Clinical trial NCT03046056
Conditions: Small Bowel Crohn's Disease
Sponsor: Gilead Sciences
Start date: 2017-04-11; Completion date: 2020-07-20
Enrollment: 78 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the efficacy of filgotinib, when compared to placebo, in establishing clinical remission defined as Crohn's disease activity index (CDAI) \< 150, at Week 24 in participants with small bowel Crohn's disease (CD). Participants will have the option to enter a separate long-term extension study if they meet eligibility requirements.

Detailed description:

Arms: arm 1: Filgotinib 200 mg tablet + placebo to match (PTM) filgotinib 100 mg tablet for up to 27 weeks. arm 2: Filgotinib 100 mg tablet + PTM filgotinib 200 mg tablet for up to 26.3 weeks. arm 3: PTM filgotinib 200 mg tablet + PTM filgotinib 100 mg tablet for up to 28.7 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 
Small Bowel Crohn’s Disease (SBCD)
Sponsor:
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404, USA
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
129646
2016-003179-23
NCT03046056
Indication:
Small Bowel Crohn’s Disease 
Protocol ID:
GS-US-419-4015
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:
16 December 2016
Amendment 2:
26 June 2017
Amendment 3:
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The information contained in this document, particularly unpublished data, is the property or 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.
(rJ GI LEAi) Galapago s 


Filgotinib 
Protocol GS-US-419-4015 
Gilead Sciences, lnc. 
Final 
Amendment3 
TABLE OF CONTENTS 
TABLE OF CONTENTS .............................................................................................................................................. 2 
LIST OF IN-TEXTTABLES ........................................................................................................................................ 5 
LIST OF IN-TEXT FIG URES ...................................................................................................................................... 5 
PROTOCOL SYNOPSIS .............................................................................................................................................. 6 
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS .................................................................... 16 
DEFINITION OF TERMS .......................................................................................................................................... 20 
I. 
INTRODUCTION .............................................................................................................................................. 2 1 
1.1. 
Background ............................................................................................................................................ 2 1 
1.2. 
Filgotinib (GS-6034) .............................................................................................................................. 23 
1.2.1. 
General Information ............................................................................................................. 23 
1.2.2. 
Preclinical Pharmacology and Toxicology ........................................................................... 24 
1.2.3. 
Clinical Trials of Filgotinib .................................................................................................. 26 
1.3. 
Rationale for This Study ........................................................................................................................ 27 
1.4. 
Rationale for Dose .................................................................................................................................. 29 
1.5. 
Risk/Benefit Assessment for the Study .................................................................................................. 29 
1.6. 
Compliance ............................................................................................................................................ 30 
2. 
OBJECTIVES ..................................................................................................................................................... 3 1 
3. 
STUDY DESIGN ................................................................................................................................................ 33 
3.1. 
3.2. 
3.3. 
3.4. 
3.5. 
3.6. 
3.7. 
3.8. 
3.9. -
Endpoints ............................................................................................................................................... 33 
Study Design .......................................................................................................................................... 34 
Study Treatments ................................................................................................................................... 35 
Duration of Treatment ............................................................................................................................ 36 
Criteria for Study Drug lntenuption or Discontinuation ........................................................................ 36 
3 .5.1. 
Study Dmg Interruption Considerations ............................................................................... 36 
3.5.2. 
Study Dmg Discontinuation Considerations ........................................................................ 37 
Non-Responding Subjects ...................................................................................................................... 39 
Disease Worsening Criteria .................................................................................................................... 39 
End of Study ........................................................................................................................................... 39 
Post Stud Care ...................................................................................................................................... 39 
4. 
SUBJECT POPULATION .................................................................................................................................. 42 
4.1. 
Number of Subjects and Subject Selection ............................................................................................ 42 
4.2. 
Inclusion Criteria .................................................................................................................................... 42 
4.3. 
Exclusion Criteria ................................................................................................................................... 46 
5. 
INVESTIGATIONAL MEDICINAL PRODUCTS ........................................................................................... 49 
5.1. 
Randomization, Blinding and Treatment Codes .................................................................................... 49 
5.1.1. 
Procedures for Breaking Treatment Codes ........................................................................... 49 
5.1.2. 
Blinding ................................................................................................................................ 49 
5.2. 
Description and Handling of Filgotinib and Placebo to Match (PTM) Filgotinib .................................. 50 
5.2.1. 
Formulation .......................................................................................................................... 50 
5.2.2. 
Packaging and Labeling ....................................................................................................... 50 
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5.2.3. 
Storage and Handling ........................................................................................................... 50 
5.3. 
Dosage and Administration of Study Drug ............................................................................................ 51 
5.4. 
Prior and Concomitant Medications ....................................................................................................... 51 
5.4.1. 
Allowed Concomitant Medications ...................................................................................... 52 
5.4.2. 
Prohibited Concomitant Medications ................................................................................... 53 
5.4.3. 
Corticosteroid Tapering ........................................................................................................ 53 
5.5. 
Vaccine Guidelines ................................................................................................................................ 54 
5.6. 
Accountability for Study Drug ............................................................................................................... 54 
5.6.1. 
lnvestigational Medicinal Product Return or Disposal ......................................................... 54 
6. 
STUDY PROCEDURES .................................................................................................................................... 55 
6.1. 
6.2. 
6.3. 
6.4. 
6.5. 
6.7. 
" 
6.10. 
Subject Enrollment and Treatment Assignment ..................................................................................... 55 
Sequence of Assessments ....................................................................................................................... 55 
COAi Score and e-Diary ........................................................................................................................ 55 
Randomization and Study Dmg Administration .................................................................................... 56 
Magnetic Resonance Enterogra h ........................................................................................................ 56 
aety ..................................................................................................................................................... 57 
6.7.1. 
Clinical Laboratory Evaluations ........................................................................................... 57 
6.7.2. 
Pregnancy Testing (for females of childbearing potential only) .......................................... 59 
6.7.3. 
Vital Signs ............................................................................................................................ 59 
6.7.4. 
Physical Examination ........................................................................................................... 59 
6.7.5. 
12-lead Electrocardiogram ................................................................................................... 59 
Post-Treatment Assessments ................................................................................................................. . 
Early Termination Assessments ............................................................................................................. 60 
7. 
ADVERSE EVENTS AND TOXICITY MANAG EMENT ............................................................................... 61 
7. I. 
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events ................................. 6 I 
7. I. I. 
Adverse Events ..................................................................................................................... 61 
7 .1.2. 
Serious Adverse Events ........................................................................................................ 61 
7.2. 
Assessment of Adverse Events and Serious Adverse Events ................................................................. 62 
7 .2.1. 
Assessment of Causality for Study Drugs and Procedures ................................................... 62 
7 .2.2. 
Assessment of Severity ........................................................................................................ 63 
7.3. 
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to Gilead ....................................................................................................................... 63 
7.3.1. 
Adverse Events ..................................................................................................................... 63 
7.3.2. 
Serious Adverse Events ........................................................................................................ 64 
7.4. 
Gilead Reporting Requirements ............................................................................................................. 65 
7.5. 
Clinical Laboratory Abnormalities ......................................................................................................... 65 
7.6. 
Toxicity Management ............................................................................................................................ 66 
7 .6.1. 
Grades I and 2 Laboratory Abnormality or Clinical Event... ............................................... 66 
7 .6.2. 
Grade 3 Laboratoty Abnormality or Clinical Event ............................................................. 66 
7.6.3. 
Grade 4 Laboratoty Abnormality or Clinical Event ............................................................. 66 
7.7. 
Special Situations Reports ...................................................................................................................... 67 
7.7.1. 
Definitions of Special Situations .......................................................................................... 67 
7.7.2. 
lnstmctions for Reporting Special Situations ....................................................................... 68 
8. 
STA TIS TI CAL CONSIDERATIONS ................................................................................................................ 70 
8.1. 
Analysis Objectives and Endpoints ........................................................................................................ 70 
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Final 
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8.2. 
8.3. 
8.4. 
8.5. 
8.6. 
I 
8.10. 
8.11. 
8.1.1. 
Analysis Objectives .............................................................................................................. 70 
8.1.2. 
Primary Endpoint ................................................................................................................. 70 
8.1.3. 
Secondar End oint ............................................................................................................. 70 
.
ysis Conventions ............................................................................................................................. 7 1 
8.2.1. 
Analysis Sets ........................................................................................................................ 7 1 
Data Handling Conventions ................................................................................................................... 72 
Demographic Data and Baseline Characteristics ................................................................................... 72 
Efficacy Analysis ................................................................................................................................... 72 
8.5.1. 
Primary Analysis .................................................................................................................. 72 
8.5.2. 
Secondar Anal ses ............................................................................................................. 73 
• 
Ana ys1s ....................................................................................................................................... 74 
8.6.1. 
Extent of Exposure ............................................................................................................... 74 
8.6.2. 
Adverse Events ..................................................................................................................... 74 
8.6.3. 
Laboratory Evaluations ........................................................................................................ 74 
8.6.4. 
Other Safe 
Evaluations ...................................................................................................... 75 
Samp e Size ............................................................................................................................................ 75 
Data Monitoring Committee .................................................................................................................. 76 
Cardiovascular Safety Endpoint Adjudication Committee (CVEAC) ................................................... 76 
9. 
RESPONSIBILITIES .......................................................................................................................................... 78 
9.1. 
Investigator Responsibilities .................................................................................................................. 78 
9.1.1. 
Good Clinical Practice .......................................................................................................... 78 
9.1.2. 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Review and Approval ........................................................................................................... 78 
9 .1.3. 
Informed Consent ................................................................................................................. 78 
9.1 .4. 
Confidentiality ...................................................................................................................... 79 
9.1.5. 
Study Files and Retention of Records .................................................................................. 79 
9.1.6. 
Case Report Forms ............................................................................................................... 80 
9.1.7. 
Investigational Medicinal Product Accountability and Return ............................................. 81 
9 .1.8. 
Inspections ............................................................................................................................ 81 
9 .1.9. 
Protocol Comp I iance ............................................................................................................ 81 
9 .2. 
Sponsor Responsibilities ........................................................................................................................ 82 
9 .2.1. 
Protocol Modifications ......................................................................................................... 82 
9 .2.2. 
Study Report and Publications ............................................................................................. 82 
9 .3. 
Joint Investigator/Sponsor Responsibilities ........................................................................................... 82 
9.3.1. 
Payment Reporting ............................................................................................................... 82 
9.3.2. 
Access to Information for Monitoring .................................................................................. 83 
9 .3 .3. 
Access to Information for Auditing or Inspections .............................................................. 83 
9.3.4. 
Study Discontinuation .......................................................................................................... 83 
10. REFERENCES ................................................................................................................................................... 84 
11. APPENDICES .................................................................................................................................................... 87 
Appendix I. 
Appendix 2. 
Appendix 3. 
Appendix 4. 
Appendix 5. 
CONFIDENTIAL 
Investigator Signature Page .................................................................................................... 88 
Study Procedures Table .......................................................................................................... 89 
Management of Clinical and Laboratory Adverse Events ...................................................... 93 
Crohn's Disease Activity Index (CDAI) and Patient Reported Outcomes - 2 items 
(PRO2) ................................................................................................................................... 94 
MaRJA (Magnetic Resonance Index of Activity) Scoring System ......................................... 95 
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Appendix 6.
CTCAE Grading Scale for Severity of Adverse Events.........................................................96
Appendix 7.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................97
Appendix 8.
Clinical Laboratory Assessment Table.................................................................................100
LIST OF IN-TEXT TABLES
Table 5-1.
Prohibited Concomitant Medications .....................................................................................53
Table 7-1.
Grading of Adverse Event Severity........................................................................................63
LIST OF IN-TEXT FIGURES
Figure 3-1.
Study Design Schematic.........................................................................................................34


Filgotinib
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Final
Gilead Sciences, Inc.
Amendment 3
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PROTOCOL SYNOPSIS
Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Study Title:
A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study 
Evaluating the Efficacy and Safety of Filgotinib in the Treatment of 
Small Bowel Crohn’s Disease (SBCD)
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
129646
2016-003179-23
NCT03046056
Study Centers 
Planned:
Approximately 80 centers in North America and Europe
Objectives:
The primary objective of this study is:

To evaluate the efficacy of filgotinib, when compared to placebo,
in establishing clinical remission, defined as Crohn’s disease 
activity index (CDAI) < 150, at Week 24
The secondary objectives of this study are:

To evaluate the impact of filgotinib, when compared to placebo, 
on change in segmental MaRIA (Magnetic Resonance Index of 
Activity) score for all assessed small bowel segments at Week 24

To evaluate the efficacy of filgotinib, when compared to placebo, 
in establishing segment level MaRIA remission at Week 24

To evaluate the efficacy of filgotinib, when compared to placebo, 
in establishing segment level MaRIA response at Week 24

To evaluate the efficacy of filgotinib, when compared to placebo, 
in establishing subject level small bowel MaRIA remission at 
Week 24

To evaluate the efficacy of filgotinib, when compared to placebo, 
in establishing subject level small bowel MaRIA response at 
Week 24

To evaluate the efficacy of filgotinib, when compared to placebo, 
in establishing clinical remission, defined as CDAI < 150, at 
Week 10

To evaluate the impact of filgotinib, when compared to placebo, 
on change in CDAI scores

To evaluate the safety and tolerability of filgotinib


Filgotinib 
Protocol GS-US-419-4015 
Gilead Sciences, lnc. 
Study Design: 
CONFIDENTIAL 
Final 
Amendment3 
This is a Phase 2 randomized, double-blind, placebo-controlled study 
to evaluate the efficacy and safety of filgotinib in treating subjects 
with SBCD. Approximately 100 subjects aged 18 to 75 years with 
SBCD will be randomized to 1 of 3 treatment groups in a 2:2: 1 ratio. 
Oay1 
FIL 200 mg 
(n~) 
... 
Week 10 
I 
Nonof'e1p,o,n,dilir'l,*ot 
-•t1119d1, .... 
wors•ntng cn11M1r 
FIL 
filgotinib; PBO 
placebo; mg 
milligram. 
Week 24 1 ond;>Olnl) 
* 
Non responders are subjects who never achieved a 2:: 70 po int COAi reduction from 
baseline or COAi < 150 at any point up to and induding Week I 0 
** Disease worsening is defined as a 2:: I 00 point increase in COAi score from the Week I 0 
value and COAi score 2:: 220 oints at 2 consecutive visits 
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Protocol GS-US-419-4015 
Gilead Sciences, lnc. 
CONFIDENTIAL 
Final 
Amendment3 
Treatment group 1 (n 40): Filgotinib 200 mg and placebo-to-match 
(PTM) filgotinib 100 mg, once daily 
Treatment group 2 (n 40): Filgotinib 100 mg and PTM filgotinib 
200 mg, once daily 
Treatment group 3 (n 20): 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 (TNFa) antagonist 
and vedolizumab) will be randomized in a 2: 1 ratio to either filgotinib 
100 mg or matching placebo. 
Treatment assignment will be stratified by: 
• 
Concomitant use of oral, systemically absorbed corticosteroids 
(eg, prednisone) at Day 1, (Yes or No) 
• 
Concomitant use of i1mnu11omodulators ( eg, 6-MP, azathioprine, 
methotrexate [MTX]) at Day 1, (Yes or No) 
• 
Prior exposure to biologics (eg, TNFa antagonists or 
vedolizumab ), (Yes or No) 
This study includes: 
• 
Screening (Days -30 to -1) 
• 
Randomization (Day 1) 
• 
Blinded treatment (Day 1 to Week 24) 
Efficacy assessment: At Week 24, CDAI score to assess 
clinical remission; magnetic resonance enterography (MRE) to 
assess radiographic changes 
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-
Number of 
Subjects Plaimed: 
Target 
Population: 
Duration of 
Treatment: 
Duration of 
Study: 
CONFIDENTIAL 
• 
Post-Treatment (PTx) safety assessments 
Final 
Amendment3 
Non-responders are subjects who never achieved a~ 70 point CDAI 
reduction from baseline or CDAI < 150 at any point up to and 
including 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. 
Up to 100 
Adults with moderately to severely active CD based on CDAI 200 to 
450 (inclusive), with evidence of small bowel involvement ai1d 
baseline MaRIA score of~ 7 in at least one of the following 
segments: tenninal ileum ( distal 15 cm of ileum, as measured from 
ileocecal valve), distal ileum (the portion of the ilemn proximal to 
tenninal ilemn ), and jejunum (small bowel located at the left upper 
quadrant) 
24 weeks 
Up to 33 weeks 
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Gilead Sciences, Inc.
Amendment 3
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Diagnosis and 
Main Eligibility 
Criteria:
For a complete list of study inclusion and exclusion criteria, 
please refer to Section 4.
Main Eligibility Criteria
Subjects must meet all of the following inclusion criteria to be eligible 
for participation in this study:

Males or non-pregnant, nonlactating females, ages 18 to 75 years, 
inclusive based on the date of screening visit

Moderately or severely active CD as defined by screening CDAI 
200 to 450 (inclusive)

Minimum duration of CD of at least 6 months, documented by at 
least one of the following: 
A histopathology report showing features consistent with CD 
as determined by the pathologist
Imaging consistent with diagnosis of CD or 
Medical record documentation of or an ileocolonoscopy report 
showing features consistent with CD

Presence of diseased SB segments on MRE with segmental 
MaRIA score of ≥ 7 in at least 1 of the following segments: 
terminal ileum, distal ileum, or jejunum

Patients with additional colonic involvement of CD are permitted 
in study as long as SBCD is present

Previously demonstrated an inadequate clinical response, loss of 
response to, or intolerance to at least 1 of the following agents 
(depending on current country treatment 
recommendations/guidelines):
Corticosteroids
■
Active disease despite a history of an induction regimen of 
a dose equivalent to oral prednisone 30 mg daily for 
2 weeks or intravenously (IV) for 1 week, OR
■
Two failed attempts to taper steroids below a dose 
equivalent of 10 mg daily prednisone, OR
■
History of steroid intolerance including, but not limited to, 
Cushing’s syndrome, osteopenia/osteoporosis, 
hyperglycemia, insomnia, serious infections, depression, 
allergic reactions, mood disturbances, or any other 
condition that contributed to discontinuation of the agent


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Gilead Sciences, Inc.
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Immunomodulators
■
Active disease despite a history of at least a 12-week 
regimen of oral azathioprine (≥2 mg/kg/day) or 
6-mercaptopurine (6-MP) (≥1 mg/kg/day), or MTX 
(25 mg subcutaneous [SC] or intramuscular [IM] per week 
for induction and ≥15 mg IM per week for maintenance), 
OR
■
History of intolerance to at least 1 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
TNFα Antagonists
■
Active disease despite a history of at least 1 induction 
regimen of infliximab, adalimumab, certolizumab or 
biosimilar as follows:
○
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)
○
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. 
○
Certolizumab: A 8-week induction regimen of 400 mg 
SC at Weeks 0, 2, and 4
OR
■
Recurrence of symptoms during maintenance therapy with 
the above agents, OR
History of intolerance to any TNFα antagonists including, but 
not limited to, serious infections, hepatotoxicity, heart failure, 
allergic reactions, or any other condition that contributed to 
discontinuation of the agent
Vedolizumab
■
Active disease despite a history of at least a 14-week 
induction regimen of vedolizumab consisting of 300 mg 
IV at Weeks 0, 2, and 6, OR
■
History of intolerance to vedolizumab including, but not 
limited to, serious infections, hepatotoxicity, cytopenia, 
allergic reactions, or any other condition that contributed 
to discontinuation of the agent


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Gilead Sciences, Inc.
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Ustekinumab
■
Active disease despite a history of a 8-week induction 
regimen with a single dose of ustekinumab IV per 
weight-based dosing (260 mg for up to 55 kg; 390 mg for 
greater than 55 to 85 kg; 520 mg for greater than 85 kg) at 
Week 0, OR
■
Recurrence of symptoms during maintenance therapy with 
ustekinumab SC, OR
■
History of intolerance to ustekinumab including, but not 
limited to, serious infections, allergic reactions, or any 
other condition that contributed to discontinuation of the 
agent

Willing and able to undergo MRE per protocol requirements
Subjects who meet any of the following exclusion criteria are not to 
be enrolled in this study:

Presence of symptomatic or clinically significant (eg, obstructive 
or symptomatic) strictures or stenosis.

Presence of fistulae

Evidence of short bowel syndrome

Isolated colonic CD, or isolated CD that does not involve some 
segment of the small bowel

Presence of ulcerative colitis, indeterminate colitis, ischemic 
colitis, fulminant colitis, or toxic mega-colon

History of total colectomy, subtotal colectomy, presence of 
ileostomy or colostomy, or likely requirement for surgery during 
the study

Has used any TNFα antagonist or vedolizumab ≤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

Active TB or history of latent TB that has not been treated 
(see Inclusion Criterion 10 for more details)
Study Procedures/
Frequency:
Study visits for all subjects will occur at screening, Day 1, Weeks 2, 
4, 6, 10, 14, 18, 20 (if applicable), and 24, post-treatment, and early
study drug discontinuation, if applicable. 


Filgotinib 
Protocol GS-US-419-4015 
Gilead Sciences, lnc. 
Test Product, Dose, 
and Mode of 
Administration: 
Reference Therapy, 
Dose, and Mode of 
Administration: 
Criteria for 
Evaluation: 
Safety: 
CONFIDENTIAL 
Final 
Amendment3 
Screening assessments will include complete medical history and 
physical examination (PE), vital signs, laboratory assessment, CDAI, 
PRO2, MRE, pregnancy test (for females of childbearing potential as 
defined in Appendix 7) subject eDiary and HRQoL review, 
standard 12-lead ECG, adverse events (AEs), and concomitant 
medication assessment. 
Adverse events and concomitant medications will be assessed at each 
visit. 
Concomitant Crohn's Disease Medication Management: 
Subjects on pennitted concomitant medications for CD that are 
described in the inclusion criteria ( eg, 5-ASA, corticosteroid, and 
i1mnunomodulators) must remain on stable doses (no change in dose) 
until Week 10. 
Refer to Section 5.4.2 for a complete list of prohibited concomitant 
medications. 
Filgotinib 200 mg oral tablet, once daily 
Filgotinib 100 mg oral tablet, once daily 
PTM filgotinib 200 mg oral tablets, once daily 
PTM filgotinib 100 mg oral tablets, once daily 
Assessment of AEs and concomitant medications will continue 
throughout the duration of the study. Safety evaluations include 
documentation of AEs, vital signs, and clinical laboratory evaluations 
(hematology, chemistry, urinalysis). An ECG will be perfonned at 
screening and at Week 10 or ET if subject tenninates prior to 
Week 10. 
A data monitoring c01mnittee (DMC) will meet twice to evaluate all 
available safety data from 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 the subjects reach the Week 10 visit. 
Additional DMC meetings may be convened, if needed. 
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Gilead Sciences, lnc. 
Amendment 3 
Efficacy: 
Primary efficacy will be assessed by the CDAI. Clinical remission is 
defined as CDAI < 150. 
-
Statistical Methods: 
The primary analysis set for efficacy analyses will be the Full 
Analysis Set (FAS), which includes all randomized subjects who 
received at least 1 dose of study drug. 
CONFIDENTIAL 
The primary efficacy endpoint is the proportion of subjects achieving 
clinical remission, defined as CDAI < 150, at Week 24. 
Secondary efficacy endpoints include: 
• 
Change from baseline in tenninal ileum segmental MaRIA score 
at Week 24 
• 
Change from baseline in distal ilemn segmental MaRIA score at 
Week 24 
• 
Change from baseline in jejunum segmental MaRIA score at 
Week 24 
• 
Proportion of subjects achieving MaRIA remission in tenninal 
ileum segment at Week 24 
• 
Proportion of subjects achieving MaRIA remission in distal ileum 
segment at Week 24 
• 
Proportion of subjects achieving MaRIA remission in jejunum 
segment at Week 24 
• 
Proportion of subjects achieving MaRIA response in tenninal 
ilemn segment at Week 24 
• 
Proportion of subjects achieving MaRIA response in distal ileum 
segment at Week 24 
• 
Proportion of subjects achieving MaRIA response in jejm1mn 
segment at Week 24 
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Amendment 3
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
Proportion of subjects achieving subject level small bowel MaRIA 
remission at Week 24

Proportion of subjects achieving subject level small bowel MaRIA 
response at Week 24

Proportion of subjects achieving early clinical remission by CDAI 
at Week 10

Change from baseline in CDAI scores at Week 10

Change from baseline in CDAI scores at Week 24
For the primary efficacy endpoint, the number and proportion of 
subjects achieving clinical remission at Week 24 for each treatment 
group will be summarized with 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 continuous endpoints will be summarized using descriptive 
statistics (n, mean, standard deviation [SD], median, 1st quartile [Q1], 
3rd quartile [Q3], minimum, maximum) by treatment group and 
timepoint. 
Safety will be evaluated by assessment of clinical laboratory tests, 
physical examinations, 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 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 sample size of 40 subjects in each of the filgotinib treatment groups
and 20 subjects in the placebo group is considered adequate to assess 
the safety, tolerability, and efficacy of filgotinib in a descriptive 
manner.  Assuming a clinical remission rate of 40% for the filgotinib 
treatment groups (200 mg and 100 mg), the 2-sided 90% exact 
confidence interval is (26.9%, 54.2%).
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.


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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
ANCOVA
analysis of covariance
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
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
CVEAC
Cardiovascular safety endpoint adjudication committee
CYP
Cytochrome P450
DMC
data monitoring committee
DSS
dextran sodium sulfate
EC
ethics committee
E.coli
Escherichia coli
ECG
electrocardiogram
eCRF
electronic case report form(s)
EDC
Electronic Data Capture 


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EMA
European Medicines Agency
EQ-5D
EuroQol five dimensions
ET
early termination
EU
European Union
EudraCT
European clinical trials database
FAS
Full Analysis Set
FDA
(United States) Food and Drug Administration
GCP
Good Clinical Practice (Guidelines)
GHAS
Global Histologic Disease Activity Score
GSI
Gilead Sciences, Inc. 
h
hours
HDL
high-density lipoprotein
HBV
Hepatitis B Virus
HBcAb
HBV core antibody
HCV
Hepatitis C Virus
HDPE
high density polyethylene
HIV
Human Immunodeficiency Virus
HLGT
High-Level Group Term
HLT
High-Level Term
HRQoL
health-related quality of life
IB
investigator brochure
IBD
inflammatory bowel disease
IBDQ
Inflammatory Bowel Disease Questionnaire
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


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LOCF
Last Observation Carried Forward
LTE
long-term extension
MaRIA
Magnetic Resonance Index of Activity
MedDRA
Medical Dictionary for Regulatory Activities
mg
milligram
mL
milliliter
MMRM
mixed effect model repeat measurement
MPO
myeloperoxidase
MRE
magnetic resonance enterography
MTX
methotrexate
NOEL
no-observed-effect-levels
NRI
non-responder imputation
nM
nanomolar
OAT
organic anion transporters
O&P
ova and parasites test
OLE 
open-label extension
P-gp
p-glycoprotein
PBMC
peripheral blood mononuclear cell
PBO
placebo
PD
pharmacodynamic
PE
physical examination
PEG
polyethylene glycol
PI 
principal investigator
PK
pharmacokinetic
PRO2
patient reported outcomes consisting of 2 items: abdominal pain severity 
and liquid stool frequency
PT
preferred term
PTx
Post-Treatment
PTM
placebo to match
PVE
Pharmacovigilance & Epidemiology (formerly Drug Safety and Public 
Health [DSPH])
RA
rheumatoid arthritis
RHI 
Robarts Histopathology Index
RNA
ribonucleic acid
RT-PCR
reverse transcription polymerase chain reaction
SADR
serious adverse drug reaction
SAE
serious adverse event
SAP
Statistical Analysis Plan
SC
subcutaneous
SD
standard deviation


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SF-36
Short Form Health Survey
SOC
system organ class
SOP
standard operating procedure
spp
Species
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
vfPBMC
viably frozen peripheral blood mononuclear cell
WBC
white blood cell
WPAI
Work Productivity and Activity Impairment


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DEFINITION OF TERMS
Clinical Remission by CDAI
CDAI score < 150 points
Corticosteroid-free CDAI 
Remission
CDAI < 150 with no steroid use for at least 4 weeks prior to Week 24 for 
subjects on steroids at baseline
Disease Worsening
A ≥100 point increase in CDAI score from the Week 10 value and CDAI score 
≥220 points at 2 consecutive visits
Non-responder
Subjects who never achieves a ≥ 70 point CDAI reduction from baseline or 
CDAI < 150 at any point up to and including Week 10 
Minimal Detectable Difference 
(MDD) by MRE
For segments with baseline MaRIA score ≥ 15, the MDD is 6.5 units.
For segments with baseline MaRIA score < 15, the MDD is 4 units.
Segment with Active Disease
Segmental MaRIA score ≥ 7
Segment with Presence of 
Ulcerative Lesions (Moderate 
to Severe Radiographic 
Disease Activity)
Segmental MaRIA score ≥ 11
Segment with Mild 
Radiographic Disease Activity
Segmental MaRIA score ≥ 7 but < 11
Segment Level MaRIA 
Remission
For segments with baseline MaRIA score ≥ 7, a segmental MaRIA score < 7 at 
Week 24
Segment Level MaRIA 
Response
For segments with baseline MaRIA score ≥ 15, a segmental MaRIA score < 11,
or a decrease from baseline in a segmental MaRIA score ≥MDD.
For segments with baseline MaRIA score < 15 (but ≥7), a segmental MaRIA 
score < 11.
Subject Level Small Bowel 
MaRIA Remission
MaRIA score of < 7 in each of 3 segments:

terminal ileum = distal 15 cm of ileum, measured from ileocecal valve

distal ileum = the portion of the ileum proximal to terminal ileum

jejunum = small bowel located at the left upper quadrant
Subject Level Small Bowel 
MaRIA Response
All small bowel segments with baseline MaRIA score ≥7 achieve segment 
level MaRIA response, with no increase in MaRIA score ≥ MDD in any other 
evaluable small bowel segment(s)
Subject with Stable Small 
Bowel Disease 
At least 1 small bowel segment doesn’t achieve segment level response, while 
no ≥MDD increase detected in any evaluable small bowel segment.
Subject with Small Bowel
Disease Progression
At least 1 small bowel segment has MaRIA score > 11, while ≥MDD increase 
in MaRIA score in at least 1 small bowel segment.


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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.
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}.
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 or manifest with intra-abdominal abscess, a condition which can be 
life threatening if not treated early with systemic antibiotics. In addition, CD may demonstrate 
extra-intestinal manifestations 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}.
Crohn’s disease may impact any part of the alimentary tract but commonly affects the terminal 
ileum. During the course of the disease, anatomical location may vary. In a population based 
study, more than half of 306 patients were diagnosed between the ages of 17 and 40 years. 
Crohn’s disease at diagnosis was located in the terminal ileum in 45% (L1), colon in 32% (L2 by 
the Montreal modification of Vienna classification), ileocolon in 19% (L3), and upper gastro 
intestinal tract in 0.3% (L4). Most patients (81%) had a non-stricturing, nonpenetrating 
phenotype (B1), 5% a stricturing (B2) and 14% a penetrating (B3) phenotype {Thia 2010}. The 
presence of ileal as well as upper gastrointestinal involvement were strongly associated with 
progression towards strictures or penetrating disease {Thia 2010}. While isolated SBCD is an 
uncommon phenotypic presentation of CD, involvement of some portion of the small bowel, 
particularly the ileum, is usual for the disease. Precise estimates of SB involvement vary in the 


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literature, but generally, some involvement of the small bowel occurs in up to 70% of patients 
with isolated small bowel disease reported in up to a third of patients {Hall 2015}. One cohort of 
subjects with CD in Northern France (1988-1999) who underwent a comprehensive bowel 
investigation identified 20.6% of the subjects as demonstrating pure SB involvement, 
60.7% with ileocolonic lesions, and 18.7% of pure colonic lesions {Molinie 2004}.
SBCD may result in significant morbidity, including malnutrition, anemia, and weight loss, as 
well as typical symptoms of abdominal pain and diarrhea. Extensive small bowel disease and 
more proximal disease may be associated with a worse long-term prognosis; jejunal disease in 
particular may be a significantly greater risk factor for stricturing disease and need for abdominal 
surgeries than esophagogastroduodenal disease or isolated ileal disease {Lazarev 2013}.  The 
present study seeks to evaluate the impact of filgotinib on the small bowel due to the overall 
disease burden, the difficulty in imaging small bowel disease and following disease progression 
and response to treatment in that location, and the influence of proximal disease on prognosis.
To assess disease severity in CD, a number of clinical scoring systems are utilized based upon 
signs, symptoms, laboratory parameters, imaging modalities, and endoscopy. The 
Crohn’s Disease Activity Index (CDAI) is one such scoring tool which ranges from 0 to over 
600 based upon a composite of symptoms (eg, abdominal pain, liquid stools), signs 
(eg, the presence of abdominal mass and weight), laboratory values (eg, hematocrit), general 
well-being, and physician clinical assessment. Patients with a score of 220 to 450 are defined as 
having moderate to severe disease activity, those 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} or clinical response defined as a 70 or
100 point decrease in CDAI from baseline.  
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.
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}; in general, providers use the same 
treatments for ileocolonic CD as SBCD. 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 TNFα, are currently 
marketed for the treatment of CD in the EU and US: infliximab (Remicade®), adalimumab


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(Humira®) and certolizumab pegol (Cimzia® [approved in US only]). 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 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. Safe and effective treatment options which 
may be conveniently administered in a chronic setting would provide a significant treatment 
advance for patients with moderately to severely active 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 and a 6-month carcinogenicity study in 
transgenic (TgrasH2) mice. Ongoing studies include carcinogenicity studies in rats and mice, a 
rat pre- and post-natal development study, and a 4-week impurity qualification study in rats.
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 of rats only. Effects on the lymphoid system were fully 
reversible. Testicular toxicity demonstrated partial reversibility; however, sperm 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 targeted exposure toxicity study, respectively.
GS-829845-related findings in the repeat-dose toxicity studies were generally similar to those of 
the parent 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 marrow micronucleus 
assay.
In embryofetal development studies, filgotinib and GS-829845 caused embryolethality and 
teratogenicity in pregnant rats and rabbits. Teratogenicity was observed at exposures slightly 
higher or similar to the human exposure at 200 mg once daily of filgotinib in subjects with CD.  
Administration of filgotinib did not affect female fertility but impaired fertility 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 fertility parameters 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, randomized, double-blind, placebo-controlled, multicenter study with filgotinib was 
performed in subjects with active CD with evidence of mucosal ulceration {Vermeire 2017}. In 
Part 1, a total of 174 subjects were randomized (3:1) to receive either filgotinib 200 mg once 
daily or placebo for 10 weeks. Part 2 of the study was exploratory and not powered for statistical 
comparison of clinical end points. Based on their clinical response in Part 1, subjects in Part 2 
either continued their current treatment or were reassigned to a different treatment for an 
additional 10 weeks.
The efficacy of filgotinib was assessed by evaluating clinical remission (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
The present study seeks to evaluate the impact of filgotinib on a subset of CD patients with SB 
disease present on MRI.  The majority of available evidence pertaining to mucosal healing and 
remission in CD is based on ileocolonoscopic data {Kopylov 2015} and trials have historically 
involved endpoints centered on patient-reported symptoms with ileocolonoscopy being used 
more recently to objectively report endoscopic healing. Colonoscopy with ileoscopy enables 
direct visualization and biopsy of the rectum, colon, and terminal ileum, but examination of the 
SB is limited to the ileum when using colonoscopy, and the ileum cannot be accessed in all 
patients. In one observational cohort of 112 subjects, subjects with a diagnosis of CD for at least 
6 months with symptoms or altered biomarkers were examined endoscopically and only 62% of 
subjects had a complete colonoscopy with ileoscopy, with 80% reaching the cecum
{Jauregui-Amezaga 2015}.  Other measures to evaluate SB disease include balloon-assisted 
enteroscopy and capsule endoscopy; the former requires significant technical expertise and 
generally requires anesthesia, with risks of procedural and anesthetic complications.  Retention 
of capsule or bowel obstruction may result from the use of capsule endoscopy, and data to 
support widespread use is limited {Arguelles-Arias 2014}. Endoscopic visualization also has a 
known limited ability to evaluate fistulizing disease and other extraenteric complications which 
cannot be identified luminally. Optical endoscopy may also be limited in its capacity to evaluate 
critically ill patients due to procedural risks in that setting. The impact of present therapies on SB 
disease is poorly characterized partially due to limitations in assessing and imaging the small 
bowel in a consistent and controlled fashion. Disease complications for SBCD in particular are 
poorly characterized by luminal ileocolonoscopy. CT enterography (CTE) may image the small 
bowel but requires large volume oral contrast and repeat scans are undesirable given the risk of 
ionizing radiation. Use of a low-risk noninvasive modality to assess SBCD inflammation, 
transmural fibrosis, strictures, and overall disease burden represents a significant unmet clinical 
and diagnostic need in IBD.  
MRE (magnetic resonance enterography) represents a promising alternative imaging technique 
and in some institutions has largely replaced CTE as a cross-section imaging modality for 
evaluation of IBD. MRE combines oral contrast distention with contrast-enhancing sequences to 
evaluate features such as bowel wall thickening, wall edema, ulceration, and even mucosal 
healing. Morphological and penetrating complications can be visualized by MRE. MRE may be 
beneficial in determining disease anatomy, activity during relapse periods, extraintestinal and 
extraluminal findings, and assessing both inflammation and fibrosis {Moy 2016}. Advantages of 
MRE over ileocolonoscopy include the lack of need for bowel preparation, absence of 
perforation risk, broad capacity for anatomical imaging, ease of serial scanning, and a higher 
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An objective MRE-based scoring system entitled the Magnetic Resonance Index of Activity 
(MaRIA) score, correlated with traditional endoscopic scoring systems, has been developed as a 
novel endpoint in assessing disease activity in CD {Rimola 2011, Rimola 2009}. The MaRIA 
score is highly concordant with the Crohn’s Disease Endoscopic Index of Severity (CDEIS). In 
1 cohort of 50 patients with CD, clinical disease was evaluated by both endoscopic means 
(using CDEIS score) and MRE, with significant correlation between segmental CDEIS and an 
MR index calculation using wall thickness, contrast enhancement, presence of edema, and 
presence of ulcers {Rimola 2009}.  Segmental MRE scores quantifying activity in each segment 
were calculated as follows: MaRIA (segment)
 1.5(wall thickness mm) + .02(Relative Contrast 
Enhancement [RCE]) + 5(edema) + 10(ulceration) (see Appendix 5). The MaRIA index had a 
high (r 0.81) and significant (p<0.001) correlation with CEDEIS of the corresponding segment. 
A global MaRIA score is calculated as the sum of the subscores of the rectum, sigmoid, 
descending, transverse, and ascending colon and ileum {Rimola 2009}. In agreement with the 
initial study characterizing the MaRIA index, a second study of 48 subjects provided an external 
validation of MRI predictors of CD severity using CDEIS as a reference, demonstrating a high 
stability of the MRI model for scoring. A MaRIA cutoff of ≥7 was confirmed to be indicative of 
active disease and ≥11 confirmed to be indicative of severe disease (ulcerative lesions) on a 
segment by segment analysis {Rimola 2011}.  Conversely, a MaRIA score of < 7 indicated 
mucosal healing with < 11 representing ulcer healing. A third cohort of 48 CD subjects with 
endoscopic disease (with ulcers) was assessed with ileocolonoscopy and MRE, treated with an 
induction of remission regimen of adalimumab or corticosteroids, and then reevaluated at 
12 weeks. Endoscopic mucosal healing defined as CDEIS < 3.5 was achieved in 52% of 
subjects; an overall MaRIA score < 50 had a high diagnostic accuracy for predicting endoscopic 
ulcer healing with a sensitivity of 75% and specificity of 80%. The same cutoff (MaRIA < 50) 
predicted endoscopic mucosal healing (CDEIS < 3.5) with a sensitivity of 83% and a specificity 
of 84%. Mucosal healing based on MaRIA < 50 was noted in 50% of subjects at Week 12, with 
good endoscopic and MRE agreement. The correlation between overall CDEIS and MaRIA was 
highly significant at baseline and Week 12 but correlation between MaRIA and CDAI was only 
significant at Week 12 {Ordas 2014}. Based on data validating the MaRIA score as an objective 
radiographic disease activity measure, the present study will assess the impact of filgotinib on 
changes in the MaRIA score at the segment level for the jejunum, distal ileum, and terminal 
ileum segment and on the all small bowel segments combined in patients with small bowel CD.  
Though multiple clinically-based scoring systems have been developed to assess disease activity 
and provide a basis for assessment of therapeutic modalities, no system is specific to SB disease. 
Clinical scoring systems are generally based upon global signs, symptoms, laboratory 
parameters, imaging modalities, and endoscopy. In the present study, CDAI remission at 
24 weeks will remain the primary endpoint as it is still widely used.  
 
In conclusion, the present study uses MRE to characterize the disease extent and response to 
filgotinib treatment in subjects with SBCD.  Given the general rarity of isolated SB disease and 
the frequent involvement of the colon in CD, the present study will include subjects with 
anatomically diverse disease.
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1.4.
Rationale for Dose
In Phase 2 trials in RA, pooled data with an exposure response analysis demonstrated a 
dose-dependent increase in efficacy up to 200 mg total daily dose.  In the Phase 2 study of CD, 
subjects treated in the 200 mg arm showed favorable response and remission rates 
(47% remission over 23% placebo and 59% response over 41% placebo). The remission 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 observed between filgotinib exposures and inhibition of pSTAT1 activation 
(ex-vivo) following single and multiple filgotinib doses, where maximal inhibition of pSTAT1 
activation (~78%) was achieved at or above 200 mg total daily dose and intermediate inhibition 
(~47%) at 100 mg {Namour 2015}. pSTAT1 data, in conjunction with considerations around the 
margin for nonclinical testicular findings, suggests assessing doses above 200 mg is not 
indicated. The presence of response in CD subjects in the exploratory 10 to 20 week arm of 
Study GLPG0634-CL-211, and study of multiple doses (ie, 100 mg and 200 mg once daily) in 
the present study will enable establishment of an appropriate nominal dose and determine the 
dose with the most favorable risk/benefit profile for SBCD subjects.
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
moderate to severe disease. The lifelong nature of IBD increases the probability that subjects
have cycled through various therapies, leaving few approved options. SBCD diagnosis and 
therapy faces the unique challenge of difficulty imaging and tracking response to therapy, and 
represents a subset of CD with increased risk of complications such as penetrating disease.
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-week 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 


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the United States will be limited to subjects who have failed at least 2 biologic therapies 
(any TNFα antagonists and vedolizumab). Refer 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; the use of highly effective contraception in the subject 
population is expected to mitigate this risk.
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.
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 trial, 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 SBCD. 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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2. 
OBJECTIVES 
The primary objective of this study is: 
Final 
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• 
To evaluate the efficacy of filgotinib, when compared to placebo, in establishing clinical 
remission, defined as CDAI < 150, at Week 24 
The secondary objectives of this study are: 
• 
To evaluate the impact of filgotinib, when compared to placebo, on change in segmental 
MaRIA score for all assessed small bowel segments at Week 24 
• 
To evaluate the efficacy of filgotinib, when compared to placebo, in establishing segment 
level MaRIA remission at Week 24 
• 
To evaluate the efficacy of filgotinib, when compared to placebo, in establishing segment 
level MaRIA response at Week 24 
• 
To evaluate the efficacy of filgotinib, when compared to placebo, in establishing subject 
level small bowel MaRIA remission at Week 24 
• 
To evaluate the efficacy of filgotinib, when compared to placebo, in establishing subject 
level small bowel MaRIA response at Week 24 
• 
To evaluate the efficacy of filgotinib, when compared to placebo, in establishing clinical 
remission, defined as CDAI < 150, at Week 10 
• 
To evaluate the impact of filgotinib, when compared to placebo, on change in CDAI scores 
• 
To evaluate the safety and tolerability of filgotinib 
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3.
STUDY DESIGN
3.1.
Endpoints
The primary endpoint of this study is:

Proportion of subjects achieving clinical remission, defined as CDAI < 150, at Week 24
The secondary endpoints of this study are:

Change from baseline in terminal ileum segmental MaRIA score at Week 24

Change from baseline in distal ileum segmental MaRIA score at Week 24

Change from baseline in jejunum segmental MaRIA score at Week 24

Proportion of subjects achieving MaRIA remission in terminal ileum segment at Week 24

Proportion of subjects achieving MaRIA remission in distal ileum segment at Week 24

Proportion of subjects achieving MaRIA remission in jejunum segment at Week 24

Proportion of subjects achieving MaRIA response in terminal ileum segment at Week 24

Proportion of subjects achieving MaRIA response in distal ileum segment at Week 24

Proportion of subjects achieving MaRIA response in jejunum segment at Week 24

Proportion of subjects achieving subject level small bowel MaRIA remission at Week 24

Proportion of subjects achieving subject level small bowel MaRIA response at Week 24

Proportion of subjects achieving early clinical remission by CDAI at Week 10

Change from baseline in CDAI scores at Week 10

Change from baseline in CDAI scores at Week 24
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3.2. 
Study Design 
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This study is a Phase 2, randomized, double-blind, placebo-controlled study to evaluate the 
efficacy and safety of filgotinib in treating subjects with SBCD. A schematic of this study is 
provided in Figure 3-1. 
Figure 3-1. 
-
..-
I 
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<-? 
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(I) e. .... 
a, 
C: c 
41 
Q) 
'-
0 en 
Day 1 
C: 
0 
'$ 
N ·e 
0 
"0 
C: 
Study Design Schematic 
Week 10 
I 
Non-responc,«s· or 
meeting disuse 
worsening crtttrla" 
FIL 
filgotinib; PBO 
placebo; mg milligram. 
Week 24 (1°endpornt) 
* 
Non responders are subjects who never achieved a 2:: 70 point COAi reduction from baseline or COAi < 150 at any point up 
to and induding Week 10 
** Disease worsening is defined as a 2:: I 00 point increase in COAi score from the Week IO value and COAi score 2:: 220 points 
at 2 consecutive visits 
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This study includes: 
• 
Screening (Days -30 to -1) 
• 
Randomization (Day 1) 
• 
Blinded Treatment Period (Day 1 to Week 24) 
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Efficacy assessment: At Week 24, CDAI score to assess clinical remission; MRE to 
assess radiographic changes 
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Post-Treatment (PTx) safety assessments 
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3.3. 
Study Treatments 
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 follows: 
Treatment group 1 (n 
40): Filgotinib 200 mg and PTM filgotinib 100 mg, once daily 
Treatment group 2 (n 
40): Filgotinib 100 mg and PTM filgotinib 200 mg, once daily 
Treatment group 3 (n 
20): PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily 
Note: US males who have not failed at least 2 biologic therapies (any TNFa antagonist and 
vedolizumab) will be randomized in a 2: 1 ratio to either filgotinib 100 mg or matching placebo. 
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Treatment assignments will be stratified according to the following factors:

Concomitant use of oral, systemically absorbed corticosteroids (eg, prednisone) at Day 1, 
(Yes or No)

Concomitant use of immunomodulators (eg, 6-MP, azathioprine, MTX) at Day 1, 
(Yes or No)

Prior exposure to biologics (eg, TNFα antagonists or vedolizumab), (Yes or No)
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 who meet 
disease worsening criteria after Week 10 (see Section 3.7) 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 Gilead 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 Gilead 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 pausing should be determined in 
consultation with the Gilead Medical Monitor

Any subject who develops a new infection during the study should undergo prompt and 
complete diagnostic testing appropriate for an immuncompromised 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.


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3.5.2.
Study Drug Discontinuation Considerations
The Gilead 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

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 Gilead Medical Monitor.


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
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: < 0.75 x109 cells/L)
Two sequential (3 to 5 days apart) platelet counts 
< 75,000 platelets/mm3(SI: < 75.0 x109 cells/L)
2 sequential aspartate aminotransferase (AST) or alanine aminotransferase (ALT)
elevations > 3x the upper limit of normal (ULN) and at least one of the following 
confirmed values: 
■
total bilirubin >2x ULN 
■
INR > 1.5
■
or accompanied by symptoms consistent with hepatic injury
For any subject with an initial AST or ALT elevation > 3x the 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.


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Subjects withdrawing from the study should complete Early Tennination (ET), followed by PTx 
assessments 30 days after the last dose of study drug. 
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 tenninate 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 infonned of the reason for study tenn ination. 
3.6. 
Non-Responding Subjects 
Subjects who are non-responders to study treatment are subjects who have never achieved a 
70 point CDAI reduction or CDAI < 150 at an 
oint u to and includin Week 10 when 
com ared to the baseline value. 
3.7. 
Disease Worsening Criteria 
Subjects meeting the followin 
criterion after Week 10 must be discontinued 
from blinded treatment 
• 
A ~100 point increase in CDAI score from the Week 10 value and CDAI score~ 220 points 
at 2 consecutive visits 
3.8. 
Detenn ination of disease worsening may be made at scheduled or m1scheduled visits 
( eg, a study visit followed by an unscheduled visit, or 2 sequential m1scheduled visits 
anytime subsequent to the Week 10 visit). 
End of Study 
End of Study is defined as 30 days after the last dose administered to the last subject. 
3.9. 
Post Study Care 
a ter t e su ~ect 
completed their study participation, the long-tenn care of the participant will remain the 
responsibility of their primary treating physicians. 
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4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Up to 100 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, nonlactating females, ages 18 to 75 years, inclusive based on the date 
of screening visit.
3) Females of child bearing potential (as defined in Appendix 7) must have a negative 
pregnancy test at screening and Day 1.
4) Males and females of child bearing potential who engage in heterosexual intercourse must 
agree to use protocol specified methods of contraception as described in Appendix 7.
5) Moderately or severely active CD as defined by screening CDAI 200 to 450 (inclusive).
6) Minimum duration of CD of at least 6 months, documented by at least one of the following: 
a) A histopathology report showing features consistent with CD as determined by the 
pathologist
b) Imaging consistent with diagnosis of CD or 
c) Medical record documentation of or an ileocolonoscopy report showing features 
consistent with CD
7) Presence of diseased SB segments on MRE with segmental MaRIA score of ≥7 in at least 1 
of the following segments: terminal ileum, distal ileum, or jejunum.
8) Patients with additional colonic involvement of CD are permitted in study as long as SBCD 
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9) Previously demonstrated an inadequate clinical response, loss of response to, or intolerance 
to at least 1 of the following agents (depending on current country treatment 
recommendations/guidelines):
a) Corticosteroids
i)
Active disease despite a history of an induction regimen of a dose equivalent to oral
prednisone 30 mg daily for 2 weeks or intravenously (IV) for 1 week, OR
ii) Two failed attempts to taper steroids below a dose equivalent of 10 mg daily 
prednisone, OR
iii) History of steroid intolerance including, but not limited to, Cushing’s syndrome, 
osteopenia/osteoporosis, hyperglycemia, insomnia, serious infections, depression, 
allergic reactions, mood disturbances, or any other condition that contributed to 
discontinuation of the agent
b) Immunomodulators
i)
Active disease despite a history of at least a 12-week regimen of oral azathioprine 
(≥2 mg/kg/day) or 6-mercaptopurine (6-MP) (≥1 mg/kg/day), or MTX (25 mg
subcutaneous [SC] or intramuscular [IM] per week for induction and ≥15 mg IM per 
week for maintenance), OR
ii) History of intolerance to at least 1 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
c) TNFα Antagonists
i)
Active disease despite a history of at least 1 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
OR
ii) Recurrence of symptoms during maintenance therapy with the above agents, OR
iii) History of intolerance to any TNFα antagonists including, but not limited to, serious 
infections, hepatotoxicity, heart failure, allergic reactions, or any other condition that 
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d) Vedolizumab
i)
Active disease despite a history of at least a 14-week induction regimen of 
vedolizumab consisting of 300 mg IV at Weeks 0, 2, and 6, OR
ii) History of intolerance to vedolizumab including, but not limited to, serious infections, 
hepatotoxicity, cytopenia, allergic reactions, or any other condition that contributed to 
discontinuation of the agent
e) Ustekinumab
i)
Active disease despite a history of a 8-week induction regimen with a single dose of 
ustekinumab IV per weight-based dosing (260 mg for up to 55 kg; 390 mg for greater 
than 55 to 85 kg; 520 mg for greater than 85 kg) at Week 0, OR
ii) Recurrence of symptoms during maintenance therapy with ustekinumab SC, OR
iii) History of intolerance to ustekinumab including, but not limited to, serious infections, 
allergic reactions, or any other condition that contributed to discontinuation of the 
agent
10) 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.


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Cases falling under category “b” and “c” need to be approved by the Sponsor prior to enrollment 
in the study. No subject with currently active TB may be enrolled in the study, regardless of past 
or present anti-TB medication use.
11) Laboratory parameters (subjects who fail to meet the parameters of any of the below
reference laboratory tests may be re-tested 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 formula
c) Hemoglobin ≥ 8 g/dL (both males and females)
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
12) 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.
b) Oral corticosteroid therapy (prednisone prescribed at a stable dose ≤30 mg/day or 
budesonide prescribed at a stable dose of ≤9 mg/day) provided the dose prescribed has 
been stable for 4 weeks prior to randomization.
c) Azathioprine or 6-MP or methotrexate provided the dose prescribed has been stable for 
4 weeks prior to randomization.
d) Antibiotics for the treatment of CD (eg, metronidazole, ciprofloxacin) provided the dose 
prescribed has been stable for 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. 
13) Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks 
after last dose of study drug.
14) Willing and able to undergo MRE per protocol requirements
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 7.
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) Presence of symptomatic or clinically significant (eg, obstructive or symptomatic) strictures 
or stenosis.
7) Presence of fistulae.
8) Evidence of short bowel syndrome.
9) Any other complication of CD that could preclude the use of CDAI to assess response to 
therapy or would confound the evaluation of benefit from treatment with filgotinib.
10) Claustrophobia to a degree that prevents tolerance of MRE scanning procedure (sedation is 
permitted at discretion of investigator).
11) Metallic implant of any sort that prevents MRE 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 MRE examination.
12) Known hypersensitivity to gadolinium
13) Isolated colonic CD, or isolated CD that does not involve some segment of the small bowel.
14) Evidence of any other CD manifestation that might require imminent surgery or would 
possibly confound the evaluation of benefit from treatment with filgotinib.
15) Have any current or prior abscesses, unless they have been drained and treated at least 
6 weeks prior to Day 1 and are not anticipated to require surgery.
16) History of major surgery or trauma within 30 days prior to screening.


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17) Presence of ulcerative colitis, indeterminate colitis, ischemic colitis, fulminant colitis, 
or toxic mega-colon.
18) Dependence on parenteral nutrition.
19) History of total colectomy, subtotal colectomy, presence of ileostomy or colostomy, or likely 
requirement for surgery during the study. 
20) History or evidence of incompletely resected colonic mucosal dysplasia.
21) Stool sample positive for Clostridium difficile (C. diff) toxin, pathogenic Escherichia coli
(E. coli), Salmonella species (spp), Shigella spp, Campylobacter spp, or Yersinia spp.
22) Stool sample positive for ova or parasites test (O&P) unless approved by the Medical 
Monitor
23) Has used any TNFα antagonist or vedolizumab ≤ 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.
24) Use of any prohibited concomitant medication as described in Section 5.4.2.
25) History of leukocytapheresis ≤ 6 months prior to screening.
26) 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 requiring oral anti-infective therapy within 2 weeks of screening (or 6 weeks of 
Day 1).
27) Co-Infection with human immunodeficiency virus (HIV), HBV, or HCV.
28) Presence of Child-Pugh Class C hepatic impairment
29) 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 study protocol.
30) 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.
31) History of opportunistic infection or immunodeficiency syndrome.
32) Active TB or history of latent TB that has not been treated (see Inclusion Criterion 10 for 
more details).


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33) History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, 
or multiple myeloma.
34) History of treatment with lymphocyte depleting therapies, including but not limited to 
alemtuzumab, cyclophosphamide, total lymphoid irradiation, and rituximab.
35) Administration of live or attenuated vaccine within 30 days of randomization.
36) Currently on any chronic systemic (oral or intravenous) anti-infective therapy for chronic 
infection (such as pneumocystis, CMV, herpes zoster, atypical mycobacteria).
37) History of disseminated Staphylococcus aureus. 
38) 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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5.
INVESTIGATIONAL MEDICINAL PRODUCTS
5.1.
Randomization, Blinding and Treatment Codes
5.1.1.
Procedures for Breaking Treatment Codes
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) system for that subject. Gilead recommends but does not require that 
the investigator contact the Gilead Medical Monitor before breaking the blind. Treatment 
assignment should remain blinded unless that knowledge is necessary to determine subject 
emergency medical care. The rationale for unblinding must be clearly explained in source 
documentation and on the electronic eCRF, along with the date on which the treatment 
assignment was obtained. The investigator is requested to contact the Gilead Medical Monitor 
promptly in case of any treatment unblinding.
Blinding of study treatment is critical to the integrity of this clinical trial; therefore, if a subject’s 
treatment assignment is disclosed to the investigator, the subject will have study treatment 
discontinued. All subjects will be followed until study completion unless consent to do so is 
specifically withdrawn by the subject.
Gilead Pharmacovigilance & Epidemiology (PVE) may independently unblind cases for 
expedited reporting 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 drug will be dispensed by the study pharmacist, or designee, in a blinded 
fashion to the subjects. The
 File Administrator, or designee, in Bioanalytical 
Operations and/or Clinical Data Management, who facilitates the data transfer of 
 files 
between Gilead and vendors, will remain unblinded. Individuals in Clinical Packaging & 
Labeling or Clinical Supply Management who have an Unblinded Inventory Manager role in the 
interactive voice/web response system for purposes of study drug inventory management will 
remain unblinded. Individuals in PVE responsible for safety signal detection, investigational new 
drug safety reporting, and/or expedited reporting of SUSARs may be unblinded to individual 
case data and/or group-level summaries. External (ie, contract research organizations) 
Biostatisticians and Programmers will be unblinded to support data monitoring committee data 
review and 
PD data merge. Regulatory Quality and Compliance personnel in Research and 
Development may also be unblinded for purposes of supporting Quality Assurance activities 
and/or Regulatory Agency inspections.
CCI
CCI
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5.2.
Description and Handling of Filgotinib and Placebo to Match (PTM) 
Filgotinib
5.2.1.
Formulation
Filgotinib is available 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 to the respective 
active tablets in appearance. 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 
Final 
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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 
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 Medications 
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-com1ter 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 medications 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 Gilead 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 Medications
The allowed concomitant medication(s) for CD must be maintained at a stable dose for the noted 
time without dosing 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 ≤ 30 mg/day or 
budesonide prescribed at a stable dose of ≤9 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

Antibiotics for the treatment of CD (eg, metronidazole, ciprofloxacin) provided the dose 
prescribed has been stable for 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

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 


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5.4.2.
Prohibited Concomitant Medications 
The prohibited medications are as follows:
Table 5-1.
Prohibited Concomitant Medications
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 Medications
Corticosteroids
Dose equivalent to > 30 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
Vedolizumab and 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
Other (non-biologic)
Cyclosporine, thalidomide, tacrolimus,
leflunomide, any JAK inhibitors 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 Medications
Chronic Nonsteroidal 
Antiinflammatory 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.
5.4.3.
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 


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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 30 mg/day 
prednisone [or equivalent] or budesonide 9 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.
5.5.
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.
5.6.
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 date, quantity of used and unused study drug returned, along with the initials of 
the person recording the information.
5.6.1.
Investigational Medicinal Product Return or Disposal
Please refer to Section 9.1.7.


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Final 
Amendment3 
The study procedures to be conducted for each subject enrolled in the study are detailed in 
tabular fonn in Appendix 2. Key procedures are described in the text that follows. 
Written infonned 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 document 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 
Subject-reported outcomes are reco1mnended to be completed before any other study procedures. 
Invasive study procedures such as blood draws should be perfonned at the end of a study visit, as 
much as possible. Investigator questionnaires/assessments should be perfonned prior to 
reviewing subject-reported outcomes for that visit, as much as possible. 
6.3. 
CDAI Score and e-Diary 
The Crohn's Disease Activity Index or CDAI is a tool used to assess the activity of Crohn's 
disease. Refer to Appendix 4 for details. The PRO2 consists of 2 patient reported outcomes of 
liquid or very soft stool and abdominal pain which are components of the CDAI. 
Provide subject with the electronic diary ( eDiary) and instructions for daily docmnentation of 
stool frequency, abdominal pain, and general well-being at the screening visit. Subjects must 
continue to complete their daily eDiary for the duration of their participation on the study. 
Subjects should be instructed that all stools in the same toilet visit should be counted as 
one stool. If they pass more than one stool during a toilet visit, they will still count as one 
stool. 
Conduct phone call approximately 4 days after the screening visit to encourage compliance with 
daily documentation of abdominal pain, stool frequency, and general well-being. 
Prior to randomization ensure that each subject's eDiary is reviewed for compliance. 
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Non-patient reported variables that are required to calculate CDAI score must be collected or 
reviewed at each study visit (see Appendix 4). 
CDAI score will be calculated centrally after all components have been captured electronically. 
6.4. 
Randomization and Study Drug Administration 
• 
Enter subject infonn ation in the IWRS to receive treatment assigmn ent 
• 
Dispense study drug as directed by the IWRS 
• 
Instruct the subject on the packaging, storage, and administration of the study drug 
• 
Observe the subject taking the first dose of study drug and record the time of first dose 
6.5. 
Magnetic Resonance Enterography 
A centrally read MRE will be conducted at screening and Week 24 to characterize the disease 
extent and response to filgotinib treatment in subjects with SBCD. 
Screening MRE should be perfonned only after subject eligibility based on CDAI is confinned. 
If there are any outstanding screening clinical laboratory assessments at the time the baseline 
CDAI is calculated, these results must also be confinn ed as being within eligibility requirements 
prior to conducting the MRE. Consideration should be given to central reader review turnaround 
times to ensure results are available prior to Day 1. Screening MRE may not be repeated. 
Week 24 MRE should be perfonned 7 to 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 MRE. 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 MRE. 
For additional details on the MRE procedure, refer to the MRE Manual. 
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6.7. 
Safety 
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Safety will be assessed via AEs, concomitant medications, physical examinations (complete and 
symptom-driven), vital signs, ECGs, and clinical laboratory results. 
6.7.1. 
Clinical Laboratory Evaluations 
The hematology and serum chemistry analyses will be perfonned 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. 
will be collected by venipuncture 
-
in the ann 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. 
Refer to Appendix 8 for table of clinical laboratory tests. The details of sample handling and 
shipment instructions will be provided in a separate laboratory manual. 
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6.7.1.1.
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 Gilead Medical Monitor.
6.7.1.2.
Laboratory Re-tests
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.
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 Medical Monitor. If the subject does not begin the treatment within this 30-day window, 
specific screening evaluation procedures may need to be repeated at the direction of the 
Gilead Medical Monitor. No more than 1 repeat screening visit is allowed for each subject, 
unless prior written approval has been provided by the Sponsor.
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]).
6.7.1.3.
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.


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6.7.1.4.
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).
6.7.2.
Pregnancy Testing (for females of childbearing potential only)
All females meeting the childbearing potential criteria (Appendix 7) 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.
6.7.3.
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.
6.7.4.
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.
6.7.5.
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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6.9. 
Post-Treatment Assessments 
• 
Symptom-directed PE 
Final 
Amendment3 
• 
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 childbearing potential only) 
6.10. 
Early Termination Assessments 
For subjects who early tenn inate from the study, the following tests and procedures will be 
perfonned and docmnented: 
• 
Symptom-directed PE 
• 
Obtain body weight and vital signs (resting blood pressure, respiratory rate, pulse and 
temperature) 
• 
Perfonn 12-Lead ECG (for subjects who tenninate prior to Week 10) 
• 
Review AEs and concomitant medications 
• 
Collect eDiary back from subject 
• 
Collect the variables to calculate CDAI score (see Appendix 4) 
• 
Obtain blood samples (see Study Procedures Table [Appendix 2]) 
• 
Obtain urine sample for pregnancy test (for females of childbearing potential only) 
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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 (eg, 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 6.
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 medication, 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.


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7.3.2. 
Serious Adverse Events 
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All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (ie, signing the infonned 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 PYE as instructed. This also includes any SAEs resulting from 
protocol-associated procedures perfonned after infonned consent is signed. 
Any SAEs and deaths that occur after the post-treatment follow-up visit but within 30 days of the 
last dose of study IMP, regardless of causality, should also be reported. 
Investigators 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 participation has 
concluded and the event is deemed relevant to the use of IMP, he/she should promptly document 
and report the event to Gilead PYE. 
• 
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 start, SAEs may be reported using a paper serious adverse event 
reporting fonn. During the study conduct, sites may transition to an electronic SAE ( eSAE) 
system. 
Electronic Serious Adverse Event Reporting Process 
• 
Site perso1mel record all SAE data in the eCRF database and from there transmit the SAE 
infonnation to Gilead PYE within 24 hours of the investigator's knowledge of the event. 
Detailed instructions can be fom1d in the eCRF completion guidelines. 
• If for any reason it is not possible to record the SAE infonnation electronically, ie, the eCRF 
database is not functioning, record the SAE on the paper serious adverse event reporting 
fonn and submit within 24 hours to: 
Gilead PYE: 
Fax: 
E-mail: 
PD 
PD 
• 
As soon as it is possible to do so, any SAE reported via paper must be transcribed into the 
eCRF Database according to instructions in the eCRF completion guidelines. 
• If an SAE has been reported via a paper fonn because the eCRF database has been locked, 
no further action is necessary. 
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
For fatal or life-threatening events, copies of hospital case reports, autopsy reports, 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 traceability of a document to the subject identifiers.

Additional information may be requested to ensure the timely completion of accurate safety 
reports.

Any medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s eCRF and the event description section of the SAE form.
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
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 3). 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.


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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 Gilead Medical Monitor should be consulted prior 
to study drug discontinuation when medically feasible.
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.


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Treatment-emergent toxicities will be noted by the investigator and brought to the attention of 
the Gilead 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 Gilead 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.  
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 a medicinal 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.


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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. 
7.7.2.1. 
Instructions for Reporting Special Situations 
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 PYE using the pregnancy report fonn within 24 hours of becoming aware of the 
pregnancy. 
Refer to Section 7.3 and the eCRF completion guidelines for full instructions on the mechanism 
of pregnancy reporting. 
The pregnancy itself is not considered an AE nor is an induced elective abortion to tenninate a 
pregnancy without medical reasons. 
Any premature tennination of pregnancy ( eg, a spontaneous abortion, an induced therapeutic 
abortion 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 tenn. 
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.3.2. Furthennore, any SAE occurring as an adverse pregnancy outcome post study 
must be reported to Gilead PYE. 
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to Gilead PYE using the pregnancy outcome report 
fonn. If the end of the pregnancy occurs after the study has been completed, the outcome should 
be reported directly to Gilead PYE. Gilead PYE contact infonnation is as follows: 
Gilead PYE: 
Fax: 
E-mail: 
PD 
PD 
Pregnancies of female partners of male study subjects exposed to Gilead or other study drugs 
must also be reported and relevant infonnation should be submitted to Gilead PYE using the 
pregnancy and pregnancy outcome fonns within 24 hours. Monitoring of the pregnancy should 
continue until its conclusion. If the end of the pregnancy occurs after the study has been 
completed, the outcome should be reported directly to Gilead PYE. 
Gilead PYE: 
Fax: 
E-mail: 
PPD 
PPD 
Refer to Appendix 7 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements. 
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7.7.2.2.
Reporting Other Special Situations
All other special situation reports must be reported on the special situations report form and 
forwarded to Gilead PVE within 24 hours of the investigator becoming aware of the situation. 
These reports must consist of situations that involve study drug and/or Gilead concomitant 
medications, but do not apply to non-Gilead concomitant medications. 
Special situations involving non-Gilead concomitant medications do not need to be reported on 
the special situations report form; however, special situations that result in AEs due to a 
non-Gilead concomitant medication, must be reported as an AE. 
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 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.
STATISTICAL CONSIDERATIONS
8.1.
Analysis Objectives and Endpoints
8.1.1.
Analysis Objectives
The primary, secondary,
objectives of this study are detailed in Section 2.
8.1.2.
Primary Endpoint
The primary endpoint is the proportion of subjects achieving clinical remission, defined as CDAI 
< 150, at Week 24.
8.1.3.
Secondary Endpoint
Secondary endpoints are:

Change from baseline in terminal ileum segmental MaRIA score at Week 24

Change from baseline in distal ileum segmental MaRIA score at Week 24

Change from baseline in jejunum segmental MaRIA score at Week 24

Proportion of subjects achieving MaRIA remission in terminal ileum segment at Week 24

Proportion of subjects achieving MaRIA remission in distal ileum segment at Week 24

Proportion of subjects achieving MaRIA remission in jejunum segment at Week 24

Proportion of subjects achieving MaRIA response in terminal ileum segment at Week 24

Proportion of subjects achieving MaRIA response in distal ileum segment at Week 24

Proportion of subjects achieving MaRIA response in jejunum segment at Week 24

Proportion of subjects achieving subject level small bowel MaRIA remission at Week 24

Proportion of subjects achieving subject level small bowel MaRIA response at Week 24

Proportion of subjects achieving early clinical remission by CDAI at Week 10

Change from baseline in CDAI scores at Week 10

Change from baseline in CDAI scores at Week 24
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8.2. 
8.2.1. 
8.2.1.1. 
Analysis Conventions 
Analysis Sets 
Efficacy 
Final 
Amendment3 
The primary analysis set for efficacy analysis is the Full Analysis Set (FAS), defined as all 
randomized subjects who received at least one dose of study drug. 
8.2.1.2. 
Safety 
The primary analysis set for safety analyses is the Safety Analysis Set, defined as all subjects 
who receive at least one dose of study drug. 
- -
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8.3. 
Data Handling Conventions 
Final 
Amendment3 
Values for missing safety laboratory data will not be imputed. However, a missing baseline result 
will be replaced with a screening result, if available. If no pre-treatment laboratory value is 
available, the baseline value will be assumed to be nonnal (ie, no grade [Grade 0]) for the 
summary of graded laboratory abnonnalities. 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 smmnary 
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. 
Laboratory 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 laboratory test is 
< 20, a value of 19 will be assigned; if the result of a continuous laboratory test is < 20.0, a value 
of 19.9 will be assigned). 
Procedures for handling missing data for CDAI, MaRIA, and PRO2 will be described in the 
statistical analysis plan (SAP). 
8.4. 
Demographic Data and Baseline Characteristics 
Demographic and baseline measurements will be smmnarized separately by treatment group 
using standard descriptive statistics (n, mean, standard deviation [SD], median, 1st quartile [Q 1 ], 
3rd quartile [Q3], minimum, maximum) for continuous variables and nmnber and percentage of 
subjects for categorical variables. 
Demographic smmnaries will include age, sex, race and ethnicity. Baseline characteristics may 
include height, weight, body mass index (BMI), CDAI score, MaRIA score, PRO2 score, 
number of years since dia 
osis of CD concomitant use of oral corticosteroids, concomitant use 
of immunomodulators, 
, and other variables of 
interest. 
8.5. 
8.5.1. 
Efficacy Analysis 
Primary Analysis 
For the primary efficacy endpoint, the nmnber and proportion of subjects achieving clinical 
remission at Week 24 for each treatment group will be summarized with 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 detennine efficacy endpoints will be considered failures (ie, non-responder 
imputation [NRI]). No fonnal hypothesis testing will be perfonned. 
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8.5.2.
Secondary Analyses
The same statistical methods used for analyzing the primary endpoint will be utilized for 
analyzing the secondary endpoints for proportions. Continuous endpoints will be summarized 
using descriptive statistics (n, mean, SD, median, Q1, Q3, minimum, maximum) by treatment 
group and timepoint. An analysis of covariance (ANCOVA) model that includes treatment 
(filgotinib 200 mg, filgotinib 100 mg, or placebo), stratification factors as fixed-effect factors,
and baseline value as covariates will also be implemented. Last Observation Carried Forward 
(LOCF) approach will be considered to impute the missing values. The estimated means of 
treatment effects and estimated differences in treatment effects between each filgotinib dose 
group and placebo will be presented with 90% CIs. 


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8.6. 
Safety Analysis 
Final 
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Safety will be evaluated by assessment of clinical laboratory tests, physical examinations, 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 drug administration for the 
entire study (Day 1) up to 30 days after pennanent discontinuation of study drug will be 
summarized by treatment group according to the study drug received. 
All data collected during the course of study will be included in data listings. 
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 Tenn (HLGT), High-Level Tenn 
(HL T), Preferred Tenn (PT), and Lower-Level Tenn (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 pennanent discontinuation of study drug. 
• 
Any AEs leading to premature discontinuation of study drug. 
Smmnaries (number and percentage of subjects) ofTEAEs by SOC and PT will be provided by 
treatment group. TEAEs will also be smmnarized by relationship to study drug and severity. In 
addition, TEAEs leading to premature discontinuation of study drug will be smmnarized and 
listed. 
8.6.3. 
Laboratory Evaluations 
Selected laboratory data (using conventional m1its) will be smmnarized using only observed data. 
Absolute value and change from baseline at all scheduled time points will be smmnarized. 
Graded laboratory abnonnalities will be defined using the grading scheme defined in the 
Co1mnon Tenninology Criteria for Adverse Events (CTCAE) in Appendix 6. 
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Incidence of treatment-emergent laboratory abnonnalities 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 abnonnality (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/abnonnalities or descriptive statistics as 
appropriate. 
8.9. 
Sample Size 
A sample size of 40 subjects in each of the filgotinib treatment groups and 20 subjects in the 
placebo group is considered adequate to assess the safety, tolerability, and efficacy of filgotinib 
in a descriptive manner. Assuming a clinical remission rate of 40% for the filgotinib treatment 
groups (200 mg and 100 mg), the 2-sided 90% exact CI is (26.9%, 54.2%). 
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8.10.
Data Monitoring Committee
An external data monitoring committee (DMC) comprised of an independent statistician and 
two independent gastroenterologists will review the progress of the study and perform interim 
reviews of safety data and provide recommendation to Gilead whether the nature, frequency, and 
severity of adverse effects associated with study treatment warrant the early termination 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 from 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 the subjects reach 
the Week 10 visit. Additional DMC meetings may be convened, if needed. 
An ad hoc convening of the DMC may be triggered 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 8.11)
Any subject develops a Grade 5, related, unexpected AE. The definition of an unexpected 
AE will be based on the reference safety information that is on file at the time the event 
occurs
The DMC’s specific activities will be defined by a mutually agreed upon charter, 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 early study termination, 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 
team will be unblinded to confirm the DMC recommendation.  
8.11.
Cardiovascular Safety Endpoint Adjudication Committee (CVEAC)
An independent adjudication committee will be formed to periodically review and adjudicate all 
potential major adverse cardiovascular events 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.


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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 IRB/IEC


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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);

Documentation of the reason(s) a consented subject is not enrolled


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
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, United States, 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 have been received. Subsequent to data entry, a study monitor will perform source data 
verification within the 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 


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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 Medical Monitor 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
Arguelles-Arias F, Rodriguez-Oballe J, Duarte-Chang C, Castro-Laria L, Garcia-Montes JM, 
Caunedo-Alvarez A, et al. Capsule endoscopy in the small bowel Crohn's disease. 
Gastroenterology research and practice 2014;2014:529136.
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.
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.
Fukunaga K, Matsumoto T. Current status and future perspectives of leukocytapheresis for 
inflammatory bowel disease. J Gastroenterol Hepatol 2012;27 (6):997-1003.
Hall B, Holleran G, McNamara D. Small bowel Crohn's disease: an emerging disease 
phenotype? Dig Dis 2015;33 (1):42-51.
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.
Jauregui-Amezaga A, Rimola J, Ordas I, Rodriguez S, Ramirez-Morros A, Gallego M, et al. 
Value of endoscopy and MRI for predicting intestinal surgery in patients with 
Crohn's disease in the era of biologics. Gut 2015;64 (9):1397-402.
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.
Kopylov U, Yablecovitch D, Lahat A, Neuman S, Levhar N, Greener T, et al. Detection of Small 
Bowel Mucosal Healing and Deep Remission in Patients With Known Small 
Bowel Crohn's Disease Using Biomarkers, Capsule Endoscopy, and Imaging. Am 
J Gastroenterol 2015;110 (9):1316-23.
Korzenik JR. Investigational therapies in the medical management of Crohns disease. Available 
at: http://www.uptodate.com/contents/investiga. UpToDate 2016.
Lazarev M, Huang C, Bitton A, Cho JH, Duerr RH, McGovern DP, et al. Relationship between 
proximal Crohn's disease location and disease behavior and surgery: a cross-
sectional study of the IBD Genetics Consortium. Am J Gastroenterol 2013;108 
(1):106-12.


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Molinie F, Gower-Rousseau C, Yzet T, Merle V, Grandbastien B, Marti R, et al. Opposite 
evolution in incidence of Crohn's disease and ulcerative colitis in Northern France 
(1988-1999). Gut 2004;53 (6):843-8.
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.
Moy MP, Sauk J, Gee MS. The Role of MR Enterography in Assessing Crohn's Disease Activity 
and Treatment Response. Gastroenterology research and practice 
2016;2016:8168695.
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.
Ordas I, Rimola J, Rodriguez S, Paredes JM, Martinez-Perez MJ, Blanc E, et al. Accuracy of 
magnetic resonance enterography in assessing response to therapy and mucosal 
healing in patients with Crohn's disease. Gastroenterology 2014;146 (2):374-82 
e1.
Rimola J, Ordas I, Rodriguez S, Garcia-Bosch O, Aceituno M, Llach J, et al. Magnetic resonance 
imaging for evaluation of Crohn's disease: validation of parameters of severity 
and quantitative index of activity. Inflammatory bowel diseases 2011;17 (8):1759-
68.
Rimola J, Rodriguez S, Garcia-Bosch O, Ordas I, Ayala E, Aceituno M, et al. Magnetic 
resonance for assessment of disease activity and severity in ileocolonic Crohn's 
disease. Gut 2009;58 (8):1113-20.
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.
Thia KT, Sandborn WJ, Harmsen WS, Zinsmeister AR, Loftus EV, Jr. Risk factors associated 
with progression to intestinal complications of Crohn's disease in a population-
based cohort. Gastroenterology 2010;139 (4):1147-55.
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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11.
APPENDICES
Appendix 1.
Investigator Signature Page....................................................................................................88
Appendix 2.
Study Procedures Table..........................................................................................................89
Appendix 3.
Management of Clinical and Laboratory Adverse Events......................................................93
Appendix 4.
Crohn’s Disease Activity Index (CDAI) and Patient Reported Outcomes – 2 items 
(PRO2) ...................................................................................................................................94
Appendix 5.
MaRIA (Magnetic Resonance Index of Activity) Scoring System.........................................95
Appendix 6.
CTCAE Grading Scale for Severity of Adverse Events.........................................................96
Appendix 7.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements...................................................................................................97
Appendix 8.
Clinical Laboratory Assessment Table.................................................................................100


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Appendix 1. 
Investigator Signature Page 
GILEAD SCIENCES, INC. 
333 LAKESIDE DRIVE 
FOSTER CITY, CA 94404, USA 
STUDY ACKNOWLEDGEMENT 
A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy and 
Safety ofFilgotinib in the Treatment of Small Bowel Crohn's Disease (SBCD) 
GS-US-419-4015, Amendment 3, 04 February 2020 
This protocol has been approved by Gilead Scie ces_I:.nc..J.:he.foJlo:winJ! si_QD.ature..doc.um.enL..,_ ____ _ 
:PPDvfil 
PP D 
PPD 
PPD 
Date 
(Printed) 
i--
INVESTIGATOR STATEMENT 
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
Complete Physical 
Examinationc
X
Symptom-Directed 
Physical Examinationc
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


Filgotinib
Protocol GS-US-419-4015
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 90
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
Study Drug Dispensing
X
X
X
X
X
CDAId
X
X
X
X
X
X
X
X
X
PRO2d
X
X
X
X
X
X
X
X
X
eDiary instruction & 
reviewe
X
X
X
X
X
X
X
X
X
MRE with segmental & 
global MaRIA scoreso
X
X
Stool for C. diff toxin, 
pathogenic E. coli, 
Salmonella, Shigella, 
Campylobacter and 
Yersinia testing
X
Stool O&P
X
Fecal MMP-9
X
X
Urine drug screenf
X
Urinalysisp
X
X
Pregnancy testg
X
X
X
X
X
X
X
X
X
X
X
TB screeningh
X
CCI
CCI


Filgotinib 
Protocol GS-US-419-4015 
Gilead Sciences, lnc. 
Period 
Visit 
Week 
Study Day 
Visit Window(±) 
Chest x-rayq 
HBV, HCY, HIV 
screening; 
Hematology 
Chemistry 
Fasting LipidsP 
Blood transcriptome 
sample 
vfl>BMCk 
Serum immunoglobulin 
CONFIDENTIAL 
Screening 
1 
-30 to -1 
X 
X 
X 
X 
2 
3 
4 
5 
0 
2 
4 
6 
1 
15 
29 
43 
±3 
±3 
±3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Page 91 
Final 
Amendment3 
Treatment 
Follow-Up 
6 
7 
8 
9 
IO 
PTx• 
ET 
IO 
14 
18 
20 
24 
71 
99 
127 
141 
169 
±2 
±3 
±3 
±5 
±5 
±3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
04 February 2020 


Filgotinib 
Protocol GS-US-419-4015 
Gilead Sciences, lnc. 
Final 
Amendment3 
a 
b 
C 
d 
e 
f 
g 
h 
f r 
' 
0 
p 
q 
The Post Treatment (PTx) visit should occur 30 days after the last dose of study dmg. 
For subjects who tem1inate prior to Week I 0 
A complete physical examination (PE) including, vital signs, body weight, and height will be perfom1ed at screening. A symptom directed PE may be done at other time 
points. 
The screening COAi will be used as the Day I measurement. The COAi patient reported outcomes of stool frequency and abdominal pain will be used to derive the 
PRO2 score. 
Subjects should begin filling out the eDiary the day of their initial screening visit and continue to fill it out throughout the remainder of the study. 
Positive cocaine test disqualifies subject; positive amphetamines, barbiturates, benzodiazepines, and opioids require medical monitor review 
All females meeting the childbearing potential criteria must have a semm pregnancy testing at screening and a urine pregnancy test must be completed every 4 weeks at a 
minimum. If any pregnancy test is positive, study dmg must be immediately intem1pted and the subject should have a semm 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 course of prophylaxis as per local 
standard of care for a minimum of 4 weeks prior to randomization. Subject may initiate study dmg dosing only after consultation with the Gilead Medical Monitor. 
An HIV 1/1-IIV 2 antibody test, a 1-ICV antibody test, a HBV surface antigen test, a HBV surface antibody test, and a HBV core antibody test will be perfomied on all 
subjects. Subjects with ositive 1-lBcAb re uire reflex testing for HBV DNA (conducted locally). Refer to section 6.7. 1.3 for more details. 
e er to ecllon 
or eta1 s on t e 
proce ure 
Subjects should fast (no food or drinks, except water) for at least 8 hours prior to blood sample collection at Day I, Week I 0, and Week 24 
Chest x ray (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 
CONFIDENTIAL 
Page 92 
04 February 2020 


Filgotinib
Protocol GS-US-419-4015
Final
Gilead Sciences, Inc.
Amendment 3
CONFIDENTIAL
Page 93
04 February 2020
Appendix 3.
Management of Clinical and Laboratory Adverse Events
Grade 1 
'----G-ra_d_e_2 __ 
___.I 
l~--G-n1_d_e_3_-~I 
~I _____ 
G_n-1d_e_4 ____ 
May continue 
Repeat lab to 
dosing at the 
confirm toxicity 
discretion of the 
grade 
investigator 
' 
If confirmed and possibly and/or probably related to 
investigational medicinal products: 
1. 
Withhold investigational medicinal products until 
Grade 2 
2. 
Restart all invesforntional medicinal nroducts at full dose 
l 
If Grade 3 or 4 recurrence that is confirmed and possibly or 
probably 1·elated to investigational medicinal products, 
discontinue all investigational medicinal products dosing 
nermanentlv 
l 
Repeat lab to 
confirm toxicity 
grade 
l 
Ifc onfirmed and unrelated to 
estigational medicinal 
inv 
pro 
the 
ducts, dosing may continue at 
discretion of the investigator 
If confiI-med and 
possibly or probably 
--+ related to 
investigational 
medicinal products, 
disc on tin ue 
investigational 
medicinal products 
dosing permanently 
and follow at 
periodic intervals at 
least weekly until a 
return to baseline or 
is otherwise 
explained 
If Grade 3 or 4 recurrence that is considered unrelated to 
investigational medicinal products, continue all 
investigational medicinal products at the same dose at the 
discretion of the investigator 


Filgotinib
Protocol GS–US-419-4015
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 94
04 February 2020
Appendix 4.
Crohn’s Disease Activity Index (CDAI) and Patient Reported 
Outcomes – 2 items (PRO2)
The CDAI will be calculated as follows:
Variable no.
Variable
Variable description
Multiplier
1
Liquid or very soft stool
Daily stool count is summed for 7 days
2
2
Abdominal pain
Sum of 7 days of daily ratings as
0 = none, 1 = mild, 2 = moderate, 3 = severe
5
3
General wellbeing
Sum of 7 days of daily ratings as
0 = generally well, 1 = slightly below par, 
2 = poor, 3 = very poor, 4 = terrible
7
4
Complications
Number of listed complications:
Arthritis or arthralgia
Erythema nodosum, pyoderma gangrenosum 
or apthous stomatitis
Iritis or uveitis
Anal fissures or fistulae or abscess
Other fistula
Fever over 37.8 C [100 F] during past week
20 each
5
Use of anti-diarrheal 
medications
Use of diphenoxylate or loperamide or other 
opiate for diarrhea
0 = No, 1 = Yes
30
6
Abdominal mass
0 = none, 2 = questionable, 5 = definite
10
7
Hematocrit*
Males: 47 – Hct [%]
Females: 42 – Hct [%]
*Result must be greater than or equal to 0. 
If negative result enter 0
6 × difference
8
Weight*
Percentage deviation from standard weight
(1 – weight / standard weight) × 100
*Limit of -10
1
CDAI score
TOTAL
CDAI  Crohn’s Disease Activity Index; Hct  hematocrit
{Sandborn 2002}
The patient reported outcomes of liquid or very soft stool and abdominal pain (PRO2) score will 
be assessed as follows: 
Variable no.
Variable
Variable description
1
Liquid or very soft stool
Mean of the daily (liquid or very soft) stool count for 7 days
2
Abdominal pain
Mean of 7 days of daily ratings as
0 = none, 1 = mild, 2 = moderate, 3 = severe
{Khanna 2015}
Each PRO2 score will be rounded to the nearest integer for determination of eligibility and calculation of endpoints.


Filgotinib
Protocol GS–US-419-4015
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 95
04 February 2020
Appendix 5.
MaRIA (Magnetic Resonance Index of Activity) Scoring System
1) Component Details
Item
Definition
Sequence
Wall thickness (WT) 
Maximum wall thickness (mm) of any 
portion of the segment will be the value 
for the segment.
T1 sequence after gadolinium 
injection. Perpendicular to bowel 
axis.
Relative Contrast Enhancement 
(RCE)
RCE accounts for enhancement in the 
intestinal wall using wall signal 
intensity (WSI) before and after 
contrast.  Formula is noted belowa; 
SD is standard deviation.
T1 pre-contrast, and T1 
post-contrast at 70 seconds
Edema (E)
Hyperintensity on T2-wedged 
sequences of the colon wall relative to 
the signal of the psoas muscle. Edema 
may be a score of 0 (absent) or 
1 (present).
Either single shot (SS) T2 or 
Balance gradient echo with fat 
saturation.
Ulcerations (U)
Areas of depression/irregularity in the 
inner surface of a thickened intestinal 
wall. Linear enhancing tracts within the 
bowel wall should be considered 
fissures (linear ulcers). Ulcerations 
may be a score of 0 (absent) or 
1 (present).
All
a.
RCE: [(WSI postgadolinium WSI pregadolinium) / WSI pregadolinium] × (SD pregadolimium / SD postgadolinium) ×
100
2) Segmental Score Calculation
Segmental MaRIA  [1.5 * WT(mm)] + [0.02* RCE] + [5* E] + [10*U]


Filgotinib
Protocol GS–US-419-4015
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 96
04 February 2020
Appendix 6.
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-419-4015
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 97
04 February 2020
Appendix 7.
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-419-4015
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 98
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-419-4015
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 99
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.
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-419-4015
Final
Gilead Sciences, Inc. 
Amendment 3
CONFIDENTIAL
Page 100
04 February 2020
Appendix 8.
Clinical Laboratory Assessment Table
Hematology
Chemistry
Urinalysis
Other
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 corpuscular 
volume (MCV)
Alkaline phosphatase
Aspartate 
aminotransferase (AST)
Alanine aminotransferase 
(ALT)
Total bilirubin
Direct and indirect 
bilirubin
Total protein
Albumin
Bicarbonate
Blood urea nitrogen 
(BUN)
Calcium
Chloride
Serum creatinine
Creatinine clearance 
CC&G
Glucose
Phosphorus
Magnesium
Potassium
Sodium
Creatine Phosphokinase 
(CPK)
Appearance
Blood
Color
Glucose
Leukocyte esterase
pH
Protein
Urobilinogen
Microscopy
Urine drug screen for:
Amphetamines
Cocaine
Barbiturates
Opiates
Benzodiazepines
C-reactive protein (CRP)
QuantiFERON® TB –
Gold In-Tube Analysis 
(if required per inclusion 
criteria)
Serum immunoglobulin
Prothrombin Time (PT)
Partial thromboplastin time 
(PTT)
International Normalized Ratio 
(INR)
Serology
Fasting lipids
Stool
Pregnancy
Hepatitis B surface 
antigen (HBsAg)
Hepatitis B surface 
antibody (Ab)
Hepatitis B Core Ab
Hepatitis C Ab
HIV Ag/Ab
Triglycerides
Total Cholesterol
High-density lipoprotein 
cholesterol [HDL-C] 
Low-density lipoprotein 
cholesterol [LDL-C])
Bacterial stool culture
C-Diff Toxin
Ova and Parasites (O&P) 
In females of childbearing 
potential:
Serum pregnancy
Urine pregnancy

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): 
(rJ GILEAU 
STATISTICAL ANALYSIS PLAN 
A Phase 2, Double-Blind, Randomized, Placebo-Controlled 
Study Evaluating the Efficacy and Safety of Filgotinib in the 
Treatment of Small Bowel Crohn's Disease (SBCD) 
Filgotinib 
GS-US-419-4015 
Original (12 September 2016) 
Amendment 1 (16 December 2016) 
Amendment 2 (26 June 2017) 
Amendment 3 (04 February 2020) 
Final Analysis 
1.0 
01 October 2020 
PD 
PD 
CONFIDENTIAL AND PROPRIETARY INFORMATION 


Filgotinib 
GS-US-419-4015 Statistical Analysis Plan 
Version 1.0 
TABLE OF CONTENTS 
TABLE OF CONTENTS .............................................................................................................................................. 2 
LIST OF IN-TEXTTABLES ........................................................................................................................................ 4 
LIST OF IN-TEXT FIGURES ...................................................................................................................................... 4 
LIST OF ABBREVIA TIONS ........................................................................................................................................ 5 
DEFINITION OF TERMS ............................................................................................................................................ 8 
I. 
INTRODUCTION ................................................................................................................................................ 9 
1.1. 
Study Objectives ...................................................................................................................................... 9 
1.2. 
Study Design .......................................................................................................................................... I 0 
1.3. 
Sample Size and Power .......................................................................................................................... 12 
2. 
TYPE OF PLANNED ANALYSIS .................................................................................................................... 13 
2.1. 
Data Monitoring Committee (DMC) Analyses ...................................................................................... 13 
2.2. 
Final Analysis ........................................................................................................................................ 13 
3. 
GENERAL CONSIDERATIONS FOR DAT A ANALYSES ............................................................................ 14 
3.1. 
3.2. 
3.3. 
3.4. 
3.5. 
3.6. 
3.7. 
3.8. 
Analysis Sets .......................................................................................................................................... 14 
3.1.1. 
All Randomized Analysis Set ............................................................................................... 14 
3 .1.2. 
Full Analysis Set .................................................................................................................. 14 
3.1.3. 
Safe 
Anal sis Set ............................................................................................................... 14 
Subject Grouping ................................................................................................................................... 15 
Strata and Covariates .............................................................................................................................. 15 
Examination of Subject Subgroups ........................................................................................................ 15 
Missing Data and Outliers ...................................................................................................................... 16 
3.5.1. 
Missing Data ........................................................................................................................ 16 
3.5.2. 
Outliers ................................................................................................................................. 16 
Data Handling Conventions and Transformations ................................................................................. 16 
Analysis Visit Windows ......................................................................................................................... 18 
3.7.1. 
Definitions ............................................................................................................................ 18 
3.7.2. 
Analysis Visit Windows ....................................................................................................... 18 
3.7.3. 
Selection of Data in the Event of Multiple Records in an Analysis Visit 
Window ................................................................................................................................ 20 
Assess ofCoronavirus Disease 2019 lmpact. ......................................................................................... 2 1 
4. 
SUBJECT DISPOSITION .................................................................................................................................. 22 
4.1. 
Subject Enrollment and Disposition ....................................................................................................... 22 
4.2. 
Extent of Study Dtug Exposure and Adherence ..................................................................................... 23 
4.2.1. 
Duration of Exposure to Study Dtug .................................................................................... 23 
4.2.2. 
Adherence to Study Drug ..................................................................................................... 23 
4.3. 
Protocol Deviations ................................................................................................................................ 24 
4.4. 
Missed and Virtual Visits due to COVID-19 ......................................................................................... 25 
5. 
BASELINE CHARACTERISTICS .................................................................................................................... 26 
5.1. 
Demographics and Other Baseline Characteristics ................................................................................ 26 
5.2. 
Baseline Disease Characteristics ............................................................................................................ 26 
5.3. 
Medical History ...................................................................................................................................... 29 
6. 
EFFICACY ANALYSES ................................................................................................................................... 30 
CONFIDENTIAL 
Page 2 
0 I October 2020 


Filgotinib 
GS-US-419-4015 Statistical Analysis Plan 
Version 1.0 
6.1. 
General Considerations .......................................................................................................................... 30 
6.1.1. 
Calculation ofCDAI and PRO2 Scores ............................................................................... 32 
6.1.2. 
Calculation of MaRJA Scores and Corresponding Endpoints .............................................. 33 
6.2. 
Primary Efficacy Endpoint ..................................................................................................................... 33 
6.2.1. 
Definition of the Primary Efficacy Endpoint ....................................................................... 33 
6.2.2. 
Analysis of the Primary Efficacy Endpoint .......................................................................... 33 
6.3. 
Secondary Efficacy Endpoints ............................................................................................................... 33 
6.3. I. 
Definition of the Secondary Efficacy Endpoints .................................................................. 33 
6.3.2. 
Anal sis ofthe Secondar Efficac End oints .................................................................... 34 
6.5. 
7. 
SAFETY ANALYSES ........................................................................................................................................ 39 
7.1. 
Adverse Events and Deaths .................................................................................................................... 39 
7.1.1. 
Adverse Event Dictionary .................................................................................................... 39 
7.1.2. 
Adverse Event Severity ........................................................................................................ 39 
7.1.3. 
Relationship of Adverse Events to Study Drug .................................................................... 39 
7 .1 .4. 
Serious Adverse Events ........................................................................................................ 39 
7.1.5. 
Treatment-Emergent Adverse Events ................................................................................... 39 
7 .1.6. 
Summaries of Adverse Events and Deaths ........................................................................... 40 
7.1.7. 
Adverse Events of Interest ................................................................................................... 42 
7.2. 
Laboratory Evaluations .......................................................................................................................... 43 
7.2.1. 
Summaries of Numeric Laboratory Results ......................................................................... 44 
7.2.2. 
Graded Laboratory Values ................................................................................................... 45 
7 .2.3. 
Liver-related Laboratory Evaluations ................................................................................... 46 
7.3. 
Body Weight, Height and Yitai Signs .................................................................................................... 46 
7.4. 
Prior and Concomitant Medications ....................................................................................................... 47 
7.4.1. 
Prior Medications ................................................................................................................. 47 
7.4.2. 
Concomitant Medications ..................................................................................................... 47 
7.5. 
Electrocardiogram Results ..................................................................................................................... 48 
7.6. 
Other Safety Measures ........................................................................................................................... 48 
7.7. 
Changes from Protocol-Specified Safety Analyses ................................................................................ 48 
I 
I 
10. REFERENCES ................................................................................................................................................... 51 
11. SOFTWARE ....................................................................................................................................................... 52 
12. SAP REYISION .................................................................................................................................................. 53 
13. APP ENDICES .................................................................................................................................................... 54 
CONFIDENTIAL 
Page 3 
0 I October 2020 


Filgotinib
GS-US-419-4015 Statistical Analysis Plan
Version 1.0
CONFIDENTIAL
Page 4
01 October 2020
LIST OF IN-TEXT TABLES
Table 3-1
Analysis Visit Windows for CDAI, PRO2 
 Endpoints ..................19
Table 3-2
Analysis Visit Windows for MaRIA Score-related Efficacy Endpoints.................................19
Table 3-3
Analysis Visit Windows for Body Weight, Vital Signs, ECG, Hematology, 
Chemistry, Fasting Lipid Profile, Serum Immunoglobulin, 
 
.........................................................................................19
Table 6-1.
Definitions of Dichotomous Efficacy Endpoints....................................................................30
Table 13-1.
Calculation of CDAI Score ....................................................................................................59
Table 13-2.
Calculation of PRO2 Components .........................................................................................59
Table 13-3.
Calculation of CDAI Patient-Reported Outcome Components and PRO2 Scores at 
Screening................................................................................................................................61
Table 13-4.
Calculation of CDAI Patient-Reported Outcome Components and PRO2 Scores at 
Post-Screening Visits..............................................................................................................62
Table 13-5.
Sources of Information for Calculating CDAI and PRO2 Scores ..........................................63
Table 13-6.
Examples of Search Terms for “COVID-19” and “Virtual” used to Identify Missed 
and Virtual Visits....................................................................................................................70
Table 13-7.
Examples of Extraneous Text Terms to Eliminate from the Comment Fields .......................70
LIST OF IN-TEXT FIGURES
Figure 1-1.
Study Design Schematic.........................................................................................................11
Figure 13-1.
Selection of Diary Data for the Calculation at Screening.......................................................60
Figure 13-2.
Selection of Diary Data for Calculation at Post-Screening Visits ..........................................62
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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)
EQ-5D
EuroQol five dimensions
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
HLGT
high-level group term
HLT
high-level term
HRQoL
health-related quality of life
hs-CRP
high-sensitivity C-reactive protein
IBD
inflammatory bowel disease
IBDQ
inflammatory bowel disease questionnaire
ID
identification
IM
intramuscularly
IV
intravenously


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IWRS
interactive web response system
LDL
low-density lipoprotein
LLOQ
lower limit of quantification
LLT
lower-level term
LOCF
last observation carried forward
LOQ
limit of quantification
LTE
long-term extension
MACE
major adverse cardiovascular events
MaRIA
Magnetic Resonance Index of Activity
MDD
minimal detectable difference
MedDRA
Medical Dictionary for Regulatory Activities
MI
myocardial infarction
MMP-9
matrix metallopeptidase-9
MRE
Magnetic Resonance Enterography
MST
MedDRA search term
MTX
methotrexate
NLP
Natural Language Processing
NRI
non-responder imputation
O&P
ova and parasites test
OIs
opportunistic infections
PBMC
peripheral blood mononuclear cell
PBO
placebo
PK
pharmacokinetic
PO
orally
PR
rectally
PRO2
patient reported outcomes consisting of 2 items: abdominal pain severity 
and liquid stool frequency
PT
preferred term
PTM
placebo to match
PTx
Post-Treatment
Q1, Q3
first quartile, third quartile
RCE
relative contrast enhancement
SAE
serious adverse event
SAP
statistical analysis plan
SBCD
small bowel Crohn’s disease
SD
standard deviation
SE
standard error
SF-36
short-form 36 health survey
SMQ
Standardised MedDRA Queries
SOC
system organ class
TEAE
treatment-emergent adverse event


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TFLs
tables, figures, and listings
TNFα
tumor necrosis factor-alpha
ULN
upper limit of the normal range
US
United States
vfPBMC
viably frozen peripheral blood mononuclear cell
V-Day
visit day
VTE
venous thromboembolism
WHO
World Health Organization
WPAI
Work Productivity and Activity Impairment


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DEFINITION OF TERMS
Clinical Remission by CDAI
CDAI score < 150 points
Corticosteroid-free CDAI 
Remission
CDAI < 150 with no steroid use for at least 4 weeks prior to Week 24 for 
subjects on steroids at baseline
Disease Worsening
A ≥ 100 point increase in CDAI score from the Week 10 value and CDAI score 
≥220 points at 2 consecutive visits
Non-responder
Subjects who never achieves a ≥ 70 point CDAI reduction from baseline or 
CDAI < 150 at any point up to and including Week 10 
Minimal Detectable Difference 
(MDD) by MRE
For segments with baseline MaRIA score ≥ 15, the MDD is 6.5 units.
For segments with baseline MaRIA score < 15, the MDD is 4.0 units.
Segment with Active Disease
Segmental MaRIA score ≥ 7
Segment with Presence of 
Ulcerative Lesions (Moderate 
to Severe Radiographic 
Disease Activity)
Segmental MaRIA score ≥11
Segment with Mild 
Radiographic Disease Activity
Segmental MaRIA score ≥ 7 but < 11
Segment Level MaRIA 
Remission
For segments with baseline MaRIA score ≥ 7, a segmental MaRIA score < 7 at 
Week 24
Segment Level MaRIA 
Response
For segments with baseline MaRIA score ≥ 11, a segmental MaRIA score < 11, 
or a decrease from baseline in segmental MaRIA score ≥ MDD
For segments with baseline MaRIA score < 11 (but ≥ 7), a segmental MaRIA 
score <7 or a decrease from baseline in segmental MaRIA score ≥ MDD
Segment Level Disease Stable
For segments with baseline MaRIA score ≥ 7, absence of segment level 
MaRIA response and:
if baseline MaRIA score ≥ 11, no increase in segmental MaRIA score ≥ MDD
if baseline MaRIA score < 11, a segmental MaRIA score < 11
For segments with baseline MaRIA score < 7, no segment level disease 
worsening
Segment Level Disease 
Worsening
An increase in segmental MaRIA ≥ MDD with a segmental MaRIA score 
≥7 at Week 24, or a segmental MaRIA score ≥ 11 at Week 24 while baseline 
MaRIA score < 11
Subject Level Small Bowel 
MaRIA Remission
MaRIA score of < 7 in each of 3 segments:
terminal ileum = distal 15 cm of ileum, measured from ileocecal valve
distal ileum = the portion of the ileum proximal to terminal ileum
jejunum = small bowel located at the left upper quadrant
Subject Level Small Bowel 
MaRIA Response
All small bowel segments with baseline MaRIA score ≥ 7 achieve segment 
level MaRIA response, with no segment level disease worsening in any other 
segment(s)
Subject with Stable Small 
Bowel Disease 
At least 1 small bowel segment with baseline MaRIA score ≥ 7 doesn’t achieve 
segment level response, while no segment level disease worsening in any other
evaluable small bowel segment(s)
Subject with Small Bowel 
Disease Progression
At least 1 small bowel segment demonstrates segment level disease worsening


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1.
INTRODUCTION
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 report (CSR) 
for Study GS-US-419-4015. This SAP is based on the study protocol Amendment 3 dated 
04 February 2020 and the electronic case report form (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 primary objective of this study is:

To evaluate the efficacy of filgotinib, when compared to placebo, in establishing clinical 
remission, defined as CDAI < 150, at Week 24
The secondary objectives of this study are:

To evaluate the impact of filgotinib, when compared to placebo, on change in segmental 
MaRIA score for all assessed small bowel segments at Week 24

To evaluate the efficacy of filgotinib, when compared to placebo, in establishing segment 
level MaRIA remission at Week 24

To evaluate the efficacy of filgotinib, when compared to placebo, in establishing segment 
level MaRIA response at Week 24

To evaluate the efficacy of filgotinib, when compared to placebo, in establishing subject 
level small bowel MaRIA remission at Week 24

To evaluate the efficacy of filgotinib, when compared to placebo, in establishing subject 
level small bowel MaRIA response at Week 24

To evaluate the efficacy of filgotinib, when compared to placebo, in establishing clinical 
remission, defined as CDAI < 150, at Week 10

To evaluate the impact of filgotinib, when compared to placebo, on change in CDAI scores

To evaluate the safety and tolerability of filgotinib


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1.2. 
Study Design 
Version 1.0 
This is a Phase 2 randomized, double-blind, placebo-controlled study to evaluate the efficacy and 
safety of filgotinib in treating subjects with SBCD. A schematic of this study is provided in 
Figure 1-1. Subjects who meet protocol eligibility criteria will be randomized in a blinded fashion 
to 1 of 3 treatment groups in a 2:2: 1 ratio: 
• 
Treatment group 1 (n 40): Filgotinib 200 mg and placebo-to-match (PTM) filgotinib 
100 mg, once daily 
• 
Treatment group 2 (n 40): Filgotinib 100 mg and PTM filgotinib 200 mg, once daily 
• 
Treatment group 3 (n 20): 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 (ie, any 
tumor necrosis factor-alpha [TNFa] antagonist and vedolizumab) will be randomized in a 
2: 1 ratio to receive either filgotinib 100 mg or matching placebo. 
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Figure 1-1. 
Study Design Schematic 
Oay1 
Week 10 
Week 24 <t•coo;,o nt) 
'7 
g 
g 
I 
Ill 
>, e. 
i 
-
.... 
N 
N -
C: 
0 -s 
N I 
'--------.:~----------------' 
FIL 200 mg 
(n~O) 
Non-•pono.n-" 0t 
mHCln9 CIIHHe 
wol"Ssenlng cntlf1a•· 
FIL 
filgotinib; PBO 
placebo; mg 
milligram. 
*Non responders are subjects who never achieved a 2:: 70 point COAi reduction from baseline or COAi < 150 at any point up to 
and including Week 10 
**Disease worsening is defined as a ::: JOO point increase in COAi score from the Weck JO value and COAi score ::: 220 points at 
2 consecutive visits 
Treatment assignments will be stratified according to the following factors: 
• 
Concomitant use of oral, systemically absorbed corticosteroids ( eg, prednisone) at Day 1, 
(Yes or No) 
• 
Concomitant use of nmnunomodulators ( eg, 6-mercaptopurine [6-MP], azathioprine, 
methotrexate [MTX]) at Day 1, (Yes or No) 
• 
Prior exposure to biologics ( eg, TNFa antagonists or vedolizumab ), (Yes or No) 
This study includes: 
• 
Screening (Days -30 to -1) 
• 
Randomization (Day 1) 
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• 
Blinded treatment (Day 1 to Week 24) 
Efficacy assessment: At Week 24, CDAI score to assess clinical remission; MRE to 
assess radiographic changes 
• 
Post-Treatment (PTx) safety assessments 
• 
Steroid tapering must begin at Week 10 for subjects who are considered responders. 
1.3. 
Sample Size and Power 
A sample size of 40 subjects in each of the filgotinib treatment groups and 20 subjects in the 
placebo group is considered adequate to assess the safety, tolerability, and efficacy of filgotinib 
in a descriptive manner. Assuming a clinical remission rate of 40% for the filgotinib treatment 
groups (200 mg and 100 mg), the 2-sided 90% exact confidence interval is (26.9%, 54.2%). The 
clinical remission rate for placebo group is assumed to be 20%. 
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2.
TYPE OF PLANNED ANALYSIS
2.1.
Data Monitoring Committee (DMC) 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. The 
DMC is to recommend to the sponsor whether the nature, frequency, and severity of adverse 
effects associated with the study treatment warrant the early termination 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 from 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 the subjects reach 
the Week 10 visit. Additional DMC meetings may be convened, if needed. 
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.
No formal interim efficacy analysis, which may lead to early termination for efficacy or futility, 
is planned.
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.


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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 category will be presented; for continuous variables, 
the number of subjects (n), mean, standard deviation (SD) or standard error (SE), median, first 
quartile (Ql), third quartile (Q3), minimum, and maximum will be presented. By-subject listings 
will be presented for all subjects in the All Randomized Analysis Set and sorted 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 randomized in the study. 
The All Randomized Analysis Sets are the primary analysis sets 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 
drug. This is the primary 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 drug. This is the 
primary analysis set for safety analyses. 
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3.2. 
Subject Grouping 
For analyses based on the All Randomized Analysis Set and FAS, subjects will be grouped 
according to the treatment to which the were randomized. For analyses based on the Safety 
Analysis Set 
, subjects will be grouped according to the actual 
treatment received. The actual treatment received will differ from the randomized treatment only 
when their actual treatment differs from randomized treatment for the entire treatment duration. 
3.3. 
Strata and Covariates 
Subjects will be randomly assigned to treatment groups via the interactive web response system 
(IWRS) in a 2:2: 1 ratio using a stratified randomization schedule. Stratification will be based on 
the following variables: 
• 
Concomitant use of oral, systemically absorbed corticosteroids ( eg, prednisone) at Day 1, 
(Yes or No) 
• 
Concomitant use of immunomodulators ( eg, 6-MP, azathioprine, methotrexate) at Day 1, 
(Yes or No) 
• 
Prior exposure to biologics ( eg, TNFa antagonists or vedolizumab ), (Yes or No) 
If there are discrepancies in stratification 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 medication use at Day 1, the start date of such medication should be 
before or on the same date of the first dose of study drug and with either the stop date of such 
medication being on or after the first dose of study drug or with "ongoing" status. 
Efficacy endpoints will be evaluated using stratification factors as covariates or stratification 
variables for analyses, as specified in Section 6. 
3.4. 
Examination of Subject Subgroups 
There are no prespecified subject subgroupings for efficacy and safety analyses. 
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3.5.
Missing Data and Outliers
3.5.1.
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 drug, imputation rules are described in Section 4.2.1. 
Imputation and calculation rules for missing patient diary data and other CDAI components are 
described in Appendix 3. Imputation and calculation rules for missing MaRIA data are described 
in Section 6.3. 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 laboratory data will not be imputed. However, a missing baseline result 
will be replaced with a screening result, if available. If no pre-treatment laboratory value is 
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. All data, 
including outliers, will be included in the data analysis, unless otherwise specified.
3.6.
Data Handling Conventions and Transformations
In general, age (in years) on the date of the first dose of study drug will be used for analyses and 
presentation in listings. If an enrolled subject was not dosed with any study drug, the 
randomization date will be used instead of the first dosing date of study drug. For screen failures, 
the date the informed consent was signed will be used for age calculation. If only the birth year is 
collected on the eCRF, “01 July” will be used for the unknown birth day and month for the 
purpose of age calculation. If only birth year and month are collected, “15” will be used for the 
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Duration of CD (years) is the number of years between the diagnosis date of CD and date of first 
dose of study drug. The partial diagnosis date of 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.
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 for calculation of 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 for 
calculation of 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 for calculation of 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 for calculation of descriptive statistics if the datum is reported in the 
form of “≤ x” or “≥ x” (where x is considered the LOQ).
Natural logarithm transformation will be used for plasma concentrations. 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 postbaseline time points.
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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3.7.
Analysis Visit Windows
3.7.1.
Definitions 
The First Dosing Date is defined as the date when subjects take the first dose of study drug, as 
recorded in the Study Drug Administration eCRF. 
The Last Dosing Date is defined as the date when subjects take the last dose of study drug as 
recorded in the Study Drug Administration eCRF.
Study Day will be calculated from the first dosing date of study drug 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 drug administration.
Baseline is defined as the last available observation on or prior to the first dosing date, unless 
specified otherwise. 
3.7.2.
Analysis Visit Windows
Subject visits may not occur on protocol-specified days. Therefore, for the purpose of analysis, 
observations will be assigned to analysis windows.
The analysis windows for efficacy endpoints including CDAI, PRO2,
endpoints are based on study day and are provided in Table 3-1.
The analysis windows for MaRIA score-related efficacy endpoints are based on study day and 
provided in Table 3-2.
The analysis windows for body weight, vital signs, ECG, safety laboratory parameters 
(hematology, chemistry, fasting lipid profile, and serum immunoglobulin), 
 
are provided in 
Table 3-3. 
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Table 3-1
Analysis Visit Windows for CDAI, PRO2
-related 
Endpoints
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
197
Note: For analysis purpose, PRO2 from Screening and Visit Day 1 will be calculated and both visits will be considered for the
derivation of baseline, which is defined as the last available observation on or prior to the first dosing date of the study drug.
Table 3-2
Analysis Visit Windows for MaRIA Score-related Efficacy Endpoints
Nominal Visit
Analysis Visit
Nominal Day
(Study Day)
Lower Limit 
(Study Day)
Upper Limit
(Study Day)
Screening
Baseline
1
(none)
1
Week 24
Week 24
169
142
197
Table 3-3
Analysis Visit Windows for Body 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, 
 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.
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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.
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.


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3.8.
Assess of Coronavirus Disease 2019 Impact
This study was ongoing during the coronavirus disease 2019 (COVID-19) pandemic.
The assessment on 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 within that 
stratum. 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 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 

Did not complete study drug with reasons for premature discontinuation of study drug

Completed study 

Did not complete the study with reasons for premature discontinuation of study
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.
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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 Safety 
Analysis Set.
A by-subject listing 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: Day 1, Weeks 2, 
4, 6, 10, 14, 18, 20, and 24. Summaries will be provided by treatment group for the Safety 
Analysis Set.
No formal statistical testing is planned.
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


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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:
Total Amount of Study Drug Administered
On-Treatment Adherence (%) = 
 x 100
Study Drug Expected to be Administered on Treatment






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).
4.3.
Protocol Deviations 
Subjects who did not meet the eligibility criteria for study entry, but enrolled in the study will be 
summarized. 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 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 for the All Randomized Analysis Set. A by-subject listing will be provided for subjects 
with any important protocol deviations.
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 
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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.
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 explanation of the 
algorithm is provided in Appendix 7.  


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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

Height

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 CD (years) from date of diagnosis to first dosing date of study drug

Duration of CD (< 1 year, ≥ 1 to < 3 years, ≥3 to < 7 years, ≥7 years)

CDAI score 

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
Active disease in (yes if segmental MaRIA ≥7; otherwise no)
Terminal ileum
Distal ileum
Jejunum
At least 2 of the following segments: terminal ileum, distal ileum, or jejunum

Presence of ulcerative lesions in (yes if segmental MaRIA ≥ 11; otherwise no)
Terminal ileum
Distal ileum
Jejunum
At least 2 of the following segments: terminal ileum, distal ileum, or jejunum

Complications of CD: Fistula (yes, no), Stricture (yes, no), Abscess (yes, no)

History of surgeries due to CD (yes, no)

CD treatment history
Number of prior exposure to biologic agent as listed in Appendix 2 (0, 1, 2, ≥ 3)
Prior use of systemic corticosteroids (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 antagonist 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
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 both TNFα antagonist and vedolizumab (yes, no)
Prior failure of both TNF-alpha antagonist and vedolizumab 
■
Yes (dual refractory, defined as those who have failed at least 2 classes of biologic 
therapies [any TNFα antagonist and vedolizumab])
○
United States (US) Males
○
Subjects other than US Males
■
No 
○
US Males
○
Subjects other than US Males
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, 
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
Concomitant treatment at baseline:
Concomitant use of systemically absorbed corticosteroids and/or immunomodulator at 
baseline including: a) systemically absorbed corticosteroids only, b) immunomodulator 
only, c) both, and d) neither
Prednisone equivalent dose for subjects who are on systemically absorbed corticosteroids 
at baseline (mg/day)
Prednisone equivalent dose for subjects who are 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  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 
Regulatory Activities (MedDRA).


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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.
The definitions of dichotomous efficacy endpoints are provided in Table 6-1. Appendix 6
includes a detailed definition of study treatment failure and the corresponding data handling rules 
for efficacy analysis.
Table 6-1.
Definitions of Dichotomous Efficacy Endpoints
Type
Endpoint
Definition
Primary
Clinical remission by CDAI at 
Week 24
CDAI score < 150 points at Week 24
Secondary
MaRIA remission in terminal ileum 
segment at Week 24
MaRIA score < 7 in terminal ileum segment at 
Week 24 among subjects with MaRIA score 
≥7 in the same segment at Baseline
Secondary
MaRIA remission in distal ileum 
segment at Week 24
MaRIA score < 7 in distal ileum segment at 
Week 24 among subjects with MaRIA score 
≥7 in the same segment at Baseline
Secondary
MaRIA remission in jejunum 
segment at Week 24
MaRIA score < 7 in jejunum segment at Week 24 
among subjects with MaRIA score ≥7 in the 
same segment at Baseline
Secondary
MaRIA response in terminal ileum 
segment at Week 24
Among subjects with Baseline MaRIA score 
≥7 in terminal ileum:

if baseline MaRIA score ≥ 11, a segmental 
MaRIA score < 11, or a decrease from 
baseline in segmental MaRIA score ≥MDD
in terminal ileum

if baseline MaRIA score < 11, a segmental 
MaRIA score < 7, or a decrease from 
baseline in segmental MaRIA score ≥MDD
in terminal ileum
Secondary
MaRIA response in distal ileum 
segment at Week 24
Among subjects with Baseline MaRIA score 
≥7 in distal ileum:

if baseline MaRIA score ≥ 11, a segmental 
MaRIA score < 11, or a decrease from 
baseline in segmental MaRIA score ≥MDD
in distal ileum

if baseline MaRIA score < 11, a segmental 
MaRIA score < 7, or a decrease from 
baseline in segmental MaRIA score ≥MDD
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Type
Endpoint
Definition
Secondary
MaRIA response in jejunum 
segment at Week 24
Among subjects with Baseline MaRIA score 
≥7 in jejunum:

if baseline MaRIA score ≥ 11, a segmental 
MaRIA score < 11, or a decrease from 
baseline in segmental MaRIA score ≥MDD
in jejunum

if baseline MaRIA score < 11, a segmental 
MaRIA score < 7, or a decrease from 
baseline in segmental MaRIA score ≥MDD
in jejunum
Secondary
Subject level small bowel MaRIA 
remission at Week 24
MaRIA score < 7 at Week 24 in each of the 
3 small bowel segments: terminal ileum, distal 
ileum, and jejunum, among subjects with MaRIA 
score ≥ 7 in at least 1 small bowel segment at 
Baseline
Secondary
Subject level small bowel MaRIA 
response at Week 24
All small bowel segments with Baseline MaRIA
score ≥ 7 achieve segment level MaRIA 
response, with no segment level disease 
worsening in any other segment(s) at Week 24, 
among subjects with MaRIA score ≥7 in at least 
1 small bowel segment at Baseline
Secondary
Early Clinical remission by CDAI 
at Week 10
CDAI score < 150 points at Week 10
Summary of Dichotomous Efficacy Endpoints
Numbers and percentages of subjects achieving each of the dichotomous efficacy endpoints 
defined above, 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 
3) Subjects who are protocol-specified CDAI non-responders at Week 10 and discontinued 
study drug  
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4) Subjects who do not meet the endpoint due to study drug discontinuation led by 
protocol-specified disease worsening 
5) Subjects who do not have sufficient measurements to determine the endpoint due to study 
drug discontinuation for other reasons 
6) Subjects who do not have sufficient measurements to determine the endpoint while on study 
drug 
Non-Responder Imputation
For analysis of binary efficacy endpoints defined in Table 6-1, subjects who do not have 
sufficient measurements due to any reason (including treatment failures and CDAI 
non-responders at Week 10) to determine the endpoint will be considered non-responders 
(ie, non-responder imputation [NRI]).
6.1.1.
Calculation of CDAI and PRO2 Scores
The CDAI system is a composite index of 8 disease activity variables (components) with scores 
ranging from 0 to over 600 based upon a composite of symptoms (eg, abdominal pain), 
signs (the presence of abdominal mass and body weight), laboratory values (eg, hematocrit), 
and physician assessment amongst others. The CDAI has 3 patient reported outcome 
components: liquid or very soft stool frequency, abdominal pain, and general wellbeing. The 
clinical remission by CDAI endpoint is defined by the CDAI score, calculated as a weighted sum 
of all 8 component subscores. 
If subjects have 3 or more of the 8 component subscores missing, then the subjects will be 
considered as having insufficient data to determine response status and their CDAI score will be 
considered missing. If subjects have 1 or 2 CDAI components missing, then the missing 
component will be imputed by the Last Observation Carrying Forward (LOCF) method using the 
previous valid component score calculated at the most recent analysis visit (eg, use the 
component score from Week 6 to impute missing component at Week 10, or use the component 
score from Week 18 to impute missing component at Week 24). If the component score from the 
most recent analysis visit is also missing, the missing value will be imputed with corresponding 
component score at baseline.
The PRO2 has 2 patient reported outcome components: liquid or very soft stool frequency 
subscore and abdominal pain subscore. If either subscore is missing, no imputation will be done.
For further information on CDAI, PRO2, and calculation rules at screening and post-screening, 
refer to Appendix 3.


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6.1.2.
Calculation of MaRIA Scores and Corresponding Endpoints
The MaRIA scoring system is a composite index of 4 components. These components are edema, 
ulcers, gut wall thickness, and relative contrast enhancement (RCE). A segmental MaRIA score 
can be calculated at Screening (used as the baseline) and Week 24 as a weighted sum of these 
4 components for each of the 3 small bowel segments (terminal ileum, jejunum, and duodenum). 
For segment level remission or response based on MaRIA score, if a bowel segment that was 
identified at baseline has a segmental MaRIA score missing at Week 24, no imputation will be 
done and the subject will be considered as having insufficient data to determine segment level 
remission or response status and treated as a non-responder in that specific segment. 
For subject level remission or response based on MaRIA score, if more than one small bowel 
segment that was identified at baseline is missing at Week 24, the subject will be considered as 
having insufficient data to determine remission or response status and will be considered as a 
non-responder. If only one small bowel segment that was identified at baseline is missing at 
Week 24, then LOCF will be used to impute the missing segment. Small bowel segments with 
missing segmental MaRIA scores at baseline will not be considered when assessing subject level 
response status.
Detailed information on MaRIA score calculation rules are provided in Appendix 5.  
6.2.
Primary Efficacy Endpoint
6.2.1.
Definition of the Primary Efficacy Endpoint
The primary endpoint is the proportion of subjects achieving clinical remission, defined as CDAI 
score < 150 points at Week 24. 
6.2.2.
Analysis of the Primary Efficacy Endpoint
For the primary efficacy endpoint, the number and proportion of subjects achieving clinical 
remission by CDAI at Week 24 for each treatment group will be summarized with 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. No formal hypothesis testing will be 
performed. Bar-chart of proportions of subjects achieving clinical remission at Week 24, defined 
as CDAI score < 150 points, will be provided by treatment group.
6.3.
Secondary Efficacy Endpoints
6.3.1.
Definition of the Secondary Efficacy Endpoints
The secondary efficacy endpoints are:

Change from baseline in terminal ileum segmental MaRIA score at Week 24

Change from baseline in distal ileum segmental MaRIA score at Week 24


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
Change from baseline in jejunum segmental MaRIA score at Week 24

Proportion of subjects achieving MaRIA remission in terminal ileum segment at Week 24

Proportion of subjects achieving MaRIA remission in distal ileum segment at Week 24

Proportion of subjects achieving MaRIA remission in jejunum segment at Week 24

Proportion of subjects achieving MaRIA response in terminal ileum segment at Week 24

Proportion of subjects achieving MaRIA response in distal ileum segment at Week 24

Proportion of subjects achieving MaRIA response in jejunum segment at Week 24

Proportion of subjects achieving subject level small bowel MaRIA remission at Week 24

Proportion of subjects achieving subject level small bowel MaRIA response at Week 24

Proportion of subjects achieving early clinical remission by CDAI at Week 10

Change from baseline in CDAI scores at Week 10

Change from baseline in CDAI scores at Week 24
Refer to Table 6-1 for dichotomous secondary endpoints definitions.
6.3.2.
Analysis of the Secondary Efficacy Endpoints
For binary endpoints, the same statistical analysis methods described in Section 6.2.2 for 
analyzing the primary efficacy endpoint will be utilized. 
Continuous endpoints will be summarized using descriptive statistics (n, mean, SD, median, Q1, 
Q3, minimum, maximum) by treatment group and analysis visit. 
An analysis of covariance (ANCOVA) model that includes treatment (filgotinib 200 mg, 
filgotinib 100 mg, or placebo), stratification factors as fixed-effect factors, and baseline value as 
covariates will also be implemented. The estimated means of treatment effects and estimated 
differences in treatment effects between each filgotinib dose group and placebo will be presented 
with 90% CIs. Before the ANCOVA model is conducted, the following imputation will be 
performed:

For change from baseline in segmental MaRIA score, if segmental MaRIA score is missing 
at Week 24, then corresponding segmental MaRIA score at baseline will be used to impute 
the missing value. 

For change from baseline in CDAI score, any missing CDAI component score will be 
imputed by LOCF method using the previous valid component score calculated at most 
recent analysis visit (eg, use the component score from Week 6 to impute missing component 
at Week 10, or use the component score from Week 18 to impute missing component at 
Week 24). If the component score from the most recent analysis visit is also missing, the 
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The observed mean change from baseline values for CDAI scores will be summarized and 
plotted over all analysis visits by treatment group. 
In addition, subjects' small bowel disease status (remission, response, stable, and progression) 
based on MaRIA score will be smmnarized by treatment group for Week 24. A detailed 
definition of disease status in MaRIA score is provided in definition of tenns. 
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6.5.
Change from Protocol-Specified Efficacy Analyses
The definitions of the following terms are modified in this SAP:

In the protocol, the definition of segment level MaRIA response states “For segments with 
baseline MaRIA score ≥ 15, a segmental MaRIA score < 11, or a decrease from baseline in a 
segmental MaRIA score ≥ MDD. For segments with baseline MaRIA score < 15 (but ≥ 7), a 
segmental MaRIA score < 11”. 
In the SAP, the definition is modified to “For segments with baseline MaRIA score ≥ 11, a 
segmental MaRIA score < 11, or a decrease from baseline in segmental MaRIA score 
≥MDD. For segments with baseline MaRIA score < 11 (but ≥ 7), a segmental MaRIA score 
<7 or a decrease from baseline in segmental MaRIA score ≥ MDD”.

In the protocol, segment level disease stable is not defined.
In the SAP, the definition is “For segments with baseline MaRIA score ≥ 7, absence of
segment level MaRIA response and: if baseline MaRIA score ≥ 11, no increase in segmental 
MaRIA score ≥ MDD; if baseline MaRIA score < 11, a segmental MaRIA score < 11. For 
segments with baseline MaRIA score < 7, no segment level disease worsening”.

In the protocol, segment level disease worsening is not defined.
In the SAP, the definition is “An increase in segmental MaRIA ≥ MDD with a segmental 
MaRIA score ≥ 7 at Week 24, or a segmental MaRIA score ≥ 11 at Week 24 while baseline 
MaRIA score < 11”.

In the protocol, the definition of subject level small bowel MaRIA response states “All small 
bowel segments with baseline MaRIA score ≥ 7 achieve segment level MaRIA response, 
with no increase in MaRIA score ≥ MDD in any other evaluable small bowel segment(s)”. 
In the SAP, the definition is modified to “All small bowel segments with baseline MaRIA 
score ≥ 7 achieve segment level MaRIA response, with no segment level disease worsening 
in any other segment(s)”.

In the protocol, the definition of subject with stable small bowel disease states “At least 
1 small bowel segment doesn’t achieve segment level response, while no ≥ MDD increase 
detected in any evaluable small bowel segment”.
In the SAP, the definition is modified to “At least 1 small bowel segment with baseline 
MaRIA score ≥ 7 doesn’t achieve segment level response, while no segment level disease 
worsening in any other evaluable small bowel segment(s)”.

In the protocol, the definition of subject with small bowel disease progression states “At least 
1 small bowel segment has MaRIA score > 11, while ≥ MDD increase in MaRIA score in at 
least 1 small bowel segment”.
In the SAP, the definition is modified to “At least 1 small bowel segment demonstrates 
segment level disease worsening”.


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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 last dosing date 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 dose 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 dose temporary interruption of study drug
7.1.7.
Adverse Events of Interest
Adverse events of interest (AEI) include infections, gastrointestinal perforations, herpes zoster, 
malignancies (excluding non-melanoma skin cancers), non-melanoma skin cancers, 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 non-melanoma skin cancers, utilizing a MST list developed 
by Gilead 

AEs of non-melanoma skin cancers, utilizing an MST list developed by Gilead

AEs of gastrointestinal perforation, 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 
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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 for 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 a MST list developed by Gilead

MI, utilizing a narrow scope SMQ

Unstable angina (meeting hospitalization criteria), utilizing a MST list developed by Gilead

Transient ischemic attack, utilizing a MST list developed by Gilead

Stroke, utilizing an MST list developed by Gilead

Cardiac failure (meeting hospitalization criteria), utilizing a MST list developed by Gilead

Percutaneous coronary intervention, utilizing a 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 
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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 CTCAE severity grade will be flagged in the data listings, 
as appropriate.
Hematocrit collected from local laboratory 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 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 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 and percentage 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, total cholesterol, LDL, 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 
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7.2.2.
Graded Laboratory Values
The CTCAE Version 4.03 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 lab 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 
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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 × ULN; 
(c) > 10 × ULN; (d) > 20 × ULN

ALT: (a) > 3 × ULN; (b) > 5 × ULN; (c) > 10 × ULN; (d) > 20 × ULN

AST or ALT > 3 × ULN and total bilirubin > 2 × 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 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 
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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 medication taken before a subject took the first dose of 
study drug at baseline.
General prior and CD-specific prior medications 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 
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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
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.


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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
Summary of Revision
Reason for Revision
Original Version


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13.
APPENDICES
Appendix 1.
Schedule of Assessments
Appendix 2.
List of Biologics for CD Treatment
Appendix 3.
Crohn’s Disease Activity Index (CDAI) and Patient Reported Outcomes – 2 items 
(PRO2)
Appendix 4.
Calculation of Standard Body Weight
Appendix 5.
MaRIA (Magnetic Resonance Index of Activity) Scoring System
Appendix 6.
Study Treatment Failure Rules
Appendix 7.
Determining 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
Complete Physical 
Examinationc
X
Symptom Directed 
Physical Examinationc
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
CDAId
X
X
X
X
X
X
X
X
X
PRO2d
X
X
X
X
X
X
X
X
X
eDiary instruction & 
reviewe
X
X
X
X
X
X
X
X
X
MRE with segmental & 
global MaRIA scoreso
X
X
Stool for C. diff toxin, 
pathogenic E. coli, 
Salmonella, Shigella, 
X


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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 
Campylobacter and 
Yersinia testing 
Stool O&P 
X -----------
Urine drng screen' 
X 
Uri alysisP 
X 
e na cy test& 
X 
X 
X 
X 
X 
X 
X 
TB screenin h 
C es 
rayq 
HBV, I-ICY, HIV 
X 
screening; 
Hematology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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b 
C 
d 
e 
f 
g 
h 
r 
r 
' 
0 
p 
q 
The Post Treatment (PTx) visit should occur 30 days after the last dose of study drng. 
For subjects who tem1inate prior to Week 10 
A complete physical examination (PE) including, vital signs, body weight, and height will be perfom1ed at screening. A symptom directed PE may be done at other time 
points. 
The screening COAi will be used as the Day I measurement. The COAi patient reported outcomes of stool frequency and abdominal pain will be used to derive the 
PRO2 score. 
Subjects should begin filling out the eDiary the day of their initial screening visit and continue to fill it out throughout the remainder of the study. 
Positive cocaine test disqualifies subject; positive amphetamines, barbiturates, benzodiazepines, and opioids require medical monitor review 
All females meeting the childbearing potential criteria must have a semm pregnancy testing at screening and a urine pregnancy test must be completed every 4 weeks at a 
minimum. If any pregnancy test is positive, study drng must be immediately intem1pted and the subject should have a semm 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 course of prophylaxis as per local 
standard of care for a minimum of 4 weeks prior to randomization. Subject may initiate study drng dosing only after consultation with the Gilead Medical Monitor. 
An HIV 1/1-IIV 2 antibody test, a I-ICY antibody test, a 1-IBV surface antigen test, a HBV surface antibody test, and a HBV core antibody test will be perfomied on all 
subjects. Subjects with ositive 1-IBcAb re uire reflex testing for 1-IBV DNA (conducted locally). Refer to Protocol section 6. 7. 1.3 for more details. 
e er to rotoco 
ecllon . 
or eta1 s on t e 
procedure 
Subjects should fast (no food or drinks, except water) for at least 8 hours prior to blood sample collection at Day 1, Week 10, and Week 24 
Chest x ray (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 
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Appendix 2.
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 3.
Crohn’s Disease Activity Index (CDAI) and Patient Reported 
Outcomes – 2 items (PRO2)
The CDAI score is a weighted sum of all 8 variables as specified in Table 13-1.The PRO2 scores 
will be assessed according to Table 13-2. Details for the calculations of CDAI and PRO2 scores 
at screening and post-screening visits are provided in this appendix.
Table 13-1.
Calculation of CDAI Score
Variable no.
Variable
Variable description
Multiplier
1
Liquid or very soft stool
Daily stool count is summed for 7 days
2
2
Abdominal pain
Sum of 7 days of daily ratings as
0 = none, 1 = mild, 2 = moderate, 3 = severe
5
3
General wellbeing
Sum of 7 days of daily ratings as
0 = generally well, 1 = slightly below par, 2 = poor, 
3 = very poor, 4 = terrible
7
4
Complications
Number of listed complications:
Arthritis or arthralgia
Erythema nodosum, pyoderma gangrenosum or 
apthous stomatitis
Iritis or uveitis
Anal fissures or fistulae or abscess
Other fistula
Fever over 37.8 C [100 F] during past week
20 each
5
Use of anti-diarrheal 
medications
Use of diphenoxylate or loperamide or other opiate 
for diarrhea
0 = No, 1 = Yes
30
6
Abdominal mass
0 = none, 2 = questionable, 5 = definite
10
7
Hematocrit*
Males: 47 – Hct [%]
Females: 42 – Hct [%]
*Result must be greater than or equal to 0. 
If negative result enter 0
6 × difference
8
Weight*
Percentage deviation from standard weight
(1 – weight / standard weight) × 100
*Limit of -10 (Result must be greater than or equal 
to -10)
1
CDAI score
TOTAL
CDAI = Crohn’s Disease Activity Index; Hct = hematocrit
{Sandborn 2002}
Table 13-2.
Calculation of PRO2 Components
Variable no.
Variable
Variable Description
1
Liquid or very soft stool
Mean of the daily (liquid or very soft) stool count for 7 days
2
Abdominal pain
Mean of 7 days of daily ratings as
0 = none, 1 = mild, 2 = moderate, 3 = severe
{Khanna 2015}
Each PRO2 subscore will be rounded to the nearest integer (eg, 2) for calculation of endpoints.


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The 3 patient-reported outcome components for CDAI (and each subscore for PRO2) are 
determined using an electronic daily diary, which collects subject reported components directly.  
Given that the MRE procedure and lower endoscopy procedure (including protocol-directed and 
non-protocol-directed procedures) may impact the validity of the diary data, diary data collected 1 
day prior to and on the day of the procedure (either MRE or lower endoscopy) will not be used in 
the calculation of CDAI and PRO2 subscores for all visits. Those days are called non-evaluable 
days. 
Calculation of CDAI and PRO2 Scores at Screening 
MRE is required to be performed during screening. The calculations of CDAI and PRO2 at 
screening are specified below:
1) Define T-Day 1  subject activation date on the electronic diary device during screening. 
2) Define a 10-day window using T-Day 1 as the anchor date, and the window starts the day 
after T-Day 1 and ends 10 days after T-Day 1. 
3) For each CDAI patient-reported outcome component, if there are 7 or more evaluable records 
within the 10-day window, take the sum of the 7 evaluable records closest to T-Day 1. For 
each PRO2 component, take the average of the 7 evaluable records within the 10-day 
window closest to T-Day 1.
a) If there are 4 or more (but less than 7) evaluable records within this 10-day window, the 
average of the available records will be taken, and then multiplied by 7 for the 
corresponding CDAI patient-reported component. For the corresponding PRO2 
component, the average of the available records will be taken.
b) If subjects do not have at least 4 evaluable records within this 10-day window, the 
corresponding CDAI patient-reported component and PRO2 component will not be 
calculated and will be considered as missing. 
A schema of this approach and some examples are included below for further illustration:
Figure 13-1.
Selection of Diary Data for the Calculation at Screening
Subject Activation 
Date on Electronic 
I 
I 
I 
I 
Baseline 
Device (T-Day 1) 
T-Day 2 
T-Day 11 
(Day 1) 
1' 
t 
t 
t 
.. 
L 
-1,, 
L 
10-day window to calculate diary data 
MREDate 


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Table 13-3.
Calculation of CDAI Patient-Reported Outcome Components and 
PRO2 Scores at Screening
Example
Diary Day Looking Forward from subject 
activation date (T-Day)
Days for 
Calculation
Sum of 7 Days 
(CDAI Patient-
Reported 
Component)
Average of 
7 Days 
(PRO2)
2
3
4
5
6
7
8
9
10
11
Diary 
Subscore 1
1
2
M
1
2
2
M
0
1
2
2,3,5,6,7,9,10
9.0
1.3
Diary 
Subscore 2
M
M
1
M
2
1
M
2
M
M
4,6,7,9
10.5
1.5
Diary 
Subscore 3
2
M
M
0
M
2
M
M
M
M
2,5,7
Missing
Missing
Diary 
Subscore 4
1
2
1
1
X
R
3
3
1
2
2,3,4,5,8,9,10
12.0
1.7
M  Missing. R 
MRE day or lower endoscopy day; X
non evaluable (due to preparation for MRE or lower endoscopy).
Days are named relative to subject activation date on electronic diary device during screening (T Day 1). Rounding of subscores 
into one decimal place is for displaying purpose only. When calculating the CDAI scores, the subscores will not be rounded.
4) For the non-diary components (ie, complications, use of anti-diarrheal medications, 
abdominal mass, hematocrit, and weight) of the CDAI, in the case of multiple records 
collected during screening, the value collected on the same date as T-Day 1 will be used; 
otherwise, the earliest valid value during screening will be used. If no valid value is available 
during screening, then the value on Day 1 will be used.
5) The CDAI score at screening is based on a weighted sum (rounded to the nearest integer) of 
all 8 components (no rounding applied to the subscore for each component when calculating 
the CDAI score, but the subscore will be displayed with one decimal place for displaying 
purpose). The weight (multiplier) of each component is specified in Table 13-1. For example, 
if the sum of the 7-day scores for abdominal pain is 10, then the abdominal pain CDAI 
subscore is 10 x 5  50, where 5 is the multiplier for abdominal pain. The CDAI score will be 
set to 0 in the case the calculation leads to a CDAI score of < 0.
6) The PRO2 subscores at screening are based on the calculation of liquid or very soft stool 
frequency and abdominal pain subscores individually (rounded to the nearest integer).
Calculation of CDAI and PRO2 Scores at Post-Screening Visits
The calculations of CDAI and PRO2 scores at post-screening visits are specified below:
1) CDAI and PRO2 are not assessed on Day 1 by the study sites, but for analysis purpose, the 
PRO2 results will be calculated for Day 1. Both screening and Day 1 values will be 
considered for the derivation of baseline results for PRO2. CDAI at Day 1 will not be 
calculated and CDAI at screening will be the baseline.
2) The visit date will be used as the anchor day for post-screening visits. The visit date for each 
analysis visit will be selected among all scheduled visits and unscheduled visits where CDAI 
were assessed within the analysis window as defined in Section 3.7.2. For Day 1, the date of 
visit from the nominal visit Day 1 will be used. Only diary data collected on evaluable days 
within a 10-day window, which starts 10 days prior to the visit date (V-Day 1) and ends on 
the day prior to V-Day 1 will be used for calculation. 


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3) If there are 7 or more evaluate records within the 10-day window, take the sum of the 
7 evaluable records closest to V-Day 1 for the corresponding CDAI subject-reported 
component. For the corresponding PRO2 component, take the average of the 7 evaluable 
records within the 10-day window closest to V-Day 1.
a) If there are 4 or more (but less than 7) evaluable records within this 10-day window, 
the average of the available records will be taken, and then multiplied by 7 for the 
corresponding CDAI patient-reported component. For the corresponding PRO2 
component, the average of the available records will be taken.
b) If subjects do not have at least 4 evaluable records within this 10-day window, the 
corresponding CDAI patient-reported component, and the corresponding PRO2 
component will not be calculated and will be considered as missing for that visit.
A schema of this approach and some examples are included below for further explanation:
Figure 13-2.
Selection of Diary Data for Calculation at Post-Screening Visits
Table 13-4.
Calculation of CDAI Patient-Reported Outcome Components and 
PRO2 Scores at Post-Screening Visits
Example
Diary Day Looking Backwards from Visit Date 
(V-Day)
Days for 
Calculation
Sum of 7 
Days (CDAI 
Patient-
Reported 
Component)
Average
of 7 
Days 
(PRO2)
-10
-9
-8
-7
-6
-5
-4
-3
-2
-1
Diary 
Subscore 1
1
2
2
M
0
1
2
2
1
X
-2,-3,-4,-5,-6,
-8,-9
10.0
1.4
Diary 
Subscore 2
M
M
1
M
X
R
2
2
1
M
-2,-3,-4, -8
10.5
1.5
Diary 
Subscore 3
M
M
1
X
R
M
M
2
1
M
-2,-3,-8
Missing
Missing
Diary 
Subscore 4
0
M
2
2
1
0
M
2
X
R
-3,-5,-6,-7,-8,
-10
8.2
1.2
M  Missing; R  MRE day or lower endoscopy day; X
non evaluable (due to preparation for MRE or lower endoscopy).
Days are named relative to visit date (V Day 1), where V Day 1 is the day prior to V Day 1.
Rounding of subscores into one decimal place is for displaying purpose only. When calculating the CDAI scores, the subscores 
will not be rounded.
V-Day -10 
V-Day-1 
10-day window to calculate diary data 
Visit Day (Post-Screening) 


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4) The CDAI score for a specific visit is based on a weighted sum (rounded to the nearest 
integer) of all 8 components. The CDAI score will be set to 0 in the case the calculation leads 
to a CDAI score of < 0.  Each component will be selected within the analysis window as 
defined in Section 3.7.2.
a) If subjects have 3 or more of the 8 CDAI components missing, then the subjects will be 
considered as having insufficient data to determine response status and their CDAI score 
will be considered missing. If at least 1 out of the 6 complications under the complication 
component is missing, then the complication component will be considered missing.
b) If subjects have 1 or 2 components missing, then the missing component will be imputed 
by the LOCF method using the previous valid component score calculated at most recent 
analysis visit (eg, use the component score from Week 6 to impute missing component at 
Week 10, or use the component score from Week 18 to impute missing component at 
Week 24). If the component score from the most recent analysis visit is also missing, the 
missing value will be imputed with corresponding component score at baseline.
5) The PRO2 subscores for a specific visit are based on the evaluation of liquid or very soft 
stool frequency and abdominal pain subscores individually (rounded to the nearest integer) 
within the analysis window as defined in Section 3.7.2. If either subscore is missing, no 
imputation will be done. 
Source of Information Used for Calculation
The sources of information used for the calculations of CDAI and PRO2 scores as described 
above are given in Table 13-5 (the calculated scores from ERT data will not be used for data 
analysis). Hematocrit collected from local laboratory and weight measured at home due to 
COVID-19 impact will be used in CDAI calculation.
Table 13-5.
Sources of Information for Calculating CDAI and PRO2 Scores
Variable in Calculation
Data Source
MRE Procedure Date
MREDAT in MRE dataset from eCRF data for Screening and Week 24
Lower Endoscopy Procedure Date
QSORRES in CDAI dataset with QSTEST  “Date of Procedure” from vendor ERT 
data
Visit Date
VISITDAT in VISDT dataset from eCRF data
Subject Activation Date on Electronic 
Device
QSORRES in CDAI dataset with QSTEST “Date of Visit” and Visit “Screening” 
from vendor ERT data
Stool Frequency Diary Data
QSSTRESN in DIARY dataset with QSTESTCD “SOFSTOOL” from vendor ERT 
data
Abdominal Pain Diary Data
QSSTRESN in DIARY dataset with QSTESTCD “ABDPAIN” from vendor ERT 
data
Subject Standard Weight 
Sex in DM dataset and HEIGHT STD in VSPERF dataset from eCRF data will be 
used to determine the standard weight based on Appendix 4.
Subject Actual Weight
WEIGHT STD in VSPERF dataset from eCRF data
Hematocrit Value
CNVRESN in COVLAB dataset with LBTEST “Hematocrit” from vendor 
Covance data or LBORRES in LB HEM dataset with LBTEST “Hematocrit” from
eCRF data if collected in local laboratory due to COVID 19 impact
Note: eCRF  electronic case report form(s). ERT is the vendor that electronically collects patient and investigator reported
outcomes.


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Appendix 4.
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 5.
MaRIA (Magnetic Resonance Index of Activity) Scoring System
1) Component Details
Item
Definition
Sequence
Wall thickness (WT) 
Maximum wall thickness (mm) of any 
portion of the segment will be the value for 
the segment.
T1 sequence after gadolinium injection. 
Perpendicular to bowel axis.
Relative Contrast Enhancement 
(RCE)
RCE accounts for enhancement in the 
intestinal wall using wall signal intensity 
(WSI) before and after contrast.  Formula is 
noted belowa; SD is standard deviation.
T1 pre contrast, and T1 post contrast at 
70 seconds.
Edema (E)
Hyperintensity on T2 wedged sequences of 
the colon wall relative to the signal of the 
psoas muscle. Edema may be a score of 0 
(absent) or 1 (present).
Either single shot (SS) T2 or Balance 
gradient echo with fat saturation.
Ulcerations (U)
Areas of depression/irregularity in the inner 
surface of a thickened intestinal wall. 
Linear enhancing tracts within the bowel 
wall should be considered fissures (linear 
ulcers). Ulcerations may be a score of 0 
(absent) or 1 (present).
All
a)
RCE: [(WSI postgadolinium WSI pregadolinium)/ WSI pregadolinium] x (SD pregadolinium / SD postgadolinium) x 100
2) Segmental MaRIA Score Calculation 
Segmental MaRIA  [1.5 * WT(mm)] + [0.02* RCE] + [5* E] + [10*U]


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Appendix 6.
Study Treatment Failure Rules
Study treatment failure rules apply to treatment failure that occurs during the course of the study. 
Study treatment failure rules will be applied to all efficacy endpoints, unless otherwise specified. 
All 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. 
1) Potentially effective corticosteroid use 
Potentially effective corticosteroids, for the purpose of this SAP, are corticosteroids that may 
impact disease under study. Potentially effective corticosteroids include the following 
corticosteroids when administered for an indication of CD:
a) 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)
b) 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. The 
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 local actions 
(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. 
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)


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2) 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 an indication of CD. 
3) 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.


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Appendix 7.
Determining Missing and Virtual Visits due to COVID-19
This appendix describes the site collection of COVID-19 data as pertains 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 (CCG) 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 a visit which was to be conducted in-person 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 and can be modified and/or 
corrected to tune the NLP model. For each comment field the following algorithm was applied:
STEP 1: Eliminate extraneous text from each comment field, e.g. “and”, “or”, “for”, etc.  This is 
done using the list of extraneous terms given in Table 13-7.
STEP 2: Check each of the remaining comment text strings against the “COVID-19” terms and 
“Virtual” terms with the Levenshtein distance, using SAS function COMPGED (computes a 
generalized edit distance using the Levenshtein operations to compute/summarize the degree of 
difference between 2 text strings): 
i)
If Levenshtein distance < 149 for any of the “COVID-19” terms then COVIDFL
 1, 
else COVIDFL
 0
ii) If Levenshtein distance < 149 for any of the “Virtual” terms then VIRTFL
 1, else 
VIRTFL
 0
STEP 3: For any comments with COVIDFL
 1, assign “Missed Visit” or “Virtual Visit” as 
follows:
i)
IF COVIDFL 
1 and the visit date is missing then result is “Missed Visit”
ii) IF COVIDFL 
1 and VIRTFL  1 then result is “Virtual 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
virtual
corona
telemed
coronavirus
telehealth
pandemic
telephone
outbreak
remote
crisis
telemedicine
lockdown
teleconsultation
quarantine
telephonically
shelter
phone
home visit
zoom
skype
Table 13-7.
Examples of Extraneous Text Terms to Eliminate from the Comment 
Fields
a
down
in
she'd
until
about
during
into
she'll
up
above
each
is
she's
very
after
few
it
should
was
again
for
its
so
we
against
from
it's
some
we'd
all
further
itself
such
we'll
am
had
i've
than
were
an
has
let's
that
we're
and
have
me
that's
we've
any
having
more
the
what
are
he
most
their
what's
as
he'd
my
theirs
when
at
he'll
myself
them
when's
be
her
nor
themselves
where
because
here
of
then
where's
been
here's
on
there
which
before
hers
once
there's
while
being
herself
only
these
who
below
he's
or
they
whom
between
him
other
they'd
who's
both
himself
ought
they'll
why
but
his
our
they're
why's
by
how
ours
they've
with
could
how's
ourselves
this
would


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did
i
out
those
you
do
i'd
over
through
you'd
does
if
own
to
you'll
doing
i'll
same
too
your
down
i'm
she
under
you're
you've
yourself
yourselves
yours


GS-US-419-4015 SAP v1.0
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Biostatistics eSigned
01-Oct-2020
17:23:29
Clinical Research eSigned
01-Oct-2020
18:19:18
PPD
PPD