Combined Phase 3, Double-blind, Randomized, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Filgotinib in the Induction and Maintenance of Remission in Subjects With Moderately to Severely Active Crohn's Disease
Phase: PHASE3
Conditions: Crohn's Disease
Sponsor: Galapagos NV

CLINICAL STUDY PROTOCOL
Study Title:
Combined Phase 3, Double-blind, Randomized, Placebo-Controlled 
Studies Evaluating the Efficacy and Safety of Filgotinib in the 
Induction and Maintenance of Remission in Subjects with 
Moderately to Severely Active Crohn’s Disease
Sponsor:
Galapagos NV
Generaal De Wittelaan L11 A3
2800 Mechelen, Belgium
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
129646
2016-001367-36
NCT02914561
Indication:
Crohn’s Disease 
Protocol ID:
GS-US-419-3895
Galapagos Medical 
Leader:
Name:
Protocol 
Version/Date:
Original:
15 July 2016
Amendment 1:
07 September 2016
Amendment 2:
11 November 2016
Amendment 3:
19 January 2017
Amendment 4:
15 June 2017
Amendment 5:
05 March 2018
Amendment 6:
07 February 2019
Amendment 7:
22 August 2019
Amendment 8:
01 May 2020
Amendment 8.1:
04 September 2020 (Germany and Portugal)
Amendment 9:
02 December 2021
CONFIDENTIALITY STATEMENT
The information contained in this document is privileged and confidential. It is the property of 
Galapagos NV and may not be used, disclosed, reproduced or otherwise disseminated within 
your organization or communicated to any third parties without the express written 
authorization of Galapagos NV.
PPD

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 4
02 December 2021
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse Events .................................95
7.1.1.
Adverse Events......................................................................................................................95
7.1.2.
Serious Adverse Events.........................................................................................................95
7.2.
Assessment of Adverse Events and Serious Adverse Events..................................................................96
7.2.1.
Assessment of Causality for Study Drugs and Procedures ...................................................96
7.2.2.
Assessment of Severity..........................................................................................................97
7.3.
Investigator Requirements and Instructions for Reporting Adverse Events and Serious 
Adverse Events to the Sponsor................................................................................................................97
7.3.1.
Adverse Events......................................................................................................................97
7.3.2.
Serious Adverse Events.........................................................................................................98
7.4.
Sponsor Reporting Requirements............................................................................................................99
7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as Adverse Events or 
Serious Adverse Events...........................................................................................................................99
7.6.
Toxicity Management............................................................................................................................100
7.6.1.
Grades 1 and 2 Laboratory Abnormality or Clinical Event ................................................100
7.6.2.
Grade 3 Laboratory Abnormality or Clinical Event............................................................100
7.6.3.
Grade 4 Laboratory Abnormality or Clinical Event............................................................100
7.7.
Special Situations Reports.....................................................................................................................101
7.7.1.
Definitions of Special Situations.........................................................................................101
7.7.2.
Instructions for Reporting Special Situations......................................................................102
8.
STATISTICAL CONSIDERATIONS...............................................................................................................104
8.1.
Analysis Objectives and Endpoints.......................................................................................................104
8.1.1.
Analysis Objectives.............................................................................................................104
8.1.2.
Primary Endpoints...............................................................................................................111
8.1.3.
Secondary Endpoints...........................................................................................................112
8.2.
Analysis Conventions............................................................................................................................118
8.2.1.
Analysis Sets .......................................................................................................................118
8.3.
Data Handling Conventions ..................................................................................................................119
8.4.
Demographic Data and Baseline Characteristics ..................................................................................120
8.5.
Efficacy Analysis...................................................................................................................................120
8.5.1.
Primary Analyses.................................................................................................................120
8.5.2.
Secondary Analyses.............................................................................................................121
8.5.3.
Multiplicity Adjustments.....................................................................................................121
8.6.
Safety Analysis......................................................................................................................................131
8.6.1.
Extent of Exposure ..............................................................................................................131
8.6.2.
Adverse Events....................................................................................................................132
8.6.3.
Laboratory Evaluations .......................................................................................................133
8.6.4.
Other Safety Evaluations.....................................................................................................133
8.7.
Pharmacokinetic Analysis .....................................................................................................................133
8.9.
Sample Size ...........................................................................................................................................134
8.9.1.
Induction Studies (Cohorts A and B) ..................................................................................134
8.9.2.
Maintenance Study ..............................................................................................................134
8.10.
Data Monitoring Committee..................................................................................................................135
8.11.
Cardiovascular Safety Endpoint Adjudication Committee ...................................................................136
9.
RESPONSIBILITIES.........................................................................................................................................138
9.1.
Investigator Responsibilities .................................................................................................................138
9.1.1.
Good Clinical Practice.........................................................................................................138
9.1.2.
Institutional Review Board/Independent Ethics Committee Review and 
Approval..............................................................................................................................138
CCI
CCI
CCI

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 5
02 December 2021
9.1.3.
Informed Consent ................................................................................................................139
9.1.4.
Confidentiality.....................................................................................................................139
9.1.5.
Study Files and Retention of Records .................................................................................139
9.1.6.
Case Report Forms ..............................................................................................................141
9.1.7.
Investigational Medicinal Product Accountability and Return ...........................................141
9.1.8.
Inspections...........................................................................................................................142
9.1.9.
Protocol Compliance ...........................................................................................................142
9.2.
Sponsor Responsibilities .......................................................................................................................142
9.2.1.
Protocol Modifications ........................................................................................................142
9.2.2.
Study Report and Publications ............................................................................................142
9.3.
Joint Investigator/Sponsor Responsibilities ..........................................................................................143
9.3.1.
Payment Reporting ..............................................................................................................143
9.3.2.
Access to Information for Monitoring.................................................................................143
9.3.3.
Access to Information for Auditing or Inspections .............................................................143
9.3.4.
Study Discontinuation .........................................................................................................143
10.
REFERENCES...................................................................................................................................................144
11.
APPENDICES....................................................................................................................................................146
Appendix 1.
Investigator Signature Page...................................................................................................147
Appendix 2.
Study Procedures Table.........................................................................................................148
Appendix 3.
Management of Clinical and Laboratory Adverse Events.....................................................153
Appendix 4.
Crohn’s Disease Activity Index (CDAI) and Patient Reported Outcomes – 2 items 
(PRO2)...................................................................................................................................154
Appendix 5.
Simple Endoscopic Score for Crohn’s Disease (SES-CD)....................................................155
Appendix 6.
CTCAE Grading Scale for Severity of Adverse Events........................................................156
Appendix 7.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements..................................................................................................157
Appendix 8.
Clinical Laboratory Assessment Table..................................................................................161
LIST OF IN-TEXT TABLES
Table 3-1.
Re-Randomization of Induction Cohorts A and B to Maintenance Study ..............................60
Table 5-1.
Prohibited Concomitant Medications ......................................................................................81
Table 7-1.
Grading of Adverse Event Severity.........................................................................................97
LIST OF IN-TEXT FIGURES
Figure 3-1.
Study Design Schematic..........................................................................................................58
Figure 8-1.
Induction Studies (Cohorts A and B): Testing Strategy for the Primary and Key 
Secondary Hypotheses...........................................................................................................124
Figure 8-2.
Maintenance Study: Testing Strategy for the Primary and Key Secondary 
Hypotheses.............................................................................................................................127
Figure 8-3.
Maintenance Study: EU-Specific Testing Strategy for the Primary and Key 
Secondary Hypotheses...........................................................................................................130

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 6
02 December 2021
PROTOCOL SYNOPSIS
Galapagos NV
Generaal De Wittelaan L11 A3
2800 Mechelen, Belgium
Study Title: 
Combined Phase 3, Double-blind, Randomized, Placebo-Controlled 
Studies Evaluating the Efficacy and Safety of Filgotinib in the 
Induction and Maintenance of Remission in Subjects with 
Moderately to Severely Active Crohn’s Disease
IND Number:
EudraCT Number:
Clinical Trials.gov 
Identifier:
129646
2016-001367-36
NCT02914561
Study Centers 
Planned:
Approximately 500 sites globally
Objectives:
The overall objective of the study is to evaluate the effect of 
treatment with filgotinib on the induction and maintenance of clinical 
remission, as well as, endoscopic response in subjects with 
moderately to severely active Crohn's disease (CD). Subjects who 
are biologic-naïve or biologic-experienced will be enrolled in 
Cohort A and subjects who are biologic-experienced will be enrolled 
in Cohort B, respectively. Treatment assignments will be randomized 
within each Cohort. 
Cohort A: Biologic-Naïve and Biologic-Experienced Subjects, 
Induction Study
The primary objectives of Cohort A Induction Study are:

To evaluate the efficacy of filgotinib as compared to placebo in 
establishing clinical remission by Crohn’s Disease Activity Index 
(CDAI) at Week 10 

To evaluate the efficacy of filgotinib as compared to placebo in 
establishing endoscopic response at Week 10
The key secondary objectives of Cohort A Induction Study are: 

To evaluate the efficacy of filgotinib as compared to placebo in 
establishing clinical remission by Patient Reported Outcomes 
(PRO2) at Week 10 

To evaluate the efficacy of filgotinib as compared to placebo in 
establishing clinical response by CDAI at Week 10

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 15
02 December 2021

Re-randomization (Week 11) 
Subjects in Cohorts A and B who complete the Induction 
Study and achieve either clinical remission by PRO2 or 
endoscopic response by SES-CD at Week 10 will be 
re-randomized into the Maintenance Study at Week 11
Subjects who do not achieve clinical remission by PRO2 or 
endoscopic response at Week 10 will have the option to enter 
a separate, Long-Term Extension (LTE) study 
(GS-US-419-3896; Galapagos Study ID GLPG0634-CL-310)

Blinded Maintenance Study (Weeks 11 to 58)

Post-Treatment (PTx) safety assessments
Subjects who opt out of the LTE study (GS-US-419-3896) 
will return 30 days after the last dose of study drug for PTx 
safety assessments 
Subjects who complete all procedures per protocol, including 
the endoscopy, of the 58-week study will be offered the 
option to continue into the LTE study (GS-US-419-3896)
Subjects who are eligible and opt to participate in the LTE 
study (GS-US-419-3896) can continue into the study without 
PTx safety assessments.
Treatment Regimen (Cohorts A and B Induction Studies)
Subjects who meet protocol eligibility criteria will be assigned to the 
respective Cohort and subsequently randomized in a blinded fashion 
in a 1:1:1 ratio to 1 of 3 treatments as follows: 
Treatment 1 (n = 220): filgotinib 200 mg and placebo-to-match 
(PTM) filgotinib 100 mg, once daily
Treatment 2 (n = 220): filgotinib 100 mg and PTM filgotinib 
200 mg, once daily
Treatment 3 (n = 220): PTM filgotinib 200 mg and PTM filgotinib 
100 mg, once daily
Note: United States (US) and Korea males who have not failed at 
least two prior biologic therapies (any tumor necrosis factor-alpha 
[TNFα] antagonist and vedolizumab) will be randomized in a 
1:1 ratio to either filgotinib 100 mg or matching placebo.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 16
02 December 2021
Within each Cohort, treatment assignments will be stratified 
according to the following factors in the Induction studies:
Stratification Factors (Cohort A, Biologic-Naïve and 
Biologic-Experienced Induction Study)

History of  exposure to no biologic agent, one biologic agent, or 
more than one biologic agent

Concomitant use of oral, systemically absorbed corticosteroids 
(eg, prednisone) at Day 1, (Yes or No)

Concomitant use of immunomodulators (eg, 6-mercaptopurine 
[6-MP], azathioprine, methotrexate [MTX]) at Day 1, 
(Yes or No)
Stratification Factors (Cohort B, Biologic-Experienced Induction 
Study)

Exposure to one biologic agent versus more than one biologic 
agent

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)
Subjects from Cohort A or B who are eligible for the Maintenance 
study will be re-randomized to treatment as follows:
Treatment Assignment Induction Studies
Cohorts A and B
Maintenance Study
Re-randomization
Treatment 1, 200 mg 
Treatment 1, filgotinib 200 mg
Treatment 3, Placebo
Treatment 2, 100 mg
Treatment 2, filgotinib100 mg
Treatment 3, Placebo
Treatment 3, Placebo
Continue Treatment 3, Placebo 
Note: Subjects receiving Treatment 1 or 2 in the Induction study will be randomized in a 
2:1 manner to either continue on the assigned filgotinib regimen or to placebo for the 
duration of the Maintenance study
Stratification Factors (Maintenance Study)

History of exposure to a biologic agent (Yes or No)

Concomitant use of oral, systemically absorbed corticosteroids 
(eg, prednisone) at Day 1, (Yes or No)

Concomitant use of immunomodulators (eg, 6-mercaptopurine 
[6-MP], azathioprine, methotrexate [MTX]) at Day 1, 
(Yes or No)

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 18
02 December 2021

Documented diagnosis of CD with a minimum disease duration 
of 3 months with involvement of the ileum and/or colon at a 
minimum, documented by the following:
a) Medical record documentation of, or an ileocolonoscopy 
(full colonoscopy with the intubation of terminal ileum) 
report dated ≥ 3 months before enrollment, which shows 
features consistent with CD, determined by the procedure 
performing physician, AND
b) Medical record documentation of, or a histopathology report 
showing features consistent with CD, determined by the 
pathologist.

Moderately to severely active CD determined by CDAI 220 to 
450 (inclusive), AND PRO2 (abdominal pain score ≥ 2 [on a 
scale of 0 to 3] OR stool frequency ≥ 4), AND centrally read 
SES-CD score ≥ 6 (or ≥ 4 if disease is limited to the ileum and/or 
right colon) 

May be receiving the following drugs (subjects on these therapies 
must be willing to remain on stable doses for the noted time):
a) Oral 5-aminosalicylate (5-ASA) compounds provided the 
dose prescribed has been stable for at least 4 weeks prior to 
randomization; dose must remain stable for the first 10 weeks 
after randomization
b) Azathioprine or 6-MP or MTX provided the dose prescribed 
has been stable for 4 weeks prior to randomization; dose must 
remain stable for the first 10 weeks after randomization
c) 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 2 weeks prior to randomization; dose must remain stable 
for the first 14 weeks after 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.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 19
02 December 2021

Must not have the current following complications of CD:
a) Symptomatic strictures, OR
b) Severe (impassable) rectal/anal stenosis, OR
c) Fistulae other than perianal fistulae, OR
d) Short bowel syndrome, OR
e) Any other manifestation that might require surgery, OR
f)
Any other complications which could preclude the use of the 
CDAI to assess response to therapy, or would possibly 
confound the evaluation of benefit from treatment with 
filgotinib

Must not have ulcerative colitis, indeterminate colitis, ischemic 
colitis, fulminant colitis, or toxic mega-colon 

Must not have active tuberculosis (TB) or history of latent TB 
that has not been treated (see inclusion criterion 7 for further 
information)

Must not use any prohibited concomitant medications as 
described in Section 5.4.2 
Cohort A (Biologic-Naïve and Biologic-Experienced) Induction 
Study 
Main Eligibility Criteria, Cohort A ONLY 
Subjects must meet all of the additional criteria to be eligible for 
participation in Cohort A Induction Study.
Biologic-Naïve Subjects

Previously demonstrated an inadequate clinical response, loss of 
response to, or intolerance of at least one of the following agents 
(depending on current country treatment 
recommendations/guidelines):
a) Corticosteroids
i)
Active disease despite a history of at least 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

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 20
02 December 2021
b) Immunomodulators
i)
Active disease despite a history of at least a 12 week 
regimen of oral azathioprine (≥ 2  mg/kg/day) or 6-MP 
(≥ 1 mg/kg/day), or MTX (25 mg subcutaneously [SC] or 
intramuscularly [IM] per week for induction and ≥ 15 mg 
IM per week for maintenance), OR
ii)
History of intolerance to at least one immunomodulator 
including, but not limited to, serious infections, 
hepatotoxicity, cytopenia, pancreatitis, thiopurine 
methyltransferase (TPMT) genetic mutation, allergic 
reactions, or any other condition that contributed to 
discontinuation of the agent

No prior or current use of any TNFα antagonist including 
(but not limited to) infliximab, adalimumab, golimumab, 
certolizumab, or biosimilar agents at any time

No prior or current use of vedolizumab at any time

No prior or current use of ustekinumab at any time
Biologic-Experienced Subjects

Previously demonstrated an inadequate clinical response, loss of 
response to, or intolerance of, at least one of the following agents 
(depending on current country treatment 
recommendations/guidelines) or discontinuation of use of at least 
one of the following agents for reasons other than inadequate 
clinical response, loss of response, or intolerance:
a) TNFα Antagonists
i)
Active disease despite a history of at least one 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 one day or 
two 40-mg injections per day for two 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

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 21
02 December 2021
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 
contributed to discontinuation of the agent
b) 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
c) Ustekinumab
i)
Active disease despite a history of a 8 week induction 
regimen with a single dose of ustekinumab IV per 
weight-based dosing (260mg for up to 55kg; 390mg for 
greater than 55 to 85kg; 520mg for greater than 85kg) 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

Must not have 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. Subjects who have an 
undetectable serum level of a biologic agent since its last dose 
using a commercially available assay can undergo study 
screening without the above-mentioned waiting period.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 22
02 December 2021
Cohort B (Biologic-Experienced) Induction Study 
Main Eligibility Criteria, Cohort B ONLY 

Previously demonstrated an inadequate clinical response, loss of 
response to, or intolerance of, at least one of the following agents 
(depending on current country treatment 
recommendations/guidelines):
a) TNFα Antagonists
i)
Active disease despite a history of at least one 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 one day or 
two 40-mg injections per day for two 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
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 
contributed to discontinuation of the agent
b) 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

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 23
02 December 2021
c) Ustekinumab
i)
Active disease despite a history of a 8 week induction 
regimen with a single dose of ustekinumab IV per 
weight-based dosing (260mg for up to 55kg; 390mg for 
greater than 55 to 85kg; 520mg for greater than 85kg) 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

Must not have 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. Subjects who have an 
undetectable serum level of a biologic agent since its last dose 
using a commercially available assay can undergo study 
screening without the above-mentioned waiting period.
Maintenance Study
Main Eligibility Criteria:

Completion of Cohort A or Cohort B Induction Study with either 
clinical remission by PRO2 or endoscopic response at Week 10
Study Procedures/
Frequency:
Adverse events and concomitant medications will be assessed at each 
visit.
Non-responding subjects completing all Week 10 assessment will be 
eligible to enter the LTE study (GS-US-419-3896). 
Subjects who opt out of the LTE study (GS-US-419-3896) will 
return 30 days after the last dose of study drug for PTx safety 
assessments. 
Subjects who are eligible and opt to participate in the LTE study 
(GS-US-419-3896) can continue into the study without PTx safety 
assessments.
Subjects who complete the Week 58 visit will have the option to 
continue study drug in a blinded fashion in the LTE study 
(GS-US-419-3896)

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 24
02 December 2021
Concomitant Crohn’s Disease Medication Management:
Subjects on permitted concomitant medications for CD that are 
described in the inclusion criteria (eg, 5-ASA, and 
immunomodulators) must remain on stable doses until Week 10. 
Steroids must remain stable to Week 14.
Starting at Week 14, 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).  Subjects who are on budesonide should have 
their daily dose reduced by 3 mg every 3 weeks until they are 
completely off steroids.  For subjects undergoing taper, steroids may 
be increased or restarted at doses up to and including their baseline 
dose if return of symptoms is apparent. These subjects will not be 
considered treatment failures. Subjects who need to restart or 
increase steroid treatment at a dose that exceeds their baseline dose 
of steroids (dose may not exceed 30 mg prednisone [or equivalent] or 
budesonide 9 mg/day) will be considered treatment failures for all 
clinical end points but will be permitted to remain in the study.

For additional prohibited CD medications, reference Table 5-1.
Test Product, Dose, 
and Mode of 
Administration:

Filgotinib 200 mg oral tablet, once daily

Filgotinib 100 mg oral tablet, once daily
Reference Therapy, 
Dose, and Mode of 
Administration:

PTM filgotinib 200 mg oral tablet, once daily

PTM filgotinib 100 mg oral tablet, once daily
Criteria for 
Evaluation:
Safety:
Assessment of AEs and concomitant medications will continue 
throughout the duration of the study. Safety evaluations include 
documentation of AEs, PE (complete or symptom driven), vital 
signs, and clinical laboratory evaluations (hematology, chemistry, 
urinalysis). An ECG will be performed at screening, Week 10 (or at 
Early Termination (ET) if subject terminates prior to Week 10), 
Week 26 and Week 58.
A data monitoring committee (DMC) will meet to evaluate all 
available safety data accumulated during the study. The initial 
meeting will occur after approximately 100 subjects reach Week 10 
in Cohorts A and B combined. Following this, subsequent meetings 
will occur approximately once every 4 months or at a frequency 
determined by the DMC.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 26
02 December 2021
The Cochran-Mantel-Haenszel (CMH) approach adjusting for 
stratification factors will be used for hypothesis testing of the 
co-primary end points. Subjects who do not have sufficient 
measurements to determine efficacy end points will be considered 
failures (ie, non-responder imputation [NRI]).
The graphical approach {Bretz 2009} of sequentially rejective 
Beonferroni-based iterative multiple test procedures will be used to 
control a family-wise type I error rate (FWER) at 5% (ie, α = 0.05) 
for hypothesis testing on co-primary and key secondary end points. 
See Section 8.5.3 for details and the significance level that will be 
used to declare a statistically significant treatment effect for each 
filgotinib dose group when compared to placebo.
Cohorts A and B End-of-Induction Analysis
Efficacy and safety data will be evaluated by the DMC after all 
subjects in Cohorts A and B complete Week 10 dosing 
(or prematurely discontinue study drug but complete PTx 
assessments). Data from Cohorts A and B (examined independently) 
will be used to evaluate the study overall for possible discontinuation 
(See Section 8.10 for details).
Maintenance Study
The primary analysis set for efficacy analyses is FAS, which 
includes all re-randomized subjects who met the protocol definition 
of clinical remission by PRO2 or endoscopic response at Week 10, 
and received at least 1 dose of study drug in the Maintenance Study 
(Weeks 11 to 58).
The primary analysis will compare each filgotinib dose group to 
placebo on each co-primary end point (the proportion of subjects 
achieving clinical remission by CDAI at Week 58 and the proportion 
of subjects achieving endoscopic response at Week 58). In the EU, 
the primary analysis will compare each filgotinib dose group to 
placebo on each co-primary end point (the proportion of subjects 
achieving clinical remission by PRO2 at Week 58 and the proportion 
of subjects achieving endoscopic response end points at Week 58). 
The CMH approach adjusting for stratification factors will be used 
for hypothesis testing of the co-primary end points. Subjects who do 
not have sufficient measurements to determine efficacy end points 
will be considered failures (ie, NRI).

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 27
02 December 2021
The graphical approach {Bretz 2009} of sequentially rejective 
Beonferroni-based iterative multiple test procedures will be used to 
control a FWER at 5% (ie, α = 0.05) for hypothesis testing on 
co-primary and key secondary end points. See Section 8.5.3 for 
details and the significance level that will be used to declare a 
statistically significant treatment effect for each filgotinib dose group 
when compared to placebo.
Pharmacokinetics:
Plasma concentrations of filgotinib and its metabolite GS-829845 
will be listed and summarized using descriptive statistics.
Sample Size:
Induction Studies (Cohorts A and B)
The sample size was chosen to ensure that a clinically meaningful 
difference in both clinical remission rate by CDAI at Week 10 and 
endoscopic response rate at Week 10 could be detected when 
comparing filgotinib 200 mg to placebo within each Induction Study.
A sample size of 220 subjects in each treatment group (n = 660 total) 
will provide an overall power of 97% for filgotinib 200 mg group 
comparison to placebo at a 2-sided 0.05 significance level to detect a 
treatment difference of 20% in clinical remission rate by CDAI at 
Week 10 (45% on filgotinib 200 mg and 25% on placebo) and a 
treatment difference of 15% in endoscopic response rate at Week 10 
(25% on filgotinib 200 mg and 10% on placebo). Since each end 
point needs to achieve statistical significance, the overall power of 
97% is calculated as the product of the two individual powers based 
on each end point. 
For the EU, the sample size was chosen to ensure that a clinically 
meaningful difference in both clinical remission rate by PRO2 at 
Week 10 and endoscopic response rate at Week 10 could be detected 
when comparing filgotinib 200 mg to placebo within each Induction 
Study.
A sample size of 220 subjects in each treatment group (n = 660 total) 
will provide an overall power of 93% for filgotinib 200 mg dose 
group comparison to placebo at a 2-sided 0.05 significance level to 
detect a treatment difference of 15% in clinical remission rate by 
PRO2 at Week 10 (30% on filgotinib 200 mg and 15% on placebo) 
and a treatment difference of 15% in endoscopic response rate at 
Week 10 (25% on filgotinib 200 mg and 10% on placebo). Since 
each end point needs to achieve statistical significance, the overall 
power of 93% is calculated as the product of the two individual 
powers based on each end point.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 28
02 December 2021
Maintenance Study
Assuming an induction response rate (ie, proportion of subjects 
achieving either clinical remission by PRO2 or endoscopic response 
at Week 10) of 40% among subjects receiving filgotinib 200 mg or 
filgotinib 100 mg treatment, approximately 176 subjects from each 
filgotinib dose group from Cohorts A and B Induction Studies 
combined would be eligible to be re-randomized into the 
Maintenance Study.
The sample size was chosen to ensure that a clinically meaningful 
difference in both clinical remission rate by CDAI and endoscopic 
response rate at Week 58 could be detected when comparing 
filgotinib 200 mg to placebo in the Maintenance Study.
A sample size of 60 subjects in the placebo group and 120 subjects in 
the filgotinib group at the same dose level as the induction dose will 
provide an overall 94% power for filgotinib 200 mg comparison to 
placebo at a 2-sided 0.05 significance level to detect a treatment 
difference of 30% in maintenance clinical remission rate by CDAI at 
Week 58 and maintenance endoscopic response rate at Week 58 
(50% on filgotinib 200 mg and 20% on placebo). Since each end 
point needs to achieve statistical significance, the overall power of 
94% is calculated as the product of the two individual powers based 
on each end point.
For the EU, the sample size was chosen to ensure that a clinically 
meaningful difference in both clinical remission rate by PRO2 and 
endoscopic response rate at Week 58 could be detected when 
comparing filgotinib 200 mg to placebo in the Maintenance Study.
A sample size of 60 subjects in the placebo group and 120 subjects in 
the filgotinib group at the same dose level as the induction dose will 
provide an overall 94% power for filgotinib 200 mg comparison to 
placebo at a 2-sided 0.05 significance level to detect a treatment 
difference of 30% in maintenance clinical remission rate by PRO2 at 
Week 58 and maintenance endoscopic response rate at Week 58 
(50% on filgotinib 200 mg and 20% on placebo). Since each 
end point needs to achieve statistical significance, the overall power 
of 94% is calculated as the product of the two individual powers 
based on each end point.
This study will be conducted in accordance with the guidelines of Good Clinical Practice (GCP) 
including archiving of essential documents.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 29
02 December 2021
GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS
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
AP
abdominal pain
AST
aspartate aminotransferase
AUC
area under the plasma/serum/peripheral blood mononuclear cell 
concentration, drug versus time curve
BLQ 
below the limit of quantitation
BMI
body mass index
C. diff
Clostridium difficile
CC&G
Cockcroft-Gault
CD
Crohn’s disease
CDAI
Crohn’s Disease Activity Index
CES
Carboxylesterases
CFR
Code of Federal Regulations
CI
confidence interval
CIA
collagen-induced arthritis
CK
creatine kinase
Cmax
the maximum observed serum/plasma/peripheral blood mononuclear 
(PBMC) concentration of drug
CMH
Cochran-Mantel-Haenszel
CMV
cytomegalovirus
CNS
central nervous system
CPK 
creatine phosphokinase
CRF
case report form(s)
CRO
contract (or clinical) research organization 
CSR
clinical study report
CTCAE
Common Terminology Criteria for Adverse Events
CVEAC
Cardiovascular Safety Endpoint Adjudication Committee
CYP
Cytochrome P450
DAI
disease activity index
DMC
data monitoring committee
DNA
deoxyribonucleic acid
CCI
CCI

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 30
02 December 2021
DSS
dextran sodium sulfate
E.coli
Escherichia coli
EC
ethics committee
ECG
Electrocardiogram
eCRF
electronic case report form(s)
EDC
Electronic Data Capture 
e-Diary
electronic diary
EMA
European Medicines Agency
eSAE system
electronic SAE system
ET
early termination
EU
European Union
EudraCT
European clinical trials database
FAS
Full Analysis Set
FDA
(United States) Food and Drug Administration
FWER
family-wise type I error rate
GCP
Good Clinical Practice (Guidelines)
 
GI
gastrointestinal
HBcAB
Hepatitis B Virus core antibody
HBsAB
Hepatitis B Virus surface antibody
HBsAG
Hepatitis B Virus surface antigen
HBV
Hepatitis B virus
HCV
Hepatitis C virus
HDL
high-density lipoprotein
HDPE
high density polyethylene
hERG
human ether-a-gogo
HIV
Human Immunodeficiency Virus
HLGT
High-Level Group Term
HLT
High-Level Term
IB
investigator brochure
IBD
inflammatory bowel disease
IC50
concentration of an inhibitor that is required for 50-percent inhibition 
ICF
informed consent form
ICH
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use
IEC
independent ethics committee
CCI
CCI
CCI
CCI
CCI

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 31
02 December 2021
IL
Interleukin
IM
intramuscularly
IMP
investigational medicinal product
IND
Investigational new drug
INR
International Normalized Ratio
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)
LAM
lactational amenorrhea method 
LDL
low-density lipoprotein
LLOQ
Lower limit of quantitation
LLT
Lower-Level Term
LOCF
Last Observation Carried Forward
LTE
long-term extension
mAb
monoclonal antibody 
MACE
Major Adverse Cardiovascular Events
MedDRA
Medical Dictionary for Regulatory Activities
MPO
myeloperoxidase 
MTX
Methotrexate
NOEL
no-observed-effect-levels
NRI
non-responder imputation
NSAID
Nonsteroidal Anti-inflammatory Drugs
O&P
ova and parasites test
OAT
organic anion transporters
PBMC
peripheral blood mononuclear cell
PCP
pneumocystis
PD
pharmacodynamics
PE
physical examination
PEG
polyethylene glycol
P-gp
p-glycoprotein
PI
principal investigator
PK
Pharmacokinetic
PRO2
patient reported outcomes consisting of 2 items: abdominal pain severity 
and liquid stool frequency
CCI
CCI

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 32
02 December 2021
PT
Preferred Term
PTM
Placebo-to-match
PTx
Post-Treatment
Q1
1st quartile
Q3
3rd quartile
RA
rheumatoid arthritis
 
RNA
ribonucleic acid
ROC
receiver operating characteristic
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
SES-CD
Simple Endoscopic Score for Crohn’s Disease
SF
stool frequency
SI
international system of units 
SOC
system organ class
SOP
standard operating procedure
spp
Species
STAT
signal transducer and activator of transcription
SUSAR
suspected unexpected serious adverse reaction
TB
Tuberculosis
TEAE
treatment-emergent adverse event
TgrasH2
transgenic
TNFα
tumor necrosis factor-alpha
TPMT
thiopurine methyltransferase
TYK
Tyrosine kinase
UC
ulcerative colitis
UGT
uridine 5’ diphosphate glucuronosyltransferase
ULN
upper limit of the normal range
US
United States
WBC
white blood cell
CCI
CCI
CCI
CCI

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 34
02 December 2021
1.
INTRODUCTION
1.1.
Background
Crohn’s disease (CD) is a relapsing and remitting form of inflammatory bowel disease (IBD) that 
causes gastrointestinal signs and symptoms of diarrhea, abdominal pain, weight loss, and the 
passage of blood or mucous per rectum. The inflammation of CD can involve the mucosal 
surface of the gastrointestinal tract and penetrate through the full thickness of the gastrointestinal 
wall, including the serosal surface. Crohn’s disease is characterized by phenotype and location of 
involved bowel. The phenotypes include inflammatory, stricturing, and penetrating subtypes. 
Stricture formation can result in intestinal obstruction requiring surgical management. Over time, 
patients with repeated surgeries are at risk for developing short bowel syndrome and/or intestinal 
failure. Penetrating disease is characterized by fistula formation, which can be bowel to bowel, 
bowel to skin, or bowel to adjacent organ. Depending on location, penetrating disease can also 
require surgical management. Penetrating disease can also manifest with intra-abdominal 
abscess, a condition which can be life threatening if not treated early with systemic antibiotics. In 
addition, CD may affect other organ systems leading to rashes, joint pain and stiffness, fever, and 
weight loss {Baumgart 2012}.
The incidence and prevalence of CD has been increasing, with bimodal peaks affecting young 
adults (15 to 35 years of age) and older adults aged 50 to 70 with the age of onset often occurring 
in children < 12 years of age. Although geographic variation does occur, the overall incidence of 
CD in the northern hemisphere ranges from 7 to 20 per 100,000 person years, with a prevalence 
of up to 300 per 100,000 people. In the United States (US) and Europe, up to 1.5 million 
individuals may be affected and the incidence is on the rise in parts of Asia and the Middle East 
{Molodecky 2012}.
The cause of CD is poorly understood, however a complex interplay of genetic predisposition, 
aberrant immune activation, and early infection during childhood may be involved. The 
importance of environmental triggers is suggested by increasing rates due to industrialization and 
improved domestic hygiene and sanitation. This “hygiene hypothesis” has also been implicated 
in various other autoimmune disorders {Ventham 2013}.
To assess disease severity, a number of clinical scoring systems are utilized based upon signs, 
symptoms, laboratory parameters, imaging modalities, and endoscopy. The Crohn’s Disease 
Activity Index (CDAI) is one such scoring tool with scores ranging from 0 to over 600 based 
upon a composite of symptoms (eg, abdominal pain), signs (the presence of abdominal mass 
and weight), laboratory values (eg, hematocrit), and physician assessment amongst others. In this 
scoring system, patients with a score > 220 are defined as moderate to severe these comprise the 
patients with the greatest unmet medical need. The CDAI can also be used to determine how 
well a therapy is working, with therapeutic remission defined as a CDAI of < 150 points 
{Dignass 2010}.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 35
02 December 2021
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. 
The Simple Endoscopic Score for Crohn’s Disease (SES-CD) was first validated in 2004 and has 
been used extensively in clinical trials to demonstrate endoscopic improvement in disease 
activity following interventions. It measures presence and size of ulcers, proportion of surface 
affected with ulcers, proportion of surface affected by other lesions, and the presence and 
severity of stenotic lesions {Daperno 2004}. The bowel is divided into segments (ileum, right 
colon, transverse colon, left colon, and rectum) and each segment is scored individually, then the 
segment scores are summed for a total score (range: 0 to 60). A 50% or higher reduction in the 
overall SES-CD score is generally used as a sign of treatment response {Ferrante 2013}.
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 
 {Cheifetz 2013}. The ultimate aim is to change the natural 
course of the disease by slowing down or halting its progression, thus avoiding surgery or 
hospitalization. This is achieved by utilizing earlier, aggressive, and goal-directed therapy. Risk 
assessment and prediction by means of complex clinical, biochemical, and endoscopic markers 
has become the key to patient management, therapy optimization, and prediction of the outcome 
and side effects of medical therapy. 
Currently available biologic therapies focus on neutralizing cytokine activity or altering T-cell 
differentiation and homing. Three monoclonal antibodies which inhibit tumor necrosis 
factor-alpha (TNFα), are currently marketed for the treatment of CD: infliximab (Remicade®), 
adalimumab (Humira® [approved in US and European Union {EU}]) and certolizumab pegol 
(Cimzia® [approved in US]). Vedolizumab (Entivyo®), a monoclonal antibody against 
α4β7 integrin is also approved for moderately to severely active CD. Recently, ustekinumab 
(Stelara®), a monoclonal antibody directed against the p40 subunit of IL-23 and therefore an 
antagonist for both IL-12 and IL-23 signaling, has been approved for the treatment 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).
CCI

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 36
02 December 2021
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 proinflammatory 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. 
Filgotinib is approved in the European Union (EU), Japan, and Great Britain for treatment of 
moderate to severe active RA in adult patients. It is also approved for the treatment of 
moderately to severely active ulcerative colitis (UC) in adults in the EU, and is currently under 
regulatory review for the treatment of UC in Japan and Great Britain. The compound has shown 
good preliminary efficacy in CD patients in Phase 2 studies. 
In humans, filgotinib is metabolized to form one 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).
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.  

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 37
02 December 2021
Additional toxicology studies conducted include phototoxicity studies and dose-range finding 
studies in support of a definitive juvenile toxicity study. A definitive juvenile toxicology study in 
rats is ongoing.
1.2.2.1.
Nonclinical Pharmacology 
In cellular assays, filgotinib inhibits JAK1 signaling with the concentration of an inhibitor that is 
required for 50% inhibition (IC50) values of ≥ 179 nM, and demonstrates 30-fold selectivity over 
JAK2 in a human whole blood assay. Filgotinib has been profiled against 451 kinases and it is 
highly selective for JAK1; only 2.5% of kinases were inhibited ≥ 50% at 50-fold higher 
concentration than IC50 for JAK1. Broad receptor profiling (~70 receptors, ion channels, 
transporters and enzymes) did not reveal any off-target liabilities of the compound. Filgotinib 
demonstrated high potency in the rat collagen-induced arthritis (CIA) model as well as in the 
mouse dextran sulfate sodium (DSS)-induced colitis model, the latter of which is detailed below. 
The major human metabolite of filgotinib GS-829845 exhibits a similar JAK1 selectivity profile 
but is approximately 10-fold less potent as compared to parent filgotinib in vitro.
The efficacy of filgotinib was evaluated in a prophylactic setting of the chronic mouse DSS 
dextran model in two 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 end points 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.
1.2.2.2.
Safety Pharmacology
Filgotinib and GS-829845 had no relevant effects on cardiovascular parameters 
(human ether-a-gogo [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).

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 38
02 December 2021
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’- diphosphate -
glucuronosyltransferase (UGTs), and no relevant inhibition of key drug transporters, including 
organic anion transporters (OATs), by filgotinib or GS-829845.  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 
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. 

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 39
02 December 2021
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 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 and 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. 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).
The primary end point 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 and endoscopic response 
compared with placebo. 
Overall, the safety profile of filgotinib in CD subjects was consistent with prior studies. 
For additional details about the efficacy and safety of filgotinib in CD, reference is made to the 
IB. 

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 40
02 December 2021
1.3.
Rationale for This Study
A need for safer, better tolerated, durable efficacious therapies for patients with CD exists. 
Despite significant uptake in the use of anti-TNF agents, tolerability of anti-TNFs due to allergic 
and autoimmune reactions, lack of durable response, and significant increased risk of infection 
remain problematic. Filgotinib is a once daily, oral therapy that may prove efficacious without 
the risk of allergic and autoimmune phenomena observed with anti-TNF agents. 
This is a double-blind, placebo controlled trial (GS-US-419-3895; Galapagos Study ID 
GLPG0634-CL-309) comparing the efficacy of filgotinib versus placebo in the induction and 
maintenance of clinical remission and endoscopic response in subjects with moderately to 
severely active CD. A previous Phase 2 study with filgotinib demonstrated the efficacy of 
filgotinib 200 mg in inducing clinical remission in 10 weeks. Thus the onset of response is 
expected to occur early in the course of treatment. 
The use of placebo in this type of design has an important value, as “placebo response” is widely 
known to occur during clinical studies conducted in CD. The addition of a placebo arm is 
important, as this enables a control for potential influences derived from the natural course of CD 
and other effects that are inherent to overall medical care. Therefore the inclusion of a placebo 
arm in this study is necessary to prove efficacy of filgotinib. However, exposure to placebo has 
been kept as minimal as possible.
1.3.1.
Rationale for Endpoint and Timing
The co-primary end points for this study are assessed by the CDAI and SES-CD. In the EU, 
based on the Committee for Medicinal Products for Human Use Guideline on the Development 
of New Medicinal Products for the Treatment of Crohn’s Disease, the co-primary end points are 
assessed by PRO2 and SES-CD. 
Part 1 of Study GLPG0634-CL-211 supports the efficacy of filgotinib in CD at Week 10. The 
study assessed for clinical remission, defined by CDAI < 150 as the primary end point.  
Week 10 CDAI and un-weighted stool frequency (SF) and abdominal pain (AP) data from 
Study GLPG0634-CL-211 in the subset of subjects with available data was evaluated to 
determine a PRO2 responder (clinical remission by PRO2) definition corresponding to achieving 
clinical remission as assessed by a CDAI score < 150. A receiver operating characteristic (ROC) 
curve analysis was conducted to find the optimal cutoffs for SF and AP corresponding to CDAI 
score < 150. The optimal cutoffs (specificity, sensitivity) for SF and AP are 3.071 (0.803, 0.755) 
and 0.929 (0.902, 0.755), respectively. A responder definition of 3 or less daily stools 
(SF score ≤ 3) AND mild or no abdominal pain (AP score ≤ 1) is well reflective of the state of 
minimal to mild disease activity equivalent to clinical remission. Based on the Phase 2 CDAI 
data, a clinical remission by PRO2 response definition of achieving 3 or less liquid stools and a 
maximum abdominal pain score of 1 (based upon CDAI scale of 0 to 3 in which 1 represents 
mild abdominal pain) will be used to define clinical response as co-primary end points.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 41
02 December 2021
The rationale for the change in the clinical co-primary end point from PRO2 to CDAI is that the 
US Food and Drug Administration (FDA) informed the Sponsor, in 2019, that it had recently 
accepted proposals from other sponsors to define the co-primary end points in CD studies as 
clinical remission using a CDAI score of < 150 and 
 or response using the 
SES-CD score. The rationale provided by the FDA for this recommendation was the paucity of 
available prospective data validating the best cutoffs for PRO-based scoring that define either 
eligibility or clinical remission. Therefore, the Study GS-US-419-3895 protocol was revised in 
Amendment 8 to align with this recommendation. CDAI remission is a well-established clinical 
primary end point that has been evaluated in clinical trials for products approved for the 
treatment of moderate to severely active CD in the US, the EU, and other regions.
Endoscopic response will be another co-primary end point assessed by SES-CD. Use of centrally 
read endoscopy will further reduce bias in assessment of 
. Maintenance and 
durability of response and remission will be explored in the 48-week maintenance phase using a 
traditional model of induction-maintenance design. 
1.3.2.
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). Remission rates 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 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 CD subjects.
The induction portion of the study will evaluate 2 doses of filgotinib. The purpose of the 
maintenance phase is to evaluate the ability of drug to sustain remission in subjects who have 
responded at a given dose. Therefore, the re-randomization will occur into 2 arms for active 
treated subjects: continuation of the induction dose or re-randomization to placebo.  
In conclusion, JAK inhibition represents a promising target in the treatment of moderate to 
severe CD, and filgotinib, a safe and well tolerated oral therapy based on Phase 2 data.  The 
present study is intended to establish the safety and efficacy of JAK-selective inhibition on a life 
threatening disease with presently inadequate treatment options.
CCI
CCI

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 42
02 December 2021
1.4.
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.
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 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 the US and 
Korea with CD or UC will be limited to subjects who have failed at least two biologic therapies 
(any TNFα antagonist and vedolizumab). Refer to the IB for further information about 
nonclinical and clinical testicular findings.
Filgotinib has shown an increase of embryofetal malformations in 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 
the global studies in filgotinib, in general, active treated 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 clinically significant 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 inclusion criteria. For further details about infections and malignancies, please 
refer to the IB.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 43
02 December 2021
The potential benefits of JAK inhibition include improvement in clinical symptoms and mucosal 
and 
 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 and experienced 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 100 subjects reach Week 10 in Cohorts A and B combined. Following this, 
subsequent meetings will occur approximately once every 4 months or at a frequency determined 
by the DMC. 
Taking all of these considerations into account with respect to the filgotinib program, the early 
signals for efficacy demonstrated in the CD clinical trials, as well as the beneficial findings in 
nonclinical models of disease and the overall safety, tolerability, and PK characteristics of 
filgotinib that have been elucidated to date, there is a favorable benefit-risk profile for this agent 
in continued development as a treatment for CD. The overall risk/benefit balance of this study is 
considered favorable. 
For additional information about the risks of filgotinib, reference is made to the filgotinib IB.
1.5.
Compliance
This study will be conducted in compliance with this protocol, Good Clinical Practice (GCP), 
and all applicable regulatory requirements.
CCI

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 59
02 December 2021
These studies include:

Screening (Days -30 to -1)

Randomization (Day 1)

Blinded Induction Studies (Day 1 – Week 11)
Cohorts A and B Week 10 efficacy assessments:
■
At Week 10, CDAI and PRO2 to assess clinical remission 
■
At Week 10, SES-CD to assess endoscopic response 
Blinded Bridge Phase (Week 10 to 11): dosing will continue in a blinded fashion through 
the end of Week 10 until re-randomization at Week 11

Re-randomization (Week 11) 
Subjects in Cohort A and B who complete the Induction Study and achieve either clinical 
remission by PRO2 or endoscopic response by SES-CD at Week 10 will be 
re-randomized into the Maintenance Study at Week 11
Subjects who achieve neither clinical remission by PRO2 nor endoscopic response at 
Week 10 will have the option to enter a separate Long-Term Extension (LTE) study 
(GS-US-419-3896 [Galapagos Study ID GLPG0634-CL-310])

Blinded Maintenance Study (Weeks 11 to 58)

Post-Treatment (PTx) safety assessments:
 Subjects who opt out of the LTE study (GS-US-419-3896) will return 30 days after the 
last dose of study drug for PTx safety assessments
Subjects who complete all procedures per protocol, including the endoscopy, of the 
58 week study will be offered the option to continue into the LTE study 
(GS-US-419-3896)
Subjects who are eligible and opt to participate in the LTE study (GS-419-3896) can 
continue into the study without PTx safety assessments
3.3.
Study Treatments
Subjects who meet protocol eligibility criteria will be assigned to the respective Cohort and 
subsequently randomized in a blinded fashion in a 1:1:1 ratio to 1 of 3 treatments as follows: 
Treatment 1 (n = 220): filgotinib 200 mg and placebo-to-match (PTM) filgotinib 100 mg, 
once daily
Treatment 2 (n = 220): filgotinib 100 mg and PTM filgotinib 200 mg, once daily
Treatment 3 (n = 220): PTM filgotinib 200 mg and PTM filgotinib 100 mg, once daily

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 60
02 December 2021
Note: US and Korea males who have not failed at least two biologic therapies (any TNFα 
antagonist and vedolizumab) will be randomized in a 1:1 ratio to either filgotinib 100 mg or 
matching placebo.
Within each Cohort, treatment assignments will be stratified according to the following factors in 
the Induction studies:
Stratification Factors (Cohort A, Biologic-Naïve and Biologic-Experienced Induction 
Study)

History of exposure to no biologic agent, one biologic agent, or more than one biologic agent

Concomitant use of oral, systemically absorbed corticosteroids (eg, prednisone) at Day 1, 
(Yes or No)

Concomitant use of immunomodulators (eg, 6-mercaptopurine [6-MP], azathioprine, MTX) 
at Day 1, (Yes or No)
Stratification Factors (Cohort B, Biologic-Experienced Induction Study)

Exposure to one biologic agent versus more than one biologic agent

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)
Subjects from Cohorts A and B who are eligible for the Maintenance Study will be 
re-randomized to treatment as follows:
Table 3-1.
Re-Randomization of Induction Cohorts A and B to Maintenance 
Study
Treatment Assignment Induction Studies
Cohorts A and B
Maintenance Study
Re-randomization
Treatment 1, 200 mg
Treatment 1, filgotinib 200 mg
Treatment 3, Placebo
Treatment 2, 100 mg
Treatment 2, filgotinib 100 mg
Treatment 3, Placebo
Treatment 3, Placebo
Continue Treatment 3, Placebo
Note:
Subjects receiving Treatment 1 or 2 in the Induction study will be randomized in a 2:1 manner to either continue on the 
assigned filgotinib regimen or to placebo for the duration of the Maintenance study

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 61
02 December 2021
Stratification Factors (Maintenance Study)

History of exposure to a biologic agent (Yes or No)

Concomitant use of oral, systemically absorbed corticosteroids (eg, prednisone) at Day 1, 
(Yes or No)

Concomitant use of immunomodulators (eg, 6-mercaptopurine [6-MP], azathioprine, 
methotrexate [MTX]) at Day 1, (Yes or No)
3.4.
Duration of Treatment
Randomized subjects will receive a maximum of 58 weeks of study drug. Subjects who are 
non-responders based on the results of the Week 10 assessments will be offered the option to 
receive open-label filgotinib by entering into the LTE study (GS-US-419-3896).
Subjects meeting disease worsening criteria at Week 11 or later must be discontinued from 
blinded treatment and will be offered the option to receive open-label filgotinib in the LTE study 
(See Section 3.6, Disease Worsening Criteria).
Subjects who complete all procedures per protocol, including the endoscopy of the Week 58 
visit, will have the option to continue study drug in a blinded fashion in the LTE study.
3.5.
Criteria for Study Drug Interruption or Discontinuation 
3.5.1.
Study Drug Interruption Considerations
The 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 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 medical monitor.

Any subject who develops a new infection during the study should undergo prompt and 
complete diagnostic testing appropriate for an immunocompromised individual, and the 
subject should be closely monitored. 
NOTE: During the time of study drug interruption for any of the above, the subject may continue 
to have study visits and to take part in procedures and assessments, if deemed medically 
appropriate by the investigator.
The medical monitor should consult the medical leader as needed.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 62
02 December 2021
3.5.2.
Study Drug Discontinuation Considerations
The 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 HCV during the study, as evidenced by HCV RNA positivity

Evidence of active 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 the Sponsor, 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 medical monitor.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 63
02 December 2021

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).
2 sequential neutrophil counts < 750 neutrophils/mm3 (international system units [SI]: 
< 0.75x109 cells/L)
2 sequential platelet counts < 75,000 platelets/mm3(SI: < 75.0x109 cells/L)
2 sequential aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 
> 3 times the upper limit of normal range (ULN) and at least one of the following 
confirmed values: 
■
total bilirubin > 2x ULN
■
international normalized ratio (INR) > 1.5
■
or accompanied by symptoms consistent with hepatic injury
For any subject with an initial AST or ALT elevation > 3x the upper limit of normal 
(ULN),  at the time of the second confirmatory draw, an INR, prothrombin time (PT) 
and partial thromboplastin time (PTT) must also be drawn. 
2 sequential AST or ALT > 5x ULN
2 sequential values for estimated creatinine clearance (CrCl) < 35 mL/min based on the 
Cockcroft-Gault (CC&G) formula
Male
[(140–age in years) × (weight in kg)]/[72 × (serum creatinine in mg/dL)] = CLcr 
(mL/min)
Female
[(140–age in years) × (weight in kg) × 0.85]/[72 × (serum creatinine in mg/dL)] 
= CLcr (mL/min)

Subjects are free to withdraw from the study at any time without providing reason(s) for 
withdrawal and without prejudice to further treatment. The reason(s) for withdrawal will be 
documented in the electronic case report form (eCRF). 

Subjects who permanently discontinue study drug for any reason should discuss their 
continued  care plan with their physician. 

Subjects who permanently discontinue study drug  for pregnancy should not continue in the 
study; if there are any questions regarding permanent discontinuation, these should be 
discussed with the Sponsor.

Subjects withdrawing from the study should complete Early Termination (ET), followed by 
Post-Treatment  (PTx) assessments 30 days  after the last dose of study drug.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 64
02 December 2021
Reasonable efforts will be made to contact subjects who are lost to follow-up. All contacts and 
contact attempts must be documented in the subject’s file.
The Sponsor has the right to terminate the study at any time in case of safety concerns or if 
special circumstances concerning the study medication or the company itself occur, making 
further treatment of subjects impossible. In this event, the investigator(s) and relevant authorities 
will be informed of the reason for study termination.
The medical monitor should consult the medical leader as needed.
3.6.
Disease Worsening Criteria
Subjects meeting the following disease worsening criteria evaluated after Week 11 must be 
discontinued from blinded treatment and will be offered the option to receive open-label 
filgotinib by entering into the separate LTE study (GS-US-419-3896).

Increase in CDAI score ≥ 100 points from the Week 10 value and CDAI score ≥ 220 points 
at 2 consecutive visits.
The disease worsening visits may include unscheduled visits (eg, a study visit followed 
by an unscheduled visit, or 2 sequential unscheduled visits anytime subsequent to the 
Week 11 visit).

If a subject experiences significant worsening of underlying CD, which requires any of the 
prohibited medications (refer to Section 5.4.2), or surgical intervention at any point during 
the study, treatment discontinuation should be considered at investigator’s discretion, 
in consultation with medical monitor if feasible (refer to Section 3.5.2); these subjects do not 
qualify for LTE study.    
3.7.
End of Study 
End of Study is defined as when the last subject has completed 58 weeks of treatment plus 
30 days follow-up. 
3.8.
Post Study Care 
All subjects completing all study related procedures, including endoscopy at Week 58, will be 
offered an opportunity to participate in the LTE study (GS-US-419-3896). For those subjects 
who do not participate in the LTE study, after the subject has completed their study participation, 
the long-term care of the participant will remain the responsibility of their primary treating 
physicians. 

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 67
02 December 2021
4.
SUBJECT POPULATION
4.1.
Number of Subjects and Subject Selection
Cohort A Induction Study
Approximately 660 subjects who meet the eligibility criteria at screening will be randomized in a 
blinded fashion in a 1:1:1 ratio to filgotinib 200 mg, filgotinib 100 mg, or matching placebo.
Cohort B Induction Study
Approximately 660 subjects who meet the eligibility criteria at screening will be randomized in a 
blinded fashion in a 1:1:1 ratio to filgotinib 200 mg, filgotinib 100 mg, or matching placebo.
Maintenance Study
Subjects from Cohorts A and B who achieve either clinical remission by PRO2 or endoscopic 
response at Week 10 will be re-randomized at Week 11 in a blinded fashion in a 2:1 ratio to 
either the same dose of filgotinib or placebo. Refer to Section 3.3, Table 3-1.
In order to manage the total study enrollment, the Sponsor, at its sole discretion, may suspend 
screening and/or enrollment at any site or study-wide at any time.
4.2.
Induction Study (Cohorts A and B) 
4.2.1.
Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for participation in either 
the Cohort A or B Induction Study.
1) Must have the ability to understand and sign a written ICF, which must be obtained prior to 
initiation of study procedures
2) Males or non-pregnant, non-lactating females, ages 18 to 75 years, inclusive based on the 
date of the screening visit
3) Females of childbearing potential (as defined in Appendix 7) must have a negative serum 
pregnancy test at screening and a negative urine pregnancy test at baseline
4) Male subjects and female subjects of childbearing potential who engage in heterosexual 
intercourse must agree to use protocol specified method(s) of contraception as described in 
Appendix 7

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 68
02 December 2021
5) Documented diagnosis of CD with a minimum disease duration of 3 months with 
involvement of the ileum and/or colon at a minimum, documented by the following:
a) Medical record documentation of, or an ileocolonoscopy (full colonoscopy with the 
intubation of terminal ileum) report dated ≥ 3 months before enrollment, which shows 
features consistent with CD, determined by the procedure performing physician AND
b) Medical record documentation of or a histopathology report showing features consistent 
with CD, determined by the pathologist. 
6) Moderately or severely active CD as defined by: 
a) CDAI total score between 220 and 450 inclusive (refer to Appendix 4), AND
b) PRO2 score consisting of abdominal pain ≥ 2 (on CDAI scale of 0 to 3) OR daily stool 
frequency ≥ 4 (refer to Appendix 4), AND
c) Evidence of active disease as measured by SES-CD (refer to Appendix 5) based on 
central reading:
i)
Total score ≥ 6, OR
ii) If disease is limited to the ileum and/or right colon, a combined score ≥ 4 in these 
two segments
7) Meet one of the following TB screening criteria: 
a) No evidence of active or latent TB ie,
i)
A negative QuantiFERON® TB-Gold In-Tube test (or centrally reported equivalent 
assay) 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 (or centrally reported equivalent assay) 
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.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 69
02 December 2021
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 [or centrally reported equivalent assay]) in which active TB has been ruled out and 
for which appropriate, ongoing, prophylactic treatment for latent TB has been initiated 
for a minimum of 4 weeks prior to the first administration of study medication. Adequate 
treatment for latent TB is defined according to local country guidelines for 
immunocompromised subjects. Quantiferon testing may not be repeated except in the 
case of a single repeat for indeterminate results.
Cases falling under category “b” and “c” need to be approved by the Sponsor prior to enrollment 
in the study. No subject with currently ACTIVE TB may be enrolled in the study, regardless of 
past or present anti-TB medication use.
8) Laboratory parameters (subjects who fail to meet 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 times ULN
b) Estimated CrCl ≥ 40 ml/min as calculated by the CC&G equation
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
9) May be receiving the following drugs (subjects on these therapies must be willing to remain 
on stable doses for the noted times):
a) Oral 5-aminosalicylate (5-ASA) compounds provided the dose prescribed has been stable 
for at least 4 weeks prior to randomization; dose must remain stable for the first 10 weeks 
after randomization
b) Azathioprine or 6-MP or MTX provided the dose prescribed has been stable for 4 weeks 
prior to randomization; dose must remain stable for the first 10 weeks after 
randomization
c) 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 2 weeks prior to randomization; dose must remain stable for the 
first 14 weeks after 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. 

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 70
02 December 2021
10) Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks 
after last dose.
11) Must be up to date on colorectal cancer screening and surveillance as standard of care 
according to local guidelines.
4.2.2.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in either the 
Cohort A or B induction study.
1) Pregnant or lactating females
2) Males and females of reproductive potential who are unwilling to abide by protocol-specified 
contraceptive methods as defined 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) Currently have any of the following complications of CD:
a) Symptomatic strictures, OR
b) Severe (impassable) rectal/anal stenosis, OR
c) Fistulae other than perianal fistulae, OR 
d) Short bowel syndrome, OR
e) Any other complications which could preclude the use of the CDAI to assess response to 
therapy, or would possibly confound the evaluation of benefit from treatment with 
filgotinib
7) 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
8) History of major surgery or trauma within 30 days prior to screening 
9) Presence of UC, indeterminate colitis, ischemic colitis, fulminant colitis, or toxic mega-colon 
10) History of total colectomy, subtotal colectomy, presence of ileostomy or colostomy, or likely 
requirement for surgery during the study
11) Dependence on parenteral nutrition
12) History or evidence of incompletely resected colonic mucosal dysplasia 

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 71
02 December 2021
13) Stool sample positive for Clostridium difficile (C. diff) toxin, pathogenic Escherichia coli 
(E. coli), Salmonella species (spp), Shigella spp, Campylobacter spp, or Yersinia spp
14) Stool sample positive for ova and parasites test (O&P) unless approved by the medical 
monitor
15) 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)
16) Infection with HIV, hepatitis B, or hepatitis C
17) Presence of Child-Pugh Class C hepatic impairment
18) Active TB or history of latent TB that has not been treated (See inclusion criterion 7 for 
further information)
19) 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
20) History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, 
or multiple myeloma
21) History of treatment with lymphocyte-depleting therapies, including but not limited to 
alemtuzumab, cyclophosphamide, total lymphoid irradiation, and rituximab
22) History of cytapheresis ≤ 2 months prior to screening
23) Use of any prohibited concomitant medications as described in Section 5.4.2 
24) 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 or Sponsor, would make the subject unsuitable for the study or 
would prevent compliance with the study protocol
25) Administration of a live or attenuated vaccine within 30 days of randomization
26) History of opportunistic infection or immunodeficiency syndrome
27) Currently on any chronic systemic (oral or intravenous) anti-infective therapy for chronic 
infection (such as pneumocystis (PCP), cytomegalovirus (CMV), herpes zoster, atypical 
mycobacteria)
28) History of disseminated Staphylococcus aureus
29) 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

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 72
02 December 2021
4.3.
Cohort A (Biologic-Naïve and Biologic-Experienced) Induction Study
4.3.1.
Inclusion Criteria for Biologic-Naïve Subjects Enrolled in Cohort A
Biologic-Naïve subjects must meet all of the additional inclusion criteria to be eligible for 
Cohort A.
1) Previously demonstrated an inadequate clinical response, loss of response to, or intolerance 
to at least one of the following agents (depending on current country treatment 
recommendations/guidelines):
a) Corticosteroids
i)
Active disease despite a history of at least 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-MP (≥ 1 mg/kg/day), or MTX (25 mg subcutaneously [SC] or 
intramuscularly [IM] per week for induction and ≥ 15mg IM per week for 
maintenance), OR
ii) History of intolerance to at least one immunomodulator including, but not limited to, 
serious infections, hepatotoxicity, cytopenia, pancreatitis, thiopurine 
methyltransferase (TPMT) genetic mutation, allergic reactions, or any other condition 
that contributed to discontinuation of the agent
4.3.2.
Exclusion Criteria for Biologic-Naïve Subjects Enrolled in Cohort A 
Biologic-Naïve subjects who meet any of the following exclusion criteria are not eligible for 
Cohort A.
1) Prior or current use of TNFα antagonist, including (but not limited to) infliximab, 
adalimumab, golimumab, certolizumab, or biosimilar agent
2) Prior or current use of vedolizumab at any time
3) Prior or current use of ustekinumab at any time

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 73
02 December 2021
4.3.3.
Inclusion Criteria for Biologic-Experienced Subjects Enrolled in Cohort A
Biologic-Experienced subjects must meet all of the additional inclusion criteria to be eligible for 
Cohort A.
1) Previously demonstrated an inadequate clinical response, loss of response to, or intolerance 
to at least one of the following agents (depending on current country treatment 
recommendations/guidelines) or discontinuation of use of at least one of the following agents 
for reasons other than inadequate clinical response, loss of response, or intolerance:
a) TNFα Antagonists
i)
Active disease despite a history of at least one 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 one day or two 40-mg injections per day for two 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
i)
Recurrence of symptoms during maintenance therapy with the above agents, OR
ii) 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 
b) 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
c) 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

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 74
02 December 2021
4.3.4.
Exclusion Criteria for Biologic-Experienced Subjects Enrolled in Cohort A
Biologic-Experienced subjects who meet the following exclusion criterion are not eligible for 
Cohort A.
1) Have 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. Subjects who have an undetectable serum level of a biologic agent since its last dose 
using a commercially available assay can undergo study screening without the 
above-mentioned waiting period.
4.4.
Cohort B (Biologic-Experienced) Induction Study
4.4.1.
Inclusion Criteria, Cohort B ONLY
Subjects must meet all of the additional inclusion criteria to be eligible for participation in 
Cohort B induction study.
1) Previously demonstrated an inadequate clinical response, loss of response to, or intolerance 
to at least one of the following agents (depending on current country treatment 
recommendations/guidelines):
a) TNFα Antagonists
i)
Active disease despite a history of at least one 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 one day or two 40-mg injections per day for two 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
i)
Recurrence of symptoms during maintenance therapy with the above agents, OR
ii) 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

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 75
02 December 2021
b) 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
c) Ustekinumab
i)
Active disease despite a history of a 8 week induction regimen with a single dose of 
ustekinumab IV per weight-based dosing (260mg for up to 55kg; 390mg for greater 
than 55 to 85kg; 520mg for greater than 85kg) 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
4.4.2.
Exclusion Criteria, Cohort B ONLY
Subjects who meet the following exclusion criterion are not to be enrolled in Cohort B induction 
study.
1) Have 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. Subjects who have an undetectable serum level of a biologic agent since its last dose 
using a commercially available assay can undergo study screening without the 
above-mentioned waiting period.
4.5.
Maintenance Study 
4.5.1.
Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for participation in the 
Maintenance Study.
1) Completion of Cohort A or B induction study with either clinical remission by PRO2 or 
endoscopic response at Week 10
2) Willingness to refrain from live or attenuated vaccines during the study and for 12 weeks 
after last dose
3) May be on oral corticosteroid therapy (prednisone prescribed at a stable dose ≤ 30 mg/day or 
budesonide at a dose of ≤ 9 mg/day); dose must remain stable to Week 14

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 76
02 December 2021
4.5.2.
Exclusion Criteria
Subjects who meet any of the following exclusion criteria are not to be enrolled in the 
maintenance study.
1) Males and females of reproductive potential who are unwilling to abide by protocol-specified 
contraceptive methods as defined by Appendix 7
2) 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
3) Male subjects unwilling to refrain from sperm donation during the study and for at least 
90 days after the last dose of study drug
4) Use of any prohibited concomitant medications as described in Section 5.4.2 

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 77
02 December 2021
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) for that subject. The Sponsor recommends but does not require that the 
investigator contact the 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 
eCRF, along with the date on which the treatment assignment was obtained. The investigator is 
requested to contact the 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.
The Sponsor 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 pharmacokinetics file administrator, or designee, in Bioanalytical 
Operations and/or Clinical Data Management, who facilitates the data transfer of PK files 
between the Sponsor and vendors, will remain unblinded. Individuals in Clinical Packaging and 
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 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 PK/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.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 78
02 December 2021
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 US 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. 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. 

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 79
02 December 2021
5.3.
Dosage and Administration 
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 1: filgotinib 200 mg and PTM filgotinib 100 mg, once daily

Treatment 2: filgotinib 100 mg and PTM filgotinib 200 mg, once daily

Treatment 3: PTM filgotinib 200 mg  and PTM filgotinib 100 mg, once daily
Subjects who are non-responders based on the results of the Week 10 assessments will be offered 
the option to receive open-label filgotinib by entering into the LTE study (GS-US-419-3896). 
Subjects meeting disease worsening criteria after Week 11 must be discontinued from blinded 
treatment and will be offered the option to receive open-label filgotinib 200 mg (See Section 3.6, 
Disease Worsening Criteria), except for US and Korea males who will be offered filgotinib 
100 mg unless they have failed at least 2 other biologic therapies (any TNFα antagonist and 
vedolizumab). Subjects who complete the Week 58 visit will have the option to continue study 
drug in a blinded fashion in the LTE study.
For missed dose(s) of study medication, subjects should be instructed to take the missed dose(s) 
of study medication as soon as possible during the same day. If the missed dose is not taken on 
the original day, then subjects should not take the missed dose and the missed dose should be 
returned to the study drug bottle. Subjects should be cautioned not to double the next dose 
(ie, taking the missed dose of study drug with that day’s dose).
5.4.
Prior and Concomitant 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-counter medications, including 
vaccines, vitamins, herbal, dietary supplements, and minerals) must be recorded in the 
concomitant therapy section of the eCRF. 
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 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 the Sponsor as soon as he/she is 
aware of the use of the excluded medication.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 80
02 December 2021
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.
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 ≤ 30 mg/day or 
budesonide prescribed at a stable dose of ≤ 9 mg/day) provided the dose prescribed has been 
stable for 2 weeks prior to randomization; dose must be stable for the first 14 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

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 81
02 December 2021
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,
Antimycobacterials
Rifabutin, rifapentine, rifampin
Herbal/Natural 
Supplements
St. John’s wort, danshen 
(Salvia Miltiorrhiza)
30 days prior to screening through the 
end of the study
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 screeningd through the 
end of the study
Integrin antagonist
Vedolizumab and natalizumab
8 weeks prior to screeningd through the 
end of the study
Interleukin antagonist
Ustekinumab
12 weeks prior to screeningd through 
the end of the study
Cyclosporine, thalidomide, tacrolimus, 
leflunomide, and any investigational agent
30 days prior to screening through the 
end of the study
Other (non-biologic)
Any JAK inhibitor
Any time before and 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 
Anti-inflammatory 
Drugs (NSAIDs)b 
Aspirin, ibuprofen, naproxen, diclofenac, 
indomethacin, COX-2 inhibitors
From screening through the end of the 
study
Other biologicsc
Antibody based or other systemic 
biologics, eg, denosumab, trastuzumab
Requires medical monitor consultation
Abbreviations: COX-2=Cyclooxygenase-2; JAK=Janus Kinase; NSAID=Nonsteroidal Anti-inflammatory Drugs; TNFα=tumor 
necrosis factor-alpha
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.
d
Subjects who have an undetectable serum level of a biologic agent since its last dose using a commercially available assay 
can undergo study screening without the above-mentioned waiting period.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 82
02 December 2021
5.4.3.
Corticosteroid Tapering
Starting at Week 14, 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 subject is no longer on steroids. Subjects who are on 
budesonide should have their daily dose reduced by 3 mg every 3 weeks until they are 
completely off steroids. For subjects undergoing taper, steroids may be increased or restarted at 
doses up to and including their baseline dose if return of symptoms is apparent. These subjects 
will not be considered treatment failures. Subjects who need to restart or increase steroid 
treatment at a dose that exceeds their baseline dose of steroids (dose may not exceed 30 mg 
prednisone [or equivalent] or budesonide 9 mg/day) will be considered treatment failures for all 
clinical end points but will be permitted to remain in the study.
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 dispensed to subjects must be returned to the site.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 83
02 December 2021
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 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.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 84
02 December 2021
6.
STUDY PROCEDURES
The study procedures to be conducted for each subject enrolled in the study are presented in 
tabular form in Appendix 2 and described in the text that follows. 
The investigator must document any deviation from protocol procedures and notify the Sponsor 
or contract research organization (CRO).
6.1.
Subject Enrollment and Treatment Assignment
Subjects who meet the protocol criteria will be assigned to the respective cohort and 
subsequently randomized in a blinded fashion in a 1:1:1 ratio to filgotinib, or matching placebo.

Treatment 1 (n = 220) : filgotinib 200 mg and  PTM filgotinib 100 mg, once daily 

Treatment 2 (n = 220) : filgotinib100 mg and PTM filgotinib 200 mg, once daily

Treatment 3 (n = 220): PTM filgotinib 200 mg and PTM filgotinib100 mg, once daily
Note: US and Korea males who have not failed at least two biologic therapies (any TNFα 
antagonist and vedolizumab) will be randomized in a 1:1 ratio to either filgotinib 100 mg or 
matching placebo.
Within each Cohort, treatment assignments will be stratified according to the following factors in 
the Induction and Maintenance studies:
Stratification Factors (Cohort A, Biologic-Naïve and Biologic-Experienced Induction 
Study)

History of  exposure to no biologic agent, one biologic agent, or more than one biologic 
agent

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)
Stratification Factors (Cohort B, Biologic-Experienced Induction Study)

Exposure to one biologic agent versus more than one biologic agent

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)

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 85
02 December 2021
Stratification Factors (Maintenance Study)

History of exposure to a biologic agent, (Yes or No)

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)
Refer to Section 3.3, Table 3-1 for re-randomization in the Maintenance Study.
6.2.
Pretreatment Assessments
6.2.1.
Screening Visit
Subjects will be screened within 30 days before randomization to determine eligibility for 
participation in the study. The following will be performed and documented during the screening 
period:

Obtain written informed consent
Additional consent will be required from subjects participating in the PK substudy , 
 and left-over samples for future research 

Review inclusion/exclusion criteria and other protocol restrictions (Section 4)

Obtain medical history and concomitant medications, including CD history and treatment


Ask Anchor Questions for abdominal pain and stool frequency

Complete physical examination (PE) including, vital signs, body weight, and height

Perform 12-Lead ECG

Record any SAEs and all AEs related to protocol mandated procedures occurring after 
signing of the informed consent form.

Instruct subjects to maintain concomitant medication at a stable dose

Provide subject with the electronic diary (e-Diary) and instructions for daily documentation 
of stool frequency, abdominal pain and general well-being
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
CCI
CCI

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 86
02 December 2021

Conduct phone call approximately 4 days after screening visit to encourage compliance with 
daily documentation of abdominal pain, stool frequency and general well-being

Collect the variables to calculate baseline CDAI score (reference Appendix 4)
Site enters patient assessments from screening visit
CDAI score calculated centrally after all components have been captured electronically

Baseline PRO2 (Appendix 4) – centrally calculated using the patient reported symptoms of 
stool frequency and abdominal pain captured in the e-Diary

TB Assessment – Must have negative QuantiFERON® test (or centrally reported equivalent 
assay) 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 results must not be repeated. An 
indeterminate result should be repeated once and the second result (if positive or negative) 
will be accepted. Two sequential indeterminate results is considered a positive result for the 
purpose of the study. Subjects with previously treated latent or active TB requires sponsor 
approval (See inclusion criterion 7 for details). 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 medical monitor.

Obtain blood samples (reference Study Procedures Table [Appendix 2])
HCV Screening Guidelines
■
Subjects with positive HCV antibody at Screening require reflex testing for  HCV 
RNA. Subjects with HCV RNA ≥ lower limit of quantification (LLOQ) at Screening 
will be excluded. Subjects with positive HCV antibody but HCV RNA < LLOQ are 
eligible.
HBV Screening and Surveillance Guidelines
■
Subjects with positive HBV surface antigen (HBsAg) at Screening are excluded.
■
Subjects who are positive for HBV surface antibody (HBsAb), but negative for both 
HBsAg and HBV core antibody (HBcAb) at Screening are eligible.
■
Subjects with positive HBcAb require reflex testing for HBV DNA. Subjects with 
HBV DNA ≥ LLOQ at Screening will be excluded. Subjects with positive HBcAb 
and HBV DNA < LLOQ are eligible, but will require ongoing HBV DNA monitoring 
every 3 months during this study. These subjects may require prophylactic treatment 
per investigator discretion in accordance with local guidelines/standard of care.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 87
02 December 2021
■
In Japan and where required by local guidelines, subjects with positive HBcAb and/or 
positive HBsAb will require reflex testing for HBV DNA at Screening. Subjects with 
positive HBcAb and/or HBsAb but with HBV DNA < LLOQ at Screening are 
eligible for the study. These subjects will require ongoing HBV DNA monitoring 
every 4 weeks in accordance with local guidelines during this study.  
■
Any subject who has HBV DNA ≥ LLOQ during the study will be discontinued  
(reference Section 3.5.2).
HIV Screening Guidelines
■
Subjects who have HIV infection, regardless of virologic status, are excluded from 
the study.  

Obtain blood samples for serum pregnancy test (for females of childbearing potential only)

Obtain stool sample (reference Study Procedures Table [Appendix 2])
A stool sample will be obtained for culture for pathogenic bacteria, ova and parasite 
evaluation, and C. difficile toxin assay during screening for the purposes of determining 
eligibility.

Obtain urine sample (reference Study Procedures Table [Appendix 2])

Obtain urine sample for urine drug screen (reference Study Procedures Table [Appendix 2])

Review subject eligibility criteria (centrally calculated CDAI, PRO2 and labs), prior to 
performing a full video ileocolonoscopy with biopsies within 14 days prior to baseline visit: 
Biopsy samples will be collected and sent to central laboratory for storage and then to 
specialty laboratories for subsequent analysis.
Record local endoscopic assessment

Baseline SES-CD scoring and calculation performed by central reader (Appendix 5). 
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 screening if they receive permission from the 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 medical monitor. 
No more than one repeat screening visit is allowed for each subject, unless prior written approval 
has been provided by the Sponsor. All screening procedures will need to be repeated during the 
repeat screening visit except for the ileocolonoscopy procedures. Ileocolonoscopy procedures 
from the previous screening attempt that fall within the specified timeframe (i.e, ileocolonoscopy 
with biopsies within 14 days prior to Day 1 visit) do not need to be repeated.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 89
02 December 2021
6.3.
Randomization
Please refer to Section 6.1.
6.3.1.
Randomization and Study Drug Administration

Enter subject information in the IWRS to receive treatment assignment

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 
6.4.
Study Assessments
Please refer to the Study Procedure Table in Appendix 2 for all procedures and time points to be 
conducted after randomization.
6.4.1.
Priority of Assessments
Subject-reported outcomes are recommended to be completed before any other study procedures. 
Invasive study procedures such as blood draws and biopsies should be done at the end of a study 
visit, as much as possible. Investigator questionnaires/assessments should be performed prior to 
reviewing subject-reported outcomes for that visit, as much as possible. 
6.4.2.
Efficacy
Efficacy assessments will be performed at the time points indicated in the Study Procedures 
Table (Appendix 2). 
6.4.2.1.
Crohn’s Disease Activity Index (CDAI) and Patient Reported Outcomes – 2 items 
(PRO2)
The Crohn's Disease Activity Index or CDAI is a tool used to assess the disease activity of 
Crohn's disease. Refer to Appendix 4.  The PRO2 is 2 patient reported outcomes of liquid or very 
soft stool and abdominal pain which are components of the CDAI.
6.4.2.2.
Patient Global Impression – Severity (PGI-S) and Patient Global Impression 
- Change (PGI-C)
The Patient Global Impression of Severity (PGI-S) is a global index that is used to rate the 
severity of Crohn’s disease by patients (a single-state scale). The Patient Global Impression of 
Change (PGI-C) is a scale that aims at evaluating all aspects of patients' health related to Crohn’s 
disease and determining if there has been an improvement or not. The patient has to select the 
one response from the response options that gives the most accurate description of his/her state 
of health (overall status).

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 91
02 December 2021
6.4.3.
Safety
Safety will be assessed via AEs, concomitant medications, physical examinations (complete and 
symptom-driven), vital signs, ECGs, and clinical laboratory results.
6.4.3.1.
Clinical Laboratory Evaluations
The hematology, serum chemistry, coagulation laboratory, and stool analyses will be performed 
at a central laboratory. Reference ranges will be supplied by the central laboratory and will be 
used by the investigator to assess the laboratory data for clinical significance and pathological 
changes.
Blood samples will be collected by venipuncture (or optional indwelling catheter for PK 
sampling days) in the arm at the time points indicated in the Study Procedures Table 
(Appendix 2). In addition, urine samples for the clinical laboratory assessments will be collected. 
An overnight fast (no food or drinks, except water) of at least 8 hours will be required prior to 
collection of blood samples for lipid testing.
A stool sample should also be collected at any time during the study for culture for pathogenic 
bacteria, ova and parasites, and C. diff toxin assay when a subject becomes symptomatic, 
including worsening or return of disease activity.
Refer to Appendix 8 for table of clinical laboratory tests.
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 
7-14 days apart] ).
The details of sample handling and shipment instructions will be provided in a separate 
laboratory manual.
6.4.3.2.
Pregnancy Testing (for females of childbearing potential)
All females meeting the childbearing potential criteria (Appendix 7) must have a serum 
pregnancy testing at screening 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.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 92
02 December 2021
6.4.3.3.
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.
6.4.3.4.
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. 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 at 
all other visits based on reported signs and symptoms.
6.4.3.5.
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.
6.4.3.6.
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).
6.4.4.
Pharmacokinetics Assessments
The PK sample at Week 4 is collected post-dose (at least 30 minutes and up to 3 hours after 
study drug dosing). For this visit, it is preferred that study drug dosing is done in clinic. The PK 
sample at Weeks 26 can be collected at any time without regard to dosing. The PK sample at 
Weeks 10 and 58 are collected at pre-dose (within 2 hours prior to dosing).

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 94
02 December 2021
6.6.
Early Termination Assessments 
The following will be performed and documented:

Symptom-directed PE

Obtain body weight and vital signs (resting blood pressure, respiratory rate, pulse and 
temperature)

Perform 12-Lead ECG (for subjects who terminate prior to Week 10)

Review AEs and concomitant medications

 

Collect the variables to calculate CDAI score (reference Appendix 4)
Site collects patient assessments at each visit
CDAI score calculated centrally after all components have been captured electronically

PRO2 score calculated centrally

Obtain fasting blood samples (reference Study Procedures Table (Appendix 2)

Obtain urine sample (reference Study Procedures Table [Appendix 2])
Pregnancy test (for females of child bearing potential only)
6.7.
End of Study
Please refer to Section 3.7
6.8.
Post Study Care
Please refer to Section 3.8
CCI

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 95
02 December 2021
7.
ADVERSE EVENTS AND TOXICITY MANAGEMENT
7.1.
Definitions of Adverse Events, Adverse Reactions, and Serious Adverse 
Events
7.1.1.
Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study subject 
administered an investigational 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 an investigational product, whether or not 
considered related to the investigational product. Adverse events 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 adverse event 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 
eCRF.
7.1.2.
Serious Adverse Events
A serious adverse event (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.)

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 96
02 December 2021

In-patient hospitalization or prolongation of existing hospitalization

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 
investigational 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 
investigational medicinal product (IMP) therapy using clinical judgment and the following 
considerations:

No: Evidence exists that the adverse event 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 adverse event 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 adverse event has an etiology other than the study procedure.

Yes: The adverse event occurred as a result of protocol procedures (eg, venipuncture)

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 97
02 December 2021
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 adverse event. 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 the Sponsor
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 eCRF: all SAEs and adverse events 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 adverse event is stable, if possible. 
The Sponsor may request that certain AEs be followed beyond the protocol defined follow up 
period.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 98
02 December 2021
7.3.2.
Serious Adverse Events
All SAEs, regardless of cause or relationship, that occurs after the subject first consents to 
participate in the study (ie, signing the informed consent) and throughout the duration of the 
study, including the protocol-required post-treatment follow-up period, must be reported to the 
eCRF database and the Sponsor as instructed. This also includes any SAEs resulting from 
protocol-associated procedures performed after informed 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 the Sponsor.

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 form. During the study conduct, sites may transition to an electronic SAE (eSAE) 
system.
Electronic Serious Adverse Event Reporting Process 

Site personnel record all SAE data in the eCRF database and from there transmit the SAE 
information to the Sponsor within 24 hours of the investigator’s knowledge of the event. 
Detailed instructions can be found in the eCRF completion guidelines.

If for any reason it is not possible to record the SAE information electronically, ie, the eCRF 
database is not functioning, record the SAE on the paper serious adverse event reporting 
form and submit within 24 hours as described below.
Email: 
DIVERSITY_safety@glpg.com

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 form because the eCRF database has been locked, 
no further action is necessary.

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.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 99
02 December 2021

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.
Sponsor 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, the Sponsor 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), the Sponsor or a 
specified designee will notify worldwide regulatory agencies and the relevant IRB/IEC in 
concerned Member States of applicable SUSARs as outlined in current regulations.
Assessment of expectedness for SAEs will be determined by the Sponsor or designee using 
reference safety information specified in the investigator's brochure (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. 
To minimize the possibility of exposing study subjects to unusual risk, the safety information 
from this study will also be reviewed periodically by an independent DMC (as described 
in Section 8.10). The DMC may have access to partially blinded or unblinded data and will make 
recommendations regarding the study according to the DMC charter
7.5.
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events
Laboratory abnormalities are usually not recorded as AEs or SAEs. However, laboratory 
abnormalities (eg, clinical chemistry, hematology, and urinalysis) independent of the 
underlying medical condition that require medical or surgical intervention or lead to 
investigational medicinal product interruption or discontinuation must be recorded as an AE, 
as well as an SAE, if applicable. In addition, laboratory or other abnormal assessments (eg, ECG, 
x-rays, vital signs) that are associated with signs and/or symptoms must be recorded as an AE or 
SAE if they meet the definition of an AE (or SAE) as described in Sections 7.1.1 and 7.1.2. If the 
laboratory abnormality is part of a syndrome, record the syndrome or diagnosis (ie, anemia) not 
the laboratory result (ie, decreased hemoglobin).
Severity should be recorded and graded according to the CTCAE Grading Scale for Severity of 
Adverse Events and Laboratory Abnormalities (Appendix 6). 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.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 100
02 December 2021
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 below general toxicity guidelines, and in general, where discrepancy is present, the 
more conservative criteria apply. The 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.  

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 101
02 December 2021
Treatment-emergent toxicities will be noted by the investigator and brought to the attention of 
the 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 medical monitor. The 
medical monitor should consult the medical leader as needed.
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 of 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 the health care professional, patient, or consumer. Medication errors may be classified 
as a medication error without an AE, which includes situations of missed dose; medication error 
with an AE; intercepted medication error; or potential medication error.
Abuse is defined as persistent or sporadic intentional excessive use of an investigational product 
by a subject.
Misuse is defined as any intentional and inappropriate use of an investigational product that is 
not in accordance with the protocol instructions or the local prescribing information.
An overdose is defined as an accidental or intentional administration of a quantity of an 
investigational product given per administration or cumulatively which is above the maximum 
recommended dose as per protocol or in the product labelling (as it applies to the daily dose of 
the subject in question). In cases of a discrepancy in drug accountability, overdose will be 
established only when it is clear that the subject has taken the excess dose(s). Overdose cannot 
be established when the subject cannot account for the discrepancy except in cases in which the 
investigator has reason to suspect that the subject has taken the additional dose(s).
Occupational exposure is defined as exposure to an investigational product as a result of one's 
professional or non-professional occupation. 
Drug interaction is defined as any drug/drug, drug/food, or drug/device interaction.
Unexpected benefit is defined as an unintended therapeutic effect where the results are judged to 
be desirable and beneficial. 

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 102
02 December 2021
Transmission of infectious agents is defined as any suspected transmission of an infected agent 
through an investigational product.
Product complaint is defined as complaints arising from potential deviations in the manufacture, 
packaging, or distribution of the investigational product.  
Counterfeit or falsified medicine: Any investigational product with a false representation of: 
a) its identity, b) its source, or c) its history.
7.7.2.
Instructions for Reporting Special Situations
7.7.2.1.
Instructions for Reporting Pregnancies
The investigator should report pregnancies in female study subjects that are identified after 
initiation of study drug and throughout the study, including the post study drug follow-up period, 
to DIVERSITY_safety@glpg.com using the pregnancy report form 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 terminate a 
pregnancy without medical reasons.
Any premature termination 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 term.
A spontaneous abortion is always considered to be an SAE and will be reported as described in 
Section 7.3. Furthermore, any SAE occurring as an adverse pregnancy outcome post study must 
be reported to DIVERSITY_safety@glpg.com.
The subject should receive appropriate monitoring and care until the conclusion of the 
pregnancy. The outcome should be reported to DIVERSITY_safety@glpg.com using the 
pregnancy outcome report form. If the end of the pregnancy occurs after the study has been 
completed, the outcome should be reported directly to DIVERSITY_safety@glpg.com. 
Pregnancies of female partners of male study subjects exposed to the Sponsor’s or other study 
drugs must also be reported and relevant information should be submitted to 
DIVERSITY_safety@glpg.com using the pregnancy and pregnancy outcome forms within 24 
hours. Monitoring of the subject should continue until the conclusion of the pregnancy. If the end 
of the pregnancy occurs after the study has been completed, the outcome should be reported 
directly to DIVERSITY_safety@glpg.com. 
Refer to Appendix 7 for Pregnancy Precautions, Definition for Female of Childbearing Potential, 
and Contraceptive Requirements.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 103
02 December 2021
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 DIVERSITY_safety@glpg.com within 24 hours of the investigator becoming 
aware of the situation. These reports must consist of situations that involve study drug, but do not 
apply to concomitant medications. 
Special situations involving concomitant medications do not need to be reported on the special 
situations report form; however, special situations that result in AEs due to a 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.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 112
02 December 2021
8.1.2.2.1.
EU-Specific Primary Endpoints for the Cohort B Induction Study 

The proportion of subjects achieving clinical remission by PRO2 at Week 10

The proportion of subjects achieving endoscopic response at Week 10 
8.1.2.3.
Maintenance Study

The proportion of subjects achieving clinical remission by CDAI at Week 58

The proportion of subjects achieving endoscopic response at Week 58
8.1.2.3.1.
EU-Specific Primary Endpoints for the Maintenance Study

The proportion of subjects achieving clinical remission by PRO2 at Week 58

The proportion of subjects achieving endoscopic response at Week 58
8.1.3.
Secondary Endpoints
8.1.3.1.
Cohort A Induction Study
The key secondary end points of Cohort A are:

The proportion of subjects achieving clinical remission by PRO2 at Week 10

The proportion of subjects achieving clinical response by CDAI at Week 10
The other secondary end point of Cohort A is:

PK characteristics for filgotinib and its metabolite GS-829845 
8.1.3.1.1.
EU-Specific Secondary Endpoints for the Cohort A Induction Study 
The EU-specific key secondary end points of Cohort A are:

The proportion of subjects achieving clinical remission by CDAI at Week 10

The proportion of subjects achieving both clinical remission by PRO2 and endoscopic 
response (combined into a single end point on a patient level) at Week 10
The EU-specific other secondary end point of Cohort A is:

PK characteristics for filgotinib and its metabolite GS-829845 

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 113
02 December 2021
8.1.3.2.
Cohort B Induction Study
The key secondary end points of Cohort B are:

The proportion of subjects achieving clinical remission by PRO2 at Week 10

The proportion of subjects achieving clinical response by CDAI at Week 10
The other secondary end point of Cohort B is:

PK characteristics for filgotinib and its metabolite GS-829845 
8.1.3.2.1.
EU-Specific Secondary Endpoints for the Cohort B Induction Study 
The EU-specific key secondary end points of Cohort B are:

The proportion of subjects achieving clinical remission by CDAI at Week 10

The proportion of subjects achieving both clinical remission by PRO2 and endoscopic 
response (combined into a single end point on a patient level) at Week 10
The EU-specific other secondary end point of Cohort B is:

PK characteristics for filgotinib and its metabolite GS-829845 
8.1.3.3.
Maintenance Study
The key secondary end points of the Maintenance Study are:

The proportion of subjects achieving clinical remission by PRO2 at Week 58

The proportion of subjects achieving clinical response by CDAI at Week 58

The proportion of subjects achieving sustained clinical remission by CDAI at Weeks 10 
and 58

The proportion of subjects achieving 6-month corticosteroid-free remission by CDAI at 
Week 58

The proportion of subjects achieving sustained clinical remission by PRO2 at Weeks 10 
and 58

The proportion of subjects achieving 6-month corticosteroid-free remission by PRO2 at 
Week 58
The other secondary end point of the Maintenance Study is:

PK characteristics for filgotinib and its metabolite GS-829845 

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 120
02 December 2021
Laboratory data that are continuous in nature but are less than the LLOQ 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, PRO2 and SES-CD (and components) will be 
described in the statistical analysis plan (SAP).
8.4.
Demographic Data and Baseline Characteristics
Demographic and baseline measurements for each individual study (Cohort A Induction Study, 
Cohort B Induction Study, and Maintenance Study) will be summarized separately by treatment 
group using standard descriptive statistics (n, mean, standard deviation [SD], median, 1st quartile 
[Q1], 3rd quartile [Q3], minimum, maximum) for continuous variables and number and 
percentage of subjects for categorical variables. 
Demographic summaries will include age, sex, race and ethnicity. Baseline characteristics may 
include height, weight, body mass index (BMI), SES-CD score, CDAI score, PRO2 score, 
number of years since diagnosis of CD, concomitant use of oral corticosteroids, concomitant use 
of immunomodulators, 
, and other variables of interest.
8.5.
Efficacy Analysis
8.5.1.
Primary Analyses
For each Induction Study (Cohort A and Cohort B), the primary analysis will compare a 
filgotinib dose group to placebo on the proportion of subjects achieving clinical remission by 
CDAI at Week 10 and the proportion of subjects achieving endoscopic response at Week 10. In 
the EU, for each Induction Study (Cohort A and Cohort B), the primary analysis will compare a 
filgotinib dose group to placebo on the proportion of subjects achieving clinical remission by 
PRO2 at Week 10 and the proportion of subjects achieving endoscopic response at Week 10. 
Similarly, for the Maintenance Study, the primary analysis will compare a filgotinib dose group 
to placebo on the proportion of subjects achieving clinical remission by CDAI at Week 58 and 
the proportion of subjects achieving endoscopic response at Week 58. In the EU, for the 
Maintenance Study, the primary analysis will compare a filgotinib dose group to placebo on the 
proportion of subjects achieving clinical remission by PRO2 at Week 58 and the proportion of 
subjects achieving endoscopic response at Week 58. For a dose group to demonstrate significant 
treatment effect over placebo, statistical significance needs to be achieved on both clinical 
remission by CDAI and endoscopic response end points at significance level that is specified in 
Section 8.5.3. In the EU, for a dose group to demonstrate significant treatment effect over 
placebo, statistical significance needs to be achieved on both clinical remission by PRO2 and 
endoscopic response end points at significance level that is specified in Section 8.5.3. 
CCI

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 121
02 December 2021
The Cochran-Mantel-Haenszel (CMH) approach adjusting for stratification factors will be used 
for hypothesis testing of each primary end point within each study. For calculation of reduction 
from baseline in SES-CD score in the endoscopic response, SES-CD score at screening will be 
used as baseline value. For calculation of CDAI and PRO2 scores, refer to Appendix 4. 
Subjects who do not have sufficient measurements to determine efficacy end points will be 
considered failures (ie, non-responder imputation [NRI]). Sensitivity analyses will be described 
in the SAP.
8.5.2.
Secondary Analyses
The same statistical methods used for testing the primary end points will be utilized for testing 
the key secondary end points in each study (Cohort A Induction Study, Cohort B Induction 
Study, and Maintenance Study) separately. Subjects who do not have sufficient measurements to 
determine efficacy end points will be considered failures (ie, NRI).
8.5.3.
Multiplicity Adjustments
The graphical approach {Bretz 2009} of sequentially rejective Beonferroni-based iterative 
multiple test procedures will be used to control a family-wise type I error rate (FWER) at 5% 
(ie, α = 0.05) for hypothesis testing on co-primary and key secondary end points for each 
individual study (Cohort A Induction Study, Cohort B Induction Study, and Maintenance Study). 
This procedure strongly protects the FWER on all the primary and key secondary end points.
8.5.3.1.
Induction Studies (Cohorts A and B)
The hypotheses to be tested for the induction studies are outlined below. 
The primary null hypotheses to be tested:

H11: The clinical remission by CDAI rate in the filgotinib 200 mg group is equal to the 
clinical remission by CDAI rate in the placebo group at Week 10

H12: The endoscopic response rate in the filgotinib 200 mg group is equal to the endoscopic 
response rate in the placebo group at Week 10

H21: The clinical remission by CDAI rate in the filgotinib 100 mg group is equal to the 
clinical remission by CDAI rate in the placebo group at Week 10

H22: The endoscopic response rate in the filgotinib 100 mg group is equal to the endoscopic 
response rate in the placebo group at Week 10

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 122
02 December 2021
The key secondary null hypotheses to be tested:

H13: The clinical remission by PRO2 rate in the filgotinib 200 mg group is equal to the 
clinical remission by PRO2 rate in the placebo group at Week 10

H14: The clinical response by CDAI rate in the filgotinib 200 mg group is equal to the 
clinical response by CDAI rate in the placebo group at Week 10

H23: The clinical remission by PRO2 rate in the filgotinib 100 mg group is equal to the 
clinical remission by PRO2 rate in the placebo group at Week 10 

H24: The clinical response by CDAI rate in the filgotinib 100 mg group is equal to the 
clinical response by CDAI rate in the placebo group at Week 10
Each co-primary endpoint for filgotinib 200 mg compared with placebo will be tested at 2-sided 
0.05 significance level first. If it fails to reject the null hypothesis for at least one co-primary end 
point, then no further formal testings will be performed. If the null hypotheses for both 
co-primary endpoints are rejected, testing will proceed in two sequences as describe below:

Key secondary end points for filgotinib 200 mg compared with placebo at 2-sided 
0.025 significance level in a sequential order

Each co-primary end point for filgotinib 100 mg compared with placebo at 2-sided 
0.025 significance level. If the null hypotheses for both co-primary end points are rejected, 
then the key secondary end points for filgotinib 100 mg compared with placebo at 2-sided 
0.025 significance level will be tested in a sequential order
If all the null hypotheses within the same sequence are rejected, then the respective alpha can be 
passed on to the other sequence. If an end point fails to reach statistical significance within the 
sequence, then formal testing will stop, and only nominal significance will be reported for the 
remaining end points.
A graphical illustration of the testing strategy for the primary and key secondary hypotheses in 
the Induction Studies is shown in Figure 8-1.
8.5.3.1.1.
EU-Specific Multiplicity Adjustments for the Induction Studies 
(Cohorts A and B)
The EU-specific hypotheses to be tested for the induction studies are outlined below. 

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 123
02 December 2021
The EU-specific primary null hypotheses to be tested:

H11: The clinical remission by PRO2 rate in the filgotinib 200 mg group is equal to the 
clinical remission by PRO2 rate in the placebo group at Week 10

H12: The endoscopic response rate in the filgotinib 200 mg group is equal to the endoscopic 
response rate in the placebo group at Week 10

H21: The clinical remission by PRO2 rate in the filgotinib 100 mg group is equal to the 
clinical remission by PRO2 rate in the placebo group at Week 10

H22: The endoscopic response rate in the filgotinib 100 mg group is equal to the endoscopic 
response rate in the placebo group at Week 10
The EU-specific key secondary null hypotheses to be tested:

H13: The clinical remission by CDAI rate in the filgotinib 200 mg group is equal to the 
clinical remission by CDAI rate in the placebo group at Week 10

H14: The clinical remission by PRO2 and endoscopic response rate (combined into a single 
end point at patient level) in the filgotinib 200 mg group is equal to the clinical remission by 
PRO2 and endoscopic response rate (combined into a single end point at patient level) in the 
placebo group at Week 10

H23: The clinical remission by CDAI rate in the filgotinib 100 mg group is equal to the 
clinical remission by CDAI rate in the placebo group at Week 10

H24: The clinical remission by PRO2 and endoscopic response rate (combined into a single 
end point at patient level) in the filgotinib 100 mg group is equal to the clinical remission by 
PRO2 and endoscopic response rate (combined into a single end point at patient level) in the 
placebo group at Week 10
Each co-primary end point for filgotinib 200 mg compared with placebo will be tested at 2-sided 
0.05 significance level first. If it fails to reject the null hypothesis for at least one co-primary end 
point, then no further formal testings will be performed. If the null hypotheses for both 
co-primary end points are rejected, testing will proceed in two sequences as describe below:

Key secondary end points for filgotinib 200 mg compared with placebo at 2-sided 
0.025 significance level in a sequential order

Each co-primary end point for filgotinib 100 mg compared with placebo at 2-sided 
0.025 significance level. If the null hypotheses for both co-primary end points are rejected, 
then the key secondary end points for filgotinib 100 mg compared with placebo at 2-sided 
0.025 significance level will be tested in a sequential order

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 124
02 December 2021
If all the null hypotheses within the same sequence are rejected, then the respective alpha can be 
passed on to the other sequence. If an end point fails to reach statistical significance within the 
sequence, then formal testing will stop, and only nominal significance will be reported for the 
remaining end points.
A graphical illustration of the testing strategy for the primary and key secondary hypotheses in 
the Induction Studies is shown in Figure 8-1.
Figure 8-1.
Induction Studies (Cohorts A and B): Testing Strategy for the 
Primary and Key Secondary Hypotheses
8.5.3.2.
Maintenance Study
The hypotheses to be tested for the Maintenance Study are outlined below. 
The primary null hypotheses to be tested:

H11: The clinical remission by CDAI rate in the filgotinib 200 mg group is equal to the 
clinical remission by CDAI rate in the placebo group at Week 58

H12: The endoscopic response rate in the filgotinib 200 mg group is equal to the endoscopic 
response rate in the placebo group at Week 58

H21: The clinical remission by CDAI rate in the filgotinib 100 mg group is equal to the 
clinical remission by CDAI rate in the placebo group at Week 58

H22: The endoscopic response rate in the filgotinib 100 mg group is equal to the endoscopic 
response rate in the placebo group at Week 58

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 125
02 December 2021
The key secondary null hypotheses to be tested:

H13: The clinical remission by PRO2 rate in the filgotinib 200 mg group is equal to the 
clinical remission by PRO2 rate in the placebo group at Week 58 

H14: The clinical response by CDAI rate in the filgotinib 200 mg group is equal to the 
clinical response by CDAI rate in the placebo group at Week 58 

H15: The sustained clinical remission by CDAI rate in the filgotinib 200 mg group is equal to 
sustained clinical remission by CDAI rate in the placebo group at Weeks 10 and 58

H16: The 6-month corticosteroid-free remission by CDAI rate in the filgotinib 200 mg group 
is equal to the 6-month corticosteroid-free remission by CDAI rate in the placebo group at 
Week 58

H17: The sustained clinical remission by PRO2 rate in the filgotinib 200 mg group is equal to 
the sustained clinical remission by PRO2 rate in the placebo group at Weeks 10 and 58

H18: The 6-month corticosteroid-free remission by PRO2 rate in the filgotinib 200 mg group 
is equal to 6-month corticosteroid-free remission by PRO2 rate in the placebo group at 
Week 58

H23: The clinical remission by PRO2 rate in the filgotinib 100 mg group is equal to the 
clinical remission by PRO2 rate in the placebo group at Week 58 

H24: The clinical response by CDAI rate in the filgotinib 100 mg group is equal to the 
clinical response by CDAI rate in the placebo group at Week 58 

H25: The sustained clinical remission by CDAI rate in the filgotinib 100 mg group is equal to 
sustained clinical remission by CDAI rate in the placebo group at Weeks 10 and 58

H26: The 6-month corticosteroid-free remission by CDAI rate in the filgotinib 100 mg group 
is equal to the 6-month corticosteroid-free remission by CDAI rate in the placebo group at 
Week 58

H27: The sustained clinical remission by PRO2 rate in the filgotinib 100 mg group is equal to 
the sustained clinical remission by PRO2 rate in the placebo group at Weeks 10 and 58

H28: The 6-month corticosteroid-free remission by PRO2 rate in the filgotinib 100 mg group 
is equal to 6-month corticosteroid-free remission by PRO2 rate in the placebo group at 
Week 58

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 126
02 December 2021
Each co-primary end point for filgotinib 200 mg compared with placebo will be tested at 2-sided 
0.05 significance level first. If it fails to reject the null hypothesis for at least one co-primary end 
point, then no further formal testings will be performed. If the null hypotheses for both 
co-primary end points are rejected, testing will proceed in two sequences as describe below:

Key secondary end points for filgotinib 200 mg compared with placebo at 2-sided 
0.025 significance level in a sequential order

Each co-primary end point for filgotinib 100 mg compared with placebo at 2-sided 
0.025 significance level. If the null hypotheses for both co-primary end points are rejected, 
then the key secondary end points for filgotinib 100 mg compared with placebo at 2-sided 
0.025 significance level will be tested in a sequential order
If all the null hypotheses within the same sequence are rejected, then the respective alpha can be 
passed on to the other sequence. If an end point fails to reach statistical significance within the 
sequence, then formal testing will stop and only nominal significance will be reported for the 
remaining endp oints.
Graphical illustrations for the testing strategies for the primary and key secondary hypotheses in 
the Maintenance Study are shown in Figure 8-2.  

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 127
02 December 2021
Figure 8-2.
Maintenance Study: Testing Strategy for the Primary and Key 
Secondary Hypotheses
8.5.3.2.1.
EU-Specific Multiplicity Adjustments for the Maintenance Study
The EU-specific hypotheses to be tested for the Maintenance Study are outlined below. 

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 128
02 December 2021
The EU-specific primary null hypotheses to be tested:

H11: The clinical remission by PRO2 rate in the filgotinib 200 mg group is equal to the 
clinical remission by PRO2 rate in the placebo group at Week 58

H12: The endoscopic response rate in the filgotinib 200 mg group is equal to the endoscopic 
response rate in the placebo group at Week 58

H21: The clinical remission by PRO2 rate in the filgotinib 100 mg group is equal to the 
clinical remission by PRO2 rate in the placebo group at Week 58

H22: The endoscopic response rate in the filgotinib 100 mg group is equal to the endoscopic 
response rate in the placebo group at Week 58
The EU-specific key secondary null hypotheses to be tested:

H13: The clinical remission by CDAI rate in the filgotinib 200 mg group is equal to the 
clinical remission by CDAI rate in the placebo group at Week 58

H14: The sustained clinical remission by PRO2 rate in the filgotinib 200 mg group is equal to 
sustained clinical remission by PRO2 rate in the placebo group at Weeks 10 and 58 

H15: The clinical remission by PRO2 and endoscopic response rate (combined into a single 
end point at patient level) in the filgotinib 200 mg group is equal to the clinical remission by 
PRO2 and endoscopic response rate (combined into a single end point at patient level) in the 
placebo group at Week 58

H16: The 6-month corticosteroid-free remission by PRO2 rate in the filgotinib 200 mg group 
is equal to the 6-month corticosteroid-free remission by PRO2 rate in the placebo group at 
Week 58

H23: The clinical remission by CDAI rate in the filgotinib 100 mg group is equal to the 
clinical remission by CDAI rate in the placebo group at Week 58

H24: The sustained clinical remission by PRO2 rate in the filgotinib 100 mg group is equal to 
sustained clinical remission by PRO2 rate in the placebo group at Weeks 10 and 58

H25: The clinical remission by PRO2 and endoscopic response rate (combined into a single 
end point at patient level) in the filgotinib 100 mg group is equal to the clinical remission by 
PRO2 and endoscopic response rate (combined into a single end point at patient level) in the 
placebo group at Week 58

H26: The 6-month corticosteroid-free remission by PRO2 rate in the filgotinib 100 mg group 
is equal to the 6-month corticosteroid-free remission by PRO2 rate in the placebo group at 
Week 58

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 129
02 December 2021
Each co-primary end point for filgotinib 200 mg compared with placebo will be tested at 2-sided 
0.05 significance level first. If it fails to reject the null hypothesis for at least one co-primary end 
point, then no further formal testings will be performed. If the null hypotheses for both 
co-primary end points are rejected, testing will proceed in two sequences as describe below:

Key secondary end points for filgotinib 200 mg compared with placebo at 2-sided 
0.025 significance level in a sequential order

Each co-primary end point for filgotinib 100 mg compared with placebo at 2-sided 
0.025 significance level. If the null hypotheses for both co-primary end points are rejected, 
then the key secondary end points for filgotinib 100 mg compared with placebo at 2-sided 
0.025 significance level will be tested in a sequential order
If all the null hypotheses within the same sequence are rejected, then the respective alpha can be 
passed on to the other sequence. If an end point fails to reach statistical significance within the 
sequence, then formal testing will stop and only nominal significance will be reported for the 
remaining end points.
Graphical illustrations for the testing strategies for the EU-specific primary and key secondary 
hypotheses in the Maintenance Study are shown in Figure 8-3.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 132
02 December 2021
8.6.2.
Adverse Events
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). System Organ Class (SOC), High-Level Group Term (HLGT), High-Level Term 
(HLT), Preferred Term (PT), and Lower-Level Term (LLT) will be attached to the clinical 
database.
Treatment-Emergent Adverse Events (TEAEs) are defined as 1 or both of the following:
Induction Studies (Cohorts A and B)

Any AEs with an onset date of on or after the study drug start date for each Induction study 
(Day 1) and up to:
30 days after last dose date, for subjects who prematurely discontinued study drug prior 
to or at Week 10 OR
Week 10, for subjects who completed Week 10 dosing and continued on study drug

Any AEs leading to premature discontinuation of study drug prior to Week 10.
Maintenance Study

Any AEs with an onset date of on or after the study drug start date for the Maintenance study 
(Week 11) and up to 30 days after permanent discontinuation of study drug.

Any AEs leading to premature discontinuation of study drug after first dose of study drug 
administration for the Maintenance study (Week 11).
Overall (Induction and Maintenance)

Any AEs with an onset date of on or after the study drug start date for the entire study 
(Day 1) and up to 30 days after permanent discontinuation of study drug.

Any AEs leading to premature discontinuation of study drug.
Summaries (number and percentage of subjects) of TEAEs by SOC and PT will be provided by 
treatment group. TEAEs will also be summarized by relationship to study drug and severity. In 
addition, TEAEs leading to premature discontinuation of study drug will be summarized and 
listed.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 135
02 December 2021
The sample size was chosen to ensure that a clinically meaningful difference in both clinical 
remission rate by CDAI and endoscopic response rate at Week 58 could be detected when 
comparing filgotinib 200 mg to placebo in the Maintenance Study.
A sample size of 60 subjects in the placebo group and 120 subjects in the filgotinib group at the 
same dose level as the induction dose will provide an overall 94% power for a filgotinib 200 mg 
comparison to placebo at a 2-sided 0.05 significance level to detect a treatment difference of 
30% in maintenance clinical remission rate by CDAI at Week 58 and maintenance endoscopic 
response rate at Week 58 (50% on filgotinib 200 mg and 20% on placebo). Since each end point 
needs to achieve statistical significance, the overall power of 94% is calculated as the product of 
the two individual powers based on each end point.
8.9.2.1.
EU-Specific Sample Size for the Maintenance Study
The sample size was chosen to ensure that a clinically meaningful difference in both clinical 
remission rate by PRO2 at Week 58 and endoscopic response rate at Week 58 could be detected 
when comparing filgotinib 200 mg to placebo in the Maintenance Study.
A sample size of 60 subjects in the placebo group and 120 subjects in the filgotinib group at the 
same dose level as the induction dose will provide an overall 94% power for filgotinib 200 mg 
comparison to placebo at a 2-sided 0.05 significance level to detect a treatment difference of 
30% in maintenance clinical remission rate by PRO2 at Week 58 and maintenance endoscopic 
response rate at Week 58 (50% on filgotinib 200 mg and 20% on placebo). Since each end point 
needs to achieve statistical significance, the overall power of 94% is calculated as the product of 
the two individual powers based on each end point.
8.10.
Data Monitoring Committee
An external DMC will review the progress of the study and perform interim reviews of safety 
data and provide recommendation to the Sponsor 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 initial meeting will occur after approximately 100 subjects reach Week 10 in Cohorts A and 
B combined. Following this, subsequent meetings will occur approximately once every 4 months 
or at a frequency determined by the DMC. 
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 the Sponsor regarding future conduct of the study, 
including possible early study termination, the Sponsor retains final decision-making authority 
on all aspects of the study. If the DMC recommends stopping the study for lack of efficacy, the 
Sponsor’s Executive team will be unblinded to confirm the DMC recommendation.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 136
02 December 2021
Cohorts A and B End-of-Induction Analysis
Efficacy and safety data will be evaluated by the DMC after all subjects in both cohorts complete 
Week 10 dosing (or prematurely discontinue study drug but complete post-treatment 
assessments).
Both cohorts will be examined independently.
Taking into account data in Cohort A and Cohort B, if ALL the following 4 criteria are met for 
BOTH cohorts, the DMC may recommend overall study discontinuation. 

2-sided p-value for filgotinib 200 mg vs placebo comparison is larger than 0.05 on clinical 
remission by CDAI at Week 10

2-sided p-value for filgotinib 100 mg vs placebo comparison is larger than 0.05 on clinical 
remission by CDAI at Week 10

2-sided p-value for filgotinib 200 mg vs placebo comparison is larger than 0.05 on 
endoscopic response at Week 10

2-sided p-value for filgotinib 100 mg vs placebo comparison is larger than 0.05 on 
endoscopic response at Week 10
If any of the above criteria is not met from either cohort, the DMC may recommend that the 
study continue without modification.
Ad-hoc DMC Meetings
An ad-hoc DMC meeting may be triggered by the following conditions:

≥ 2 subjects develop the same (by preferred term) related, Grade 4, unexpected AE in the 
infections and infestations system organ class

≥ 2 subjects develop any related, Grade 4, thromboembolic event that has 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
8.11.
Cardiovascular Safety Endpoint Adjudication Committee 
An independent adjudication committee will be formed to periodically review and adjudicate all 
potential major adverse cardiovascular events (MACE) and thromboembolic events in a blinded 
manner.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 137
02 December 2021
The Cardiovascular Safety End point Adjudication Committee (CVEAC)’s specific activities 
will be governed by a mutually agreed charter, which will define the CVEAC’s membership, 
conduct, and meeting schedule.
The following events will be adjudicated and classified by the CVEAC:

Cardiovascular death

Myocardial infarction

Stroke 

Arterial thromboembolism

Venous thromboembolism (eg, deep venous thrombosis, pulmonary embolism)
Further details will be specified in the CVEAC Charter.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 138
02 December 2021
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 EU Clinical Trials 
Directive 2001/20/EC and GCP Directive 2005/28/EC.
The investigator will ensure adherence to the basic principles of GCP, 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 the Sponsor, 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 the Sponsor 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/Independent Ethics Committee 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.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 139
02 December 2021
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 
investigator must use the most current IRB/IEC approved consent form for documenting written 
informed consent. Each informed consent (or assent as applicable) will be appropriately signed 
and dated by the subject or the subject’s legally authorized representative and the person 
conducting the consent discussion, and also by an impartial witness if required by IRB/IEC or 
local requirements. The consent form will inform subjects about 
 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 the Sponsor, including but not limited 
to the IB, this protocol, eCRF, the IMP, and any other study information, remain the sole and 
exclusive property of the Sponsor 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 the 
Sponsor. 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, eCRF 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.
CCI

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 140
02 December 2021
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

Participation in study (including study number);

Study discussed and date of informed consent;

Dates of all visits;

Documentation that protocol specific procedures were performed;

Results of efficacy parameters, as required by the protocol;

Start and end date (including dose regimen) of IMP, including dates of dispensing and return;

Record of all AEs and other safety parameters (start and end date, and including causality 
and severity);

Concomitant medication (including start and end date, dose if relevant; dose changes);

Date of study completion and reason for early discontinuation, if it occurs.
All clinical study documents must be retained by the investigator until at least 2 years or 
according to local laws, whichever is longer, after the last approval of a marketing application in 
an ICH region (ie, US, Europe, or Japan) and until there are no pending or planned marketing 
applications in an ICH region; or, if no application is filed or if the application is not approved 
for such indication, until 2 years after the investigation is discontinued and regulatory authorities 
have been notified. Investigators may be required to retain documents longer if specified by 
regulatory requirements, by local regulations, or by an agreement with the Sponsor. The 
investigator must notify the Sponsor before destroying any clinical study records.
Should the investigator wish to assign the study records to another party or move them to another 
location, the Sponsor 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 the Sponsor 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.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 141
02 December 2021
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 electronic data capture (EDC) system. Original entries as well as any 
changes to data fields will be stored in the audit trail of the system. Prior to database lock (or any 
interim time points as described in the clinical data management plan), the investigator will use 
his/her log in credentials to confirm that the forms have been reviewed, and that the entries 
accurately reflect the information in the source documents. The eCRF captures the data required 
per the protocol schedule of events and procedures.  System-generated or manual queries will be 
issued to the investigative site staff as data discrepancies are identified by the monitor or the data 
management 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, the 
Sponsor 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 the Sponsor, 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 the Sponsor site files. If the site does not have 
acceptable procedures in place, arrangements will be made between the site and the Sponsor 
(or the Sponsor’s 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 the Sponsor.
The study monitor will review IMP supplies and associated records at periodic intervals.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 142
02 December 2021
9.1.8.
Inspections
The investigator will make available all source documents and other records for this trial to the 
Sponsor’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.
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 the Sponsor. 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). The 
Sponsor will ensure that the report meets the standards set out in the ICH Guideline for Structure 
and Content of CSRs (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 the Sponsor 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 the Sponsor 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 the Sponsor’s confidential 
information (See Section 9.1.4).

The investigator will comply with the Sponsor’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.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 143
02 December 2021
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, the Sponsor 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.
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 the Sponsor 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 medical monitor immediately. The investigator agrees to provide 
to representatives of a regulatory agency or the Sponsor 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, the Sponsor and the 
investigator will assure that adequate consideration is given to the protection of the subjects’ 
interests.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 144
02 December 2021
10.
REFERENCES
Baumgart DC, Sandborn WJ. Crohn's disease. Lancet 2012;380 (9853):1590-605.
Bretz F, Maurer W, Brannath W, Posch M. A Graphical Approach to Sequentially Rejective 
Multiple Test Procedures. Stat Med 2009;28:586-604.
Cheifetz AS. Management of active Crohn disease. JAMA 2013;309 (20):2150-8.
Daperno M, D'Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, et al. Development and 
validation of a new, simplified endoscopic activity score for Crohn's disease: the 
SES-CD. Gastrointestinal endoscopy 2004;60 (4):505-12.
Dignass A, Van Assche G, Lindsay JO, Lemann M, Soderholm J, Colombel JF, et al. The second 
European evidence-based Consensus on the diagnosis and management of Crohn's 
disease: Current management. Journal of Crohn's & colitis 2010;4 (1):28-62.
Ferrante M, Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, et al. 
Validation of endoscopic activity scores in patients with Crohn's disease based on 
a post hoc analysis of data from SONIC. Gastroenterology 2013;145 (5):978-86 
e5.
Fukunaga K, Matsumoto T. Current status and future perspectives of leukocytapheresis for 
inflammatory bowel disease. J Gastroenterol Hepatol 2012;27 (6):997-1003.
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.
Korzenik JR. Investigational therapies in the medical management of Crohn disease. Available 
at: www.uptodate.com/contents/4076. UpToDate 2016.
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.
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.
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.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 145
02 December 2021
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.
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.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV 
Amendment 9
CONFIDENTIAL
Page 146
02 December 2021
11.
APPENDICES
Appendix 1.
Investigator Signature Page
Appendix 2.
Study Procedures Table
Appendix 3.
Management of Clinical and Laboratory Adverse Events
Appendix 4.
Crohn’s Disease Activity Index (CDAI) and Patient Reported Outcomes – 2 items 
(PRO2)
Appendix 5.
Simple Endoscopic Score for Crohn’s Disease (SES-CD)
Appendix 6.
CTCAE Grading Scale for Severity of Adverse Events
Appendix 7.
Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Requirements
Appendix 8.
Clinical Laboratory Assessment Table

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV
Amendment 9
CONFIDENTIAL
Page 148
02 December 2021
Appendix 2.
Study Procedures Table
Period
Screen
Treatment
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
PTxa
ET
Week
0
2
4
6
10
11
14
17
20
23
26
30
34
38
42
46
50
54
58
Study Day
-30 to -1
1
15
29
43
71
78
99
120
141
162
183
211
239
267
295
323
351
379
407
Visit Window 
(±)
±3
±3
±3
±2
±3
±5
±5
±5
±5
±5
±5
±5
±5
±5
±5
±5
±5
±3
±3
Written 
Informed 
Consent 
X
Medical History 
& 
Demographics
X
Crohn’s Disease 
& Treatment 
History
X
12-lead ECG
X
X
X
X
Xb
Review of 
Inclusion/
Exclusion 
Criteria
X
X
Complete 
Physical Examc
X
Symptom-
directed Examc 
(as needed)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant 
Medications 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Randomization 
X
X
CCI

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV
Amendment 9
CONFIDENTIAL
Page 149
02 December 2021
Period
Screen
Treatment
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
PTxa
ET
Week
0
2
4
6
10
11
14
17
20
23
26
30
34
38
42
46
50
54
58
Study Day
-30 to -1
1
15
29
43
71
78
99
120
141
162
183
211
239
267
295
323
351
379
407
Visit Window 
(±)
±3
±3
±3
±2
±3
±5
±5
±5
±5
±5
±5
±5
±5
±5
±5
±5
±5
±3
±3
Study Drug 
Dispensing
X
X
X
X
X
X
X
X
X
Ileocolonoscopy 
(with Biopsies)d
X
X
X
Local 
Endoscopic 
Assessmente
X
X
X
SES-CD
X
X
X
CDAIf
X
X
X
X
X
X
X
X
X
X
X
X
X
PRO2f
X
X
X
X
X
X
X
X
X
X
X
X
X
Abdominal pain 
assessmentg 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Anchor 
Questions
X
Patient Global 
Impression  
Scalesh
X
X
X
eDiary 
instruction & 
reviewi
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Stool for C. diff 
toxin, 
pathogenic 
E. coli, 
Salmonella spp, 
Shigella  spp, 
Campylobacter 
spp or Yersinia 
spp testing j
X
Stool O&P j 
X

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV
Amendment 9
CONFIDENTIAL
Page 150
02 December 2021
Period
Screen
Treatment
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
PTxa
ET
Week
0
2
4
6
10
11
14
17
20
23
26
30
34
38
42
46
50
54
58
Study Day
-30 to -1
1
15
29
43
71
78
99
120
141
162
183
211
239
267
295
323
351
379
407
Visit Window 
(±)
±3
±3
±3
±2
±3
±5
±5
±5
±5
±5
±5
±5
±5
±5
±5
±5
±5
±3
±3
Urine drug 
screenk
X
Urinalysis
X
X
X
X
Pregnancy Testl
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
TBm 
X
Chest x-ray n
X
HBV, HCV, 
HIV screeningo
X
HBV DNA 
monitoring 
(Japan)p
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HBV DNA 
monitoring 
(other regions)p
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Lipid profile 
(fasting)q
X
X
X
X
X
Serum 
immunoglobulin
X
X
X
X
X
X
X
CCI
CCI

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV
Amendment 9
CONFIDENTIAL
Page 151
02 December 2021
Period
Screen
Treatment
Follow-Up
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
PTxa
ET
Week
0
2
4
6
10
11
14
17
20
23
26
30
34
38
42
46
50
54
58
Study Day
-30 to -1
1
15
29
43
71
78
99
120
141
162
183
211
239
267
295
323
351
379
407
Visit Window 
(±)
±3
±3
±3
±2
±3
±5
±5
±5
±5
±5
±5
±5
±5
±5
±5
±5
±5
±3
±3
Blood 
TCR/BCR 
repertoire 
sampler
X
X
X
X
X
PK collection 
(sparse) s
X
X
X
X
PK substudyu
X
CCI
CCICCI

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV
Amendment 9
CONFIDENTIAL
Page 153
02 December 2021
Appendix 3.
Management of Clinical and Laboratory Adverse Events
Grade 1
Grade 4
Grade 3
Grade 2
May continue 
dosing at the 
discretion of the 
investigator
Repeat lab to 
confirm toxicity 
grade
Repeat lab to 
confirm toxicity
grade
If confirmed and possibly and/or probably related to 
investigational medicinal products:
1.
Withhold investigational medicinal products until 
Grade 2
2.
Restart all investigational medicinal products at full dose
If confirmed and unrelated to 
investigational medicinal 
products, dosing may continue at 
the discretion of the investigator
If confirmed and 
possibly or probably 
related to 
investigational 
medicinal products, 
discontinue 
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 confirmed and possibly or 
probably related to investigational medicinal products, 
discontinue all investigational medicinal products dosing 
permanently
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-419-3895
Final
Galapagos NV
Amendment 9
CONFIDENTIAL
Page 154
02 December 2021
Appendix 4.
Crohn’s Disease Activity Index (CDAI) and Patient Reported 
Outcomes – 2 items (PRO2)
The Crohn’s Disease Activity Index (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
{Daperno 2004}
Each PRO2 score will be rounded to the nearest integer for determination of eligibility and calculation of end points.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV
Amendment 9
CONFIDENTIAL
Page 155
02 December 2021
Appendix 5.
Simple Endoscopic Score for Crohn’s Disease (SES-CD)
Score
Variables
0
1
2
3
Size of ulcers (cm)
None
Aphthous ulcers
(diameter 0.1-.05)
Large ulcers
(diameter 0.5-2)
Very large ulcers
(diameter > 2)
Ulcerated Surface (%)
None
< 10
10-30
> 30
Affected surface (%)
Unaffected 
segment
< 50
50-75
> 75
Presence of narrowings
None
Single,
can be passed
Multiple,
can be passed
Cannot be passed
*
Total SES-CD: sum of the values of the 4 variables for the 5 bowel segments. Values are given to each variable and for 
every examined bowel segment (eg, rectum, left colon, transverse colon, right colon, and ileum)
{Daperno 2004}

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV
Amendment 9
CONFIDENTIAL
Page 156
02 December 2021
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-419-3895
Final
Galapagos NV
Amendment 9
CONFIDENTIAL
Page 157
02 December 2021
Appendix 7.
Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Requirements
The administration of filgotinib in embryofetal 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 coadministration with filgotinib did not alter the pharmacokinetics of 
representative hormonal contraceptives, levonorgestrel/ethinyl estradiol.  

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV
Amendment 9
CONFIDENTIAL
Page 158
02 December 2021
For female subjects, hormonal contraceptives will be permitted as a form of contraception when 
used in conjunction with a barrier method (preferably a male condom). For male subjects, male 
condom should be used; for their female partners of childbearing potential, an accepted 
contraceptive method should also be considered. Details are outlined below.
Please refer to the latest version of the filgotinib IB for additional information.
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)

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV
Amendment 9
CONFIDENTIAL
Page 159
02 December 2021
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

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.

Filgotinib
Protocol GS-US-419-3895
Final
Galapagos NV
Amendment 9
CONFIDENTIAL
Page 160
02 December 2021
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 confirmatory serum pregnancy test in 
clinic.