES
Carboxylesterases
CI
confidence interval
Cmax
the maximum observed serum/plasma/peripheral blood mononuclear (PBMC) 
concentration of drug
CMV
cytomegalovirus
CNS
central nervous system
CPK 
creatine phosphokinase
CRF
case report form(s)
CRP
c-reactive protein
CRPhs
c-reactive protein, high sensitivity
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
CYP
cytochrome P450
DSS
dextran sodium sulfate
EC
ethics committee
E.coli
Escherichia coli
ECG
electrocardiogram
eCRF
electronic case report form(s)
EDC
Electronic Data Capture 
EMA
European Medicines Agency


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GS-US-419-4016
Final
Gilead Sciences, Inc
Amendment 5
CONFIDENTIAL
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ET
early termination
EU
European Union
EudraCT
European clinical trials database
FAS
Full Analysis Set
FDA
(United States) Food and Drug Administration
FDA
Fistula Drainage Assessment
GCP
Good Clinical Practice (Guidelines)
GHAS
Global Histologic Disease Activity Score
GSI
Gilead Sciences, Inc. 
h
Hours
HBV
Hepatitis B Virus
HCV
Hepatitis C Virus
HDL
high-density lipoprotein
HDPE
high density polyethylene
HIV
Human Immunodeficiency Virus
HLGT
High-Level Group Term
HLT
High-Level Term
IB
investigator brochure
IBD
inflammatory bowel disease
IC50
concentration of an inhibitor that is required for 50-percent inhibition
ICF
informed consent form
ICH
International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use
IEC
independent ethics committee
IM
Intramuscular
IMP
investigational medicinal product
IRB
institutional review board
IUD
intrauterine device
IV
Intravenous
IWRS
interactive web response system
JAK
Janus Kinase
JAK-STAT
Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT)
LDL
low-density lipoprotein
LLT
Lower-Level Term
LLOQ
lower limit of quantification
LOCF
Last Observation Carried Forward
LTE 
long-term extension
CCI
CCI
CCI-
-
1111 


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MedDRA 
mg 
mL 
MPO 
MTX • 
NOEL 
NRI 
NSAID 
nM 
OAT 
O&P 
OLE 
P-gp 
PBMC 
PBO 
PD 
PDAI 
PE 
PEG 
PI 
1111 
PT 
PTx 
PTM 
PVE 
RA 
RNA 
RT-PCR 
SADR 
SAE 
SAP 
SC 
SD 
soc 
SOP 
spp 
CONFIDENTIAL 
Medical Dictionary for Regulatory Activities 
milligram 
milliliter 
M yeloperoxidase 
Methotrexate 
No-observed-effect-levels 
Non-responder imputation 
Non-steroidal anti-inflammato1y dtugs 
nanomolar 
organic anion transporters 
ova and parasites test 
Open Label Extension 
p-glycoprotein 
peripheral blood mononuclear cell 
placebo 
phrumacodynamics 
Perianal Disease Activity Index 
physical exatnination 
polyethylene glycol 
principal investigator 
prefen-ed te1m 
Post-Treatment 
placebo to match 
Pha1macovigilance & Epidemiology 
rheumatoid ruihritis 
ribonucleic acid 
reverse transcription polymerase chain reaction 
serious adverse dtug reaction 
serious adverse event 
Statistical Analysis Plan 
subcutaneous 
standard deviation 
system organ class 
standard operating procedure 
species 
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SUSAR
suspected unexpected serious adverse reaction
STAT
signal transducer and activator of transcription
TB
tuberculosis
TEAE
treatment-emergent adverse event
TNFα
tumor necrosis factor-alpha
TYK
Tyrosine Kinase
UC
ulcerative colitis
UGT
uridine 5’-diphospho-glucuronosyltransferase
ULN
upper limit of the normal range
US
United States
WBC
white blood cell
CCI
CCI-
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DEFINITION OF TERMS
Simple Fistula
(for stratification purposes)
Single, unbranched submucosal or intersphincteric fistula tract, no extensions, 
no inflammatory mass/collections, single external opening
Complex Fistula(e)
(for stratification purposes)
Multiple simple fistulae OR Single branched (multiple external openings 
arising from one fistula tract), trans-, extra-, or suprasphincteric fistulae tracts, 
possible extensions, and/or focal to small collections
Perianal Fistula Closure
No fistula drainage despite gentle external compression
Clinical Fistula Remission
Perianal fistula closure of all external openings that were draining at baseline
Clinical Fistula Response
Reduction of ≥1 from baseline in the number of draining external perianal
fistula openings that were present at baseline
Combined Fistula Remission
Perianal fistula closure of all external openings that were draining at baseline, 
and absence of fluid collections > 1cm on MRI pelvis
Combined Fistula Response
Reduction of ≥1 from baseline in the number of draining external perianal
fistulae openings that were present at baseline, and absence of fluid collections 
> 1cm on MRI pelvis
Proctitis SES-CD Score
Sum of ulcer size and ulcerated surface SES-CD endoscopy subscores for the
rectum and anal canal, assessed by centrally read flexible sigmoidoscopy
Anal Canal Segmental SES-CD 
score
Sum of ulcer size and ulcerated surface SES-CD endoscopy subscores for the
anal canal segment only, assessed by centrally read flexible sigmoidoscopy
Moderately to Severely Active 
Proctitis
Proctitis SES-CD Score > 2 
Proctitis Remission
A Proctitis SES-CD Score of 0
Disease Worsening
An increase in CDAI of ≥100 points from the Week 10 value with CDAI 
≥220 at 2 consecutive visits
Non-responder (Luminal 
Disease)
Subject who had a baseline CDAI score ≥220 and never achieves a ≥70-point 
CDAI reduction from baseline at any point up to and including Week 10 OR 
had a baseline CDAI score < 220 and have an increase in CDAI of 
≥100 points from baseline, with CDAI ≥ 220 at Week 10
Non-Responder (Perianal 
Fistulizing Disease)
Subjects who meet the following criteria for PDAI symptom subscores:

“Discharge” subscore of >1 and ≥ 1-point increase from baseline at 
Week 6 and Week 10 OR

“Pain/restriction of activities” subscore of >1 and ≥ 1-point increase from 
baseline at Week 6 and Week 10


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1.
INTRODUCTION
1.1.
Background
Crohn’s disease (CD) is a relapsing and remitting form of inflammatory bowel disease (IBD) that 
causes gastrointestinal signs and symptoms of diarrhea, abdominal pain, weight loss, and the 
passage of blood or mucous per rectum. The inflammation of CD can involve the mucosal 
surface of the gastrointestinal tract and penetrate through the full thickness of the gastrointestinal 
wall, including the serosal surface. Crohn’s disease is characterized by phenotype and location of 
involved bowel. The phenotypes include inflammatory, stricturing, and penetrating subtypes. 
Stricture formation can result in intestinal obstruction requiring surgical management. Over time, 
patients with repeated surgeries are at risk for developing short bowel syndrome and/or intestinal 
failure. Penetrating disease is characterized by fistula formation, which can be bowel to bowel, 
bowel to skin, or bowel to adjacent organ. Depending on location, penetrating disease can also 
require surgical management. Penetrating disease can also manifest with intra-abdominal 
abscess, a condition which can be life threatening if not treated early with systemic antibiotics
(and/or drainage). In addition, CD may affect other organ systems leading to rashes, joint pain 
and stiffness, fever, and weight loss {Baumgart 2012}.
The incidence and prevalence of CD has been increasing, with bimodal peaks affecting young 
adults (15 to 35 years of age) and older adults aged 50 to 70 with the age of onset often occurring 
in children < 12 years of age. Although geographic variation does occur, the overall incidence of 
CD in the northern hemisphere ranges from 7 to 20 per 100,000 person years, with a prevalence 
of up to 300 per 100,000 people. In the United States (US) and Europe, up to 1.5 million 
individuals may be affected and the incidence is on the rise in parts of Asia and the Middle East 
{Molodecky 2012}.
The cause of CD is poorly understood, however a complex interplay of genetic predisposition, 
aberrant immune activation, and early infection during childhood may be involved. The 
importance of environmental triggers is suggested by increasing rates due to industrialization and 
improved domestic hygiene and sanitation. This “hygiene hypothesis” has also been implicated 
in various other autoimmune disorders {Ventham 2013}.
To assess disease severity, a number of clinical scoring systems are utilized based upon signs, 
symptoms, laboratory parameters, imaging modalities, and endoscopy. The CD Activity Index 
(CDAI) is one such scoring tool with scores ranging from 0 to over 600 based upon a composite 
of symptoms (eg, abdominal pain), signs (the presence of abdominal mass and weight), 
laboratory values (eg, hematocrit), and physician assessment amongst others. In this scoring 
system, patients with a score > 220 are defined as moderate to severe; these comprise the patients 
with the greatest unmet medical need. The CDAI can also be used to determine how well a 
therapy is working, with therapeutic remission defined as a CDAI of < 150 points 
{Dignass 2010}.


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The CDAI has 2 patient reported outcomes of interest in CD drug development: liquid or very 
soft stool frequency and abdominal pain. In the Patient Reported Outcomes (PRO2) for the 
current study, these symptoms are recorded daily for 7 days and averaged to determine subscore 
cut off values of ≤ 1 for abdominal pain and  ≤ 3 for stool frequency that define clinical 
remission. As yet, stool frequency and abdominal pain subscores of the CDAI have not been 
used on their own in prospective clinical trials.
Fistulae are frequent manifestations of the transmural nature of CD and it is estimated that up to 
50% of patients with CD are affected by fistulae according to population-based studies 
{Schwartz 2002, Solomon 1996}. One of these studies showed the high cumulative incidence of 
fistulae (33% 10 years after the diagnosis of CD, and 50% after 20 years), demonstrating the 
extent of this complication in patients with CD {Schwartz 2002}.
Fistulae are classified according to their location and their connection with continuous organs. 
They can be external (eg, perianal and enterocutaneous), or internal (eg, enteroenteric, 
enterovesical, enterouterine, enterovaginal, etc). Perianal is the most common form, which 
comprises approximately 50% of these fistulae {Schwartz 2002}. Perianal fistulae can be further 
classified as simple (a single submucosal or intersphincteric fistula tract with a single external 
opening, no branching or extensions and no evidence of rectovaginal involvement or anorectal 
stricture) or complex (trans-, extra-, or suprasphincteric fistula tract, possible extensions or 
branching that can potentially involve multiple external openings, a rectovaginal fistula, or is 
associated with an anorectal stricture, or active inflammatory rectal disease, as assessed by 
endoscopy). Complex fistulae are more difficult to treat, have decreased healing rates and are 
associated with less successful outcomes. Overall, perianal fistulae represent a major clinical 
problem in the management of inflammatory bowel disease as they often cause severe 
impairment in the affected patient’s quality of life, are refractory to conventional treatment, and 
require surgery.
A significant change in CD management and therapeutic strategy has occurred over the 
last decade. Recent therapeutic goals extend beyond symptomatic control and include long term 
mucosal and endoscopic remission {Cheifetz 2013}. The ultimate aim is to change the natural 
course of the disease by slowing down or halting its progression, thus avoiding surgery or 
hospitalization. This is achieved by utilizing earlier, aggressive, and goal-directed therapy. 
Risk assessment and prediction by means of complex clinical, biochemical, and endoscopic 
markers has become the key to patient management, therapy optimization, and prediction of the 
outcome and side effects of medical therapy. 
Currently available biologic therapies focus on neutralizing cytokine activity or altering T-cell
differentiation and homing. Three monoclonal antibodies which inhibit tumor necrosis 
factor-alpha (TNFα), are currently marketed for the treatment of CD: infliximab (Remicade®), 
adalimumab (Humira® [approved in United States (US) and European Union {EU}]) and 
certolizumab pegol (Cimzia® [approved in US]). Vedolizumab (Entivyo®), a monoclonal 
antibody against α4β7 integrin, is also approved for moderately to severely active CD. Recently, 
ustekinumab (Stelara®), a monoclonal antibody directed against the p40 subunit of IL-23 and 
therefore an antagonist for both IL-12 and IL-23 signaling, has been approved for the treatment 


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of CD. Leukocytapheresis therapy may be used in Japan {Fukunaga 2012}. Other investigational 
treatment approaches still in development include the administration of cytokines to stimulate 
innate immunity, the use of prebiotics to alter the gut flora, and blocking the IL-6 signaling 
pathway {Ito 2004, Korzenik 2016}. New treatments being tested in clinical trials include janus 
kinase (JAK) inhibitors (eg, upadacitinib) and new biologic agents such as IL-23 p19 antagonists 
(eg, risankizumab) and a monoclonal antibody directed against β7 integrin (eg, etrolizumab). 
While the introduction of biologic therapies has significantly improved response rates in patients
with moderately to severely active CD, long-term or durable remission rates are still low at 
approximately 20%. Many patients receiving biologic therapies develop neutralizing antibodies 
with resulting loss of efficacy. These agents may be associated with specific safety issues 
including but not limited to anaphylaxis, increased risk of infection including progressive 
multifocal leukoencephalopathy, and liver injury. Among these therapies, only infliximab was 
shown to be effective for the treatment of fistulizing CD in a double-blind, placebo-controlled, 
randomized and multicenter trial {Present 1999}. However, less than 40% of patients who 
received infliximab maintenance therapy had a durable fistula closure at 54 weeks {Sands 2004}.
Safe and effective treatment options which may be conveniently administered in a chronic 
setting would provide a significant treatment advance for patients with perianal fistulizing CD.
This study is designed to evaluate the safety and efficacy of filgotinib for 24 weeks in perianal 
fistulizing CD.
1.2.
Filgotinib (GS-6034)
1.2.1.
General Information
Janus kinases (JAKs) are intracellular cytoplasmic tyrosine kinases (TYKs) that transduce 
cytokine signaling from membrane receptors through signal transducer and activator of 
transcription (STAT) to the nucleus of cells. JAK inhibitors block the signaling of various 
cytokines, growth factors, and hormones, including the pro-inflammatory cytokine interleukin 
(IL)-6. Four different types of JAKs are known, JAK1, JAK2, JAK3, and TYK2 which interact 
with different sets of membrane receptors. Inhibition of JAKs is a promising therapeutic option 
for a range of inflammatory conditions including rheumatoid arthritis (RA) and CD.
Filgotinib (GS-6034, formerly known as GLPG0634) is a potent and selective inhibitor of JAK1.
The compound has shown good preliminary efficacy in RA and CD patients in Phase 2 studies.
In humans, filgotinib is metabolized to form 1 major active metabolite, GS-829845. Though the 
potency of this metabolite is lower than the parent molecule, the overall exposure and peak 
plasma concentration in humans is higher than seen in all tested animal species. As a 
consequence, dedicated pharmacology and toxicology studies have been performed with 
GS-829845. Results from pharmacodynamics (PD) testing in healthy volunteers suggest that the 
clinical activity of filgotinib could result from the combination of the parent molecule and the 
metabolite.
For further information on filgotinib, refer to the current Investigator’s Brochure (IB).


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1.2.2.
Preclinical Pharmacology and Toxicology
Filgotinib and its metabolite, GS-829845 have been extensively characterized in nonclinical 
studies. This program includes cellular assays demonstrating potency and selectivity of the 
compound against JAK1; efficacy studies in rats and mice; repeat dose toxicity studies (up to 
26 weeks in the rat and 39 weeks in the dog), in vitro and in vivo safety pharmacology and 
genetic toxicology studies, and reproductive toxicology studies in rats and rabbits. Additional 
toxicology studies conducted include phototoxicity studies and dose-range finding studies in 
support of a definitive rat juvenile toxicity study. A definitive juvenile toxicology study in rats is 
ongoing.
1.2.2.1.
Nonclinical Pharmacology
In cellular assays, filgotinib inhibits JAK1 signaling with the concentration of an inhibitor that is 
required for 50% inhibition (IC50) values of ≥ 179 nM, and demonstrates 30-fold selectivity over 
JAK2 in a human whole blood assay. Filgotinib has been profiled against 451 kinases and it is 
highly selective for JAK1; only 2.5% of kinases were inhibited ≥ 50% at 50-fold higher 
concentration than IC50 for JAK1. Broad receptor profiling (~70 receptors, ion channels, 
transporters and enzymes) did not reveal any off-target liabilities of the compound. Filgotinib 
demonstrated high potency in the rat collagen-induced arthritis (CIA) model as well as in the 
mouse dextran sulfate sodium (DSS)-induced colitis model, the latter of which is detailed below. 
The major human metabolite of filgotinib, GS-829845, exhibits a similar JAK1 selectivity profile 
but is approximately 10-fold less potent as compared to parent filgotinib in vitro.
The efficacy of filgotinib was evaluated in a prophylactic setting of the chronic mouse DSS
dextran model in 2 separate studies. Both studies evaluated oral dose levels of 10 and 30 mg/kg 
once daily. In addition to assessments of clinical score (disease activity index [DAI] and colon 
lesion score), serum markers of inflammation, immunohistochemical analysis, and expression of 
various chemokines and cytokines known to be altered in CD and UC patients were also 
evaluated in the distal colon of these mice.
In both studies, the DAI score, which takes into account body weight loss, rectal bleeding, and 
stool consistency, was reduced by filgotinib in a dose-dependent manner, demonstrating that 
filgotinib protected mice against colitis induced by DSS. Histology of the colon revealed a 
filgotinib-mediated dose-related reduction in colon lesion score, correlating with reductions in 
DAI score.
Additional endpoints evaluated across the DSS colitis model studies confirmed the suppression 
of various inflammatory markers including serum levels of C-reactive protein (CRP) and 
myeloperoxidase (MPO) and expression of IL 6 and TNFα (by reverse transcription polymerase 
chain reaction [RT-PCR]) by filgotinib. Immunohistochemical analysis of the colon confirmed 
inhibition of the JAK-STAT pathway by filgotinib as evidenced by a reduction of DSS-induced 
STAT3 phosphorylation.


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1.2.2.2.
Safety Pharmacology
Filgotinib and GS-829845 had no relevant effects on cardiovascular parameters 
(human-ether-a-go-go [hERG] and dog telemetry studies), apart from a slight non adverse 
increase in heart rate and arterial pressure with GS-829845 at exposures 8-fold that of the peak 
serum concentration (Cmax) in subjects with CD treated with 200 mg once daily filgotinib. There 
were no relevant effects on electrocardiogram (ECG) and QT. Filgotinib and GS-829845 had no 
effects on the respiratory system and central nervous system (CNS).
1.2.2.3.
Key Nonclinical Distribution, Metabolism, and Excretion Data
Filgotinib demonstrates good oral bioavailability in mice, rats, dogs, and mini-pigs but less in 
monkeys. Plasma protein binding is low (< 70%) in all species, including humans.
The pharmacokinetics (PK) of filgotinib is generally dose proportional without gender 
differences. No accumulation occurs with repeated dosing. The mean terminal half-life after oral 
administration is 4 hours and 5 hours in rats and dogs, respectively.
In the rat, filgotinib showed a rapid and even distribution throughout the body. High 
concentrations were observed only in the gastrointestinal (GI) tract and urinary bladder. 
Filgotinib does not penetrate into CNS tissues. The distribution of filgotinib indicates some 
affinity for melanin-containing tissues.
Excretion is nearly complete within 24 hours (rat) and 48 hours (dog) post-dosing. In the rat, 
fecal and urinary excretion accounted for 40% and 53% of the administered dose, respectively, 
with a bile secretion of about 15%. In the dog, fecal excretion was the primary route of excretion, 
accounting for 59% of the administered dose, with urinary excretion accounting for 25%.
In vitro metabolism studies in all species revealed one major metabolite (GS-829845). The 
formation of GS-829845 is mediated by carboxylesterases (CES) and is not dependent on 
cytochrome P450 (CYP).
In vitro experiments have shown that drug-drug interactions with filgotinib and GS-829845 
are unlikely. There is no inhibition or induction of CYPs or uridine 5’-diphospho-
glucuronosyltransferase (UGTs), and no relevant inhibition of key drug transporters, including 
organic anion transporters (OATs), by filgotinib or GS-829845. Organic cation transporter 2 
(OCT2) was inhibited by both filgotinib (IC50: 8.7 µM) and GS-829845 (IC50: 67 µM). The 
clinical relevance of the IC50 values for inhibition of OCT2 will be further evaluated. MATE1 
was also weakly inhibited by filgotinib (IC50: 94 µM) and GS-829845 (IC50: > 100 µM). 
Filgotinib was found to be a substrate of P-glycoprotein (P-gp).
1.2.2.4.
Nonclinical Toxicology
In repeat oral dose toxicity studies in both rats and dogs, the primary target tissues identified for 
filgotinib were the lymphoid tissues which are expected based on the pharmacology of JAK 
inhibition. Additional filgotinib-related findings were observed in the male reproductive organs 


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of both species, and in the incisor teeth ofrats only. Effects on the lymphoid system were fully 
reversible. Testicular toxicity demonstrated paiiial reversibility; however, spe1m counts 
remained low. When using the mean exposure (AUC) at the NOAELs for the most sensitive 
species (the dog), the exposure margins compared to a 200 mg once daily dose of filgotinib in 
CD subjects are 2.5, 1.9, and 3.6-fold for the 26-week and 39-week chronic toxicity studies and 
the 39-week tai·geted exposure toxicity study, respectively. 
GS-829845-related findings in the repeat-dose toxicity studies were generally similar to those of 
the pai·ent filgotinib, however no testicular toxicity was noted following administration of 
GS-829845. 
Filgotinib and GS-829845 were non-genotoxic when evaluated in the bacterial mutagenicity 
assay, the in vitro mouse lymphoma mutagenicity assay, and the rat bone man ow Inicronucleus 
assay. 
In emb1yofetal development studies, filgotinib and GS-829845 caused emb1yolethality and 
teratogenicity in pregnant rats and rabbits. Teratogenicity was observed at exposures slightly 
higher or similai· to the human exposure at 200 mg once daily of filgotinib in subjects with CD. 
Administration of filgotinib did not affect female fe1iility but impaired fe1iility was observed in 
male rats at exposures approximately 12-fold the human exposure at 200 mg of filgotinib in 
subjects with CD. GS-829845 did not have any effects on fe1iility pai·ameters in either male or 
female rats. 
In an in vitro phototoxicity study in 3T3 cells, the metabolite GS-829845 was positive for 
phototoxic potential and results with filgotinib were equivocal. A follow-up in vivo rat 
phototoxicity assay revealed a lack of phototoxic potential for both compounds. 
1.2.3. 
Clinical Trials of Filgotinib 
An overview of exposure, safety, and efficacy in clinical studies conducted with filgotinib is 
available in the IB. 
1.2.3.1. 
Phase 2 Study in Crohn's Disease (GLPG0634-CL-211, FITZROY) 
A Phase 2, randoinized, double-blind, placebo-controlled, multicenter study with filgotinib was 
perfo1med in subjects with active CD with evidence of mucosal ulceration {Vermeire 2017}. In 
Pait 1, a total of 17 4 subjects were randoinized 3: 1 to receive either fil otinib 200 m once 
dail or lacebo for 10 weeks. 
The efficacy of filgotinib was assessed by evaluating clinical reinission ( defined as CDAI score 
< 150), clinical response ( defined as a decrease in CDAI of at least 100 points from baseline), 
and endoscopic response ( defined as a decrease of at least 50% from baseline in the 
SES-CD score). 
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The primary endpoint of the study was met: at Week 10, 60 of 128 subjects (46.9%) who
received filgotinib achieved clinical remission versus 10 of 44 subjects (22.7%) who received
placebo, a difference of 24.1% (p-value = 0.0077). In addition, filgotinib treatment was 
associated with increases in the proportion of subjects with clinical response and endoscopic 
response compared with placebo. 
Overall, the safety profile of filgotinib in CD subjects was consistent with prior studies. 
1.3.
Rationale for This Study
Accurate assessments of perianal disease activity may help to improve treatment and prognosis, 
and therefore the patient’s quality of life. The Fistula Drainage Assessment (FDA) is one of the 
most widely used methods for the assessment, which takes the presence of purulent drainage 
from the cutaneous orifice after gentle compression as an index of activity. However, it does not 
take into account patient-reported outcomes. The Perianal Disease Activity Index (PDAI) is 
more comprehensive, as it evaluates perianal disease morbidity, particularly the presence of 
fistula discharge, pain and the restriction of daily activities, the restriction of sexual activity, the 
type of perianal disease, and the degree of induration. It is based on a simple 5-point scale, which 
can be easily used in an office setting, and is capable of quantifying the severity of perianal 
disease. A prospective study on 62 patients with perianal CD showed that the optimal PDAI 
cutoff value discriminating active and inactive perianal disease was > 4, which had an accuracy 
of 87% detecting active disease when the clinical examination was considered the reference 
standard for comparison {Losco 2009}. In the same study, the PDAI cutoff was shown to be 
well-correlated with the clinical outcome as it indicated that a PDAI of ≤4 identified inactive 
disease requiring no therapy. This study will evaluate changes in PDAI score to assess the 
treatment response of perianal fistulizing CD to filgotinib.
Evaluation of the presence and severity of proctitis is critical in the management of patients with 
perianal fistulizing CD as it determines further treatment strategy and prognosis. The absence of 
proctitis is an independent predictor for increased healing and reduced recurrence rates of 
perianal fistulae. However, rectal involvement is associated with a higher proctectomy rate 
compared with rectal sparing. In this study, centrally read flexible sigmoidoscopy will be 
conducted at baseline to assess the rectum and anal canal and the severity of proctitis determined 
by SES-CD will be used as one of the stratification factors. At Week 24, endoscopic appearance 
of the rectum and anal canal will be assessed again by centrally read flexible sigmoidoscopy.
Diagnostic modalities for fistulizing CD have improved over the last decade. An accurate 
assessment of each fistula’s anatomy before treatment is essential, and enables the physician to 
choose the most appropriate therapy. Inadequate characterization of the fistula and associated 
pathology can result in potentially poor clinical outcomes. MRI is now considered the gold 
standard imaging tool to evaluate the perianal complication of CD as it offers excellent soft 
tissue discrimination with a wide field of view and it carries no radiation hazard {Gecse 2004}.
Previous studies have shown that MRI is particularly sensitive for the detection of pelvic 
abscesses in CD patients, even in the absence of clinical signs {Lunniss 1994, Myhr 1994}. Use 
of MRI as preinclusion clinical evaluation will ensure accurate characterization of the fistulae
and detect any abscess which may require drainage.


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With the advent of anti-TNF therapy, the goal of treatment for fistulizing CD has evolved from 
symptomatic improvement ( eg, by drainage) of the fistula to complete cessation of drainage and, 
in some patients, fistula closure and fibrosis of the fistula tract { Geese 2004}. However, the 
optimal clinical index for assessing perianal CD is still under debate. Even though the endpoint 
adopted in previous trials in perianal fistulizing CD (ie, disappearance of drainage from at least 
50% of the fistulae) {Present 1999, Sands 2004} is clinically relevant, it has been shown that 
cessation of drainage from external orifices does not accurately reflect what is happening to the 
fistula track. A small prospective coho1i study including 18 subjects with perianal CD showed 
that persistent inflammato1y activity in the fistula track is observed even after long-te1m 
(46 weeks) infliximab therapy, whereas external orifices are obse1ved to heal and to stop 
draining rapidly after the therapy {Van Assche 2003}. A primaiy endpoint at 6 months into the 
treatment course was chosen to allow healing of the fistulae. 
Residual inflammation of the fistula tract may be responsible for the occmTence of de novo 
perianal abscesses and for fistula recunence in patients treated for fistulizing CD. The undetected 
pelvic abscess may become clinically appai·ent only after cessation of drainage from external 
orifices, and becomes a source of continuous inflammato1y reaction. Given these challenges in 
assessing the activity and complications of the perianal CD, it may be wairnnted to combine MRI 
assessment with clinical examination to evaluate the efficacy of study treatment. A 2 cm cutoff 
for fluid collection as entiy criteria was chosen as it represents the clinical threshold which 
waiTants drainage. A cutoff of::; 1 cm for fluid collection was chosen as paii of the combined 
prima1y endpoint to ensure a more sfringent definition of response to ti·eatment was used that is 
differentiated from the clinical threshold for drainage. 
In conclusion, this study will use MRI to evaluate healing of fistulae in addition to clinical 
assessment of drainage and fistula closure. MRI images will be cenfrally read in a blinded 
manner. These measures will provide a comprehensive and objective assessment of disease 
activity and ti·eatment response in fistulizing CD. 
1.4. 
Rationale for Dose 
In Phase 2 ti·ials in RA, pooled data with an exposure - response analysis demonsti·ated a 
dose-dependent increase in efficacy up to 200 mg total daily dose. In the Phase 2 study of CD 
(GLPG0634-CL-21 l), subjects ti·eated in the 200 mg aim showed favorable response and 
reinission rates (47% remission over 23% placebo and 59% response over 41% placebo). The 
reinission rate at Week 20 for subjects who failed placebo for the first 10 weeks and commenced 
100 mg from Weeks 10 to 20 was slightly lower (32%) though the response rate was comparable 
(59%), indicating some level of efficacy at the 100 mg dose. These results are consistent with the 
relationship obse1ved between filgotinib exposures and inhibition of pSTATl activation 
(ex-vivo) following single and multiple filgotinib doses, where maximal inhibition of pSTATl 
activation (~78%) was achieved at or above 200 mg total daily dose and inte1mediate inhibition 
(~47%) at 100 mg {Namour 2015}. pSTATl data, in conjunction with considerations around the 
margin for nonclinical testiculai· findin s, su 
ests assessin doses above 200 m is not 
indicated. 
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1.5.
Risk/Benefit Assessment for the Study
Crohn’s disease is a progressive and potentially life-threatening disease with few treatment
options, many of which result in primary or secondary nonresponse. Inflammatory bowel disease
may lead to increased risk of gastrointestinal malignancies, impairment in quality of life, and
ultimate need for life-altering surgery. Current treatment options are limited in ability to establish
mucosal healing and clinical remission and have significant safety and efficacy limitations; 
for example, biologics have significant immunogenic risks and steroids are associated with 
increased morbidity and mortality. Remission rates are generally low when compared to placebo 
rates across most therapies for IBD. There remains substantial unmet need in IBD, particularly in
fistulizing CD among all phenotypes of CD. Despite the high cumulative occurrence and 
recurrence rates and significant morbidity associated with it, there is only 1 approved therapy for 
fistulizing CD.
Nonclinical studies in rats and dogs identified lymphoid tissues and testes as target organs for
filgotinib in long-term repeat-dose toxicity studies. Although decreased lymphocyte numbers
observed in nonclinical studies have not been seen in clinical studies, hematological assessment
will be performed throughout the present study to ensure this potential risk is appropriately
monitored. In both rats and dogs, microscopic findings in the testes included germ cell depletion
and degeneration, with reduced sperm content and increased cell debris in the epididymis and
reduction in fertility in male rats. The dog was determined to be the most sensitive species. 
When using the mean exposure (AUC) at the NOAELs for dogs in the 26- and 39-week chronic 
toxicity studies, and the 39-week targeted exposure toxicity study, the exposure margins 
compared with the highest proposed clinical dose of 200 mg once daily are 2.5-, 1.9-, and 
3.6-fold respectively, in subjects with CD. A male safety study is planned to examine the 
potential effect of filgotinib on sperm/ejaculate parameters. Pending those results, the use of 
200 mg in males in the United States with CD or UC will be limited to subjects who have failed 
at least two biologic therapies (TNFα antagonists or vedolizumab). Reference is made to the IB 
for further information about nonclinical testicular findings.
Administration of filgotinib produces an increase in embryofetal malformations in pregnant rats 
and rabbits at exposures similar to, or slightly higher than, exposures associated with a 200 mg 
once daily dose in CD subjects; this risk will be mitigated with the use of highly effective 
contraception for subjects of child-bearing potential.
JAK inhibition is expected to increase the risk of infection based on mechanism of action. Across 
global studies with filgotinib, in general, active treatment arms have increased incidences of 
infection versus placebo. In the present protocol, treatment interruption and discontinuation 
considerations surrounding infections are incorporated and sites and investigators will be trained 
regarding such circumstances. All subjects will be screened for tuberculosis (TB) and subjects 
with active infections will be excluded. Malignancy has been reported in subjects on filgotinib; 
in the present trial, subjects will be required to have up to date colorectal cancer screening and 
surveillance and subjects with recent malignancies will be excluded as outlined in the eligibility
criteria. For further details about infections and malignancies, please reference the IB.


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The potential benefits of JAK inhibition include improvement in clinical symptoms and mucosal
and endoscopic healing. JAK inhibition may be efficacious in the treatment of IBD based on
results from FITZROY. A lack of response contingency after Week 10 will enable early access 
to active drug when clinically indicated. In FITZROY, an increase in mean hemoglobin 
concentration was observed, without difference between filgotinib and placebo. No clinically 
significant changes from baseline in mean neutrophil counts or liver function tests were observed 
at 10 weeks. Filgotinib treated subjects showed an increase in HDL and no significant change in 
LDL. Lipid and hemoglobin effects represent potential benefits in this population.
An independent data monitoring committee (DMC) appointed to monitor the study will provide 
an additional level of risk mitigation. The DMC may advise to continue the study unchanged, to 
modify the study, or to discontinue the study. The initial meeting will occur after approximately 
20% of the planned total number of subjects reach the Week 10 visit. Following this, the next 
meeting will occur after approximately 50% of subjects reach the Week 10 visit. Additional 
DMC meetings may be convened, if needed.
Taking all of these considerations into account with respect to the filgotinib program, the early
signals for efficacy demonstrated in the CD clinical trials, as well as the beneficial findings in
nonclinical models of disease and the overall safety, tolerability, and PK characteristics of
filgotinib that have been elucidated to date, there is a favorable benefit-risk profile for this agent
in continued development as a treatment for fistulizing CD. The overall risk/benefit balance of 
this study is considered favorable.
For additional information about the risks of filgotinib, reference is made to the filgotinib IB.
1.6.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practices (GCP), 
and all applicable regulatory requirements.


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OBJECTIVES 
The prima1y objective of this study is: 
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• 
To evaluate the efficacy of filgotinib as compared to placebo in establishing combined fistula 
response at Week 24 
The secondaiy objectives of this study are: 
• 
To evaluate the efficacy of filgotinib as compared to placebo in establishing combined fistula 
reinission at Week 24 
• 
To assess the time to clinical fistula response 
• 
To assess the time to clinical fistula remission 
• 
To evaluate the efficacy of filgotinib as compared to placebo in establishing proctitis 
reinission at Week 24, in subjects that had moderately to severely active proctitis at baseline 
• 
To evaluate the safety and tolerability of filgotinib 
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STUDY DESIGN 
3.1. 
Endpoints 
The prima1y efficacy endpoint is: 
• 
Propo1tion of subjects establishing combined fistula response at Week 24 
The secondaiy efficacy endpoints ai·e: 
• 
Proportion of subjects establishing combined fistula remission at Week 24 
• 
Time to clinical fistula response 
• 
Time to clinical fistula remission 
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Proportion of subjects achieving proctitis remission at Week 24, in subjects that had 
moderately to severely active proctitis at baseline 
3.2. 
Study Design 
This study is a Phase 2, double-blind, randomized, multicenter study evaluating the efficacy and 
safety offilgotinib versus placebo in the treatment of perianal fistulizing CD. A schematic of this 
study is provided in Figure 3-1. 
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Figure 3-1.
Study Design Schematic
FIL = filgotinib; PBO = placebo; mg = milligram.
*
Non-responders (luminal disease) are defined as subjects who either had a baseline CDAI score ≥ 220 and never achieve 
a ≥70-point CDAI reduction from baseline at any point up to and including Week 10 OR had a baseline CDAI score < 220 
and have an increase in CDAI of ≥ 100 points from baseline, with CDAI ≥ 220 at Week 10.
Non-responders (perianal fistulizing disease) are defined as subjects who meet the following criteria for PDAI symptom 
subscores: “Discharge” subscore of >1 and ≥ 1-point increase from baseline at Week 6 and Week 10 OR “Pain/restriction of 
activities” subscore of >1 and ≥ 1-point increase from baseline at Week 6 and Week 10
**
Disease worsening is defined as an increase in CDAI of ≥100 points from the Week 10 value with CDAI score ≥220 points 
at 2 consecutive visits
*** Subjects who are non-responders, meeting disease worsening criteria, or complete the study at Week 24, will have the 
option to enter a separate LTE study, if eligible.
This study includes:

Screening (Day -30 to -1)

Randomization

Blinded Treatment Period (Day 1 to Week 24)
Efficacy assessment: At Week 24, physical examination, flexible sigmoidoscopy to 
assess presence of proctitis, and MRI to assess fistula response
Subjects who complete all procedures per protocol, including the MRI at Week 24, may 
be offered the option to continue into a separate Long Term Extension (LTE) study 
(GS-US-419-3896), if deemed appropriate by the investigator
Day 1 
Week 10 
Non•r~· or 
mHtlng dlseue 
worHnlng cr1 r1,-
Week 24 ( •eoopoin ) 


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Subjects who are non-responders at Week 10 (see Section 3.6 OR Section 3.7) or who meet 
disease worsening criteria (see Section 3.8) after Week 10 will have the option to enter the 
LTE study, if eligible. 
• 
Post Treatment (PTx) safety assessments: 
3.3. 
All subjects completing this study will be offered the option to continue study drng in a 
blinded fashion in the LTE study, if eligible 
Subjects who are eligible and opt to paiiicipate in the LTE study can continue into the 
L TE study without PTx safety assessments 
Subjects who opt out of the LTE study will return to clinic 30 days after the last dose of 
study dmg for PTx safety assessments 
Study Treatments 
Based on protocol eligibility criteria, subjects will be screened for emollment and randomized 
into 1 of 3 ti·eatment groups in a blinded fashion in a 2:2: 1 ratio as follows: 
Treatment group 1 (n = 30): filgotinib 200 mg and PTM filgotinib 100 mg, once daily 
Treatment group 2 (n = 30): filgotinib 100 mg and PTM filgotinib 200 mg, once daily 
Treatment group 3 (n = 15): PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily 
Note: US males who ai·e not dual refractory will be randomized in a 2: 1 ratio to either filgotinib 
100 mg or matching placebo. For the pmposes of this protocol, US males who have failed at 
least one prior TNF antagonist AND either previously failed vedolizumab induction therapy or 
are concomitantly taking vedolizumab at Day 1 and present with actively draining perianal 
fistulae despite continued vedolizumab therapy will be considered as dual refracto1y patients. 
This assessment is based on recently published data from a subgroup analysis of the GEMINI-2 
study, showing a beneficial effect of vedolizumab ti·eatment for patients that were randomized 
with actively draining perianal fistulae at baseline (Feagan 2018). 
Treatment assigmnents will be sti·atified according to the following factors: 
• 
Anatomy of draining perianal fistulae at screening detennined by MRI (simple versus 
complex) 
• 
Receiving vedolizumab therapy concomitantly at Day 1 (Yes or No) 
• 
Presence of moderately to severely active proctitis (Yes or No) 
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3.4.
Duration of Treatment
Randomized subjects will receive a maximum of 24 weeks of study drug. Subjects who are 
non-responders based on the results of the Week 10 assessments (see Section 3.6 OR Section 3.7
or meeting disease worsening criteria after Week 10 (see Section 3.8) must be discontinued from 
blinded treatment (see Section 3.5.2).
3.5.
Criteria for Study Drug Interruption or Discontinuation
3.5.1.
Study Drug Interruption Considerations
The Study Medical Monitor should be consulted prior to study drug interruption when medically 
feasible.
Study drug interruption should be considered in the following circumstances (prior to 
resumption of study drug, the investigator should discuss the case with the Study Medical 
Monitor):

Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree

Subject is scheduled for elective or emergency surgery (excluding minor skin procedures 
under local or no anesthesia); timing of study drug interruption should be determined in 
consultation with the Study Medical Monitor

Any subject who develops a new infection during the study should undergo prompt and 
complete diagnostic testing appropriate for an immunocompromised individual, and the 
subject should be closely monitored
NOTE: During the time of study drug interruption for any of the above, the subject may continue 
to have study visits and to take part in procedures and assessments, if deemed medically 
appropriate by the investigator.
3.5.2.
Study Drug Discontinuation Considerations
The Study Medical Monitor should be consulted prior to study drug discontinuation when 
medically feasible.
Study drug must be permanently discontinued in the following instances:

Any opportunistic infection

Any serious infection that requires antimicrobial therapy or hospitalization, or any infection 
that meets SAE reporting criteria.

Febrile neutropenia (temperature > 38.3°C or a sustained temperature of > 38°C for more 
than one hour) with absolute neutrophil count of < 1,000/mm3


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
Symptomatic anemia (eg, signs/symptoms including pallor, shortness of breath, new heart 
murmur, palpitations, lethargy, fatigue) with hemoglobin < 7.5 g/dL, or if transfusion is 
indicated regardless of hemoglobin value

Complicated herpes zoster infection (with multi-dermatomal, disseminated, ophthalmic, 
or CNS involvement)

Evidence of active Hepatitis C Virus (HCV) during the study, as evidenced by HCV RNA 
positivity

Evidence of active Hepatitis B Virus (HBV) during the study, as evidenced by HBV DNA 
positivity

Any thromboembolic event that meets SAE reporting criteria

Unacceptable toxicity, or toxicity that, in the judgment of the investigator, compromises the 
subject’s ability to continue study-specific procedures or is considered to not be in the 
subject’s best interest

Subject request to discontinue for any reason

Subject noncompliance

Pregnancy during the study; refer to Section 7.7.2.1

Discontinuation of the study at the request of Gilead, a regulatory agency or an institutional 
review board or independent ethics committee (IRB/IEC)

Subject use of prohibited concurrent therapy may trigger study drug discontinuation; 
consultation should be made with the Study Medical Monitor.

Laboratory Criteria: After becoming aware of any of the below described abnormal 
laboratory changes occurring at any one time, an unscheduled visit (ie, sequential visit) 
should occur to retest within 3 to 7 days (except creatinine, which should be retested 7 to 
14 days apart).
Two sequential neutrophil counts < 750 neutrophils/mm3 (SI: < 0.75x109 cells/L)
Two sequential platelet counts < 75,000 platelets/mm3 (SI: < 75.0x109 cells/L)


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Two sequential aspartate aminotransferase (AST) or alanine aminotransferase (ALT)
elevations > 3 times the upper limit of normal range (x ULN) and at least one of the 
following confirmed values:
■
total bilirubin > 2 x ULN
■
INR > 1.5
■
or accompanied by symptoms consistent with hepatic injury
For any subject with an initial AST or ALT elevation > 3x ULN, at the time of the 
second confirmatory draw, an INR, prothrombin time (PT), and partial thromboplastin 
time (PTT) must also be drawn.
Two sequential AST or ALT > 5 x ULN
Two sequential values for estimated creatinine clearance (CLcr) < 35 mL/min based on 
the Cockcroft-Gault (CC&G) formula
Male:
(140 – age in years) × (wt in kg)
CLcr (mL/min)
72 × (serum creatinine in mg/dL)
Female:
(140 – age in years) × (wt in kg) 0.85 
CLcr (mL/min)
72 × (serum creatinine in mg/dL)
Subjects are free to withdraw from the study at any time without providing reason(s) for 
withdrawal and without prejudice to further treatment. The reason(s) for withdrawal will be 
documented in the electronic case report form (eCRF).
Subjects who permanently discontinue study drug for any reason should discuss their continued  
care plan with their physician.
Subjects who permanently discontinue study drug for pregnancy should not continue in the 
study; if there are any questions regarding permanent discontinuation, these should be discussed 
with the Sponsor.
Subjects withdrawing from the study should complete Early Termination (ET), followed by PTx 
assessments 30 days after the last dose of study drug (Refer to Section 6.13 for Post Treatment 
assessments). 
Reasonable efforts will be made to contact subjects who are lost to follow-up. All contacts and 
contact attempts must be documented in the subject’s file.
The Sponsor has the right to terminate the study at any time in case of safety concerns or if 
special circumstances concerning the study medication or the company itself occur, making 
further treatment of subjects impossible. In this event, the investigator(s) and relevant authorities 
will be informed of the reason for study termination.


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3.6.
Luminal Disease Activity - Non-Response Criteria
Subjects who are non-responders to study treatment for luminal disease activity are subjects who
either:

Had a baseline CDAI ≥220 and never achieve a ≥70-point CDAI reduction from baseline at 
any point up to and including Week 10 OR

Had a baseline CDAI score < 220 and have an increase in CDAI of ≥100 points from 
baseline, with CDAI ≥220 at Week 10
These subjects will be offered the option to receive open-label filgotinib by entering into the 
separate LTE study. Subjects will remain blinded to their treatment allocation in the current 
study. Subjects meeting non-response criteria should undergo a pelvic MRI and flexible 
sigmoidoscopy prior to exiting the study (Refer to Sections 6.5 and 6.6 for details regarding the 
flexible sigmoidoscopy and MRI).
3.7.
Perianal Fistulizing Disease Activity - Non-Response Criteria
Subjects who are non-responders to study treatment for symptoms relating to their perianal 
fistulae must meet the following criteria for PDAI symptom subscores:

“Discharge” subscore of >1 and ≥ 1-point increase from baseline at Week 6 and Week 10
OR

“Pain/restriction of activities” subscore of >1 and ≥ 1-point increase at Week 6 and Week 10
from baseline 
These subjects will be offered the option to receive open-label filgotinib by entering into the 
separate LTE study. Subjects will remain blinded to their treatment allocation in the current 
study. Subjects meeting non-response criteria should undergo a pelvic MRI and flexible 
sigmoidoscopy prior to exiting the study (Refer to Sections 6.5 and 6.6 for details regarding the 
flexible sigmoidoscopy and MRI).
3.8.
Luminal Disease Activity - Disease Worsening Criteria
Subjects meeting the following disease worsening criterion after Week 10 must be discontinued 
from blinded treatment and will be offered the option to receive open-label filgotinib by entering 
into the separate LTE study:

An increase in CDAI of ≥100 points from the Week 10 value with CDAI ≥220 at 
2 consecutive visits
Determination of disease worsening may be made at scheduled or unscheduled visits 
(eg, a study visit followed by an unscheduled visit, or 2 sequential unscheduled visits 
anytime subsequent to the Week 10 visit).


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All subjects meeting disease worsening criteria should undergo a pelvic MRI and flexible 
sigmoidoscopy prior to exiting the study (Refer to Sections 6.5 and 6.6 for details regarding 
the flexible sigmoidoscopy and MRI). 
• 
If a subject experiences significant worsening of underlying CD, which requires any of the 
prohibited medications (refer to Section 5.4.2), or surgical intervention at any point during 
the study, treatment discontinuation should be considered at investigator's discretion, 
in consultation with medical monitor if feasible (refer to Section 3.5.2); these subjects do not 
qualify for LTE study. 
3.9. 
End of Study 
End of Study is defined as 30 days after the last dose administered to the last subject. 
3.10. 
Post Study Care 
All subjects completing 24 weeks of treatment will be given the opportunity to pa1ticipate in the 
LTE study. For those subjects who do not paiticipate in the LTE study, after the subject has 
completed their study paiticipation, the long-tenn care of the paiticipant will remain the 
responsibility of their primaiy ti·eating physicians . 
• -
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Approximately 75 subjects who meet the eligibility criteria at screening will be randomized in a 
blinded fashion in a 2:2:1 ratio to filgotinib 200 mg, filgotinib 100 mg, or matching placebo.
In order to manage the total study enrollment, Gilead, at its sole discretion, may suspend 
screening and/or enrollment at any site or study-wide at any time.
4.2.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study.
1) Must have the ability to understand and sign a written informed consent form, which must be 
obtained prior to initiation of study procedures
2) Males or non-pregnant, non-lactating females, ages 18 to 75 years, inclusive based on the 
date of screening visit
3) Females of childbearing potential (as defined in Appendix 9) must have a negative pregnancy 
test at screening and baseline
4) Male subjects and female subjects of childbearing potential who engage in heterosexual 
intercourse must agree to use protocol specified method(s) of contraception (as described in 
Appendix 9)
5) Documented diagnosis of Crohn’s disease with a minimum disease duration of 3 months 
documented by the following:
a) Medical record documentation of, or an ileocolonoscopy (full colonoscopy with the 
intubation of terminal ileum) report dated ≥3 months before enrollment, which shows 
features consistent with CD, determined by the procedure performing physician; AND
b) Medical record documentation of, or a histopathology report showing features consistent 
with CD, determined by the pathologist
6) At screening, has a minimum of 1 (maximum of 3) draining perianal fistulae external 
openings of ≥4 weeks duration as a complication of CD, confirmed by MRI.
At least 1 (maximum of 3) of the draining perianal fistulae external openings present at 
screening must still be draining at the time of randomization.
Subjects with other fistula types (enterocutaneous, abdominal) in addition to the required 
minimum number of perianal fistula may be permitted on discussion with and approval by 
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7) May have concurrent noncutting perianal seton(s) at screening, which must be removed 
≥14 days prior to randomization
8) Previously demonstrated an inadequate clinical response, loss of response to, or intolerance 
of at least 1 of the following agents (depending on current country treatment 
recommendations/guidelines):
a) Antibiotics
i)
Active disease (draining perianal fistulae) despite at least a 4-week regimen of 
antibiotics (ciprofloxacin or metronidazole per local treatment guidelines) for the 
purpose of treating perianal fistulae
AND/OR
b) Immunomodulators
i)
Active disease despite a history of at least a 12-week regimen of oral azathioprine 
(≥2 mg/kg) or 6-mercaptopurine (6-MP) (≥ 1 mg/kg), or methotrexate (25 mg 
per week subcutaneously [SC] or intramuscularly [IM] per week for induction 
and ≥15 mg IM per week for maintenance), OR
ii) History of intolerance to at least one immunomodulator including, but not limited to, 
serious infections, hepatotoxicity, cytopenia, pancreatitis, TPMT genetic mutation, 
allergic reactions, or any other condition that contributed to discontinuation of the 
agent
AND/OR
c) TNFα Antagonist
i)
Active disease despite a history of at least one induction regimen of infliximab, 
adalimumab, certolizumab or biosimilar as follows:
(1) Infliximab: A 14-week induction regimen of 5 mg/kg IV at Weeks 0, 2, and 
6 (6 week induction regimen with 2 doses at Weeks 0 and 2 in EU)
(2) Adalimumab: A 4-week induction regimen consisting of 160 mg SC (four 40-mg 
injections in 1 day or two 40-mg injections per day for 2 consecutive days) on 
Day 1, followed by a second dose 2 weeks later (Day 15) of 80 mg.
(3) Certolizumab: A 8-week induction regimen of 400 mg SC at Weeks 0, 2, and 4
AND/OR
ii) Recurrence of symptoms during maintenance therapy with the above agents, 
AND/OR
iii) History of intolerance to any TNFα inhibitors including, but not limited to, serious 
infections, hepatotoxicity, heart failure, allergic reactions, or any other condition that 
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9) Is willing and able to undergo MRI per protocol requirements
10) Is willing and able to undergo flexible sigmoidoscopy per protocol requirements
11) Meet one of the following tuberculosis (TB) screening criteria:
a) No evidence of active or latent TB ie,
i)
A negative QuantiFERON® TB-Gold In-Tube test at screening, AND
ii) A chest radiograph (views as per local guidelines) taken at screening or within the 
3 months prior to screening (with the report or films available for investigator review) 
without evidence of active or latent TB infection, AND
iii) No history of either untreated or inadequately treated latent or active TB infection
b) Previously treated for TB: ie, if a subject has previously received an adequate course of 
therapy as per local standard of care for either latent TB (eg, 9 months of isoniazid in a 
location where rates of primary multi drug resistant TB infections are < 5% or an 
acceptable alternative regimen) or active TB (acceptable multi-drug regimen). In these 
cases, no QuantiFERON® TB-Gold In-Tube test need be obtained, but a chest radiograph 
must be obtained if not done so within 3 months prior to screening (with the report or 
films available for investigator review). It is the responsibility of the investigator to verify 
the adequacy of previous anti-TB treatment and provide appropriate documentation.
c) Newly identified latent TB during screening: ie, a subject who has a newly identified 
positive diagnostic TB test result (defined as a positive QuantiFERON® TB Gold in 
Tube test) in which active TB has been ruled out and for which appropriate, ongoing, 
prophylactic treatment for latent TB has been initiated for a minimum of 4 weeks prior to 
the first administration of study medication. Adequate treatment for latent TB is defined 
according to local country guidelines for immunocompromised subjects. Quantiferon 
testing may not be repeated except in the case of a single repeat for indeterminate results.
Cases falling under category “b” and “c” need to be approved by the Sponsor prior to enrollment 
in this study. No subject with currently active TB may be enrolled in the study, regardless of past 
or present anti-TB medication use.
12) Laboratory parameters (subjects who fail to meet the parameters of any of the below 
reference laboratory tests may be retested once at discretion of investigator prior to being 
considered a screen failure):
a) Hepatic panel (AST, ALT, total bilirubin) ≤2 x ULN
b) Estimated CLcr ≥ 40 ml/min as calculated by the CC&G equation
c) Hemoglobin ≥ 8 g/dL (both males and females)


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d) Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1,500/mm3)
e) Platelets ≥ 100 × 109/L
f)
White blood cells (WBC) ≥ 3.0 x 109/L
g) Absolute lymphocyte count > 750/mm3
13) May be receiving the following drugs (subjects on these therapies must be willing to remain 
on stable doses for the noted times):
a) Oral 5-aminosalicylate (5-ASA) compounds provided the dose prescribed has been stable 
for at least 4 weeks prior to randomization; dose must remain stable for the first 10 weeks 
after randomization
b) Oral corticosteroid therapy (prednisone prescribed at a stable dose ≤20 mg/day or 
budesonide prescribed at a dose of ≤ 6 mg/day) provided the dose prescribed has been 
stable for 4 weeks prior to randomization; dose must remain stable for the first 10 weeks 
after randomization
c) Azathioprine or 6-MP or methotrexate provided the dose prescribed has been stable for 
4 weeks prior to randomization; dose must remain stable for the first 10 weeks after 
randomization
d) Antibiotics for the treatment of perianal fistulizing CD (eg, metronidazole, ciprofloxacin) 
provided the dose prescribed has been stable for the 2 weeks prior to randomization.
Dose must remain stable for the first 10 weeks after randomization. Subjects who are on 
cyclic therapy must continue their standard low-dose regimen without change for the 
first 10 weeks after randomization.
e) Vedolizumab therapy (300 mg IV) for the treatment of concurrent luminal disease 
activity provided the dose has been stable for 14 weeks prior to randomization; subjects 
must remain on vedolizumab for the duration of their participation in the study. Subjects 
on concurrent vedolizumab therapy must not be taking concurrent azathioprine or 6-MP 
or methotrexate.
14) Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks 
after last dose of study drug
15) Must be up to date on colorectal cancer screening and surveillance as standard of care 
according to local guidelines.


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4.3.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) Pregnant or lactating females.
2) Males and females of reproductive potential who are unwilling to adhere to contraceptive 
guidance as outlined by Appendix 9.
3) Females who may wish to become pregnant and/or plan to undergo egg donation or egg 
harvesting for the purpose of current or future fertilization during the course of the study and 
up to 35 days after the last dose of the study drug.
4) Male subjects unwilling to refrain from sperm donation during the study and for at least 
90 days after the last dose of study drug.
5) Known hypersensitivity to filgotinib, its metabolites, or formulation excipients
6) Claustrophobia to a degree that prevents tolerance of MRI scanning procedure (sedation is 
permitted at discretion of investigator).
7) Metallic implant of any sort that prevents MRI examination, not limited to but including 
aneurysm clips, metallic foreign body, vascular grafts or cardiac implants, neural stimulator, 
metallic contraceptive device, body piercing that cannot be removed, cochlear implant; or 
other contraindication to MRI examination.
8) Known hypersensitivity to gadolinium
9) Currently have complications of CD as any of the following:
a) Symptomatic strictures, OR
b) Severe (impassable) rectal/anal stenosis, OR
c) Short bowel syndrome, OR
d) Any other complications which could preclude the use of the CDAI to assess response to 
therapy, or would possibly confound the evaluation of benefit from treatment with 
filgotinib
10) Presence of current rectovaginal, anovaginal, or enterovesicular fistulae
11) Has an abscess > 2 cm or an abscess that the Investigator feels requires drainage based on 
either clinical assessment or MRI, unless drained and treated at least 4 weeks prior to Day 1,
and are not anticipated to require surgery during the study
12) Has a CDAI score > 300


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13) History of major surgery or trauma within 30 days prior to screening
14) Presence of ulcerative colitis (UC), indeterminate colitis, ischemic colitis, fulminant colitis, 
or toxic mega-colon
15) History of total proctocolectomy, total colectomy, presence of ileostomy or colostomy, or 
likely requirement for surgery during the study
16) Dependence on parenteral nutrition
17) History or evidence of incompletely resected colonic mucosal dysplasia
18) Infection with human immunodeficiency virus (HIV), HBV or HCV
19) Presence of Child-Pugh Class C hepatic impairment
20) Stool samples positive for Clostridium difficile (C. difficile) toxin, pathogenic 
Escherichia coli (E. coli), Salmonella species (spp), Shigella spp, Campylobacter spp, or 
Yersinia spp.
21) Stool sample positive for ova and parasites test (O&P) unless approved by the medical 
monitor
22) Use of any prohibited concomitant medications as described in Section 5.4.2
23) Has used any TNFα antagonist ≤8 weeks prior to screening, ustekinumab IV or 
SC ≤12 weeks prior to screening, or any other biologic agent ≤8 weeks prior to screening or 
within 5 times the half-life of the biologic agent prior to screening, whichever is longer. 
Subjects who have an undetectable serum level of a biologic agent since its last dose using a 
commercially available assay can undergo study screening without the above-mentioned 
waiting period.
24) Active clinically significant infection or any infection requiring hospitalization or treatment 
with intravenous anti-infectives within 30 days of screening (or 8 weeks of Day 1); or any 
infection other than related to the fistula(s) requiring oral anti-infective therapy within 
2 weeks of screening (or 6 weeks of Day 1)
25) Active TB or history of latent TB that has not been treated (see inclusion criterion 11 for 
further information)
26) History of opportunistic infection or immunodeficiency syndrome
27) History of disseminated Staphylococcus aureus
28) History of symptomatic herpes zoster or herpes simplex within 12 weeks of screening, or any 
history of disseminated herpes simplex, disseminated herpes zoster, ophthalmic zoster, or 
central nervous system zoster


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29) Administration of live or attenuated vaccine within 30 days of randomization
30) Any chronic medical condition (including, but not limited to, cardiac or pulmonary disease) 
or psychiatric problem (including, but not limited to alcohol or drug abuse) that, in the 
opinion of the Investigator, would make the subject unsuitable for the study or would prevent 
compliance with the study protocol
31) History of malignancy within the last 5 years except for subjects who have been treated or 
resected for non-melanoma skin cancer or cervical carcinoma in situ
32) History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, 
or multiple myeloma
33) History of treatment with lymphocyte-depleting therapies, including but not limited to 
alemtuzumab, cyclophosphamide, total lymphoid irradiation, and rituximab
34) History of leukocytapheresis ≤ 6 months prior to Screening
35) Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, 
baricitinib, and upadacitinib)


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5. 
5.1. 
5.1.1. 
INVESTIGATION AL MEDICINAL PRODUCTS 
Randomization, Blinding and Treatment Codes 
Procedures for Breaking Treatment Codes 
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In the event of a medical emergency where breaking the blind is required to provide medical care 
to the subject, the investigator may obtain treatment assignment directly from the interactive web 
response system (IWRS) for that subject. Gilead recommends but does not require that the 
investigator contact the Study Medical Monitor before breaking the blind. Treatment assignment 
should remain blinded unless that knowledge is necessaiy to detennine subject emergency 
medical care. The rationale for unblinding must be clearly explained in source documentation 
and on the eCRF, along with the date on which the ti·eatment assignment was obtained. 
The investigator is requested to contact the Study Medical Monitor promptly in case of any 
ti·eatment unblinding. 
Blinding of study ti·eatment is critical to the integrity of this clinical ti·ial and therefore, if a 
subject's ti·eatment assignment is disclosed to the investigator, the subject will have study 
ti·eatment discontinued. All subjects will be followed until study completion unless consent to 
do so is specifically withdrawn by the subject. 
Gilead Phaimacovigilance and Epidemiology (PVE) may independently unblind cases for 
expedited repo1i ing of suspected unexpected serious adverse reactions (SUSARs). 
5.1.2. 
Blinding 
During the randomized phase, subjects and all personnel directly involved in the conduct of the 
study will be blinded to treatment assignment. Specified personnel may be unblinded based on 
their study role. Study drng will be dispensed by the study phaimacist, or designee, in a blinded 
fashion to the subjects. The Phaimacokinetics File Administi·ator or desi 
ee in Bioanal ical 
erations and/or Clinical Data Mana ement 
Individuals in Clinical Packaging & 
La e mg or C 1mca Supp y Management w o ave an Unblinded Invento1y Manager role in the 
interactive voice/web response system for purposes of study diug invento1y management will 
remain unblinded. Individuals in PVE responsible for safety signal detection, investigational new 
diug safety repo1i ing, and/or expedited repo1i ing of SUSARs may be unblinded to individual 
case data and/or group-level summaries. External (ie, conti·act research organizations) 
Biostat ~ers will be unblinded to support data monitoring committee data 
review- .  
Regulato1y Quality and Compliance personnel in Research and 
Development may also be unblinded for purposes of suppo1i ing Quality Assurance activities 
and/or Regulato1y Agency inspections. 
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5.2.
Description and Handling of Filgotinib and Placebo to Match (PTM) 
Filgotinib
5.2.1.
Formulation
Filgotinib is provided as 200 mg and 100 mg strength tablets. Filgotinib tablets, 200 mg and 
100 mg are beige, debossed with “GSI” on one side and “200” or “100” on the other, 
capsule-shaped, biconvex, film-coated tablets for clinical use. Each tablet contains the equivalent 
of 200 mg or 100 mg filgotinib free base in the form of filgotinib maleate. In addition to the 
active ingredient, filgotinib tablets contain the following inactive ingredients: microcrystalline 
cellulose, lactose monohydrate, fumaric acid, pregelatinized starch, silicon dioxide, magnesium 
stearate, macrogol/ polyethylene glycol (PEG) 3350, polyvinyl alcohol, talc, titanium dioxide, 
iron oxide yellow, and iron oxide red.
Placebo to match (PTM) filgotinib 200 mg and 100 mg tablets are identical in appearance to the 
respective active tablets. PTM filgotinib 200 mg and 100 mg tablets contain the following 
inactive ingredients: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, 
magnesium stearate, macrogol/PEG 3350, polyvinyl alcohol, talc, titanium dioxide, iron oxide 
yellow, and iron oxide red.
5.2.2.
Packaging and Labeling
Filgotinib and PTM filgotinib tablets are packaged in white, high density polyethylene (HDPE) 
bottles. Each bottle contains 30 tablets, silica gel desiccant and polyester packing material. Each 
bottle is enclosed with a white, continuous thread, child-resistant polypropylene screw cap fitted 
with an induction-sealed, aluminum-faced liner.
Study drugs to be distributed to centers in the US, EU and other participating countries shall be 
labeled to meet applicable requirements of the United States Food and Drug Administration 
(FDA), EU Guideline to Good Manufacturing Practice - Annex 13 (Investigational Medicinal 
Products), and/or other local regulations as applicable.
5.2.3.
Storage and Handling
Filgotinib and PTM filgotinib tablets should be stored at controlled room temperature of 25°C 
(77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Storage conditions 
are specified on the label. Until dispensed to the subjects, all bottles of study drugs should be 
stored in a securely locked area, accessible only to authorized site personnel.
To ensure the stability and proper identification, study drugs should not be stored in a container 
other than the container in which they were supplied. Keep the container tightly closed to protect 
from moisture. Consideration should be given to handling, preparation, and disposal through 
measures that minimize drug contact with the body. Appropriate precautions should be followed 
to avoid direct eye contact or exposure when handling.


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5.3.
Dosage and Administration of Study Drug
The study medication will consist of 200 mg and 100 mg filgotinib tablets for oral administration 
and PTM 200 mg and 100 mg filgotinib tablets for oral administration.
The following treatments will be evaluated:

Treatment group 1: 1 tablet of 200 mg filgotinib daily, 1 tablet of PTM filgotinib 100 mg 
daily

Treatment group 2: 1 tablet of 100 mg filgotinib daily, 1 tablet of PTM filgotinib 200 mg 
daily

Treatment group 3: 1 tablet of PTM filgotinib 200 mg daily, 1 tablet of PTM filgotinib 
100 mg daily
Subjects who are non-responders based on the results of the Week 10 assessments 
(see Section 3.6, Luminal Disease Activity – Non-Response Criteria OR Section 3.7, Perianal 
Fistulizing Disease Activity – Non-Response Criteria) will be offered the option to receive
open-label filgotinib by entering into the LTE study (GS-US-419-3896); prior to entering the 
LTE study, subjects must complete MRI and flexible sigmoidoscopy early termination 
procedures. Subjects meeting disease worsening criteria after Week 10 must be discontinued 
from blinded treatment and will be offered the option to receive open-label filgotinib 200 mg
(see Section 3.8, Disease Worsening Criteria), except for US males who will be offered filgotinib 
100 mg unless they are considered to be ‘dual refractory’ prior to entering the LTE study, 
subjects must complete MRI and flexible sigmoidoscopy early termination procedures. Subjects 
who complete all procedures per protocol up to the Week 24 visit (including the Week 24 MRI 
and flexible sigmoidoscopy) will have the option to continue study drug in a blinded fashion in 
the LTE study.
For missed dose(s) of study medication, subjects should be instructed to take the missed dose(s) 
of study medication as soon as possible during the same day. If the missed dose is not taken on 
the original day, then subjects should not take the missed dose and the missed dose should be 
returned to the study drug bottle. Subjects should be cautioned not to double the next dose 
(ie, taking the missed dose of study drug with that day’s dose).
5.4.
Prior and Concomitant Medication
All medications taken up to 30 days prior to the screening visit through the end of study 
(30 days after the last dose of study drug), need to be recorded in the source documents and on 
the eCRF. At each study visit, the study center will record any and all concomitant medications
taken by the subject since the last visit or during the visit (as applicable). All concomitant 
medications (prescription, peri-procedural medications, over-the-counter medications, including 
vaccines, vitamins, herbal, dietary supplements, and minerals) must be recorded in the 
concomitant therapy section of the eCRF.


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Effective current therapies should not be discontinued for the sole purpose of participating in this 
study. Subjects may receive medication as supportive care or to treat AEs as deemed necessary 
by the Investigator or the subject’s physician. Should subjects have a need to initiate treatment 
with any excluded concomitant medication, the Study Medical Monitor should be consulted prior 
to initiation of the new medication. In instances where an excluded medication is initiated prior 
to discussion with the Sponsor, the Investigator should notify Gilead as soon as he/she is aware 
of the use of the excluded medication.
5.4.1.
Allowed Concomitant Medication
The allowed concomitant medication(s) for CD must be maintained at a stable dose for the noted 
time without dose alteration or discontinuation. Subjects should not initiate new induction 
therapy prior to the screening visit. If a new therapy has been recently initiated, the full induction 
course should be completed prior to screening consideration.
The allowed medications for CD are as follows:

Oral 5-ASA compounds provided the dose prescribed has been stable for at least 4 weeks 
prior to randomization; dose must be stable for the first 10 weeks after randomization

Azathioprine, 6-MP, or MTX provided the dose prescribed has been stable for 4 weeks prior 
to randomization; dose must be stable for the first 10 weeks after randomization

Oral corticosteroid therapy (prednisone prescribed at a stable dose of ≤20 mg/day or 
budesonide prescribed at a stable dose of ≤ 6 mg/day) provided the dose prescribed has been 
stable for 4 weeks prior to randomization; dose must be stable for the first 10 weeks after 
randomization.

Antidiarrheals for chronic diarrhea are allowed throughout the study as necessary for control 
of chronic diarrhea; stable doses are encouraged.

Occasional use of non-steroidal anti-inflammatory drugs (NSAIDs) for transient symptoms is 
permitted; daily use of aspirin up to 162.5 mg for the purpose of cardiovascular prophylaxis 
is permitted.

Antibiotics for the treatment of perianal fistulizing CD (eg, metronidazole, ciprofloxacin) 
provided the dose prescribed has been stable for the 2 weeks prior to randomization. Dose 
must remain stable for the first 10 weeks after randomization. Subjects who are on cyclic 
therapy must continue their standard low-dose regimen without change for the first 10 weeks 
after randomization

Vedolizumab therapy (300 mg IV) for the treatment of concurrent luminal disease activity 
provided the dose has been stable for 14 weeks prior to randomization; subjects must remain 
on vedolizumab for the duration of their participation in the study. Subjects on concurrent 
vedolizumab therapy must not be taking concurrent azathioprine or 6-MP or methotrexate.


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5.4.2.
Prohibited Concomitant Medication
The prohibited medications are as follows:
Table 5-1.
Prohibited Concomitant Medication
Drug Class
Agents Disallowed
Prohibited Period
Strong P-gp Inducersa
Anticonvulsants
Phenobarbital, phenytoin, carbamazepine,
30 days prior to screening through the 
end of the study
Antimycobacterials
Rifabutin, rifapentine, rifampin
Herbal/Natural 
Supplements
St. John’s wort, danshen 
(salvia miltiorrhiza)
Prohibited IBD Medication
Corticosteroids
Dose equivalent to > 20 mg/day of 
prednisone
30 days prior to screening through the 
end of the study
TNFα antagonist
Infliximab, adalimumab, golimumab, 
certolizumab, or biosimilar agent
8 weeks prior to screening through the 
end of the study
Integrin antagonist
Natalizumab
8 weeks prior to screening through the 
end of the study
Interleukin antagonist
Ustekinumab
12 weeks prior to Screening through the 
end of the study
JAK inhibitors
any JAK inhibitors, including but not 
limited to tofacitinib, baricitinib, and 
upadacitinib
Any time before and through the end of 
the study
Other (non-biologic)
Cyclosporine, thalidomide, tacrolimus, 
leflunomide, and any investigational agent
30 days prior to screening through the 
end of the study
Investigational biologics
Any investigational biologic agent
8 weeks prior to screening through the 
end of the study (or at least 5 half-lives)
Lymphocyte-depleting 
therapies
Alemtuzumab, cyclophosphamide, total 
lymphoid irradiation, rituximab, and any 
other lymphocyte depleting therapy
Any time before and through the end of 
the study
Other Prohibited Medication
Chronic Nonsteroidal 
Anti-inflammatory 
Drugs (NSAIDs)b
Aspirin, ibuprofen, naproxen, diclofenac, 
indomethacin, COX-2 inhibitors
From screening through the end of the 
study
Other biologicsc
Antibody based or other systemic 
biologics, eg, denosumab, trastuzumab
Requires medical monitor consultation
a
May decrease study drug exposure and are excluded to avoid potential reduction in study drug activity. PK results indicate 
that filgotinib is a P-gp substrate, as a single dose of 200 mg itraconazole (a potent P-gp inhibitor) increased filgotinib Cmax
by 64% and AUCinf by 45% and had no effect on the major, active metabolite GS-829845.
b
Occasional use of NSAIDs for transient symptoms and daily use of aspirin up to 162.5 mg for the purpose of cardiovascular 
prophylaxis are permitted.
c
Other biologics may be allowed with the approval of the medical monitor.


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5.5.
Corticosteroid Tapering
Starting at Week 10, subjects who are on concomitant steroids must begin tapering steroid 
therapy. The dose should be reduced at a rate starting at 2.5 mg per week up to 5 mg per week 
(or equivalent taper if not prednisone) until the subject is no longer on steroids. Subjects who are 
on budesonide should have their daily dose reduced by 3 mg every 3 weeks until they are 
completely off steroids. For subjects undergoing taper, steroids may be increased or restarted at 
doses up to and including their baseline dose if return of symptoms is apparent. These subjects 
will not be considered treatment failures. Subjects who need to restart or increase steroid 
treatment at a dose that exceeds their baseline dose of steroids (dose may not exceed 20 mg/day
prednisone [or equivalent] or budesonide 6 mg/day) will be considered treatment failures for all 
clinical endpoints but will be permitted to remain in the study and continue to receive study drug.
5.6.
Vaccine Guidelines

Prior to study participation, it is recommended that the subject’s vaccinations be brought up 
to date according to local vaccination standards.

Live or attenuated vaccines (including, but not limited to varicella and inhaled flu vaccine) 
are prohibited within 30 days of Day 1, throughout the study, and for 12 weeks after the 
last dose of study drug.

Subjects should be advised to avoid routine household contact with persons vaccinated with 
live/attenuated vaccine components. General guidelines suggest that a study subject’s 
exposure to household contacts should be avoided for the below stated time periods:

Varicella or attenuated typhoid fever vaccination – avoid contact for 4 weeks following 
vaccination

Oral polio vaccination -- avoid contact for 6 weeks following vaccination

Attenuated rotavirus vaccine -- avoid contact for 10 days following vaccination

Inhaled flu vaccine -- avoid contact for 1 week following vaccination

Inactivated vaccines (such as inactivated flu vaccines) should be administered according to 
local vaccination standards whenever medically appropriate; however, there are no available 
data on the concurrent use of filgotinib and its impact on immune responses following 
vaccination.


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5.7.
Accountability for Study Drug
The investigator is responsible for ensuring adequate accountability of all used and unused study 
drug. This includes acknowledgement of receipt of each shipment of study drug (quantity and 
condition). All used and unused study drug bottles dispensed to subjects must be returned to the 
site.
Study Drug accountability records will be provided to each study site to:

Record the date received and quantity of study drug

Record the date, subject number, subject initials, the study drug bottle number dispensed

Record the return date, quantity of used and unused study drug returned, along with the 
initials of the person recording the information.
5.7.1.
Investigational Medicinal Product Return or Disposal
Please refer to Section 9.1.7.


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6. 
STUDY PROCEDURES 
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The study procedures to be conducted for each subject emolled in the study are detailed in 
tabular fonn in Appendix 2. Key procedures are described in the text that follows. 
Written info1med consent must be obtained from each sub· ect before initiation of an 
From the time of obtaining infonned consent through the Week 10 visit, subjects must maintain 
allowed concomitant medications at a stable dose (see Section 5.4.1). 
The investigator must doclllllent any deviation from protocol procedures and notify the Sponsor 
or contract research organization. 
6.1. 
Subject Enrollment and Treatment Assignment 
Subjects who meet protocol eligibility criteria will be randomized in a blinded fashion in a 
2:2:1 ratio to 1 of 3 treatment groups as described in Section 5.3. 
6.2. 
Sequence of Assessments at Study Visits 
Subject-repo1ied outcomes are recommended to be completed before any other study procedures. 
Invasive study procedures such as blood draws should be perfo1med at the end of a study visit, as 
much as possible. Investigator questionnaires/assessments should be perfo1med prior to 
reviewing subject-repo1ied outcomes for that visit, as much as possible. 
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6.4. 
Randomization and Study Drug Administration 
• 
Enter subject infonnation in the IWRS to receive treatment assignment 
• 
Dispense study drng as directed by the IWRS 
Final 
Amendment5 
• 
Instrnct the subject on the packaging, storage, and administration of the study chug 
• 
Observe the subject taking the first dose of study ch11g and record the time of first dose 
6.5. 
Flexible Sigmoidoscopy 
A centrally read flexible sigmoidoscopy will be conducted at screening to assess the rectum and 
anal canal and detennine the severity of proctitis via SES-CD (refer to Appendix 5). At Week 24, 
endoscopic appearance of the rectum and anal canal will be assessed again by centrally read 
flexible sigmoidoscopy. 
Screening flexible sigmoidoscopy should be perfo1med only after subject eligibility based on 
CDAI is confnmed. If there are any outstanding screening clinical laborato1y assessments at the 
time the baseline CDAI is calculated, these results must also be confnmed as being within 
eligibility requirements prior to conducting the flexible sigmoidoscopy. Consideration should be 
given to central reader review turnaround times to ensure results are available prior to Day 1. 
Week 24 flexible sigmoidoscopy should be perfo1med no earlier than 14 days prior to the Week 
24 visit. If possible, flexible sigmoidoscopy should be perfo1med on the same day as the MRI 
procedure. 
An early te1mination (ET) flexible sigmoidoscopy must be perfo1med prior to the subject leaving 
the study for subjects that early ET due to either: 
1) non-response of their moderately active luminal disease at Week 10, OR 
2) non-response of their perianal fistulizing disease at Week 10, OR 
3) meeting disease worsening criteria after Week 10. 
For additional details on the flexible sigmoidoscopy procedure, refer to the Endoscopy Manual. 
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6.6.
Magnetic Resonance Imaging
A centrally read MRI will be conducted at screening to determine the anatomy of draining 
perianal fistulae. At Week 24, MRI will be used to evaluate healing of fistulae in addition to 
clinical assessment of drainage and fistula closure.
Screening MRI should be performed only after subject eligibility based on CDAI is confirmed. If 
there are any outstanding screening clinical laboratory assessments at the time the baseline CDAI 
is calculated, these results must also be confirmed as being within eligibility requirements prior 
to conducting the MRI. Consideration should be given to central reader review turnaround times 
to ensure results are available prior to Day 1. 
Week 24 MRI should be performed no earlier than 14 days prior to the Week 24 visit. 
Glomerular filtration rate (GFR) using the Cockcroft-Gault Model for creatinine clearance from 
the Week 18 visit should be reviewed prior to the Week 24 MRI. Since this procedure involves 
the use of a gadolinium-based contrast, subjects with an eGFR < 40 mL/min at Week 18 require 
approval from the Medical Monitor to undergo MRI.
An ET MRI must be performed prior to the subject leaving the study for subjects that early ET 
due to either:
1) non-response of their moderately active luminal disease at Week 10, OR
2) non-response of their perianal fistulizing disease at Week 10, OR
3) meeting disease worsening criteria after Week 10. 
GFR using the Cockcroft-Gault Model for creatinine clearance from the Week 10 visit 
(for Week 10 non-responders) or the last scheduled study visit prior to disease worsening, should 
be reviewed prior to the ET MRI. Since this procedure involves the use of a gadolinium-based 
contrast, subjects with an eGFR < 40 mL/min require approval from the Medical Monitor to 
undergo MRI.
For additional details on the MRI procedure, refer to the MRI Manual. 
6.7.
Perianal Assessment
The perianal assessment entails identification of external openings of perianal fistulae and 
evaluation of their status.
For additional details on the perianal assessment and how to document it using the Perianal 
Fistula Assessment Worksheet, refer to the Perianal Fistula Assessment Manual. 


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6.11.
Safety
Safety will be assessed via AEs, concomitant medications, physical examinations (complete and 
symptom-driven), vital signs, ECGs, and clinical laboratory results.
6.11.1.
Clinical Laboratory Evaluations
The hematology and serum chemistry analyses will be performed at a central laboratory. 
Reference ranges will be supplied by the central laboratory and will be used by the investigator 
to assess the laboratory data for clinical significance and pathological changes.
Blood samples will be collected by venipuncture 
 
 in the arm at the time points indicated in the Study Procedures Table 
(Appendix 2). In addition, urine samples for the clinical laboratory assessments will be collected. 
An overnight fast (no food or drinks, except water) of at least 8 hours will be required prior 
to collection of blood samples for lipid testing.
Laboratory values outside the normal range will be flagged and clinical relevance will be 
assessed by the investigator. More frequent sampling as well as additional tests may be 
performed as deemed necessary by the investigator.
Note that in the case where clinically significant laboratory test results are a potential reason for 
discontinuation from the study drug and/or withdrawal from the study, retesting of the affected 
parameter(s) should be prompt (within 3 to 7 days [except creatinine, which should be retested 
7 to 14 days apart]).
Refer to Appendix 10 for table of clinical laboratory tests. The details of sample handling and 
shipment instructions will be provided in a separate laboratory manual.
CCI


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6.11.1.1.
Tuberculosis Testing
Subjects must have negative QuantiFERON® test during screening, and negative chest X ray 
within 3 months of or during screening for those with no evidence or history of TB. Positive or 
negative QuantiFERON® test results must not be repeated. An indeterminate result should be 
repeated once and the second result (if positive or negative) will be considered final. 
Two sequential indeterminate results constitute a screen failure. Subjects with previously treated 
latent or active TB require sponsor approval. Subjects who are diagnosed with latent TB at 
screening must initiate an adequate course of prophylaxis as per local standard of care for a 
minimum of 4 weeks prior to randomization. Subject may initiate study drug dosing only after 
consultation with the Study Medical Monitor.
6.11.1.2.
HBV Screening and Surveillance Guidelines

Subjects with positive HBV surface antigen at screening are excluded.

Subjects who are positive for HBV surface antibody but negative for both HBV surface
antigen and HBV core antibody (HBcAb) at screening are eligible.

Subjects with positive HBcAb require reflex testing for HBV DNA (conducted locally). 
Subjects with HBV DNA ≥ lower limit of quantitation (LLOQ) at screening will be 
excluded. Subjects with positive HBcAb and HBV DNA < LLOQ are eligible, but will 
require ongoing HBV DNA monitoring (conducted locally) every 3 months during this study. 
These subjects may require prophylactic treatment per investigator discretion in accordance 
with local guidelines/standard of care.
6.11.1.3.
Thromboembolic Events
Subjects experiencing a thromboembolic event should be evaluated for the overall risk of 
recurrent thromboembolism and referred to a specialist for further testing as appropriate 
(including but not limited to evaluation for an underlying inherited hypercoagulable state).
6.11.2.
Repeat Screening Assessments
A single retest of screening labs is permitted only if there is reason to believe the retest value will 
be within accepted parameters, or if the initial value was either due to a sample processing error 
or due to an extenuating circumstance.
Flexible sigmoidoscopy or MRI may be repeated with prior written approval provided by the 
Sponsor, if the original imaging assessment was not considered acceptable due to technical 
reasons (e.g. poor quality or missing sequences).
Subjects meeting all of the inclusion criteria and none of the exclusion criteria will return to the 
clinic within 30 days after screening for randomization into the study. Subjects may be 
randomized more than 30 days after initial screening if they receive permission from the Gilead
Study Director in consultation with the Study Medical Monitor. If the subject does not begin 


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treatment within this 30-day window, specific screening evaluation procedures may need to be 
repeated at the direction of the Study Medical Monitor. No more than 1 repeat screening visit is 
allowed for each subject, unless prior written approval has been provided by the Sponsor.
6.11.3.
Pregnancy Testing (for females of childbearing potential only)
All females meeting the childbearing potential criteria (Appendix 9) must have a serum 
pregnancy test at screening that will be centrally reported, and an in-clinic urine pregnancy test 
must be completed every 4 weeks at a minimum. If any pregnancy test is positive, study drug 
should be immediately interrupted and the subject should have a serum pregnancy test in clinic
that will be centrally reported. Confirmed pregnancies should be reported as outlined in 
Section 7.7.2.1.
6.11.4.
Vital Signs
Vital signs will be measured at the time points indicated in the Study Procedures Table 
(Appendix 2).
Vital signs should be taken after the subject has been resting in the seated or supine position for 
at least 5 minutes and will include pulse rate, respiratory rate, systolic and diastolic blood 
pressure, and temperature.
6.11.5.
Physical Examination
A physical examination should be performed at the time points indicated in the Study Procedures 
Table (Appendix 2). Any changes from screening will be recorded. Weight will be measured at 
all visits, except Week 20. Height will be measured at screening only. Subjects should be 
instructed to remove shoes prior to measurement of height.
At screening, a complete physical examination will be performed. A complete physical 
examination will include source documentation of general appearance and the following body 
systems: head, neck, and thyroid; eyes, ears, nose, throat, mouth and tongue; chest 
(excluding breasts); respiratory; cardiovascular; lymph nodes; abdomen; skin, hair, nails; 
musculoskeletal; and neurological. Symptom-driven physical examinations will be performed, as 
needed, at all other visits based on reported signs and symptoms.
6.11.6.
12-lead Electrocardiogram
A resting 12-lead ECG will be performed at the time points indicated in the Study Procedures 
Table (Appendix 2).
The ECG should be obtained after the subject has been resting in the supine position for at least 
5 minutes and will include heart rate (HR), inter-beat (RR), QRS, uncorrected QT, morphology, 
and rhythm analysis. Electrocardiograms will be interpreted by the investigator (or qualified
designee) for clinical significance and results will be entered into the eCRF.


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• 
6.13. 
Post-Treatment Assessments 
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All subjects must complete the PTx assessments 30 days after the last dose of study drng. 
Only subjects who choose to paiiicipate in the LTE study will not complete PTx assessments 
associated with this protocol: 
• 
Symptom-directed PE including perianal assessment 
• 
Obtain body weight and vital signs (resting blood pressure, respiratory rate, pulse, 
and temperature) 
• 
Review AEs and concomitant medications 
• 
Obtain blood samples (see Study Procedures Table [Appendix 2]) 
• 
Obtain urine sample for pregnancy test (for females of childbeai·ing potential only) 
6.14. 
Early Termination Assessments 
For subjects who eai·ly tenninate from the study, the following tests and procedures will be 
perfo1med and documented: 
• 
Symptom-directed PE including perianal assessment 
• 
MRI Pelvis 
• 
Flexible sigmoidoscopy 
• 
Obtain body weight and vital signs (resting blood pressure, respiratory rate, pulse, 
and temperature) 
• 
Perfo1m 12-Lead ECG (for subjects who te1minate prior to Week 10) 
• 
Review AEs and concomitant medications 
• 
Collect eDiaiy back from subject 
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
Obtain blood samples (see Study Procedures Table [Appendix 2])

Obtain urine sample for pregnancy test (for females of childbearing potential only) 
(see Study Procedures Table [Appendix 2])
CCI
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7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An AE is any untoward medical occurrence in a clinical study subject administered a medicinal 
product, which does not necessarily have a causal relationship with the treatment. An AE can 
therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated 
with the use of a medicinal product, whether or not considered related to the medicinal product.
AEs may also include pre- or post-treatment complications that occur as a result of protocol 
specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or occupational 
exposure. Preexisting events that increase in severity or change in nature during or as a 
consequence of participation in the clinical study will also be considered AEs.
An AE does not include the following:

Medical or surgical procedures such as surgery, endoscopy, tooth extraction, and transfusion.
The condition that led to the procedure may be an AE and must be reported.

Pre-existing diseases, conditions, or laboratory abnormalities present or detected before the 
screening visit that do not worsen

Situations where an untoward medical occurrence has not occurred (e.g., hospitalization for 
elective surgery, social and/or convenience admissions)

Overdose without clinical sequelae (see Section 7.7.1)

Any medical condition or clinically significant laboratory abnormality with an onset date 
before the consent form is signed and not related to a protocol-associated procedure is not an 
AE. It is considered to be pre-existing and should be documented on the medical history 
CRF.
7.1.2.
Serious Adverse Events
A SAE is defined as an event that, at any dose, results in the following:

Death

Life-threatening (Note: The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject 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.)

In-patient hospitalization or prolongation of existing hospitalization


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
Persistent or significant disability/incapacity

A congenital anomaly/birth defect

A medically important event or reaction: such events may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes constituting SAEs. Medical and 
scientific judgment must be exercised to determine whether such an event is a reportable 
under expedited reporting rules. Examples of medically important events include intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or 
convulsions that do not result in hospitalization; and development of drug dependency or 
drug abuse. For the avoidance of doubt, infections resulting from contaminated medicinal 
product will be considered a medically important event and subject to expedited reporting 
requirements.
7.2.
Assessment of Adverse Events and Serious Adverse Events
The investigator or qualified subinvestigator is responsible for assessing AEs and SAEs for 
causality and severity, and for final review and confirmation of accuracy of event information 
and assessments.
7.2.1.
Assessment of Causality for Study Drugs and Procedures
The investigator or qualified subinvestigator is responsible for assessing the relationship to IMP 
therapy using clinical judgment and the following considerations:

No: Evidence exists that the AE has an etiology other than the IMP. For SAEs, an alternative 
causality must be provided (eg, pre-existing condition, underlying disease, intercurrent 
illness, or concomitant medication).

Yes: There is reasonable possibility that the event may have been caused by the 
investigational medicinal product.
It should be emphasized that ineffective treatment should not be considered as causally related in 
the context of AE reporting.
The relationship to study procedures (eg, invasive procedures such as venipuncture or biopsy) 
should be assessed using the following considerations:

No: Evidence exists that the AE has an etiology other than the study procedure.

Yes: The AE occurred as a result of protocol procedures (eg, venipuncture).


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7.2.2.
Assessment of Severity
The severity of AEs will be graded using the modified Common Terminology Criteria for 
Adverse Events (CTCAE), version 4.03. For each episode, the highest grade attained should be 
reported.
If a CTCAE criterion does not exist, the investigator should use the grade or adjectives: 
Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening) or 
Grade 5 (fatal) to describe the maximum intensity of the AE. For purposes of consistency with 
the CTCAE, these intensity grades are defined in Table 7-1 and Appendix 8
Table 7-1.
Grading of Adverse Event Severity
Grade
Adjective
Description
Grade 1
Mild
Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated
Grade 2
Moderate
Local or noninvasive intervention indicated; limiting age-appropriate 
instrumental ADL
Grade 3
Severe
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care ADL
Grade 4
Life-threatening
Urgent intervention indicated
Grade 5
Death
Death related AE
*
Activities of Daily Living (ADL) Instrumental ADL refer to opening preparing meals, shopping for groceries or clothes, 
using the telephone, managing money, etc.
**
Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events 
and Serious Adverse Events to Gilead
Requirements for collection prior to study drug initiation:
After informed consent, but prior to initiation of study medication, the following types of events 
should be reported on the case report form (eCRF): all SAEs and AEs related to protocol-
mandated procedures.
7.3.1.
Adverse Events
Following initiation of study drug, all AEs, regardless of cause or relationship, until 30-days
after last administration of study IMP must be reported to the eCRF database as instructed.
All AEs should be followed up until resolution or until the AE is stable, if possible. Gilead may 
request that certain AEs be followed beyond the protocol defined follow up period.
7.3.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post treatment follow-up period, must be reported to the 
eCRF database and Gilead PVE as instructed. This also includes any SAEs resulting from 
protocol-associated procedures performed after informed consent is signed.


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Any SAEs and deaths that occur after the post tr·eatment follow-up visit but within 30-days of the 
last dose of study IMP, regardless of causality, should also be repo1ted. fuvestigators are not 
obligated to actively seek SAEs after the protocol defined follow up period. However, if the 
investigator learns of any SAEs that occur after study paiticipation has concluded and the event 
is deemed relevant to the use of IMP, he/she should promptly document and repo1t the event to 
Gilead PVE. 
• 
All AEs and SAEs will be recorded in the eCRF database within the timelines outlined in the 
eCRF completion guideline. 
• 
At the time of study strut, SAEs may be reported using a paper serious adverse event 
repo1ting fo1m. During the study conduct, sites may tr·ansition to an electr·onic SAE ( eSAE) 
system. 
Elech'onic Serious Adverse Event Repo1ting Process 
• 
Site personnel record all SAE data in the eCRF database and from there tr·ansmit the SAE 
info1mation to Gilead PVE within 24 hours of the investigator's knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines. 
• If for any reason it is not possible to record the SAE infonnation electr·onically, ie, the eCRF 
database is not functioning, record the SAE on the paper serious adverse event reporting 
fo1m and submit via fax and/or email within 24 hours to: 
GileadPVE: 
Fax: ~=--'PPD 
E-mail1P PD 
• 
As soon as it is possible to do so, any SAE repo1ted via paper must be h'anscribed into the 
eCRF Database according to instructions in the eCRF completion guidelines. 
• If an SAE has been repo1ted via a paper fonn because the eCRF database has been locked, 
no fuither action is necessaiy. 
• 
For fatal or life-threatening events, copies of hospital case repo1ts, autopsy repo1ts and other 
documents are also to be submitted by e-mail or fax when requested and applicable. 
Transmission of such documents should occur without personal subject identification, 
maintaining the tr·aceability of a document to the subject identifiers. 
• 
Additional infonnation may be requested to ensure the timely completion of accurate safety 
repo1ts. 
• 
Any medications necessaiy for tr·eatment of the SAE must be recorded onto the concomitant 
medication section of the subject's eCRF and the event description section of the SAE fonn. 
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7.4.
Gilead Reporting Requirements
Depending on relevant local legislation or regulations, including the applicable US FDA Code of 
Federal Regulations (CFR), the EU Clinical Trials Directive (2001/20/EC) and relevant updates, 
and other country-specific legislation or regulations, Gilead may be required to expedite to 
worldwide regulatory agencies reports of SAEs, serious adverse drug reactions (SADRs),
or SUSARs. In accordance with the EU Clinical Trials Directive (2001/20/EC), Gilead or a 
specified designee will notify worldwide regulatory agencies and the relevant IEC in concerned 
Member States of applicable SUSARs as outlined in current regulations.
Assessment of expectedness for SAEs will be determined by Gilead using reference safety 
information specified in the IB or relevant local label as applicable.
All investigators will receive a safety letter notifying them of relevant SUSAR reports associated 
with any study IMP. The investigator should notify the IRB or IEC of SUSAR reports as soon as 
is practical, where this is required by local regulatory agencies, and in accordance with the local 
institutional policy.
7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities are usually not recorded as AEs or SAEs. However, laboratory 
abnormalities (eg, clinical chemistry, hematology, and urinalysis) independent of the 
underlying medical condition that require medical or surgical intervention or lead to 
investigational medicinal product interruption or discontinuation must be recorded as an AE, 
as well as an SAE, if applicable. In addition, laboratory or other abnormal assessments (eg, ECG, 
x-rays, vital signs) that are associated with signs and/or symptoms must be recorded as an AE or 
SAE if they meet the definition of an AE (or SAE) as described in Sections 7.1.1 and 7.1.2. If the 
laboratory abnormality is part of a syndrome, record the syndrome or diagnosis (ie, anemia) not 
the laboratory result (ie, decreased hemoglobin).
Severity should be recorded and graded according to the CTCAE Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 8). For AEs associated with laboratory 
abnormalities, the event should be graded on the basis of the clinical severity in the context of 
the underlying conditions; this may or may not be in agreement with the grading of the 
laboratory abnormality.
7.6.
Toxicity Management
All clinical and clinically significant laboratory toxicities will be managed according to uniform 
guidelines detailed in Appendix 3, and as outlined below.
Refer to Section 3.5, Criteria for Study Drug Interruption or Discontinuation, for additional 
specific discontinuation criteria. Specific toxicity discontinuation criteria in Section 3.5
supersede the below general toxicity guidelines, and in general, where discrepancy is present, the 
more conservative criteria should apply. The Study Medical Monitor should be consulted prior to 
study drug discontinuation when medically feasible.


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7.6.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event
Continue study drug at the discretion of the investigator.
7.6.2.
Grade 3 Laboratory Abnormality or Clinical Event
For a Grade 3 clinically significant laboratory abnormality or clinical event, IMP may be 
continued if the event is considered to be unrelated to IMP.
For a Grade 3 clinical event, or clinically significant laboratory abnormality confirmed by repeat 
testing, that is considered to be related to IMP, IMP should be withheld until the toxicity returns 
to ≤ Grade 2.
If a laboratory abnormality recurs to ≥ Grade 3 following re-challenge with IMP and is 
considered related to IMP, then IMP should be permanently discontinued and the subject 
managed according to local practice. Recurrence of laboratory abnormalities considered 
unrelated to IMP may not require permanent discontinuation.
7.6.3.
Grade 4 Laboratory Abnormality or Clinical Event
For a Grade 4 clinical event or clinically significant Grade 4 laboratory abnormality confirmed 
by repeat testing that is considered related to IMP, IMP should be permanently discontinued and 
the subject managed according to local practice. The subject should be followed as clinically 
indicated until the laboratory abnormality returns to baseline or is otherwise explained, 
whichever occurs first. A clinically significant Grade 4 laboratory abnormality that is not 
confirmed by repeat testing should be managed according to the algorithm for the new toxicity 
grade.
Investigational medicinal product may be continued without dose interruption for a clinically 
non-significant Grade 4 laboratory abnormality (eg, Grade 4 creatine kinase [CK] after strenuous 
exercise or triglyceride elevation that is nonfasting or that can be medically managed) or a 
clinical event considered unrelated to IMP.
Treatment-emergent toxicities will be noted by the investigator and brought to the attention of 
the Study Medical Monitor, who will have a discussion with the investigator and decide the 
appropriate course of action. Whether or not considered treatment-related, all subjects 
experiencing AEs must be monitored periodically until symptoms subside, any abnormal 
laboratory values have resolved or returned to baseline levels or they are considered irreversible, 
or until there is a satisfactory explanation for the changes observed.
Any questions regarding toxicity management should be directed to the Study Medical Monitor.
7.7.
Special Situations Reports
7.7.1.
Definitions of Special Situations
Special situation reports include all reports of medication error, abuse, misuse, overdose, 
occupational exposure, drug interactions, exposure via breastfeeding, unexpected benefit, 
transmission of infectious agents via the product, product complaints, counterfeit or falsified 
medicine, and pregnancy reports regardless of an associated AE.


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Medication error is any unintentional error in the prescribing, dispensing, preparation for 
administration or administration of an investigational product while the medication is in the 
control of a health care professional, patient, or consumer. Medication errors may be classified as 
a medication error without an AE, which includes situations of missed dose; medication error 
with an AE; intercepted medication error; or potential medication error.
Abuse is defined as persistent or sporadic intentional excessive use of an investigational product 
by a subject.
Misuse is defined as any intentional and inappropriate use of an investigational product that is 
not in accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of an
investigational product given per administration or cumulatively which is above the maximum 
recommended dose as per protocol or in the product labelling (as it applies to the daily dose of 
the subject in question). In cases of a discrepancy in drug accountability, overdose will be 
established only when it is clear that the subject has taken the excess dose(s). Overdose cannot 
be established when the subject cannot account for the discrepancy except in cases in which the 
investigator has reason to suspect that the subject has taken the additional dose(s).
Occupational exposure is defined as exposure to an investigational product as a result of one's 
professional or non-professional occupation.
Drug interaction is defined as any drug/drug, drug/food, or drug/device interaction.
Unexpected benefit is defined as an unintended therapeutic effect where the results are judged to 
be desirable and beneficial. 
Transmission of infectious agents is defined as any suspected transmission of an infected agent 
through a GSI investigational product.
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the investigational product.
Counterfeit or falsified medicine: Any investigational product with a false representation of: a) 
its identity, b) its source, or c) its history.  
7.7.2.
Instructions for Reporting Special Situations
7.7.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study drug and throughout the study, including the post study drug follow-up 
period, to the Gilead PVE using the pregnancy report form within 24 hours of becoming aware 
of the pregnancy.


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Refer to Section 7.3 and the eCRF completion guidelines for full instructions on the mechanism 
of pregnancy repo1ting. 
The pregnancy itself is not considered an AE nor is an induced elective abo1tion to tenninate a 
pregnancy without medical reasons. 
Any premature termination of pregnancy ( eg, a spontaneous abo1tion, an induced therapeutic 
abo1tion due to complications or other medical reasons) must be reported within 24 hours as an 
SAE. The underlying medical reason for this procedure should be recorded as the AE te1m. 
A spontaneous abo1tion is always considered to be an SAE and will be repo1ted as described in 
Section 7.3.2. Fmthe1more, any SAE occuning as an adverse pregnancy outcome post study 
must be repo1ted to Gilead PVE. 
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be repo1ted to Gilead PVE using the pregnancy outcome repo1t 
fo1m. If the end of the pregnancy occurs after the study has been completed, the outcome should 
be repo1ted directly to Gilead PVE. Gilead PVE contact info1mation is as follows: 
GileadPVE: 
Fax: 
E-mail: 
PD 
PD 
Pregnancies of female paitners of male study subjects exposed to Gilead or other study diugs 
must also be repo1ted and relevant info1mation should be submitted to Gilead PVE using the 
pregnancy and pregnancy outcome fo1ms within 24 hours. If the end of the pregnancy occurs 
after the study has been completed, the outcome should be repo1ted directly to Gilead PVE. 
GileadPVE: 
Fax: 
E-mail: 
PPD 
PPD 
Refer to Appendix 9 for Pregnancy Precautions, Definition for Female of Childbeai·ing Potential, 
and Cont:I'aceptive Requirements. 
7.7.2.2. 
Repo1ting Other Special Situations 
All other special situation repo1ts must be repo1ted on the special situations repo1t fonn and 
fo1wai·ded to Gilead PVE within 24 hours of the investigator becoming aware of the situation. 
These repo1ts must consist of situations that involve study diug and/or Gilead conc01nitant 
medications, but do not apply to non-Gilead concomitant medications. 
Special situations involving non-Gilead conc01nitant medications do not need to be repo1ted on 
the special situations repo1t fo1m; however, for special situations that result in AEs due to a 
non-Gilead concomitant medication, the AE must be repo1ted as an AE. 
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Any inappropriate use of concomitant medications prohibited by this protocol should not be 
reported as “misuse,” but may be more appropriately documented as a protocol deviation.
Refer to Section 7.3 and the eCRF completion guidelines for full instructions on f special 
situations reporting.
All clinical sequelae in relation to these special situation reports will be reported as AEs or SAEs 
at the same time using the AE eCRF and/or the SAE report form. Details of the symptoms and 
signs, clinical management, and outcome will be reported, when available.


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8. 
8.1. 
8.1.1. 
STATISTICAL CONSIDERATIONS 
Analysis Objectives and Endpoints 
Analysis Objectives 
The prima1y objective is: 
Final 
Amendment5 
• 
To evaluate the efficacy of filgotinib as compared to placebo in establishing combined fistula 
response at Week 24 
The secondaiy objectives are: 
• 
To evaluate the efficacy of filgotinib as compared to placebo in establishing combined fistula 
reinission at Week 24 
• 
To assess the time to clinical fistula response 
• 
To assess the time to clinical fistula remission 
• 
To evaluate the efficacy of filgotinib as compared to placebo in establishing proctitis 
reinission at Week 24, in subjects that had moderately to severely active proctitis at baseline 
• 
To evaluate the safety and tolerability of filgotinib 
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8.1.2. 
Primary Endpoint 
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The prima1y efficacy endpoint is the propo1iion of subjects establishing combined fistula 
response at Week 24 
8.1.3. 
Secondary Endpoints 
The secondaiy efficacy endpoints ai·e: 
• 
Proportion of subjects establishing combined fistula remission at Week 24 
• 
Time to clinical fistula response 
• 
Time to clinical fistula remission 
• 
Propo1iion of subjects achieving proctitis remission at Week 24, in subjects that had 
moderately to severely active proctitis at baseline 
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8.2. 
8.2.1. 
8.2.1.1. 
Analysis Conventions 
Analysis Sets 
Efficacy 
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The prima1y analysis set for efficacy analyses will be the Full Analysis Set (FAS), defined as all 
randomized subjects who received at least one dose of study diug. 
8.2.1.2. 
Safety 
The prima1y analysis set for safety analyses is the Safety Analysis Set, defined as all subjects 
who received at least one dose of study di11g. 
- -
8.3. 
Data Handling Conventions 
Values for missing safety laborato1y data will not be imputed. However, a missing baseline result 
will be replaced with a screening result, if available. If no pre-treatment laborato1y value is 
available, the baseline value will be assumed to be nonnal (ie, no grade [Grade 0]) for the 
summary of graded laborato1y abnonnalities. If safety laborato1y results for a subject are missing 
for any reason at a time point, the subject will be excluded from the calculation of summaiy 
statistics for that time point. 
Values for missing vital signs data will not be imputed. However, a missing baseline result will 
be replaced with a screening result, if available. 
Laborato1y data that are continuous in nature but are less than the lower limit of quantitation or 
above the upper limit of quantitation will be imputed to the value of the lower or upper limit 
minus or plus one significant digit, respectively ( eg, if the result of a continuous laborato1y test 
is < 20, a value of 19 will be assigned; if the result of a continuous laborato1y test is < 20.0, a 
value of 19.9 will be assigned). 
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8.4. 
Demographic Data and Baseline Characteristics 
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Demographic and baseline measurements will be summarized separately by treatment group 
using standard descriptive statistics (n, mean, standard deviation [SD], median, pt quaiiile [QI], 
3rd quaiiile [Q3], minimum, maximum) for continuous variables and number and percentage of 
subjects for categorical vai·iables. 
Demographic summai·ies will include age, sex, race and ethnici . Baseline chai·acteristics may 
include height, weight, body mass index (BMI), 
, number 
ofyeai·s since diagnosis of CD, anatomy of draining perianal fistulae (simple versus complex), 
presence of moderately to severely active proctitis (Yes or No), Receiving vedolizumab therapy 
concomitantly at Day I (Yes or No), fecal calprotectin, fecal lactofeITin, sernm CRP, and other 
vai·iables of interest. 
8.5. 
8.5.1. 
Efficacy Analysis 
Primary Analysis 
The number and propo1iion of subjects establishing combined fistula response at Week 24 for 
each treatment group will be summai·ized with co1Tesponding exact 90% CI based on binomial 
distribution (Clopper-Peai·son method). The difference in propo1iions between each filgotinib 
dose group and the placebo group will be presented along with the associated 90% CI. Subjects 
who do not have sufficient measurements to detennine efficacy endpoint will be considered 
failures (ie, non-responder imputation [NRI]). No fonnal hypothesis testing will be perfonned. 
8.5.2. 
Secondary Analyses 
The same Sllffilnai·ies used for the primaiy endpoint will be utilized for the propo1iion of subjects 
establishing combined fistula remission at Week 24. Subjects who do not have sufficient 
measurements to detennine efficacy endpoint will be considered failures (ie, NRI). 
For time-to-event secondaiy endpoints, the summaiy statistics (eg, median, QI, Q3) from the 
Kaplan-Meier method will be provided for each treatment group. The stratified Cox propo1iional 
hazai·ds model will be used to estimate the hazai·d ratio with the co1Tesponding 90% CI. 
8.6. 
Safety Analysis 
Safety will be evaluated by assessment of clinical laborato1y tests, PE, ECG and vital signs 
measurements at various time points during the study, and by the documentation of AEs. All 
safety data collected on or after the first dose of study diug adininistration (Day I) up to 30 days 
after pennanent discontinuation of study diug will be sllffilnai·ized by treatment group according 
to the study diug received. 
All data collected during the course of the study will be included in data listings. 
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8.6.1.
Extent of Exposure
A subject’s extent of exposure to study drug will be generated from the study drug 
administration page of the eCRF. The number of doses administered and the level of adherence 
will be summarized by treatment group.
8.6.2.
Adverse Events
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). System Organ Class (SOC), High-Level Group Term (HLGT), High-Level Term 
(HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be attached to the clinical 
database.
Treatment-Emergent Adverse Events (TEAEs) are defined as 1 or both of the following:

Any AEs with an onset date of on or after the study drug start date for the entire study 
(Day 1) and up to 30 days after permanent discontinuation of study drug.

Any AEs leading to premature discontinuation of study drug.
Summaries (number and percentage of subjects) of TEAEs by SOC and PT will be provided by 
treatment group. TEAEs will also be summarized by relationship to study drug and severity. In 
addition, TEAEs leading to premature discontinuation of study drug will be summarized and 
listed.
8.6.3.
Laboratory Evaluations
Selected laboratory data (using conventional units) will be summarized using only observed data. 
Absolute value and change from baseline at all scheduled time points will be summarized.
Graded laboratory abnormalities will be defined using the grading scheme defined in the 
Common Terminology Criteria for Adverse Events (CTCAE).
Incidence of treatment-emergent laboratory abnormalities defined as values that increase at least 
1 toxicity grade from baseline at any time post baseline will be summarized by treatment group. 
If baseline data are missing, then any graded abnormality (ie, at least a Grade 1) will be 
considered treatment-emergent.
8.6.4.
Other Safety Evaluations
Individual data for physical examination findings, prior and concomitant medications and 
medical history will be provided. Twelve-lead ECGs and vital signs measurements will be listed 
by subject and summarized by incidence of events/abnormalities or descriptive statistics as 
appropriate.


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8.8. 
Sample Size 
Final 
Amendment 5 
A total of approximately 75 subjects are planned to be randomized (2:2: 1 ratio); 30 subjects to 
each of the filgotinib dose groups and 15 subjects to the placebo group. This sample size is 
considered adequate to assess the safety, tolerability, and efficacy of filgotinib in a descriptive 
manner. 
Table 8-1 provides the exact 90% CI using the binomial distribution for a given combined fistula 
response rate ranging from 20% to 80%: 
Table 8-1. 
Combined Fistula Response Rates (90% CI) 
Number 
Number of 
Response 
Lowe1· Limit of 
Upper Limit of 
Randomized 
Responders 
rate 
900/oCI 
90% CI 
30 
6 
20% 
9% 
36% 
30 
9 
30% 
17% 
47% 
30 
12 
40% 
25% 
57% 
30 
15 
50% 
34% 
66% 
30 
18 
60% 
43% 
75% 
30 
21 
70% 
53% 
83% 
30 
24 
80% 
64% 
91 % 
CI = confidence interval 
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8.9. 
Data Monitoring Committee 
Final 
Amendment5 
An external data monitoring committee (DMC) comprised of an independent statistician and 
two independent gastrnenterologists will review the progress of the study and perfonn interim 
reviews of safety data and provide recommendation to Gilead whether the nature, frequency, and 
severity of adverse effects associated with study ti·eatment wanant the early tennination of the 
study in the best interests of the participants, whether the study should continue as planned, or 
the study should continue with modifications. 
The DMC will meet twice to evaluate all available safety data of the study. The initial meeting 
will occur after approximately 20% of the planned total nlllllber of subjects complete their 
Week 10 visit. Following this, the next meeting will occur after approximately 50% of the 
subjects reach Week 10. Additionally, the DMC members may request an unscheduled review of 
the study data based on a concern for subject safety. An ad hoc DMC meeting may be ti·iggered 
by the following conditions: 
• 
:::: 2 subjects develop the same (by PT) related, Grade 4, unexpected AE in the infections and 
infestations SOC 
• 
:::: 2 subjects develop any related, Grade 4, thromboembolic events that have been positively 
adjudicated by the adjudication committee (see Section 8.10) 
• 
Any subject develops a Grade 5, related, unexpected AE. The definition of an unexpected AE 
will be based on the reference safety infonnation that is on file at the time the event occms 
After a minimlllll of 3 5 subjects ( estimated to be 7 from placebo group and 14 from each 
filgotinib ti·eatment group based on randomization ratio) are emolled and complete Week 10 visit 
or discontinue from the study, an interim futility analysis will be conducted to evaluate efficacy 
improvement in fistulizing disease. The Clllllulative safety anal sis and SllilllllaI statistics to 
evaluate erianal fistula closure of external openings, and 
improvement will be generated and provide to t e DMC. 
recommendation to either continue the study without modification or recommend that the study 
be halted due to lack of efficacy, and will be based on the totality of data available at the time of 
the interim analysis. 
The DMC's specific activities will be defined by a mutually agreed upon chaiter, which will 
define the DMC's membership, conduct and meeting schedule. 
While the DMC will be asked to advise Gilead regarding future conduct of the study, including 
possible eai·ly study tennination, Gilead retains final decision-making authority on all aspects of 
the study. If the DMC recommends stopping the study for lack of efficacy, a Gilead executive 
teain will be unblinded to confom the DMC recommendation. 
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8.10.
Cardiovascular Safety Endpoint Adjudication Committee (CVEAC)
An independent adjudication committee will be formed to periodically review and adjudicate all 
potential major adverse cardiovascular events (MACE) and thromboembolic events in a blinded 
manner.
The CVEAC’s specific activities will be governed by a mutually agreed charter, which will 
define the CVEAC’s membership, conduct, and meeting schedule.
The following events will be adjudicated and classified by the CVEAC:

Cardiovascular death

Myocardial infarction

Stroke 

Arterial thromboembolism

Venous thromboembolism (eg, deep venous thrombosis, pulmonary embolism)
Further details will be specified in the CVEAC charter.


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9.
RESPONSIBILITIES
9.1.
Investigator Responsibilities
9.1.1.
Good Clinical Practice
The investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki, International Council for Harmonisation (ICH) guidelines, or with the 
laws and regulations of the country in which the research is conducted, whichever affords the 
greater protection to the study subject. These standards are consistent with the European Union 
Clinical Trials Directive 2001/20/EC and Good Clinical Practice Directive 2005/28/EC.
The investigator will ensure adherence to the basic principles of Good Clinical Practice, as 
outlined in 21 CFR 312, subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, 
part 50, and 21 CFR, part 56.
The investigator and all applicable subinvestigators will comply with 21 CFR, Part 54, providing 
documentation of their financial interest or arrangements with Gilead, or proprietary interests in 
the investigational drug under study. This documentation must be provided prior to the 
investigator’s (and any subinvestigator’s) participation in the study. The investigator and 
subinvestigator agree to notify Gilead of any change in reportable interests during the study and 
for 1 year following completion of the study. Study completion is defined as the date when the 
last subject completes the protocol-defined activities.
9.1.2.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval
The investigator (or sponsor as appropriate according to local regulations) will submit this 
protocol, ICF, and any accompanying material to be provided to the subject (such as 
advertisements, subject information sheets, or descriptions of the study used to obtain informed 
consent) to an IRB/IEC. The investigator will not begin any study subject activities until
approval from the IRB/IEC has been documented and provided as a letter to the investigator.
Before implementation, the investigator will submit to and receive documented approval from 
the IRB/IEC any modifications made to the protocol or any accompanying material to be 
provided to the subject after initial IRB/IEC approval, with the exception of those necessary to 
reduce immediate risk to study subjects.
9.1.3.
Informed Consent
The investigator is responsible for obtaining written informed consent from each individual 
participating in this study after adequate explanation of the aims, methods, objectives, and 
potential hazards of the study and before undertaking any study-related procedures. The study 
investigator must ensure that the potential risk of infertility is discussed with all male 
subjects during the informed consent process. The investigator must use the most current


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IRB/IEC approved consent form for documenting written informed consent. Each informed 
consent (or assent as applicable) will be appropriately signed and dated by the subject or the 
subject’s legally authorized representative and the person conducting the consent discussion, and 
also by an impartial witness if required by IRB/IEC or local requirements. The consent form will 
inform subjects about genomic testing and sample retention.
9.1.4.
Confidentiality
The investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only subject initials, date of birth, another 
unique identifier (as allowed by local law) and an identification code will be recorded on any 
form or biological sample submitted to the Sponsor, IRB/IEC, or laboratory. Laboratory 
specimens must be labeled in such a way as to protect subject identity while allowing the results 
to be recorded to the proper subject. Refer to specific laboratory instructions or in accordance 
with local regulations. NOTE: The investigator must keep a screening log showing codes and 
names for all subjects screened and for all subjects enrolled in the trial. Subject data will be 
processed in accordance with all applicable regulations.
The investigator agrees that all information received from Gilead, including but not limited to the 
IB, this protocol, eCRF, the IMP, and any other study information, remain the sole and exclusive 
property of Gilead during the conduct of the study and thereafter. This information is not to be 
disclosed to any third party (except employees or agents directly involved in the conduct of the 
study or as required by law) without prior written consent from Gilead. The investigator further 
agrees to take all reasonable precautions to prevent the disclosure by any employee or agent of 
the study site to any third party or otherwise into the public domain.
9.1.5.
Study Files and Retention of Records
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following two categories: (1) investigator’s study file, 
and (2) subject clinical source documents.
The investigator’s study file will contain the protocol/amendments, CRF and query forms, 
IRB/IEC and governmental approval with correspondence, informed consent, drug records, 
staff curriculum vitae and authorization forms, and other appropriate documents and 
correspondence.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject identification (name, date of birth, gender);

Documentation that subject meets eligibility criteria, ie, history, PE, and confirmation of 
diagnosis (to support inclusion and exclusion criteria);


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
Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number);

Study discussed and date of informed consent;

Dates of all visits;

Documentation that protocol specific procedures were performed;

Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of IMP, including dates of dispensing and return;

Record of all AEs and other safety parameters (start and end date, and including causality 
and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, US, Europe, or Japan) and until there are no pending or planned marketing 
applications in an ICH region; or, if no application is filed or if the application is not approved 
for such indication, until 2 years after the investigation is discontinued and regulatory authorities 
have been notified. Investigators may be required to retain documents longer if specified by 
regulatory requirements, by local regulations, or by an agreement with Gilead. The investigator 
must notify Gilead before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, Gilead must be notified in advance.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Gilead to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
9.1.6.
Case Report Forms
For each subject consented, an eCRF will be completed by an authorized study staff member 
whose training for this function is documented according to study procedures. The eCRF should 
be completed on the day of the subject visit to enable the sponsor to perform central monitoring 
of safety data. The Eligibility Criteria eCRF should be completed only after all data related to 
eligibility has been received. Subsequent to data entry, a study monitor will perform source data 


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verification within the electronic data capture (EDC) system. Original entries as well as any 
changes to data fields will be stored in the audit trail of the system. Prior to database lock 
(or any interim time points as described in the clinical data management plan), the investigator 
will use his/her log in credentials to confirm that the forms have been reviewed, and that the 
entries accurately reflect the information in the source documents. The eCRF captures the data 
required per the protocol schedule of events and procedures. System-generated or manual queries 
will be issued to the investigative site staff as data discrepancies are identified by the monitor or 
internal Gilead staff, who routinely review the data for completeness, correctness, and 
consistency. The site coordinator is responsible for responding to the queries in a timely manner, 
within the system, either by confirming the data as correct or updating the original entry, and 
providing the reason for the update (eg, data entry error). At the conclusion of the trial, Gilead 
will provide the site with a read-only archive copy of the data entered by that site. This archive 
must be stored in accordance with the records retention requirements outlined in Section 9.1.5.
9.1.7.
Investigational Medicinal Product Accountability and Return
Where possible, IMP should be destroyed at the site. At the start of the study, the study monitor 
will evaluate each study center’s IMP disposal procedures and provide appropriate instruction for 
disposal or return of unused IMP supplies. If the site has an appropriate standard operating 
procedure (SOP) for drug destruction as determined by Gilead Sciences, the site may destroy 
used (empty or partially empty) and unused IMP supplies as long as performed in accordance 
with the site’s SOP. This can occur only after the study monitor has performed drug 
accountability during an on-site monitoring visit.
A copy of the site’s IMP Disposal SOP or written procedure (signed and dated by the Principal 
Investigator [PI] or designee) will be obtained for Gilead site files. If the site does not have 
acceptable procedures in place, arrangements will be made between the site and Gilead Sciences 
(or Gilead Sciences’ representative) for return of unused study drug supplies.
If IMP is destroyed on site, the investigator must maintain accurate records for all IMPs 
destroyed. Upon study completion, copies of the IMP accountability records must be filed at the 
site. Another copy will be returned to Gilead.
The study monitor will review IMP supplies and associated records at periodic intervals.
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to 
Gilead’s appointed study monitors, to IRBs/IECs or to regulatory authority or health authority 
inspectors.
9.1.9.
Protocol Compliance
The investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol.


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9.2.
Sponsor Responsibilities
9.2.1.
Protocol Modifications
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by Gilead. The investigator must submit all protocol modifications to the IRB/IEC in 
accordance with local requirements and receive documented IRB/IEC approval before 
modifications can be implemented.
9.2.2.
Study Report and Publications
A clinical study report (CSR) will be prepared and provided to the regulatory agency(ies). 
Gilead will ensure that the report meets the standards set out in the ICH Guideline for Structure 
and Content of Clinical Study Reports (ICH E3). Note that an abbreviated report may be 
prepared in certain cases.
Investigators in this study may communicate, orally present, or publish in scientific journals or 
other scholarly media only after the following conditions have been met:

The results of the study in their entirety have been publicly disclosed by or with the consent 
of Gilead in an abstract, manuscript, or presentation form or the study has been completed at 
all study sites for at least 2 years

The investigator will submit to Gilead any proposed publication or presentation along with 
the respective scientific journal or presentation forum at least 30 days before submission of 
the publication or presentation.

No such communication, presentation, or publication will include Gilead’s confidential 
information (see Section 9.1.4).

The investigator will comply with Gilead’s request to delete references to its confidential 
information (other than the study results) in any paper or presentation and agrees to withhold 
publication or presentation for an additional 60 days in order to obtain patent protection if 
deemed necessary.
9.3.
Joint Investigator/Sponsor Responsibilities
9.3.1.
Payment Reporting
Investigators and their study staff may be asked to provide services performed under this 
protocol, eg, attendance at Investigator's Meetings. If required under the applicable statutory and 
regulatory requirements, Gilead will capture and disclose to Federal and State agencies any 
expenses paid or reimbursed for such services, including any clinical trial payments, meal, travel 
expenses or reimbursements, consulting fees, and any other transfer of value.


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9.3.2.
Access to Information for Monitoring
In accordance with regulations and guidelines, the study monitor must have direct access to the 
investigator’s source documentation in order to verify the accuracy of the data recorded in the 
eCRF.
The monitor is responsible for routine review of the eCRF at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the eCRF. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected through any type of monitoring (central, on site) are resolved.
9.3.3.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of Gilead may conduct inspections or audits of the 
clinical study. If the investigator is notified of an inspection by a regulatory authority the 
investigator agrees to notify the Gilead Study Director immediately. The investigator agrees to 
provide to representatives of a regulatory agency or Gilead access to records, facilities, 
and personnel for the effective conduct of any inspection or audit.
9.3.4.
Study Discontinuation
Both the sponsor and the investigator reserve the right to terminate the study at any time. 
Should this be necessary, both parties will arrange discontinuation procedures and notify the 
appropriate regulatory authority(ies), IRBs, and IECs. In terminating the study, Gilead and the 
investigator will assure that adequate consideration is given to the protection of the subjects’ 
interests.


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10.
REFERENCES
Baumgart DC, Sandborn WJ. Crohn's disease. Lancet 2012;380 (9853):1590-605.
Cheifetz AS. Management of active Crohn disease. JAMA 2013;309 (20):2150-8.
Daperno M, D'Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, et al. Development and 
validation of a new, simplified endoscopic activity score for Crohn's disease: the 
SES-CD. Gastrointestinal endoscopy 2004;60 (4):505-12.
Dignass A, Van Assche G, Lindsay JO, Lemann M, Soderholm J, Colombel JF, et al. The second 
European evidence-based Consensus on the diagnosis and management of Crohn's 
disease: Current management. Journal of Crohn's & colitis 2010;4 (1):28-62.
Feagan BG, Schwartz D, Danese S, Rubin DT, Lissoos TW, Xu J, et al. Efficacy of 
Vedolizumab in Fistulising Crohn's Disease: Exploratory Analyses of Data from 
GEMINI 2. Journal of Crohn's & colitis 2018;12 (5):621-6.
Fukunaga K, Matsumoto T. Current status and future perspectives of leukocytapheresis for 
inflammatory bowel disease. J Gastroenterol Hepatol 2012;27 (6):997-1003.
Gecse K, Bemelman W, Kamm MA, Stoker J, Khanna R, Ng S, et al. A global consensus on the 
classiﬁcation,diagnosis and multidisciplinary treatment of perianal ﬁstulising 
Crohn’s disease. BMJ 2004:13.
Irvine EJ. Usual therapy improves perianal Crohn's disease as measured by a new disease 
activity index. McMaster IBD Study Group. J Clin Gastroenterol 1995;20 (1):27-
32.
Ito H, Takazoe M, Fukuda Y, Hibi T, Kusugami K, Andoh A, et al. A pilot randomized trial of a 
human anti-interleukin-6 receptor monoclonal antibody in active Crohn's disease. 
Gastroenterology 2004;126 (4):989-96; discussion 47.
Khanna R, Zou G, D'Haens G, Feagan BG, Sandborn WJ, Vandervoort MK, et al. A 
retrospective analysis: the development of patient reported outcome measures for 
the assessment of Crohn's disease activity. Aliment Pharmacol Ther 2015;41 
(1):77-86.
Korzenik JR. Investigational therapies in the medical management of Crohns disease. Available 
at: http://www.uptodate.com/contents/investiga. UpToDate 2016.


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Losco A, Vigano C, Conte D, Cesana BM, Basilisco G. Assessing the activity of perianal 
Crohn's disease: comparison of clinical indices and computer-assisted anal 
ultrasound. Inflammatory bowel diseases 2009;15 (5):742-9.
Lunniss PJ, Barker PG, Sultan AH, Armstrong P, Reznek RH, Bartram CI, et al. Magnetic 
resonance imaging of fistula-in-ano. Dis Colon Rectum 1994;37 (7):708-18.
Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, et al. Increasing incidence 
and prevalence of the inflammatory bowel diseases with time, based on 
systematic review. Gastroenterology 2012;142 (1):46-54 e42; quiz e30.
Myhr GE, Myrvold HE, Nilsen G, Thoresen JE, Rinck PA. Perianal fistulas: use of MR imaging 
for diagnosis. Radiology 1994;191 (2):545-9.
Namour F, Diderichsen PM, Cox E, Vayssiere B, Van der Aa A, Tasset C, et al. 
Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib 
(GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection. 
Clin Pharmacokinet 2015;54 (8):859-74.
Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, et al. Infliximab 
for the treatment of fistulas in patients with Crohn's disease. N Engl J Med 
1999;340 (18):1398-405.
Sandborn WJ, Feagan BG, Hanauer SB, Lochs H, Lofberg R, Modigliani R, et al. A review of 
activity indices and efficacy endpoints for clinical trials of medical therapy in 
adults with Crohn's disease. Gastroenterology 2002;122 (2):512-30.
Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, et al. Infliximab 
maintenance therapy for fistulizing Crohn's disease. N Engl J Med 2004;350 
(9):876-85.
Schwartz DA, Loftus EV, Jr., Tremaine WJ, Panaccione R, Harmsen WS, Zinsmeister AR, et al. 
The natural history of fistulizing Crohn's disease in Olmsted County, Minnesota. 
Gastroenterology 2002;122 (4):875-80.
Solomon MJ. Fistulae and abscesses in symptomatic perianal Crohn's disease. International 
journal of colorectal disease 1996;11 (5):222-6.
Van Assche G, D'Haens G, Noman M, Vermeire S, Hiele M, Asnong K, et al. Randomized, 
double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in 
severe ulcerative colitis. Gastroenterology 2003;125 (4):1025-31.
Ventham NT, Kennedy NA, Nimmo ER, Satsangi J. Beyond gene discovery in inflammatory 
bowel disease: the emerging role of epigenetics. Gastroenterology 2013;145 
(2):293-308.


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Vermeire S, Schreiber S, Petryka R, Kuehbacher T, Hebuterne X, Roblin X, et al. Clinical 
remission in patients with moderate-to-severe Crohn's disease treated with 
filgotinib (the FITZROY study): results from a phase 2, double-blind, 
randomised, placebo-controlled trial. Lancet 2017;389:266-75.


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Final 
Amendment5 
11. 
APPENDICES 
Appendix 1. 
Appendix 2. ... 
A 
endix 5. 
Appen ix 8. 
Appendix 9. 
Appendix 10. 
CONFIDENTIAL 
Investigator Signature Page 
Study Procedw-es Table 
Mana ement of Clinical and Laborat01 
ents 
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements 
Clinical Laborat01y Assessment Table 
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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404, USA 
STUDY ACKNOWLEDGEMENT 
Final 
Amendments 
A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy and 
Safety of Filgotinib in the Treatment of Perianal Fistulizing Crohn's Disease 
GS-US-419-4016, Amendment 5, 04 February 2020 
This protocol has been approved by Gilead Sciences, Inc. The following signatur 
this approval. 
[PPD 
PPD 
PPD 
Date 
PD 
I 
I 
(Printed) 
INVESTIGATOR STATEMENT 
ocuments 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Gilead Sciences, Inc. I will discuss this material with them to ensure 
that they are fully informed about the drugs and the study. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
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Appendix 2.
Study Procedures Table
Period
Screening
Treatment
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
PTxa
ET
Week
0
2
4
6
10
14
18
20
24
Study Day
-30 to -1
1
15
29
43
71
99
127
141
169
Visit Window (±)
±3
±3
±3
±2
±3
±3
±5
±5
±3
Written Informed Consent
X
Medical History & 
Demographics
X
Crohn’s Disease & 
Treatment History
X
12-lead ECG
X
X
Xb
Review of Inclusion/
Exclusion Criteria
X
X
Physical Exam (Complete 
including perianal)c
X
Physical Exam (symptom-
based) and perianal
assessmentc
X
X
X
X
X
X
X
X
X
X
Vital Signs
X
X
X
X
X
X
X
X
X
X
X
Weight
X
X
X
X
X
X
X
X
X
X
X
Height
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
Randomization
X
Study Drug Dispensing
X
X
X
X
X
eDiary instruction & 
reviewe
X
X
X
X
X
X
X
X
X
Flexible Sigmoidoscopyo
X
X
Xr
MRIf
X
X
Xs
CCI
CCI


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Protocol GS–US-419-4016
Final
Gilead Sciences, Inc.
Amendment 5
CONFIDENTIAL
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04 February 2020
Period
Screening
Treatment
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
PTxa
ET
Week
0
2
4
6
10
14
18
20
24
Study Day
-30 to -1
1
15
29
43
71
99
127
141
169
Visit Window (±)
±3
±3
±3
±2
±3
±3
±5
±5
±3
Stool for C. diff toxin, 
pathogenic E. coli, 
Salmonella, Shigella, 
Campylobacter and 
Yersinia testing
X
Stool O&P
X
Fecal Lactoferrin, 
Calprotectin
X
X
Urine drug screeng
X
Urinalysisq
X
X
Pregnancy Testh
X
X
X
X
X
X
X
X
X
X
X
TB screeningi
X
Chest x-rayq
X
HBV, HCV, HIV screeningj
X
Hematology
X
X
X
X
X
X
X
X
X
X
X
Chemistry
X
X
X
X
X
X
X
X
X
X
X
Fasting Lipidsp
X
X
X
CRP
X
X
X
X
X
X
X
X
X
X
X
Blood TCR/BCR repertoire 
samplek
X
X
X
X
Plasma biomarker sample
X
X
X
X
Serum biomarker sample
X
X
X
X
Blood transcriptome 
sample
X
X
X
X
Serum immunoglobulin
X
X
X
X
X
X
CCI
CCI
CCI


Filgotinib 
Protocol GS-US-419-4016 
Gilead Sciences, Inc. 
Final 
Amendment5 
a 
TI1e Post-Treatment (PTx) visit should occur 30 days after the last dose of study diug. Only subjects who roll over into the LTE study will not complete PTx assessments. 
b 
For subjects who terminate prior to Week IO 
c 
A complete physical examination (PE) including; vital signs, body weight, height, and perianal assessment (including completion of the Perianal Fistula Assessment 
I' 
e 
f 
g 
h 
k r 
' 
0 
p 
q 
r 
s 
Worksheet) will be pe1fon11ed at screening. A symptom-directed PE and perianal assessment(including completion of the Perianal Fistula Assessment Worksheet) should be 
e1fo1med at all other time oints. 
Su 1ects s ould begin filling out the eDiary the day of their initial screening visit and continue to fill it out throughout the remainder of the study. 
Refer to Section 6.6 for details on the MRI procedm·e 
Positive cocaine test disqualifies subject; positive amphetamines, barbittu·ates, benzodiazepines, and opioids require medical monitor review 
All females meeting the childbearing potential criteria must have a senuu pregnancy testing at screening and a urine pregnancy test must be completed every 4 weeks at a 
minimtuu. If any pregnancy test is positive, study dmg must be inimediately intem1pted and the subject should come to the site for senuu pregnancy test in clinic. 
Proof of no active or untreated latent TB at screening. Subjects who aie diagnosed with latent TB at screening must initiate an adequate cotu-se of prophylaxis as per local 
standard of care, for a minimtuu of 4 weeks prior to randomization. Subject may initiate study dmg dosing only after consultation with the Study Medical Monitor. 
An HIV-1/HIV-2 antibody test, a HCV antibody test, a HBV surface antigen test, a HBV stuface antibody test, and a HBV core antibody test will be pe1fo1med on all 
subjects. Subjects with positive HBcAb require reflex testing for HBV DNA (conducted locally). Refer to section 6.11.1.2 for further details. 
TCR: T-cell rece tor; BCR: B-cell rece tor 
Re er to Section 6.5 or eta1 s on e exi e sigmoidoscopy procedm·e 
Subjects should fast (no food or drinks, except water) for at least 8 hom·s prior to blood sample collection at Day I, Week IO, and Week 24 
Chest x-ray (views as per local guidelines) taken at screening or within the 3 months prior to screening (with the repo1t or fihus available for investigator review) without 
evidence of active or latent TB infection 
Subjects meeting non-response or disease worsening criteria should undergo a flexible sigmoidoscopy assessment prior to exiting the stt1dy. 
Subjects meeting non-response or disease wo1-sening criteria should tmdergo a pelvic MRI prior to exiting the study. 
CONFIDENTIAL 
Page 94 
04 Febrna1y 2020 


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Protocol GS–US-419-4016
Final
Gilead Sciences, Inc.
Amendment 5
CONFIDENTIAL
Page 95
04 February 2020
Appendix 3.
Management of Clinical and Laboratory Adverse Events
Grnde I 
Grnde2 
I 
I 
! 
la) continue 
dosing at the 
discretion of the 
investiaator 
Re1>eat l:lb to 
If confirmed and J>Ossibly mu oa· J>rnbably nlated to 
investigational medicinal J>rnducts: 
I. 
ithhold investigational medicinal IH'Oducts ,mtil 
~Grade2 
confirm toxicity 
grade 
2. 
Re!,tart all inve.~titational medicinal 1>roducts at full dose 
l 
If Grnde 3 or 4 recmTe1ue that is confinned and J>Ossibly 01· 
1n·obably related to inve.~tigational medicinal J>roducts 
discontinue all inve1>tigational medicinal 1n·oducts do.~ing 
1>ennanentlv 
Grnde 3 
I I 
! 
Re1>e:lt lab to 
confirm tox.icity 
gnlde 
l 
l 
If confirmed mul muelated to 
inve.~tigational medicinal 
J>•·oducts, dosing may continue at 
the di~cretion of the investigator 
Grnde 4 
If confirmed and 
1>0.~sibly or 1>robably 
_. rel:lted to 
investigation al 
medicinal 1>1·01lucts 
discontinue 
investigatiomll 
medicimll 1>roducts 
do.~ing J>ennm1ently 
mul follow at 
J>e1·iodic intei·vals at 
least weekly until a 
retm·n to baseline or 
is otherwise 
e~q>lained 
If Grnde 3 m·-' 1·ecmTence that is con!,iden.d mu·elated to 
investigational medicinal J>l'Oducts. continue all 
in e.~tigational medicinal 1>rnducts at the same dose at the 
disa-etion of the investigator 


Filgotinib 
Protocol GS-US-419-4016 
Gilead Sciences, Inc. 
-
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Final 
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Filgotinib
Protocol GS–US-419-4016
Final
Gilead Sciences, Inc.
Amendment 5
CONFIDENTIAL
Page 97
04 February 2020
Appendix 5.
Simple Endoscopic Score for Crohn’s Disease (SES-CD)
Variables
Score
0
1
2
3
Size of ulcers (cm)
None
Aphthous ulcers
(diameter 0.1-0.5)
Large ulcers
(diameter >0.5-2)
Very large ulcers
(diameter > 2)
Ulcerated Surface (%)
None
< 10
10-30
> 30
Affected surface (%)
Unaffected 
segment
< 50
50-75
> 75
Presence of narrowings
None
Single,
can be passed
Multiple,
can be passed
Cannot be passed
Total SES-CD: sum of the values of the 4 variables for the 5 bowel segments. Values are given to each variable and for every 
examined bowel segment (eg, rectum, left colon, transverse colon, right colon, and ileum); note Total SES-CD will not be 
calculated during Study GS-US-419-4016
{Daperno 2004}
For Study GS-US-419-4016, the Proctitis SES-CD score (which includes an overall assessment of both rectum and anal canal)
and Anal Canal Segmental SES-CD score will only score size of ulcers and ulcerated surface. The Proctitis SES-CD score will 
be used to provide an endoscopic measure of proctitis. 
 
CCI
-


Filgotinib
Protocol GS–US-419-4016
Final
Gilead Sciences, Inc.
Amendment 5
CONFIDENTIAL
Page 98
04 February 2020
CCI


Filgotinib 
Protocol GS-US-419-4016 
Gilead Sciences, Inc. 
I -
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Final 
Amendment5 
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04 Febrna1y 2020 


Filgotinib
Protocol GS–US-419-4016
Final
Gilead Sciences, Inc.
Amendment 5
CONFIDENTIAL
Page 100
04 February 2020
Appendix 8.
CTCAE Grading Scale for Severity of Adverse Events
Please refer to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03, 
which can be found at:
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf
For AEs associated with laboratory abnormalities, the event should be graded on the basis of the 
clinical severity in the context of the underlying conditions; this may or may not be in agreement 
with the grading of the laboratory abnormality.
The only modification to the CTCAE criteria is the addition of a Grade 1 upper respiratory 
infection as follows:
CTCAE 
v4.0 Term
Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
CTCAE v4.03 
AE Term 
Definition
Upper 
respiratory 
infection
Mild 
symptoms; 
symptomatic 
relief 
(eg, cough 
suppressant, 
decongestant)
Moderate 
symptoms; 
oral 
intervention 
indicated 
(eg, antibiotic, 
antifungal, 
antiviral)
IV antibiotic, 
antifungal, 
or antiviral 
intervention 
indicated; 
radiologic, 
endoscopic, 
or operative 
intervention 
indicated
Life-
threatening 
consequences; 
urgent 
intervention 
indicated
Death
A disorder 
characterized by 
an infectious 
process 
involving the 
upper respiratory 
tract 
(nose, paranasal 
sinuses, 
pharynx, larynx, 
or trachea).


Filgotinib
Protocol GS–US-419-4016
Final
Gilead Sciences, Inc.
Amendment 5
CONFIDENTIAL
Page 101
04 February 2020
Appendix 9.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
The administration of filgotinib in embryo-fetal animal development studies resulted in 
decreased numbers of viable rat fetuses, increased resorptions, and visceral and skeletal 
malformations. Similar effects were noted in the rabbit. A safety margin relative to human 
exposure has not been identified. Pregnancy is contraindicated during use of filgotinib.
For participation in this study, the use of highly effective contraception is required as outlined 
below for all subjects who are of childbearing potential. In addition, during the study women of 
childbearing potential must have at minimum, a urine pregnancy test every 4 weeks.
1) Definitions
a) Definition of Childbearing Potential
For the purposes of this study, a female-born subject is considered of childbearing potential 
following the initiation of puberty (Tanner stage 2) until becoming post-menopausal, unless 
permanently sterile or with medically documented ovarian failure. Women who do not meet 
below criteria for being post-menopausal, are not permanently sterile, or do not have medically 
documented ovarian failure must have pregnancy testing as outlined by the protocol.  
Women are considered to be in a postmenopausal state when they are > 54 years of age with 
cessation of previously occurring menses for > 12 months without an alternative cause.
Permanent sterilization includes hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy in a female subject of any age. Bilateral tubal ligation is not considered 
permanent sterilization.
b) Definition of Male Fertility
For the purposes of this study, a male-born subject is considered fertile after the initiation of 
puberty unless permanently sterilized by bilateral orchidectomy or has medical documentation of 
permanent male infertility. Vasectomy is not considered permanent sterilization.
2) Contraception for Female Subjects
a) Study Drug Effects on Pregnancy and Hormonal Contraception
Filgotinib is contraindicated in pregnancy as there is a possibility of human 
teratogenicity/fetotoxicity in early pregnancy based on non-clinical data. Data from a drug-drug 
interaction study of filgotinib and hormonal contraceptives (GS-US-417-3916) have 
demonstrated co-administration with filgotinib did not alter the pharmacokinetics of 
representative hormonal contraceptives levonorgestrel/ethinyl estradiol.
Please refer to the latest version of the filgotinib IB for additional information.


Filgotinib
Protocol GS–US-419-4016
Final
Gilead Sciences, Inc.
Amendment 5
CONFIDENTIAL
Page 102
04 February 2020
b) Contraception for Female Subjects of Childbearing Potential
The inclusion of female subjects of childbearing potential requires the use of highly effective 
contraceptive measures. Women must have a negative serum pregnancy test at screening and a 
negative urine pregnancy test on the Day 1 visit prior to randomization. Pregnancy tests will be 
performed at monthly intervals thereafter. In the event of a delayed menstrual period 
(> one month between menstruations), a pregnancy test must be performed to rule out pregnancy.
This is true even for women of childbearing potential with infrequent or irregular periods. 
Female subjects must agree to use one of the following methods from screening until 35 days 
following the last dose of study drug.

Complete abstinence from intercourse of reproductive potential. Abstinence is an acceptable 
method of contraception only when it is in line with the subject’s preferred and usual 
lifestyle.
Or

Consistent and correct use of 1 of the following methods of birth control listed below.
Intrauterine device (IUD) with a failure rate of < 1% per year
Tubal sterilization
Essure micro-insert system (provided confirmation of success 3 months after procedure)
Vasectomy in the male partner (provided that the partner is the sole sexual partner and 
had confirmation of surgical success 3 months after procedure)

Female subjects, who wish to use a hormonally based method, must use it in conjunction 
with a barrier method; the barrier method is to be used either by the female subject or by her 
male partner. Female subjects who utilize a hormonal contraceptive as one of their birth 
control methods must have consistently used the same method for at least three months prior 
to study dosing. Hormonally-based contraceptives and barrier methods permitted for use in 
this protocol are as follows:
Hormonal methods (each method must be used with a barrier method, preferably male 
condom )
■
Oral contraceptives (either combined estrogen/progestin or progesterone only)
■
Injectable progesterone
■
Implants of levonorgestrel
■
Transdermal contraceptive patch
■
Contraceptive vaginal ring


Filgotinib
Protocol GS–US-419-4016
Final
Gilead Sciences, Inc.
Amendment 5
CONFIDENTIAL
Page 103
04 February 2020
Barrier methods (each method must be used with a hormonal method)
■
Male or female condom with or without spermicide
■
Diaphragm with spermicide
■
Cervical cap with spermicide
■
Sponge with spermicide
All female subjects must also refrain from egg donation and in vitro fertilization during treatment 
and until at least 35 days after the last study drug dose.
3) Contraception Requirements for Male Subjects
It is theoretically possible that a relevant concentration of study drug may be achieved in a 
female partner from exposure to the male subject’s seminal fluid. Therefore, male subjects with 
female partners of childbearing potential must use condoms during study participation and for 
90 days after the last study drug dose. Female partners of male study subjects should consider 
using one of the above methods of contraception as well. Male subjects must also refrain from 
sperm donation during treatment and until at least 90 days after the end of study drug dosing.
4) Unacceptable Birth Control Methods
Birth control methods that are unacceptable include periodic abstinence (eg, calendar, ovulation, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, 
and lactational amenorrhea method (LAM). Female condom and male condom should not be 
used together.
5) Procedures to be Followed in the Event of Pregnancy
Subjects will be instructed to notify the investigator if they become pregnant at any time during 
the study, or if they become pregnant within 30 days of last study drug dose. Subjects who 
become pregnant or who suspect that they are pregnant during the study must report the 
information to the investigator and discontinue study drug immediately. Subjects whose partner 
has become pregnant or suspects she is pregnant during the study are to report the information to 
the investigator.
Instructions for reporting pregnancy, partner pregnancy, and pregnancy outcome are outlined in 
Section 7.7.2.1.
6) Pregnancy Testing
All females of childbearing potential will have urine pregnancy testing every 4 weeks (in clinic)
during their study participation. If a urine pregnancy test is positive, the subject should stop 
study drug immediately, contact the investigator, and have a confirmatory serum pregnancy test 
in clinic.


Filgotinib 
Protocol GS-US-419-4016 
Final 
Gilead Sciences, Inc. 
Amendment 5 
Appendix 10. 
Clinical Laboratory Assessment Table 
Hematology 
Hematocrit 
Hemoglobin 
Platelet count 
Red blood cell (RBC) 
count 
White blood cell 
(WBC) count 
Differentials (absolute 
and percentage), 
including: 
Lymphocytes 
Monocytes 
Neutrophils 
Eosinophils 
Basophils 
Reticulocyte count 
Mean co1puscular 
volume (MCV) 
Serology 
Hepatitis B surlace 
antigen (HBsAg) 
Hepatitis B surlace 
antibody (Ab) 
Hepatitis B Core Ab 
Hepatitis C Ab 
HIV A Ab 
CONFIDENTIAL 
Chemistry 
Alkaline phosphatase 
Aspartate 
aminotransferase (AST) 
Alanine atninotransferase 
(ALT) 
Total bilirubin 
Direct and indirect 
bilirnbin 
Total protein 
Albumin 
Bicarbonate 
Blood urea nitrogen 
(BUN) 
Calcium 
Chloride 
SelUlll creatinine 
Creatinine clearance 
(CC&G) 
Glucose 
Phosphorns 
Magnesium 
Potassium 
Sodium 
Crea.tine Phosphokinase 
(CPK) 
Fasting lipids 
Triglycerides 
Total Cholesterol 
High-density lipoprotein 
cholesterol [HDL-C] 
Low-density lipoprotein 
cholesterol [LDL-C]) 
Urinalysis 
Appearance 
Blood 
Color 
Glucose 
Leukocyte esterase 
pH 
Protein 
Urobilinogen 
Microscopy 
Stool 
Bacterial stool culture 
C-DiffToxin 
Ova and Parasites (O&P) 
Page 104 
Other 
Urine drng screen for: 
Amphetarnines 
Cocaine 
Barbiturates 
Opiates 
Benzodiazepines 
C-reactive protein (CRP) 
QuantiFERON® TB - Gold 
In-Tube Analysis (if required 
per inclusion criteria) 
Semm irnmunoglobulin 
Prothrombin Time (PT) 
Partial thromboplastin time 
(PTT) 
International Normalized Ratio 
(INR) 
Pregnancy 
In f emales of childbearing 
potential: 
SelUlll pregnancy 
Urine pregnancy 
04 Febrna1y 2020 

SAP_001.pdf: 
Study Title: 
Name of Test Drug: 
Study Number: 
Protocol Version (Date): 
Analysis Type: 
Analysis Plan Version: 
Analysis Plan Date: 
Analysis Plan Author(s): 
(r} GILEAU 
STATISTICAL ANALYSIS PLAN 
A Phase 2, Double-Blind, Randomized, Placebo-Controlled 
Study Evaluating the Efficacy and Safety of Filgotinib in the 
Treatment of Perianal Fistulizing Crohn's Disease 
Filgotinib 
GS-US-419-4016 
Amendment 1: 
Amendment 1.1 EU: 
Amendment 2: 
Amendment 3: 
Amendment 4: 
Amendment 5: 
Final Analysis 
2.0 
01 March 2021 
PPD 
06 January 2017 
28 February 2017 
26 June 2017 
11 October 2018 
11 April 2019 
04 February 2020 
CONFIDENTIAL AND PROPRIETARY INFORMATION 


Filgotinib 
GS-US-419-4016 
Statistical Analysis Plan 
Version 2.0 
TABLE OF CONTENTS 
TABLE OF CONTENTS ................................................................................................................................................ 2 
LIST OF IN-TEXT TABLES ........................................................................................................................................ .4 
LIST OF IN-TEXT FIGURES ....................................................................................................................................... .4 
LIST OF ABBREVIATIONS ......................................................................................................................................... 5 
DEFINITION OF TERMS .............................................................................................................................................. 8 
1. 
INTRODUCTION ................................................................................................................................................ 10 
1. 1. 
Study Objectives ...................................................................................................................................... 10 
1.2. 
Study Design ........................................................................................................................................... 11 
1.3. 
Sample Size and Power ........................................................................................................................... 13 
2. 
TYPE OF PLANNED ANALYSIS ...................................................................................................................... 14 
2.1. 
Data Monitoring Committee (DMC) Analyses ....................................................................................... 14 
2.1. 1. 
Safety Analyses ..................................................................................................................... 14 
2.1.2. 
Futility Analysis .................................................................................................................... 14 
2.2. 
Final Analysis .......................................................................................................................................... 14 
3. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES ............................................................................. 15 
3.1. 
3.2. 
3.3. 
3.4. 
3.5. 
3.6. 
3.7. 
3.8. 
Analysis Sets ........................................................................................................................................... 15 
3 .1. 1. 
All Randomized Analysis Set ................................................................................................ 15 
3.1.2. 
Full Analysis Set. ................................................................................................................... 15 
3.1.3. 
Safe 
Anal sis Set ................................................................................................................ 15 
Subject Grouping ..................................................................................................................................... 16 
Strata and Covariates ............................................................................................................................... 16 
Examination of Subject Subgroups ......................................................................................................... 16 
Missing Data and Outliers ....................................................................................................................... 16 
3 .5. 1. 
Missing Data .......................................................................................................................... 16 
3.5.2. 
Outliers .................................................................................................................................. 17 
Data Handling Conventions and Transfo1mations .................................................................................. 17 
Analysis Visit Windows .......................................................................................................................... 19 
3. 7. 1. 
Definitions ............................................................................................................................. 19 
3. 7.2. 
Analysis Visit Windows ........................................................................................................ 19 
3.7.3. 
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window ................................................................................................................................. 21 
Assessment of Coronavims Disease 2019 Impact. .................................................................................. 22 
4. 
SUBJECT DISPOSITION ................................................................................................................................... 23 
4.1. 
Subject Enrollment and Disposition ........................................................................................................ 23 
4.2. 
Extent of Study Thug Exposme and Adherence ...................................................................................... 24 
4.2.1. 
Duration of Exposw·e to Study Thug ..................................................................................... 24 
4.2.2. 
Adherence to Study D1ug ...................................................................................................... 25 
4.2.2.1. 
On-Treatment Adherence ................................................................................ 25 
4.3. 
Protocol Deviations ................................................................................................................................. 26 
4.4. 
Missed and Virtual Visits due to COVID-19 .......................................................................................... 26 
5. 
BASELINE CHARACTERISTICS ..................................................................................................................... 27 
5.1. 
Demographics and Other Baseline Characteristics ................................................................................. 27 
CONFIDENTIAL 
Page2 
01 March 2021 


Filgotinib 
GS-US-419-4016 
Statistical Analysis Plan 
Version 2.0 
5.2. 
Baseline Disease Characteristics ............................................................................................................. 27 
5.3. 
Medical Histoiy ....................................................................................................................................... 30 
6. 
EFFICACY ANALYSES ..................................................................................................................................... 31 
6.1. 
General Considerations ........................................................................................................................... 31 
-
6.1.2. 
Calculation of Segmental SES-CD Scores ............................................................................ 33 
6.2. 
Pri1nruy Efficacy Endpoint ...................................................................................................................... 34 
6.2.1. 
Definition of the Prima1y Efficacy Endpoint ........................................................................ 34 
6.2.2. 
Analysis of the Prima1y Efficacy Endpoint ........................................................................... 34 
6.3. 
Secondruy Efficacy Endpoints ................................................................................................................ 34 
6.3.1. 
Definition of Seconda1y Efficacy Endpoints ......................................................................... 34 
6.3.2. 
Anal sis of the Seconda1 Efficac End oints ..................................................................... 35 
---
7. 
SAFETY ANALYSES ........................................................................................................................................ .42 
7.1. 
Adverse Events and Deaths .................................................................................................................... .42 
7.1. 1. 
Adverse Event Dictiona1y .................................................................................................... .42 
7.1.2. 
Adverse Event Severity ........................................................................................................ .42 
7.1.3. 
Relationship of Adverse Events to Study Dmg .................................................................... .42 
7.1.4. 
Serious Adverse Events ........................................................................................................ .42 
7.1.5. 
Treatinent-Emergent Adverse Events ................................................................................... .42 
7.1.5.1. 
Definition of Treatinent-Emergent Adverse Events ....................................... .42 
7 .1.5.2. 
Inco1nplete Dates ............................................................................................ .43 
7.1.6. 
Summaries of Adverse Events and Deaths ........................................................................... .43 
7 .1.6.1. 
SUilllnaries of AE Incidence ........................................................................... .43 
7. 1. 7. 
Adverse Events of Interest. ................................................................................................... .45 
7 .1. 7 .1. 
Cardiovascular Safety Endpoint Adjudication Committee ............................. .46 
7.2. 
Laborato1y Evaluations .......................................................................................................................... .46 
7.2.1. 
Summaries of Numeric Laborat01y Results ......................................................................... .47 
7.2.2. 
Graded Laborato1y Values ................................................................................................... .48 
7 .2.2.1. 
Treatinent-Emergent Laborat01y Abnonnalities ............................................ .48 
7.2.2.2. 
Treatinent-Emergent Marked Laborat01y Abnormalities ............................... .48 
7 .2.2.3. 
SUilllnaries of Laborat01y Abnonnalities ....................................................... .48 
7.2.3. 
Liver-related Laborat01y Evaluations ................................................................................... .49 
7 .3. 
Body Weight, Height and Vital Signs .................................................................................................... .49 
7.4. 
Prior and Concoinitant Medications ........................................................................................................ 50 
7.4.1. 
Prior Medications .................................................................................................................. 50 
CONFIDENTIAL 
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GS-US-419-4016 
Statistical Analysis Plan 
Version 2.0 
7.4.2. 
Conco1nitant Medica.tions ...................................................................................................... 50 
7 .5. 
Electrocardiogra.1n Results ....................................................................................................................... 51 
7.6. 
Other Safety Measures ............................................................................................................................ 51 
7 .7. 
Changes from Protocol-Specified Safety Analyses ................................................................................. 51 
I 
I 
10. REFERENCES ..................................................................................................................................................... 54 
11. SOFTWARE ......................................................................................................................................................... 55 
12. SAP REVISION ................................................................................................................................................... 56 
13. APPENDICES ...................................................................................................................................................... 57 
LIST OF IN-TEXT TABLES 
Table 1-1. --
Table 6-1. 
-
and Vutual Visits ..................................................................................................................... 82 
LIST OF IN-TEXT FIGURES 
Filllire 1-1. 
Sche1natic .......................................................................................................... 11 
CONFIDENTIAL 
Page4 
01 March 2021 


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GS-US-419-4016
Statistical Analysis Plan
Version 2.0
CONFIDENTIAL
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01 March 2021
LIST OF ABBREVIATIONS
6-MP
6-mercaptopurine
AE
adverse event
AEI
adverse events of interest
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
ASTE
arterial systemic thromboembolism
BLQ
below the limit of quantitation
BMI
body mass index
CCG
eCRF Completion Guidelines
CD
Crohn’s disease
CDAI
Crohn’s Disease Activity Index
CI
confidence interval
COVID-19
coronavirus disease 2019
CRF
case report form(s)
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
CV
cardiovascular
CVEAC
cardiovascular safety endpoint adjudication committee
DMC
data monitoring committee
ECG
electrocardiogram
eCRF
electronic case report form(s)
ET
early termination
FAS
Full Analysis Set
Gilead
Gilead Sciences, Inc.
HBV
Hepatitis B Virus
HCV
Hepatitis C Virus
HDL
high-density lipoprotein
HIV
Human Immunodeficiency Virus
HLT
high-level term
HLGT
high-level group term
HRQoL
health-related quality of life
 
IBD
inflammatory bowel disease
ID
identification
IM
intramuscularly
CCI
CCI
CCI


Filgotinib 
GS-US-419-4016 
Statistical Analysis Plan 
IV 
IWRS 
LDL 
LLOQ 
LLT 
LOCF 
LOQ 
LTE 
MACE 
MRI 
MedDRA 
MI 
MST 
MTX 
NLP 
NRI -
O&P 
Ols 
PBO 
PDAI 
PO 
PR 
1111 
PT 
PTM 
PTx 
Ql, Q3 
SAE 
SAP 
SE 
SD 
SES-CD 
1111 
SMQ 
soc 
TB 
TEAE 
CONFIDENTIAL 
intra.venously 
interactive web response system 
low-density lipoprotein 
lower limit of quantification 
lower-level term 
last observation ca1ried fo1ward 
limit of quantification 
long-term extension 
major adverse cardiovascular events 
Magnetic Resonance Imaging 
Medical Dictionary for Regulatory Activities 
myocardial infarction 
MedDRA search tenn 
methotrexate 
Natural Language Processing 
non-responder imputation 
ova and parasites test 
opportunistic infections 
Placebo 
Perianal Disease Activity Index 
orally 
rectally 
prefeITed term 
placebo to match 
Post-Treatment 
first quartile, third quartile 
serious adverse event 
statistical analysis plan 
standard eITor 
standard deviation 
simple endoscopic score for Crohn's disease 
Standardized MedDRA query 
system organ class 
Tuberculosis 
treatment-emergent adverse event 
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TFLs
tables, figures, and listings
TNFα
tumor necrosis factor-alpha
ULN
upper limit of normal
US
United States
vfPBMC
viably frozen peripheral blood mononuclear cell
V-Day
visit day
VTE
venous thromboembolism
WHO
World Health Organization
CCI


Filgotinib 
GS-US-419-4016 
Statistical Analysis Plan 
Simple Fistula 
(for stratification purposes) 
Complex Fistula( e) 
(for stratification purposes) 
Perianal Fistula Closure 
Clinical Fistula Remission 
Clinical Fistula Response 
Combined Fistula Remission 
Combined Fistula Response 
Proctitis SES-CD Score 
Anal Canal Segmental SES-CD 
score 
Moderately to Severely Active 
Proctitis 
Proctitis Remission 
Disease Worsening 
Non-responder (lurninal 
disease) 
Non-Responder 
(Perianal Fistulizing Crohn's 
Disease (CD)) 
CONFIDENTIAL 
Version 2.0 
DEFINITION OF TERMS 
Single, unbranched submucosal or intersphincteric fistula tract, no extensions, 
no inflammato1y mass/collections, single extemal opening 
Multiple simple fistulae OR Single branched (multiple extemal openings 
arising from one fistula tract), trans-, extra-, or suprasphincteric fistulae tracts, 
possible extensions, and/or focal to small collections 
No fistula drainage despite gentle extemal compression 
Perianal fistula closure of all extemal openings that were draining at baseline 
Reduction ofc::: 1 from baseline in the number of draining extemal perianal 
fistula openings tltat were present at baseline 
Perianal fistula closure of all extemal openings that were draining at baseline, 
and absence of fluid collections > 1 cm on MRI pelvis 
Reduction ofc::: 1 from baseline in the number of draining extemal perianal 
fistula openings tltat were present at baseline, and absence of fluid collections 
> 1cm on MRI pelvis 
Sum of ulcer size and ulcerated surface SES-CD endoscopy subscores for the 
rectum and anal canal, assessed by centrally read flexible sigmoidoscopy 
Sum of ulcer size and ulcerated surface SES-CD endoscopy subscores for the 
anal canal segment only, assessed by centrally read flexible sigmoidoscopy 
Proctitis SES-CD Score > 2 
A Proctitis SES-CD Score of 0 
An increase in CDAI of c:: 100 points from the Week 10 value with CDAI 
c:: 220 at 2 consecutive visits 
Subject who had a baseline CDAI score c:: 220 and never achieves a c:: 70 point 
CDAI reduction from baseline at any point up to and including Week 10 OR 
had a baseline CDAI score < 220 and have an increase in CDAI of 
c:: 100 points from baseline, witlt CDAI c:: 220 at Week 10 
Subjects who meet the following criteria for PDAI symptom subscores: 
"Discharge" subscore of> 1 and c::: 1 point increase from baseline at Week 6 
and Week 10 OR 
"Pain/restriction of activities" subscore of> 1 and c:: 1 point increase from 
baseline at Week 6 and Week 10 
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Statistical Analysis Plan 
4016 hlflamma.tion Score 
4016 Anatomy Score 
Fistula Anatomy Subscore 
Fistula hlflammation Subscore 
MRI Fistula Healing 
MRI Fistula Response 
MRI Remission 
MRI Response 
CONFIDENTIAL 
Version 2.0 
Sum of the following subscores for all prima1y fistula tracts and extensions 
(if present) identified at baseline: 
Hyperintensity of TI-weighted images Subscore 
Hyperintensity of Tl-weighted Images Subscores 
Dominant Feature of Primruy Tracts and Extensions Subscore 
hlflammat01y Mass Subscore 
Presence of Proctitis Subscore 
Sum of the following subscores for all prima1y fistula tracts and extensions 
(if present) identified at baseline: 
Number of prima1y fistula. tracks 
identified 
at baseline 
Location Subscore of all primruy fistula. tracts identified at baseline 
Extension Subscore for all extensions (if present) identified at baseline 
Sum of the following subscores for ea.ch individual primruy fistula tract 
( and extensions if present) identified at baseline: 
Location Subscore 
Extension Subscore 
Sum of the following subscores for ea.ch individual primruy fistula tract and 
extensions (if present) identified at baseline: 
Hyperintensity of TI-weighted Images Subscores 
Hyperintensity of Tl-weighted Images Subscores 
Dominant Feature of Tract Subscores 
hlflammat01y Mass Subscore 
A score of zero at Week 24 for Fistula. hlflrunmation Subscore, for an 
individual primary fistula. tract ( and extensions if present) with Fistula. 
hlflammation Subscore > 0 identified at baseline 
50% decrease from baseline in Fistula hlflammation Subscore at Week 24 
for an individual fistula. tract ( and extensions if present) with Fistula. 
hlflammation Subscore > 0 identified at baseline 
All fistula. tracts ( and extensions if present) that were identified at baseline 
achieve MRI fistula healing at Week 24 
All fistula. tracts ( and extensions if present) that were identified at baseline 
achieve MRI fistula response at Week 24 
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Statistical Analysis Plan 
1. 
INTRODUCTION 
Version 2.0 
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the clinical study repo1t (CSR) 
for Study GS-US-419-4016.This SAP is based on Protocol Amendment 5 dated 04 Febmaiy 
2020 and the electronic case repo1t f01m (eCRF). The SAP will be finalized before database 
finalization. Any changes made after the finalization of the SAP will be documented in the CSR. 
1.1. 
Study Objectives 
The primaiy objective of this study is: 
• 
To evaluate the efficacy of filgotinib as compared to placebo in establishing combined fistula 
response at Week 24 
The secondaiy objectives of this study are: 
• 
To evaluate the efficacy of filgotinib as compared to placebo in establishing combined fistula 
reinission at Week 24 
• 
To assess the time to clinical fistula response 
• 
To assess the time to clinical fistula remission 
• 
To evaluate the efficacy of filgotinib as compared to placebo in establishing proctitis 
reinission at Week 24, in subjects that had moderately to severely active proctitis at baseline 
• 
To evaluate the safety and tolerability of filgotinib 
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1.2. 
Study Design 
Version 2.0 
This study is a Phase 2, double-blind, randomized, multicenter study evaluating the efficacy and 
safety of filgotinib versus placebo in the treatment of perianal fistulizing CD. A schematic of this 
study is provided in Figure 1-1. 
Figure 1-1. 
... 
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Q. _. 
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QI 
QI 
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(/) 
Study Design Schematic 
Day 1 
L 
.-
0-i ti 
C 
0 
16 
N .E 
0 
"E 
&. 
FIL 200 mg 
(n-30) 
Week 10 
Week 24 (1°endpoint) 
Non-rnponcs.rr or --7• .... ~n~~~~~i~1:ir.~U~~aj5""""--, 
meeting disease 
w0r5,ltfling crltltri.1'" 
StucSy GS-US-419-3896) 
FIL = filgotinib; mg = milligram; PBO = placebo. 
* 
Non-responders (luminal disease) are defined as subjects who either had a baseline CDAI score :::: 220 and never achieve 
a:::: 70 point CDAI reduction from baseline at any point up to and including Week 10 OR had a baseline CDAI score 
< 220 and have an increase in CDAI of:::: 100 points from baseline, with CDAI:::: 220 at Week 10 
Non-responders (perianal fistulizing CD) are defined as subjects who meet the following criteria for PDAI symptom 
subscores: "Discharge" subscore of> 1 and:::: lpoint increase from baseline at Week 6 and Week 10 OR "Pain/restriction of 
activities" subscore of> 1 and:::: lpoint increase from baseline at Week 6 and Week 10 
** Disease worsening is defined as an increase in CDAI of:::: 100 points from the Week 10 value with CDAI score:::: 220 points 
at 2 consecutive visits 
*** Subjects who are non-responders, meeting disease worsening criteria, or complete the study at Week 24, will have the 
option to enter a separate LTE study, if eligible. 
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This study includes:

Screening (Day -30 to -1)

Randomization

Blinded Treatment Period (Day 1 to Week 24)
Efficacy assessment: At Week 24, physical examination, flexible sigmoidoscopy to 
assess presence of proctitis, and MRI to assess fistula response
Subjects who complete all procedures per protocol, including the MRI at Week 24, may 
be offered the option to continue into a separate Long Term Extension (LTE) study 
(GS-US-419-3896), if deemed appropriate by the investigator

Subjects who are non-responders at Week 10 (see Section 3.6 OR Section 3.7 of study 
protocol) or who meet disease worsening criteria (see Section 3.8 of study protocol) after 
Week 10 will have the option to enter the LTE study, if eligible. 

Post-treatment safety assessments:
All subjects completing this study will be offered the option to continue study drug in a 
blinded fashion in the LTE study, if eligible
Subjects who are eligible and opt to participate in the LTE study can continue into the 
LTE study without post-treatment safety assessments
Subjects who opt out of the LTE study will return to clinic 30 days after the last dose of 
study drug for post-treatment safety assessments
Based on protocol eligibility criteria, subjects will be randomized into 1 of 3 treatment groups in 
a blinded fashion in a 2:2:1 ratio as follows:
Treatment group 1 (n = 30): filgotinib 200 mg and PTM filgotinib 100 mg, once daily
Treatment group 2 (n = 30): filgotinib 100 mg and PTM filgotinib 200 mg, once daily
Treatment group 3 (n = 15): PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily
Note: US males who are not dual refractory will be randomized in a 2:1 ratio to either filgotinib 
100 mg or matching placebo. For the purposes of this protocol, US males who have failed at 
least one prior TNF antagonist AND either previously failed vedolizumab induction therapy or 
are concomitantly taking vedolizumab at Day 1 and present with actively draining perianal 
fistulae despite continued vedolizumab therapy will be considered dual refractory subjects. This 
assessment is based on recently published data from a subgroup analysis of the GEMINI-2 study, 
showing a beneficial effect of vedolizumab treatment for subjects that were randomized with 
actively draining perianal fistulae at baseline {Feagan 2018}.


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For subjects enrolled before protocol amendment 4, treatment assignments will be stratified 
according to the following factors:

Anatomy of draining perianal fistulae at screening determined by MRI (simple versus 
complex)

Prior exposure to TNFα antagonist (Yes or No) 

Presence of moderately to severely active proctitis (Yes or No)
For subjects enrolled after protocol amendment 4, treatment assignments will be stratified 
according to the following factors:

Anatomy of draining perianal fistulae at screening determined by MRI (simple versus 
complex)

Receiving vedolizumab therapy concomitantly at Day 1 (Yes or No)

Presence of moderately to severely active proctitis (Yes or No)
1.3.
Sample Size and Power
A total of approximately 75 subjects are planned to be randomized (2:2:1 ratio): 30 subjects to 
each of the filgotinib dose groups and 15 subjects to the placebo group. This sample size is 
considered adequate to assess the safety, tolerability, and efficacy of filgotinib in a descriptive 
manner.
Table 1-1 provides the exact 90% CI using the binomial distribution for a given combined fistula 
response rate ranging from 20% to 80%:
Table 1-1.
Combined Fistula Response Rates (90% CI)
Number 
Randomized
Number of 
Responders
Response 
rate
Lower Limit of 90% 
CI
Upper Limit of 90% 
CI
30
6
20%
9%
36%
30
9
30%
17%
47%
30
12
40%
25%
57%
30
15
50%
34%
66%
30
18
60%
43%
75%
30
21
70%
53%
83%
30
24
80%
64%
91%
CI = confidence interval


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Data Monitoring Committee (DMC) Analyses
The DMC’s role and responsibilities and the scope of analysis to be provided to the DMC are 
described in a mutually agreed upon charter, which defines the DMC membership, 
meeting logistics, and meeting frequency.
2.1.1.
Safety Analyses
An external multidisciplinary DMC will review the progress of the study and perform interim 
reviews of the safety data in order to protect subject welfare and preserve study integrity. To 
ensure the best interests of the participants, the DMC will recommend to the sponsor if the 
nature, frequency, and severity of adverse effects associated with the study treatment warrant the 
early termination of the study, the continuation of the study, or the continuation of the study with 
modifications.
The DMC will meet twice to evaluate all available safety data of the study. The initial meeting 
will occur after approximately 20% of the planned total number of subjects complete their 
Week 10 visit. Following this, the next meeting will occur after approximately 50% of the 
subjects reach Week 10. Additionally, the DMC members may request an unscheduled review of 
the study data based on a concern for subject safety.  Additional meetings may be triggered by 
safety findings, predetermined or otherwise.
2.1.2.
Futility Analysis
After a minimum of 35 subjects (estimated to be 7 from the placebo group and 14 from each 
filgotinib treatment group based on the randomization ratio) are enrolled and complete the 
Week 10 visit or discontinue from the study, an interim futility analysis will be conducted to 
evaluate efficacy improvement in fistulizing disease. The cumulative safety analysis and 
summary statistics to evaluate perianal fistula closure of external openings, and 
 
 will be generated and provided to the DMC. The 
DMC will make a recommendation to either continue the study without modification or 
recommend that the study be halted due to lack of efficacy, and will be based on the totality of 
data available at the time of the interim analysis.
2.2.
Final Analysis
After all enrolled subjects have completed the study, outstanding data queries have been resolved 
or adjudicated as unresolvable, and the data have been cleaned and finalized, the study blind will 
be broken and the final analysis of the data will be performed.
CCI


Filgotinib 
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Statistical Analysis Plan 
Version 2.0 
3. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES 
Analysis results will be presented using descriptive statistics. For categorical variables, the 
number and percentage of subjects in each catego1y will be presented; for continuous variables, 
the number of subjects (n), mean, standard deviation (SD) or standard eITor (SE), median, 
first qua1t ile (Ql ), third qua1t ile (Q3), minimum, and maximum will be presented. 
By-subject listings will be presented for all subjects in the All Randoinized Analysis Set and 
s01ted by subject ID number, visit date, and time (if applicable). Data collected on log fonns, 
such as AEs, will be presented in chronological order within subject. The treatment group to 
which subjects were randomized will be used in the listings. Age, sex at birth, race, and ethnicity 
will be included in the listings, as space pennits. 
3.1. 
Analysis Sets 
Analysis sets define the subjects to be included in an analysis. Analysis sets and their definitions 
are provided in this section. The analysis set will be identified and included as a subtitle of each 
table, figure, and listing. 
For each analysis set, the number and percentage of subjects eligible for inclusion, as well as the 
number and percentage of subjects who were excluded and the reasons for their exclusion, 
will be summarized by treatment group. 
A listing of reasons for exclusion from analysis sets will be provided by subject. 
3.1.1. 
All Randomized Analysis Set 
All Randomized Analysis Set includes all subjects who were randoinized in the study. This is the 
primaiy analysis set for by-subject listings. 
3.1.2. 
Full Analysis Set 
The Full Analysis Set (FAS) includes all randomized subjects who took at least 1 dose of study 
diug. This is the primaiy analysis set for efficacy analyses. 
3.1.3. 
Safety Analysis Set 
The Safety Analysis Set includes all subjects who took at least 1 dose of study diug. This is the 
primaiy analysis set for safety analyses. 
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Statistical Analysis Plan 
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3.2. 
Subject Grouping 
Version 2.0 
For analyses based on the All Randomized Analysis Set and the FAS, subjects will be grouped 
according to the treatment to which they were randomized. For analyses based on the Safety 
Analysis Set and Biomarker Analysis Set, subjects will be grouped according to the actual 
treatment received. The actual treatment received will differ from the randomized ti·eatment only 
when their actual ti·eatment differs from randomized ti·eatment for the entire ti·eatment dmation. 
3.3. 
Strata and Covariates 
Subjects will be randomly assigned to treatment groups via the interactive voice or web response 
system (IWRS) using a su-atified randomization schedule. Details of the randomization ratio and 
sti·atification variables are provided in Section 1.2. 
If there are discrepancies in su-atification factor values between the IWRS and the clinical 
database (eCRF data), the values recorded in the clinical database will be used for analyses. For 
derivation of concomitant use of vedolizumab at Day 1, the staii date of such medication should 
be before or on the same date of the first dose of study dmg and with either the stop date of such 
medication being on or after the first dose of study dmg or with "ongoing" status. 
3.4. 
Examination of Subject Subgroups 
There are no prespecified subject subgroups for efficacy and safety analyses. 
3.5. 
3.5.1. 
Missing Data and Outliers 
Missing Data 
In general, missing data will not be imputed unless methods for handling missing data are 
specified. Exceptions are presented in this document. 
For missing last dosing date of study dmg, imputation mies are described in Section 4.2.1. 
Imputation and calculation mies for missing clinical fistula assessment and MRI data are 
described in Section 6.2.2. The handling of missing or incomplete dates for AE onset is 
described in Section 7.1.5.2, and for prior and concomitant medications in Section 7.4. 
Values for missing safety laborato1y data will not be imputed. However, a missing baseline result 
will be replaced with a screening result, if available. If no preu-eatment laborato1y value is 
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available, the baseline value will be assumed to be normal (ie, no grade) for the summary of 
graded laboratory abnormalities. If safety laboratory results for a subject are missing for any 
reason at a time point, the subject will be excluded from the calculation of summary statistics for 
that time point.
Values for missing vital signs data will not be imputed. However, a missing baseline result will 
be replaced with a screening result, if available.
3.5.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be conducted. All data, including outliers, will be included in the data 
analysis, unless otherwise specified.
3.6.
Data Handling Conventions and Transformations
The following conventions will be used for the imputation of date of birth when it is partially 
missing or not collected:

If only month and year of birth is collected, then “15” will be imputed as the day of birth

If only year of birth is collected, then “01 July” will be imputed as the day and month of birth

If year of birth is missing, then date of birth will not be imputed
In general, age collected at Day 1 (in years) will be used for analyses and presented in listings. If 
age at Day 1 is not available for a subject, then age derived based on date of birth and the Day 1 
visit date will be used instead.  If an enrolled subject was not dosed with any study drug, the 
randomization date will be used instead of the Day 1 visit date.  For screen failures, the date the 
first informed consent was signed will be used for the age derivation. Age required for 
longitudinal and temporal calculations and analyses (eg, estimates of creatinine clearance, age at 
date of AE) will be based on age derived from date of birth and the date of the measurement or 
event, unless otherwise specified.
Duration of perianal fistulizing CD in years is the number of years between the diagnosis date of 
perianal fistulizing CD and date of first dose of study drug. The partial diagnosis date of perianal 
fistulizing CD (if any) will be imputed for calculation as follows:

If day and month are missing but year is available, then the imputed day and month will be 
01 Jan.

If day is missing but the month and year are available, then the imputed day will be the 
first day of the month.

Partial date will not be imputed if the year is missing.


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Non-PK data that are continuous in nature but are less than the lower limit of quantitation (LOQ) 
or above the upper LOQ will be imputed as follows:

A value that is 1 unit less than the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “ x” (where x is considered the LOQ). For example, if the 
values are reported as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to 
calculate summary statistics. An exception to this rule is any value reported as < 1 or < 0.1, 
etc. For values reported as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be used to 
calculate summary statistics.

A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “> x” (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above.

The LOQ will be used to calculate descriptive statistics if the datum is reported in the form of 
“≤ x” or “≥ x” (where x is considered the LOQ).
Plasma concentration values that are below the limit of quantitation (BLQ) will be presented as 
“BLQ” in the concentration data listing. Values that are BLQ will be treated as 0 at predose time 
points, and one-half the value of the LOQ at postdose time points for summary purposes.
The following conventions will be used for the presentation of summary and order statistics:

If at least 1 subject has a concentration value of BLQ for the time point, the minimum value 
will be displayed as “BLQ.”

If more than 25% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum and Q1 values will be displayed as “BLQ.”

If more than 50% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, and median values will be displayed as “BLQ.”

If more than 75% of the subjects have a concentration data value of BLQ for a given time 
point, the minimum, Q1, median, and Q3 values will be displayed as “BLQ.”

If all subjects have concentration data values of BLQ for a given time point, all order 
statistics (minimum, Q1, median, Q3, and maximum) will be displayed as “BLQ.”


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Statistical Analysis Plan 
3.7. 
3.7.1. 
Analysis Visit Windows 
Definitions 
Version 2.0 
The First Dosing Date is defined as the date when subjects take the first dose of study drng, as 
recorded in the Study Drng Administration eCRF. 
The Last Dosing Date is defined as the date when subjects take the last dose of study drng as 
recorded in the Study Drng Administration eCRF. 
Study Day will be calculated from the first dosing date of study drng and derived as follows: 
• 
For days on or after first dosing date: Assessment Date - First Dosing Date + 1 
• 
For days prior to the first dosing date: Assessment Date - First Dosing Date 
Therefore, Study Day 1 is the day of the first dose of study chu g achninistration. 
Baseline is defined as the last available observation prior to or on the first dosing date, unless 
specified othe1wise. 
3.7.2. 
Analysis Visit Windows 
Subject visits inight not occm on protocol-specified days. Therefore, for the pmpose of analysis, 
observations will be assigned to analysis windows. 
The analysis windows for weight, vital signs, ECG, safety laborato1y parameters (hematology, 
chemistiy , fasting lipid profile, sernm immunoglobulin), and key inflammato1y biomarkers 
(including hs-CRP, fecal calprotectin, and fecal lactofeITin) are provided in Table 3-4. 
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Table 3-4.
Analysis Visit Windows for: Weight, Vital Signs, ECG, Hematology, 
Chemistry, Fasting Lipid Profile, Serum Immunoglobulin, 
 
 
Nominal Visit
Analysis Visit
Nominal Day
(Study Day)
Lower Limit 
(Study Day)
Upper Limit
(Study Day)
Screening/Day 1
Baseline
1
(none)
1
Week 2
Week 2
15
2
22
Week 4
Week 4
29
23
36
Week 6
Week 6
43
37
57
Week 10
Week 10
71
58
85
Week 14
Week 14
99
86
113
Week 18
Week 18
127
114
141
Week 24
Week 24
169
142
≥ 169
Note: ECG is collected postbaseline at Week 10 and the corresponding analysis windows will be applied; fasting lipid profile, 
fecal lactoferrin, and fecal calprotectin are collected postbaseline at Weeks 10 and 24 and the corresponding analysis windows 
will be applied; serum immunoglobulin is collected postbaseline at Weeks 4, 10, and 24 and the corresponding analysis windows 
will be applied.
An unscheduled visit prior to the first dosing of study drug may be included in the calculation of 
the baseline value, if applicable.
3.7.3.
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window
Depending on the statistical analysis method, single values may be required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time-to-event analysis would not require 1 value per analysis window.
If multiple, valid, nonmissing, continuous measurements exist in an analysis window, 
records will be chosen based on the following rules if a single value is needed:

In general, the baseline value will be the last nonmissing value on or prior to the first dosing 
date of study drug, unless otherwise specified. If multiple measurements occur on the same 
day, the last nonmissing value prior to the first dosing date of study drug will be considered 
as the baseline value. If these multiple measurements occur at the same time or the time is 
not available, the average of these measurements (for continuous data) will be considered the 
baseline value. 

For postbaseline visits:
The record closest to the nominal day for that visit will be selected.
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.
If there is more than 1 record on the selected day, the average will be taken, 
unless otherwise specified.
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If multiple, valid, nonmissing, categorical measurements exist in an analysis window, 
records will be chosen based on the following rules if a single value is needed:

For baseline, the last available record on or prior to the date of the first dose of study drug 
will be selected. If there are multiple records with the same time or no time recorded on the 
same day, the value with the lowest severity will be selected (eg, normal will be selected over 
abnormal for safety ECG findings).

For postbaseline visits: 
The record closest to the nominal day for that visit will be selected.
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.

If there is more than 1 record on the selected day, the worst severity will be taken 
(eg, abnormal will be selected over normal for safety ECG findings), unless otherwise 
specified.
3.8.
Assessment of Coronavirus Disease 2019 Impact
This study was ongoing during the coronavirus disease 2019 (COVID-19) pandemic.
The assessment of the impact of COVID-19 will be provided in the corresponding sections 
(eg, Section 4) throughout this SAP. Study drug and study discontinuation due to COVID-19 are 
described in Section 4.1, study drug interruptions due to COVID-19 are described in Section 4.2, 
important and non-important protocol deviations due to COVID-19 are described in Section 4.3, 
and missed and virtual visits due to COVID-19 are described in Section 4.4.
Hematocrit collected from local laboratory and weight measured at home due to COVID-19 
impact will be used in CDAI calculations only, and will not be included in the safety laboratory 
summary (Sections 7.2 and 7.3, respectively). These data will be included in listings, with a flag 
to indicate which records were collected at a local laboratory or at home, respectively.


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
A summary of subject enrollment will be provided by treatment group for each country, 
investigator within a country, and overall. The summary will present the number and percentage 
of subjects enrolled. For each column, the denominator for the percentage calculation will be the 
total number of subjects analyzed for that column.
A similar enrollment table will be provided by randomization stratum. The denominator for the 
percentage of subjects in the stratum will be the total number of enrolled subjects. If there are 
discrepancies in the value used for stratification assignment between the IWRS and the clinical 
database, the value collected in the clinical database will be used for the summary. A listing of 
subjects with discrepancies in the value used for stratification assignment between the IWRS and 
the clinical database at the time of data finalization will be provided.
The randomization schedule used for the study will be provided as an appendix to the CSR.
A summary of subject disposition will be provided by treatment group and overall. This 
summary will present the number of subjects screened, the number of subjects who met all 
eligibility criteria but were not randomized with reasons subjects were not randomized, the 
number of subjects randomized, and the number of subjects in each of the categories listed 
below:

All Randomized Analysis Set

Full Analysis Set

Safety Analysis Set

Completed study drug

Continuing study drug (for analysis other than final analysis)

Did not complete study drug with reasons for premature discontinuation of study drug

Completed study

Continuing study (for analysis other than final analysis)

Did not complete the study with reasons for premature discontinuation of study
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For the status of study drug and study completion and reasons for premature discontinuation, the 
number and percentage of subjects in each category will be provided. The denominator for the 
percentage calculation will be the total number of subjects in the Safety Analysis Set 
corresponding to that column. 
The following by-subject listings will be provided by subject identification (ID) number in 
ascending order to support the above summary tables:

Reasons for premature study drug or study discontinuation (A separate listing of reasons for 
premature study drug or study discontinuation due to COVID-19 will be created.)

Reasons for screen failure (will be provided by screening ID number in ascending order)

Lot number and kit ID of assigned study medication
4.2.
Extent of Study Drug Exposure and Adherence
Extent of exposure to study drug will be examined by assessing the total duration of exposure to 
study drug and the level of adherence to the study drug specified in the protocol. Summaries of 
extent of study drug exposure and adherence will be provided by treatment group for the Safety 
Analysis Set.
A by-subject listing of study drug administration will be provided for subjects with study drug 
interruption due to COVID-19.
4.2.1.
Duration of Exposure to Study Drug
Total duration of exposure to study drug will be defined as last dosing date minus first dosing 
date plus 1, regardless of any temporary interruptions in study drug administration, and will be 
expressed in weeks using up to 1 decimal place (eg, 4.5 weeks). If the last study drug dosing date 
is missing, the latest date among the study drug end date, clinical visit date, laboratory sample 
collection date, and vital signs assessment date that occurred during the on-treatment period will 
be used.
The total duration of exposure to study drug will be summarized using descriptive statistics 
(n, mean, SD, median, Q1, Q3, minimum, and maximum) and using the number (ie, cumulative 
counts) and percentage of subjects exposed through the following time periods: 1 day, 2 weeks, 
4 weeks, 6 weeks, 10 weeks, 14 weeks, 18 weeks, 20 weeks and 24 weeks. Summaries will be 
provided by treatment group for the Safety Analysis Set.
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4.2.2.
Adherence to Study Drug
The total number of tablets administered will be summarized using descriptive statistics. 
The presumed total number of tablets administered to a subject will be determined by the data 
collected on the drug accountability eCRF using the following formula. If the bottle was not 
returned, it is assumed that the subject took all the study drug tablets from the dispensed bottle. 
The number of tablets returned will be imputed as zero for the given bottle for study drug 
adherence calculation purpose.
Total Number of Tablets Administered =
No. of Tablets Dispensed 
―
No. of Tablets Returned
4.2.2.1.
On-Treatment Adherence
The level of on-treatment adherence to the study drug regimen will be determined by the total 
amount of study drug administered relative to the total amount of study drug expected to be 
administered during a subject’s actual on-treatment period based on the study drug regimen.
The level of on-treatment adherence will be expressed as a percentage using the following 
formula:
If the calculated on-treatment adherence is > 100%, it will be set to 100%. Descriptive statistics 
for the level of on-treatment adherence with the number and percentage of subjects belonging to 
adherence categories (eg, < 80%, ≥ 80% to < 90%, ≥ 90%) will be provided by treatment group 
for the Safety Analysis Set.
No formal statistical testing is planned.
A by-subject listing of study drug administration and drug accountability will be provided by 
subject ID number (in ascending order) and visit (in chronological order).
Total Amount of Study Drug Administered
On-Treatment Adherence (%) = 
 x 100
Study Drug Expected to be Administered on Treatment
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4.3.
Protocol Deviations
Subjects who did not meet the eligibility criteria for study entry, but enrolled in the study will be 
summarized regardless of whether they were exempted by the sponsor or not. The summary will 
present the number and percentage of subjects who did not meet at least 1 eligibility criterion and 
the number of subjects who did not meet specific criteria by treatment group and overall based 
on the All Randomized Analysis Set. A by-subject listing will be provided for those subjects who 
did not meet at least 1 eligibility (inclusion or exclusion) criterion. The listing will present the 
eligibility criterion (or criteria if more than 1 deviation) that subjects did not meet and related 
comments, if collected.
Protocol deviations occurring after subjects entered the study are documented during routine 
monitoring. The number and percentage of subjects with important protocol deviations by 
deviation category (eg, eligibility criteria, informed consent) will be summarized by treatment 
group and overall for the All Randomized Analysis Set. A by-subject listing will be provided for 
those subjects with any important protocol deviation. 
A by-subject listing will be provided for subjects with important protocol deviations related to 
COVID-19. A separate listing will be provided for subjects with non-important protocol 
deviations related to COVID-19. 
4.4.
Missed and Virtual Visits due to COVID-19 
A by-subject listing of subjects with missed or virtual visits due to COVID-19 will be provided 
by subject ID number in ascending order.
Information regarding missed or virtual visits due to COVID-19 was collected as free text in the 
CRF comment fields. The determination of missing or virtual visits due to COVID-19 was done 
using Natural Language Processing (NLP) to search the CRF comment fields. A detailed 
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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Other Baseline Characteristics
Subject demographic variables and other baseline characteristics will be summarized by 
treatment group and overall using descriptive statistics for continuous variables, and using the 
number and percentage of subjects for categorical variables. The summary of demographic data 
will be provided for the Safety Analysis Set.

Age (years, on the date of first dose of the study drug)

Age group (< 65 years, ≥ 65 years)

Sex at birth (female, male)

Race

Ethnicity (Hispanic or Latino, Not Hispanic or Latino)

Geographic region (United States [US], non-US)

Weight (in kg)

Height (in cm)

Body mass index (BMI; in kg/m2)

Smoking status (former, current, never)
A by-subject demographic listing, including the informed consent date, will be provided by 
subject ID number in ascending order.
5.2.
Baseline Disease Characteristics
Stratification factors (listed in Section 3.3) and other baseline disease characteristics listed below 
will be summarized for the Safety Analysis Set by the same method as demographic tables, using 
descriptive statistics for continuous variables and using number and percentage of subjects for 
categorical variables.

Duration of perianal fistulizing CD (years) from date of diagnosis to first dosing date of 
study drug

Duration of perianal fistulizing CD group (< 1 year, ≥ 1 to < 3 years, ≥ 3 to < 7 years, 
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
Location of CD: ileal, colonic, ileocolonic and isolated upper disease

Active Luminal Disease (CDAI ≥ 150) 

Moderately Active Luminal Disease (CDAI ≥ 220)

Baseline Proctitis SES-CD score (sum of size of ulcers and ulcerated surface for the rectum 
and anal canal segments)

Baseline Anal Canal SES-CD score (sum of size of ulcers and ulcerated surface for the anal 
canal segment)

Presence of Moderately to Severely Active Proctitis (yes, no)

Number of Draining Perianal Fistula at Baseline

Anatomy of draining perianal fistulae at screening determined by MRI (simple vs complex)

History of complications of perianal CD
Anal stenosis (yes, no)
Perirectal / perianal abscess (yes, no)

Perianal Fistulizing CD treatment history
Prior use of antibiotics (yes, no)
Prior use of immunomodulators (yes, no)
Prior use of TNFα antagonist as listed in Appendix 2 (yes, no); and for subjects with prior 
use:
■
Number of TNFα antagonists used
○
1
○
2
○
≥ 3
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Worst outcome of prior use of TNFα antagonist
○
Treatment failure
○
Intolerance, including both allergic and non-allergic intolerance
○
Other

Other CD treatment history
Prior use of systemic corticosteroids (yes, no)
Number of prior exposure to biologic agent for CD as listed in Appendix 3 (0, 1, 2, ≥ 3)
Prior use of vedolizumab (yes, no); and for subjects with prior use:
■
Worst outcome of prior use of vedolizumab
○
Treatment failure
○
Intolerance, including both allergic and non-allergic intolerance
○
Other
Prior use of ustekinumab (yes, no) and for subjects with prior use:
■
Worst outcome of prior use of ustekinumab
○
Treatment failure
○
Intolerance, including both allergic and non-allergic intolerance
○
Other
Note: The worst outcome of a prior treatment is treatment failure, followed by intolerance, 
and then other outcomes.

Concomitant CD treatment 
Antibiotic treatment for fistulizing CD at Baseline (yes, no)
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Concomitant use of systematically absorbed corticosteroids and immunomodulators
■
Systematically absorbed corticosteroids only
■
Immunomodulator only
■
Both systematically absorbed corticosteroids and immunomodulator
■
Neither
Prednisone equivalent dose for subjects who were on systemically absorbed 
corticosteroids at baseline (mg/day)
Prednisone equivalent dose for subjects who were on systemically absorbed 
corticosteroids at baseline (> 0 to 10 mg/day, > 10 to 20 mg/day, > 20 mg/day)
5-aminosalicylates (yes, no)
A by-subject listing of the above baseline characteristics will be provided by subject ID number 
in ascending order.
5.3.
Medical History
Medical history (disease-specific and general conditions) and IBD family history data will be 
collected at screening and presented in data listings.
General medical history data will be coded using the current version of Medical Dictionary for 
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6.
EFFICACY ANALYSES
6.1.
General Considerations
The efficacy analysis will be conducted on the FAS, defined in Section 3.1.2, unless otherwise 
specified. No formal hypothesis testing will be performed.
The definitions of selected efficacy endpoints are provided in Table 6-1. Appendix 10 and 
Appendix 11 include detailed definition of study treatment failure and the corresponding data 
handling rules for efficacy analysis.
Table 6-1.
Definitions of Selected Efficacy Endpoints
Type
Endpoint
Definition
Primary
Combined fistula response at 
Week 24
Reduction of ≥ 1 from baseline in the number 
of draining external perianal fistula openings 
that were present at baseline, and absence of 
fluid collections > 1cm on MRI pelvis at 
Week 24, among subjects with at least 
1 draining external perianal fistula opening at 
baseline
Secondary
Combined fistula remission at 
Week 24
Perianal fistula closure of all external 
openings that were draining at baseline, and 
absence of fluid collections > 1cm on MRI 
pelvis at Week 24, among subjects with at 
least 1 draining external perianal fistula 
opening at baseline
Secondary
Time to clinical fistula response
The time interval in days from date of 
first dosing of study drug to the first 
observation (during scheduled or unscheduled 
clinical visits) when ≥ 1 of the draining 
external perianal fistula openings that were 
present at baseline achieves perianal fistula 
closure, among subjects with at least 
1 draining external perianal fistula opening at 
baseline. Subjects not known to have a 
clinical fistula response will have their 
clinical fistula response time censored at the 
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Time to clinical fistula reinission 
Proctitis reinission at Week 24, 
in subjects that had moderately 
to severely active proctitis at 
baseline 
Summary of Dichotomous Efficacy Endpoints 
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Definition 
The time interval in days from date of first 
dosing of study drug to the first observation 
( dming schedule or unscheduled clinical 
visits) of perianal fistula closme of all 
extemal openings that were draining at 
baseline, among subjects with at least 
1 draining extemal perianal fistula opening at 
baseline. Subjects not knov.rn to have a 
clinical fistula remission will have their 
clinical fistula remission time censored at the 
last time that lack of clinical fistula rernission 
was documented. 
A Proctitis SES-CD Score (sum of ulcer size 
and ulcerated surface SES-CD endoscopy 
subscores for the rectum and anal canal) of 
0 assessed by centrally read flexible 
sigmoidoscopy at Week 24, in subjects that 
had moderately to severely active proctitis at 
baseline 
Numbers and percentages of subjects achieving each of the dichotomous efficacy endpoints 
defined in Table 6-1, and numbers and percentages of subjects not achieving those endpoints for 
the following reasons will be summarized by treatment, in a hierarchy order with the first reason 
being the highest. 
1) Subjects who do not meet the endpoint based on observed data 
2) Subjects who do not meet the endpoint due to study treatment failure 
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6) Subjects who do not have sufficient measurements to detennine the endpoint due to study 
drng discontinuation for other reasons 
7) Subjects who do not have sufficient measurements to detennine the endpoint due to other 
reasons 
Non-responder Imputation 
For analysis ofbinaiy efficacy endpoints defined in Table 6-1, subjects who do not have 
sufficient measurements due to any reason (including ti·eatment failures and CDAI or PDAI non-
responders at Week 10) to detennine the endpoint will be considered not meeting the endpoint 
(ie, non-responder imputation [NRI]). 
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6.1.2. 
Calculation of Segmental SES-CD Scores 
Proctitis SES-CD score (which includes an overall assessment of both rectum and anal canal 
segments) and Anal Canal Segmental SES-CD score will be calculated at Screening (used as 
baseline) and Week 24 visit (or eai·ly termination, if applicable). Only size of ulcers and 
ulcerated surface vai·iables will be included for the calculation of these scores (see Appendix 6). 
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6.2.
Primary Efficacy Endpoint
6.2.1.
Definition of the Primary Efficacy Endpoint
The primary efficacy endpoint is the combined fistula response at Week 24. Please refer to 
Table 6-1 in Section 6.1 for the endpoint definition.
6.2.2.
Analysis of the Primary Efficacy Endpoint
The number and proportion of subjects establishing combined fistula response at Week 24 for 
each treatment group will be summarized with corresponding 90% exact CI by Clopper-Pearson 
method. The difference in proportions between each filgotinib dose group and the placebo group 
will be presented along with the associated 90% CI. No formal hypothesis testing will be 
performed.
For subjects who completed the Week 24 visit, the following missing value imputation will be 
used before deriving the proportion of subjects establishing combined fistula response at 
Week 24:

If the clinical fistula assessment data is missing at Week 24, then the number of draining 
external perianal fistula openings at Week 24 will be imputed by Last Observation Carried 
Forward (LOCF) method using the number of draining external perianal fistulae openings 
from the last available scheduled or unscheduled visit, among draining external perianal 
fistulae openings at baseline only. 

If the MRI data is missing at Week 24, then absence of fluid collection > 1 cm will be 
imputed based on whether there was an absence of fluid collection > 1 cm at baseline 
(Yes, No), which will be derived from the size of fluid collections at baseline from the Total 
Fistula Score CRFs.
6.3.
Secondary Efficacy Endpoints
6.3.1.
Definition of Secondary Efficacy Endpoints
The secondary efficacy endpoints include the following:

Proportion of subjects establishing combined fistula remission at Week 24

Time to clinical fistula response

Time to clinical fistula remission

Proportion of subjects achieving proctitis remission at Week 24, in subjects that had 
moderately to severely active proctitis at baseline
Please refer to Table 6-1 for the definitions of the endpoints.


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Analysis of the Secondary Efficacy Endpoints 
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For bimuy endpoints, the same statistical analysis method for analyzing the prima1y efficacy 
endpoint will be utilized. 
If the proctitis SES-CD score is missing at Week 24, no imputation will be done and the subject 
will be considered a non-responder when deriving the propo1tion of subjects achieving proctitis 
remission at Week 24. 
For time-to-event secondaiy efficacy endpoints, the summaiy statistics (eg, median, Ql , Q3) 
from the Kaplan-Meier method will be provided for each treatment group. Plot of Kaplan-Meier 
cmves will also be provided. The Cox propo1tional hazards model will be used to estimate the 
hazai·d ratio with the con esponding 90% CI. Subjects not known to have a clinical fistula 
response ( or remission) will have their clinical fistula response ( or remission) time censored at 
the last perianal fistula assessment date. 
No fonnal hypothesis testing will be perfo1med. 
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7.
SAFETY ANALYSES
Unless otherwise specified, summaries of safety data will be provided for the Safety Analysis Set 
and will include data collected up to the last dose of study drug plus 30 days.
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (AEs) will be coded using the current version of Medical 
Dictionary for Regulatory Activities (MedDRA). System organ class (SOC), high-level group 
term (HLGT), high-level term (HLT), preferred term (PT), and lower-level term (LLT) will be 
provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Grade 1, 2, 3, 4, or 5 according to toxicity 
criteria specified in the protocol. The severity grade of events for which the investigator did not 
record severity will be categorized as “missing” for tabular summaries and data listings.The 
missing category will be listed last in the summary presentation.
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Related” on the AE eCRF to the 
question of “Related to Study Treatment.” Relatedness will always reflect the investigator 
assessment of causality rather than the Sponsor’s. Events for which the investigator did not 
record relationship to study drug will be considered related to study drug for summary purposes. 
However, by-subject data listings will show the relationship as missing.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if AEs met the definitions 
of SAE specified in the study protocol. SAEs captured and stored in the clinical database will be 
reconciled with the SAEs captured in the Gilead safety database before data finalization.
7.1.5.
Treatment-Emergent Adverse Events
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as 1 or both of the following:

Any AEs with an onset date on or after the study drug start date (Day 1) and no later than 
30 days after permanent discontinuation of study drug

Any AEs leading to premature discontinuation of study drug.


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7.1.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of study drug, then the month and year (or year alone if month is not recorded) of onset 
determine whether an AE is treatment emergent. The event is considered treatment emergent if 
both of the following 2 criteria are met:

The AE onset date is the same as or after the month and year (or year) of the first dosing date 
of study drug, and

The AE onset date is the same as or before the month and year (or year) of the date 
corresponding to 30 days after the date of the last dose of study drug 
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dosing date of study drug, will be considered to be treatment emergent. In 
addition, an AE with the onset date missing and an incomplete stop date with the same or later 
month and year (or year alone if month is not recorded) as the first dosing date of study drug will 
be considered treatment emergent.
7.1.6.
Summaries of Adverse Events and Deaths
Treatment-emergent AEs will be summarized based on the Safety Analysis Set. No formal 
statistical testing is planned.
7.1.6.1.
Summaries of AE Incidence 
The number and percentage of subjects who reported at least 1 TEAE will be provided and 
summarized by SOC, HLT, PT, and treatment group. For other AEs described below, summaries 
will be provided by SOC, PT, and treatment group:

TEAEs of Grade 3 or higher (by maximum severity)

TEAEs of Grade 2 or higher (by maximum severity)

All TE treatment-related AEs

TE treatment-related AEs of Grade 3 or higher (by maximum severity)

TE treatment-related AEs of Grade 2 or higher (by maximum severity)

All TE SAEs

All TE treatment-related SAEs 

All TEAEs leading to premature discontinuation of study drug


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
All TEAEs leading to premature discontinuation of study

All TE SAEs leading to death (ie, outcome of death)

All TEAEs leading to temporary interruption of study drug
A brief, high-level summary of AEs described above will be provided by treatment group 
presenting the number and percentage of subjects who reported the above AEs. All deaths 
observed in the study will be also included in this summary.
Multiple events will be counted only once per subject in each summary. Adverse events will be 
summarized and listed first in alphabetic order of SOC and HLT within each SOC (if applicable), 
and then by PT in descending order of total frequency within each SOC. For summaries by 
severity grade, the most severe grade will be used for those AEs that occurred more than once in 
an individual subject during the study. 
In addition, the following tables will be generated and summarized by PT only, in descending 
order of total frequency:

TEAEs

TEAEs of Grade 3 or higher 

TEAEs of Grade 2 or higher 

TE SAEs

TE treatment-related AEs

TE treatment-related SAEs  

TEAEs leading to premature discontinuation of study drug
Data listings will be provided for the following:

All AEs, indicating whether the event is treatment emergent

All AEs of Grade 3 or higher

All AEs of Grade 2 or higher

SAEs

Deaths

All AEs leading to death (ie, outcome of death)


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
AEs leading to premature discontinuation of study drug

AEs leading to premature discontinuation of study

AEs leading to temporary interruption of study drug
7.1.7.
Adverse Events of Interest
Adverse events of interest (AEI) include infections, malignancies (excluding nonmelanoma skin 
cancers), nonmelanoma skin cancers, gastrointestinal perforations, major adverse cardiovascular 
events (MACE), and thromboembolic events. Summaries of the following treatment-emergent 
AEIs will be produced to enhance the analysis of safety data. 

Events of infections, presented in the following subcategories:
AEs of infections, utilizing all AEs in the MedDRA Infections and Infestations SOC
AEs of serious infections, using all AEs in the MedDRA Infections and Infestations SOC 
that are classified as SAEs
AEs of herpes zoster, utilizing a MedDRA search term (MST) list developed by Gilead 
AEs of opportunistic infections (OIs), utilizing a narrow scope Standardised MedDRA 
Query (SMQ)

AEs of malignancies, excluding nonmelanoma skin cancers, utilizing an MST list developed 
by Gilead 

AEs of nonmelanoma skin cancers, utilizing an MST list developed by Gilead

AEs of gastrointestinal perforations, utilizing an MST list  developed by Gilead 

AEs of MACE, utilizing a positively adjudicated event list, presented in the following 
subcategories (Section 7.1.7.1):
Cardiovascular (CV) death
Non-fatal myocardial infarction (MI)
Non-fatal stroke

AEs of arterial systemic thromboembolism (ASTE), utilizing a positively adjudicated event 
list (Section 7.1.7.1)

AEs of venous thromboembolism (VTE), utilizing a positively adjudicated event list 
(Section 7.1.7.1)


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The number and percentage of subjects with a reported event will be summarized for each 
treatment group by PT for each AEI category. Data listings for AEIs will also be provided.
The number and percentage of subjects with positively adjudicated TE MACE, TE ASTE and 
TE VTE will be summarized by treatment group using the adjudicated category, if applicable.
A by-subject listing of subjects with potential events for adjudication (MACE, ASTE, and VTE) 
and their respective adjudication results will be provided.
A by-subject listing of thromboembolic history and risk factors will be provided for subjects with 
potential events for adjudication (MACE, ASTE, and VTE).
7.1.7.1.
Cardiovascular Safety Endpoint Adjudication Committee
An independent cardiovascular safety endpoint adjudication committee (CVEAC) will be formed 
to periodically review and adjudicate all potential MACE and thromboembolic events in a 
blinded manner.  To identify potential MACE and thromboembolic events, the following AEs 
will be sent for adjudication. Refer to the Cardiovascular Event Adjudication Committee Charter 
for more details.

All AEs leading to death

CV events (meeting seriousness criteria), utilizing an MST list developed by Gilead

MI, utilizing a narrow scope SMQ 

Unstable angina (meeting hospitalization criteria), utilizing an MST list developed by Gilead

Transient ischemic attack, utilizing an MST list developed by Gilead

Stroke, utilizing an MST list developed by Gilead

Cardiac failure (meeting hospitalization criteria), utilizing an MST list developed by Gilead

Percutaneous coronary intervention, utilizing an MST list developed by Gilead

Embolic and thrombotic events, utilizing a narrow scope SMQ  
The CVEAC will review the above AEs, and related clinical data to adjudicate whether the 
criteria for MACE (CV death, MI, and/or stroke), ASTE, and VTE have been met for each AE. 
7.2.
Laboratory Evaluations
Laboratory data collected during the study will be analyzed and summarized using both 
quantitative and qualitative methods. Summaries of laboratory data will be provided for the 
Safety Analysis Set for data collected up to the last dose of study drug plus 30 days for subjects 
who have permanently discontinued study drug. 


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The analysis will be based on values reported in conventional units. When values are below the 
LOQ, they will be listed as such, and the closest imputed value will be used for the purpose of 
calculating summary statistics as specified in Section 3.6. Test results from hemolyzed samples 
will not be included in the analysis, but they will be listed in by-subject laboratory listings.
A by-subject listing for laboratory test results will be provided by subject ID number and time 
point in chronological order for hematology, serum chemistry, urinalysis, lipid profile, and serum 
immunoglobulin separately. Values falling outside of the relevant reference range and/or having 
a severity grade of 1 or higher on the Common Terminology Criteria for Adverse Events 
(CTCAE) severity grade will be flagged in the data listings, as appropriate.
Hematocrit collected from local laboratories due to COVID-19 impact will not be included in the 
safety laboratory summary, but they will be included in the listing with a flag to indicate which 
records were collected at a local laboratory.
No formal statistical testing is planned.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics will be provided by treatment group for each laboratory test specified in the 
study protocol within hematology and chemistry panels, and also laboratory tests from lipids 
panel (under fasting status) including total cholesterol, low-density lipoprotein (LDL), 
high-density lipoprotein (HDL), triglycerides, non-HDL cholesterol (total cholesterol minus 
HDL cholesterol), LDL/HDL ratio,  and IgA, IgM, IgG, and total Ig, as follows:

Baseline values 

Values at each postbaseline time point 

Change from baseline at each postbaseline time point 
A baseline laboratory value will be defined as the last measurement obtained on or prior to the 
date of first dose of study drug. Change from baseline to a postbaseline visit will be defined as 
the visit value minus the baseline value. The mean, median, Q1, Q3, minimum, and maximum 
values will be displayed to the reported number of digits; SD values will be displayed to the 
reported number of digits plus 1.
Median (Q1, Q3) of the observed change from baseline values for aspartate aminotransferase 
(AST), alanine aminotransferase (ALT), total bilirubin, alkaline phosphatase, serum creatinine, 
creatinine clearance, creatine phosphokinase, white blood cell count, absolute neutrophils, 
absolute lymphocytes, hemoglobin, platelets, fasting total cholesterol, fasting LDL, fasting HDL, 
total Ig, IgG, IgA, and IgM, will be plotted using a line plot by treatment group and analysis 
visit.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.7.3.


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7.2.2.
Graded Laboratory Values
Modified CTCAE Version 4.03 (see Appendix 8 of the protocol) will be used for assigning 
toxicity grades (0 to 4) to laboratory results for analysis. Grade 0 includes all values that do not 
meet the criteria for an abnormality of at least Grade 1. For laboratory tests with criteria for both 
increased and decreased levels, analyses for each direction (ie, increased, decreased) will be 
presented separately. 
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last 
dose of study drug plus 30 days for subjects who permanently discontinued study drug. 
If the relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed 
within the time frame specified above will be considered treatment emergent.
7.2.2.2.
Treatment-Emergent Marked Laboratory Abnormalities
Treatment-emergent marked laboratory abnormalities are defined as values that increase at least 
3 toxicity grades from baseline at any postbaseline time point, up to and including the date of the 
last dose of study drug plus 30 days for subjects who permanently discontinued study drug.
If the relevant baseline laboratory value is missing, any Grade 3 or 4 values observed within the 
timeframe specified above will be considered treatment-emergent marked abnormalities.
7.2.2.3.
Summaries of Laboratory Abnormalities
Laboratory data that are categorical will be summarized using the number and percentage of 
subjects in the study with the given response at baseline and each scheduled postbaseline time 
point.
The following summaries (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment group; subjects will be categorized 
according to the most severe postbaseline abnormality grade for a given laboratory test:

Graded laboratory abnormalities

Grade 3 or higher laboratory abnormalities

Marked laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
nonmissing postbaseline values up to 30 days after last dosing date.
A by-subject listing of treatment-emergent Grade 3 or 4 laboratory abnormalities will be 
provided by subject ID number and time point in chronological order. This listing will include all 
test results that were collected throughout the study for the lab test of interest, with all applicable 
severity grades displayed.


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7.2.3.
Liver-related Laboratory Evaluations
Liver-related abnormalities after initial study drug dosing will be examined and summarized 
using the number and percentage of subjects who were reported to have the following laboratory 
test values for postbaseline measurements:

AST: (a) > 3 times of upper limit of the normal range (ULN); (b) > 5 x ULN; 
(c) > 10 x ULN; (d) > 20 x ULN

ALT: (a) > 3 x ULN; (b) > 5 x ULN; (c) > 10 x ULN; (d) > 20 x ULN

AST or ALT > 3 x ULN and total bilirubin > 2 x ULN
For individual laboratory tests, subjects will be counted once based on the most severe 
postbaseline values. For both the composite endpoint of AST or ALT and total bilirubin, subjects 
will be counted once when the criteria are met at the same postbaseline visit date. The 
denominator is the number of subjects in the Safety Analysis Set who have nonmissing 
postbaseline values of all relevant tests at the same postbaseline visit date. A listing of subjects 
who met at least 1 of the above criteria will be provided.
7.3.
Body Weight, Height and Vital Signs
Descriptive statistics will be provided by treatment group for body weight, BMI and vital signs 
(resting blood pressure [systolic blood pressure and diastolic blood pressure], respiratory rate, 
pulse, and temperature) as follows:

Baseline value

Values at each postbaseline time point

Change from baseline at each postbaseline time point 
A baseline value will be defined as the last available value collected on or prior to the date/time 
of first dose of study drug. Change from baseline to a postbaseline visit will be defined as the 
postbaseline value minus the baseline value. Body weight and vital signs measured at 
unscheduled visits will be included for the baseline value selection.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.7.3. No formal statistical testing is planned.
A by-subject listing of vital signs will be provided by subject ID number and time point in 
chronological order. Body weight, height, and BMI will be included in the vital signs listing, if 
space permits. If not, they will be provided separately.
Weight measured by the subjects at home from virtual visits due to COVID-19 impact will not 
be included in the vital signs summary, but they will be included in the listing with a flag to 
indicate which records were collected at home.


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7.4.
Prior and Concomitant Medications
Medications reported at screening and during the study will be coded using the current version of 
the World Health Organization (WHO) Drug dictionary.
7.4.1.
Prior Medications
Prior medications are defined as any medications taken before a subject took the first dose of 
study drug at baseline.
General prior and CD-specific prior medication will be summarized separately by preferred 
name using the number and percentage of subjects for each treatment group and overall. 
A subject reporting the same medication more than once will be counted only once when 
calculating the number and percentage of subjects who received that medication. The summary 
will be ordered by preferred term in descending overall frequency. For drugs with the same 
frequency, sorting will be done alphabetically.
For the purposes of analysis, any medication with a start date prior to the first dosing date of 
study drug will be included in the prior medication summary regardless of when the stop date is. 
If a partial start date is entered the medication will be considered prior unless the month and year 
(if day is missing) or year (if day and month are missing) of the start date are after the first 
dosing date. Medications with a completely missing start date will be included in the prior 
medication summary, unless otherwise specified.
Summaries will be based on the Safety Analysis Set. No formal statistical testing is planned.
7.4.2.
Concomitant Medications
Concomitant medications are defined as medications taken while a subject took study drug. 
General and CD-specific concomitant medications will be summarized, separately, by preferred 
name using the number and percentage of subjects for each treatment group. A subject reporting 
the same medication more than once will be counted only once when calculating the number and 
percentage of subjects who received that medication. The summary will be ordered by preferred 
term in descending overall frequency. For drugs with the same frequency, sorting will be done 
alphabetically.
For the purposes of analysis, any medication with a start date prior to or on the first dosing date 
of study drug and continued to take after the first dosing date, or started after the first dosing date 
but prior to or on the last dosing date of study drug will be considered concomitant medications. 
Medications started and stopped on the same day as the first dosing date or the last dosing date of 
study drug will also be considered concomitant. Medications with a stop date prior to the date of 
first dosing date of study drug or a start date after the last dosing date of study drug will be 
excluded from the concomitant medication summary. If a partial stop date is entered, any 
medication with the month and year (if day is missing) or year (if day and month are missing) 
prior to the date of first study drug administration will be excluded from the concomitant 
medication summary. If a partial start date is entered, any medication with the month and year (if 


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day is missing) or year (if day and month are missing) after the study drug stop date will be 
excluded from the concomitant medication summary. Medications with completely missing start 
and stop dates will be included in the concomitant medication summary, unless otherwise 
specified. Summaries will be based on the Safety Analysis Set. No formal statistical testing is 
planned.
All prior and concomitant medications (other than per-protocol study drugs) will be provided in a 
by-subject listing sorted by subject ID number and administration date in chronological order.
7.5.
Electrocardiogram Results
A shift table of the investigators’ assessment of ECG results at each visit compared with baseline 
values will be presented by treatment group using the following categories: normal; abnormal, 
not clinically significant; abnormal, clinically significant. The number and percentage of subjects 
in each cross-classification group of the shift table will be presented. Subjects with a missing 
value at baseline or postbaseline will not be included in the denominator for percentage 
calculation. No formal statistical testing is planned.
A by-subject listing for ECG assessment results will be provided by subject ID number and time 
point in chronological order.
7.6.
Other Safety Measures
A data listing will be provided for subjects who become pregnant during the study.
7.7.
Changes from Protocol-Specified Safety Analyses
There are no deviations from the protocol-specified safety analyses.


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10.
REFERENCES
Daperno M, D'Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, et al. Development and 
validation of a new, simplified endoscopic activity score for Crohn's disease: the 
SES-CD. Gastrointestinal endoscopy 2004;60 (4):505-12.
Feagan BG, Schwartz D, Danese S, Rubin DT, Lissoos TW, Xu J, et al. Efficacy of 
Vedolizumab in Fistulising Crohn's Disease: Exploratory Analyses of Data from 
GEMINI 2. Journal of Crohn's & colitis 2018;12 (5):621-6.
Irvine EJ. Usual therapy improves perianal Crohn's disease as measured by a new disease 
activity index. McMaster IBD Study Group. J Clin Gastroenterol 1995;20 (1):27-
32.
Khanna R, Zou G, D'Haens G, Feagan BG, Sandborn WJ, Vandervoort MK, et al. A 
retrospective analysis: the development of patient reported outcome measures for 
the assessment of Crohn's disease activity. Aliment Pharmacol Ther 2015;41 
(1):77-86.
Sandborn WJ, Feagan BG, Hanauer SB, Lochs H, Lofberg R, Modigliani R, et al. A review of 
activity indices and efficacy endpoints for clinical trials of medical therapy in 
adults with Crohn's disease. Gastroenterology 2002;122 (2):512-30.
Van Assche G, D'Haens G, Noman M, Vermeire S, Hiele M, Asnong K, et al. Randomized, 
double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in 
severe ulcerative colitis. Gastroenterology 2003;125 (4):1025-31.


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11.
SOFTWARE
SAS® Software Version 9.4 (SAS Institute Inc., Cary, NC, USA) is to be used for all 
programming of tables, listings, and figures.


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12. 
SAP REVISION 
Revision Date 
(DD MMM YYYY) 
Section 
Original Version 
(05 NOV 2019) 
3.5.1 
3.7.2 
3.8, 4, 7.2, 7.3 
5 
-
7.1.7 
Version 2 
(01 March 2021) 
7.2.4 
Appendix 3 
Appendix 
Global 
CONFIDENTIAL 
Summary of Revision 
Added missing data imputation rule 
for MRI data, laborato1y data and 
vital signs data 
Updated analysis visit window 
length for Week 18 and Week 24 
Added assessment of COVID-19 
impact 
Modified the list of variables to be 
summarized in baseline 
characteristic tables 
Added adverse event of interest for 
MACE, ASTE, and VTE based on 
positively adjudicated events by the 
cardiovascular safety endpoint 
adjudication committee 
Removed shift table summaries 
Added a list of biologics for CD 
treatment 
Deleted the list of prefeITed terms 
for each catego1y of adverse events 
of interest (Version 1 Appendix 11 
to 16) 
Administrative and editorial 
changes have been made throughout 
the SAP, where appropriate 
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Reason for Revision 
To clarify missing data 
imputation rule for analysis 
To map data to analysis visits 
based on more clinical 
relavent rationale 
To better understand the 
COVID-19 impact on subject 
disposition and missing data 
To provide better 
characterization of the 
investigated patient 
populations 
To better address safety 
conce1ns 
The shift table summaries are 
less useful to detect safety 
signal given small sample 
size in this study.The shift 
table summaries will be 
included in integrated safety 
analysis if needed 
To clarify biologics 
considered as general CD 
treatment 
To reduce the burden to keep 
track of the list of prefeITed 
tenns due to MedDRA 
up-versioning. The lists will 
be provided in the CSR. 
Imporve clarity and 
consistency 
01 March 2021 


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13. 
APPENDICES 
Appendix 1. 
Appendix 2. ... 
Appendix 5. 
A 
endix 6. 
Appendix 10. 
Appendix 11. 
Appendix 12. 
CONFIDENTIAL 
Schedule of Assessments 
List of Biologics for Perianal Fistulizing CD Treatment 
List ofBiolo ics for CD Treatment 
Calculation of Standard Body Weight 
Study Treatment Failure Rules for Luminal Disease Activity Related Efficacy 
Endpoints 
Study Treatment Failure Rules for Perianal Fistulizing CD Activity Related 
Efficacy Endpoints 
Dete1mining Missing and Virtual Visits due to COVID-19 
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Appendix 1.
Schedule of Assessments
Period
Screening
Treatment
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
PTxa
ET
Week
0
2
4
6
10
14
18
20
24
Study Day
-30 to -1
1
15
29
43
71
99
127
141
169
Visit Window (±)
±3
±3
±3
±2
±3
±3
±5
±5
±3
Written Informed 
Consent
X
Medical History & 
Demographics
X
Crohn’s Disease & 
Treatment History
X
12-lead ECG
X
X
Xb
Review of Inclusion/
Exclusion Criteria
X
X
Physical Exam 
(Complete including 
perianal)c
X
Physical Exam 
(symptom-based) and 
perianal assessmentc
X
X
X
X
X
X
X
X
X
X
Vital Signs
X
X
X
X
X
X
X
X
X
X
X
Weight
X
X
X
X
X
X
X
X
X
X
X
Height
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
Concomitant 
Medications
X
X
X
X
X
X
X
X
X
X
X


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Period
Screening
Treatment
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
PTxa
ET
Week
0
2
4
6
10
14
18
20
24
Study Day
-30 to -1
1
15
29
43
71
99
127
141
169
Visit Window (±)
±3
±3
±3
±2
±3
±3
±5
±5
±3
Randomization
X
Study Drug Dispensing
X
X
X
X
X
eDiary instruction & 
reviewe
X
X
X
X
X
X
X
X
X
Flexible Sigmoidoscopyo
X
X
Xr
MRIf
X
X
Xs
Stool for C. diff toxin, 
pathogenic E. coli, 
Salmonella, Shigella, 
Campylobacter and 
Yersinia testing
X
Stool O&P
X
CCI
CCI
CCI


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Period
Screening
Treatment
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
PTxa
ET
Week
0
2
4
6
10
14
18
20
24
Study Day
-30 to -1
1
15
29
43
71
99
127
141
169
Visit Window (±)
±3
±3
±3
±2
±3
±3
±5
±5
±3
Urine drug screeng
X
Urinalysisq
X
X
Pregnancy Testh
X
X
X
X
X
X
X
X
X
X
X
TB screeningi
X
Chest x-rayq
X
HBV, HCV, HIV 
screeningj
X
Hematology
X
X
X
X
X
X
X
X
X
X
X
Chemistry
X
X
X
X
X
X
X
X
X
X
X
Fasting Lipidsp
X
X
X
CRP
X
X
X
X
X
X
X
X
X
X
X
Blood TCR/BCR 
repertoire samplek
X
X
X
X
Blood transcriptome 
sample
X
X
X
X
Serum immunoglobulin
X
X
X
X
X
X
CCI
CCI
CCI


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Period 
Screening 
Treatment 
Follow-Up 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
PTx• 
ET 
Week 
0 
2 
4 
6 
10 
14 
18 
20 
24 
Study Day 
-30 to -1 
1 
15 
29 
43 
71 
99 
127 
141 
169 
Visit Window (±) 
±3 
±3 
±3 
±2 
±3 
±3 
±5 
±5 
±3 
---------------------------------------------------
---------------------------------------------------
---------------
a 
The Post-Treatment (PTx) visit should occur 30 days after the last dose of study drug. Only subjects who roll over into the LTE study will not complete PTx assessments. 
b 
For subjects who terminate prior to Week IO 
c 
A complete physical examination (PE) including; vital signs, body weight, height, and perianal assessment (including completion of the Perianal Fistula Assessment 
Worksheet) will be performed at screening. A symptom-directed PE and perianal assessment(including completion of the Perianal Fistula Assessment Worksheet) should be 
e1fo1med at all other time oints. 
r 
e 
Su 3ects s ould begin filling out the eDiary the day of their initial screening visit and continue to fill it out throughout the remainder of the study. 
f 
Refer to Section 6.6 of study protocol for details on the MRI procedure 
g 
Positive cocaine test disqualifies subject; positive amphetamines, barbittu·ates, benzodiazepines, and opioids require medical monitor review 
h 
All females meeting the childbearing potential criteria must have a senuu pregnancy testing at screening and a urine pregnancy test must be completed eve1y 4 weeks at a 
minimtuu. If any pregnancy test is positive, study drug must be inuuediately intem1pted and the subject should come to the site for serum pregnancy test in clinic. 
Proof of no active or untreated latent TB at screening. Subjects who are diagnosed with latent TB at screening must initiate an adequate coll1-se of prophylaxis as per local 
standard of care, for a minimtuu of 4 weeks prior to randomization. Subject may initiate study drug dosing only after consultation with the Study Medical Monitor. 
An HIV-I/HIV-2 antibody test, a HCV antibody test, a HBV stuface antigen test, a HBV stuface antibody test, and a HBV core antibody test will be pe1fon11ed on all 
subjects; subjects with any positivity will be excluded tmless the Hepatitis B stuface antibody is the sole positive result (indicating immtmization) 
k 
TCR: T-cell rece tor· BCR: B-cell rec tor 
r , 
o 
e er to ection . o stt1 y protoco or eta1 s on the flexible sigmoidoscopy procedm·e 
p 
Subjects should fast (no food or drinks, except water) for at least 8 hotu·s prior to blood sample collection at Day I, Week I O, and Week 24 
q 
Chest x-ray (views as per local guidelines) taken at screening or within the 3 months prior to screening (with the repo1t or fihus available for investigator review) without 
evidence of active or latent TB infection 
r 
Subjects meeting non-response or disease worsening criteria should tmdergo a flexible sigmoidoscopy assessment prior to exiting the study. 
s 
Subjects meeting non-response or disease worsening criteria should tmdergo a pelvic MRI prior to exiting the study. 
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Appendix 2.
List of Biologics for Perianal Fistulizing CD Treatment
The drug names of biologics considered as treatment for perianal fistulizing CD are listed below.
No.
Drug Class
Drug Name
1
TNFα antagonist
Adalimumab
2
TNFα antagonist
Certolizumab/Certolizumab Pegol
3
TNFα antagonist
Infliximab
4
TNFα antagonist
TNFα antagonist biosimilar (to adalimumab, 
Certolizumab/Certolizumab Pegol, or infliximab)


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Appendix 3.
List of Biologics for CD Treatment
The drug names of biologics considered as CD treatment are listed below.
No.
Drug Class
Drug Name
1
TNFα antagonist
Adalimumab
2
TNFα antagonist
Certolizumab/Certolizumab Pegol
3
TNFα antagonist
Infliximab
4
TNFα antagonist
TNFα antagonist biosimilar (to adalimumab, 
Certolizumab/Certolizumab Pegol, or infliximab)
5
Integrin antagonist
Natalizumab
6
Integrin antagonist
Vedolizumab
7
Interleukin antagonist
Ustekinumab


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Appendix 5.
Calculation of Standard Body Weight
The following table will be used to determine the standard body weight for each subject. Height 
from the eCRF will be used and is assumed to be measured without shoes. 
Women
Height in cm 
(in shoes)*
Standard Weight 
in kg
Height in cm 
(in shoes)*
Standard Weight 
in kg
127
41.2
163
60.2
128
41.7
164
60.7
129
42.3
165
61.3
130
42.8
166
61.9
131
43.3
167
62.4
132
43.8
168
62.9
133
44.4
169
63.4
134
44.9
170
63.9
135
45.4
171
64.5
136
45.9
172
65.0
137
46.4
173
65.5
138
47.0
174
66.0
139
47.5
175
66.6
140
48.0
176
67.2
141
48.6
177
67.7
142
49.1
178
68.3
143
49.6
179
68.8
144
50.2
180
69.3
145
50.7
181
69.8
146
51.2
182
70.3
147
51.8
183
70.8
148
52.3
184
71.3
149
52.8
185
71.8
150
53.1
186
72.3
151
54.1
187
72.8
152
54.5
188
73.3
153
55.0
189
73.8
154
55.4
190
74.3
155
55.9
191
74.9
156
56.4
192
75.4
157
57.0
193
76.0
158
57.5
194
76.5
159
58.1
195
77.0
160
58.6
196
77.6
161
59.1
197
78.1
162
59.6
198
78.6
*
add 2.0 cm if shoeless. Please round height to a whole number and select the appropriate standard weight 
(e.g., height 157.4 cm will be rounded to 157 cm; 157.5 cm will be rounded to 158 cm.)


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Men
Height in cm 
(in shoes)*
Standard Weight 
in kg
Height in cm 
(in shoes)*
Standard Weight 
in kg
142
54.4
179
71.9
143
54.9
180
72.4
144
55.4
181
73.0
145
55.8
182
73.6
146
56.3
183
74.3
147
56.8
184
74.8
148
57.2
185
75.5
149
57.7
186
76.2
150
58.2
187
76.9
151
58.6
188
77.6
152
59.1
189
78.2
153
59.6
190
78.8
154
60.0
191
79.6
155
60.5
192
80.4
156
61.0
193
81.2
157
61.4
194
82.1
158
61.9
195
82.9
159
62.2
196
83.8
160
62.6
197
84.7
161
62.9
198
85.4
162
63.3
199
86.1
163
63.7
200
86.7
164
64.1
201
87.4
165
64.6
202
88.0
166
65.0
203
88.8
167
65.5
204
89.4
168
66.0
205
90.1
169
66.6
206
90.7
170
67.1
207
91.4
171
67.6
208
92.1
172
68.1
209
92.7
173
68.7
210
93.4
174
69.2
211
94.1
175
69.7
212
94.8
176
70.3
213
95.5
177
70.8
214
96.1
178
71.3
 
 
*
add 2.0 cm if shoeless. Please round height to a whole number and select the appropriate standard weight 
(e.g., height 157.4 cm will be rounded to 157 cm; 157.5 cm will be rounded to 158 cm.)


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Appendix 6.
Simple Endoscopic Score for Crohn’s Disease (SES-CD)
Score
Variables
0
1
2
3
Size of 
ulcers 
(cm)
None
Aphthous ulcers
(diameter 0.1-0.5)
Large ulcers
(diameter >0.5-2)
Very large ulcers
(diameter > 2)
Ulcerated 
Surface 
(%)
None
< 10
10-30
> 30
Affected 
surface 
(%)
Unaffected segment
< 50
50-75
> 75
Presence 
of 
narrowings
None
Single,
can be passed
Multiple,
can be passed
Cannot be passed
Total SES-CD: sum of the values of the 4 variables for the 5 bowel segments. Values are given to each variable and for every 
examined bowel segment (eg, rectum, left colon, transverse colon, right colon, and ileum); Total SES-CD will not be calculated 
for Study GS-US-419-4016.
{Daperno 2004}
For Study GS-US-419-4016, the Proctitis SES-CD score (which includes an overall assessment of both rectum and anal canal) 
and Anal Canal Segmental SES-CD score will only score size of ulcers and ulcerated surface. The Proctitis SES-CD score will 
be used to provide an endoscopic measure of proctitis. 
 
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Appendix 10.
Study Treatment Failure Rules for Luminal Disease Activity Related 
Efficacy Endpoints
Study treatment failure rules described in this appendix apply to treatment failure that occurs 
during the course of the study, and will be applied to all the following efficacy endpoints related 
to luminal disease activity: 

Proportion of subjects achieving proctitis remission at Week 24, in subjects that had 
moderately to severely active proctitis at baseline
All related efficacy data will be censored (set to missing) after treatment failure criteria are met, 
regardless of the observed data. Subjects who do not have sufficient measurements after 
censoring to determine the dichotomized endpoint(s) will be considered non-responder for 
corresponding endpoint (s). Study treatment failure rules override other data handling rules.
Subjects who have any of the following events will be considered a study treatment failure after 
the earliest event through the end of the study, regardless of the actual efficacy data collected.
I.
Potentially effective corticosteroid use 
Potentially effective corticosteroids, for the purpose of this SAP, are corticosteroids that may 
impact the disease under study. Potentially effective corticosteroids include the following 
corticosteroids when administered for the indication of CD:
1) Commencement of:
Any steroid administered intramuscularly (IM), intravenously (IV), orally (PO), or rectally 
(PR) at any dose for 7 or more continuous days 

This rule applies regardless if a change in drug, dose, or route (from IM to IV to PO or 
PR or vice versa) occurs within the seven continuous days; and it includes oral steroids 
with intended local actions (eg, budesonide)
2) Escalation of concomitant steroid dose above the baseline dose for 7 or more continuous 
days. The baseline steroid dose is defined as the dose at Day 1 of the study. Prednisone 
equivalent dose will be used to determine escalation of concomitant systemic steroid dose 
even if there is a change in drug or route. For steroids with predominant local effect 
(eg, budesonide or any rectally administered steroid), this rule will apply to scenarios where 
the post-baseline dose is above the baseline dose via the same drug and the same route for 
7 or more continuous days.
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Potentially effective steroid use only includes use of steroids administered via routes that are IM, 
PO, IV, or PR. The below steroids will not be considered potentially effective steroids regardless 
of indication for use:
A) ocular steroids (ie, eye drops) 
B) topical steroids (eg, cutaneously applied solely to the skin, or topically applied to the nasal 
mucosa) 
C) inhaled steroids (eg, inhalational fluticasone for asthma)
D) intra-articular steroids (steroids administered directly into a joint)
E) neuraxial steroids (steroids administered into the epidural or spinal space)
II.
Potentially effective immunomodulator use 
Commencement of a different class of oral, IM, SC, or IV immunomodulator drugs 
(where the subject was not previously taking concomitant immunomodulators of the same class 
on Day 1), including but not limited to 6-MP, azathioprine, MTX, 6-thioguanine, and prohibited 
immunomodulators including but not limited to cyclosporine, leflunomide, tacrolimus, 
thalidomide regardless of dose, for 7 continuous days. The use of an immunomodulator will be 
considered potentially effective when it is administered for the indication of CD. 
III.
Potentially effective biologic agent use
Commencement of a biologic agent including but not limited to TNFα antagonists, 
IL-12/23 antagonists, and vedolizumab (or similar agents), regardless of indication for use and 
duration (Appendix 3).


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Study Treatment Failure Rules for Perianal Fistulizing CD Activity 
Related Efficacy Endpoints 
Study treatment failure rnles described in this appendix apply to ti·eatment failure that occurs 
during the course of the study, and will be applied to all the following efficacy endpoints related 
to perianal fistulizing CD activity: 
• 
Proportion of subjects establishing combined fistula response at Week 24 
• 
Propo1tion of subjects establishing combined fistula remission at Week 24 
• 
Time to clinical fistula response 
• 
Time to clinical fistula remission 
I 
I 
I 
All related efficacy data. will be censored (set to missing) after ti·eatment failure criteria are met, 
regardless of the observed data .. Subjects who do not have sufficient measurements after 
censoring to determine the dichotomized endpoint(s) will be considered non-responder for 
coITesponding endpoint (s). Study u-eatment failure rnles oveITide other data handling rnles. 
Subjects who have any of the following events will be considered a study ti·eatment failure after 
the earliest event through the end of the study, regardless of the actual efficacy data collected. 
I. 
Potentially effective antibiotics use 
Potentially effective antibiotics, for the pmpose of this SAP, include meti·onidazole and 
ciprofloxacin, which may impact the subject's perianal fistulizing CD when administered as 
following for the indication of perianal fistulizing CD or CD: 
• 
Commencement of a new antibiotics use after the first dosing date of study drng for 7 or 
more days; 
• 
Escalation of the dose of antibiotics above the baseline dose for 7 or more days. 
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II.
Potentially effective immunomodulator use 
Commencement of a different class of oral, IM, SC, or IV immunomodulator drugs 
(where the subject was not previously taking concomitant immunomodulators of the same class 
on Day 1), including but not limited to 6-MP, azathioprine, MTX, 6-thioguanine, and prohibited 
immunomodulators including but not limited to cyclosporine, leflunomide, tacrolimus, 
thalidomide regardless of dose, for 7 continuous days. The use of an immunomodulator will be 
considered potentially effective when it is administered for the indication of perianal fistulizing 
CD or CD. 
III.
Potentially effective biologic agent use
Commencement of a biologic agent including TNFα antagonists, regardless of indication for 
use and duration (Appendix 2).


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Appendix 12.
Determining Missing and Virtual Visits due to COVID-19
This appendix describes the clinical trial site collection of COVID-19 data pertaining to 
missed/virtual visits and the data processing algorithm used to determine which visits were 
missing and which visits were virtual.
Data collection
A COVID-19 supplement to the eCRF Completion Guidelines was provided by data 
management to instruct clinical trial sites with respect to data entry expectations pertaining to 
scenarios related to the COVID-19 pandemic. If a visit was missed, sites should enter “Visit 
missed due to COVID-19.” If an in-person visit was conducted virtually, sites should enter 
“Virtual visit due to COVID-19.”
Determination of Missed and Virtual visits
Natural Language Processing (NLP) was used to search the CRF comment fields to identify 
instances of “COVID-19” (or synonyms, see Table 13-6) and “Virtual” (or synonyms, see 
Table 13-6). The search terms are maintained in a global lookup table and can be modified to 
tune the NLP model. For any comments with COVID-19 search terms, assign “Missed Visit” or 
“Virtual Visit” as follows:
i)
If COVID-19 terms are identified through NLP and the visit date is missing, then 
result is “Missed Visit”
ii) If COVID-19 and Virtual terms are identified through NLP for a visit, then result is 
“Virtual Visit”. When there are multiple records for the same subject and the same 
visit, NLP will be based on multiple records to ensure 1 unique category per subject 
per visit
iii) Otherwise result is missing


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Table 13-6.
Examples of Search Terms for “COVID-19” and “Virtual” Used to 
Identify Missed and Virtual Visits 
Search terms for “COVID-19”
Search terms for “Virtual”
COVID19
CORONA
CORONAVIRUS
PANDEMIC
OUTBREAK
CRISIS
LOCKDOWN
QUARANTINE
SHELTER
VIRTUAL
TELEMED
TELEHEALTH
TELEPHONE
REMOTE
TELEMEDICINE 
TELECONSULTATION
TELEPHONICALLY
PHONE
HOME VISIT
ZOOM
SKYPE


GS-US-419-4016 SAP v2.0
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Biostatistics eSigned
01-Mar-2021
17:42:14
Clinical Research eSigned 01-Mar-2021
20:21:43
PPD
PPD