Clinical trial NCT02065700
Conditions: Rheumatoid Arthritis
Keywords: Methotrexate insufficient responders
Sponsor: Galapagos NV
Start date: 2014-02-25; Completion date: 2023-01-19
Enrollment: 739 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of the study was to evaluate the long-term safety and tolerability of filgotinib (formerly GLPG0634) for the treatment of rheumatoid arthritis.

Participants were enrolled in this open-label long-term follow-up study after they had completed one of the two core studies, GLPG0634-CL-203 (DARWIN1) (NCT01888874) or GLPG0634-CL-204 (DARWIN2) (NCT01894516), and were evaluated for any side effects that might have occured (long-term safety and tolerability) when taking filgotinib. During the course of the study, participants were also examined for long-term effects of filgotinib administration on disease activity (efficacy), participant's disability, fatigue, and quality of life.

Detailed description:

Arms: arm 1: Participants in Study GLPG0634-CL-203 (NCT01888874) were rolled-over to receive an oral dose of filgotinib at a daily dose of 200 milligrams (mg) in this extension study, with the exception of male participants in the United States (US) who were limited to a daily dose of 100 mg due to a Food and Drug Administration (FDA) requirement based on a non-clinical finding. Treatment was administered until marketing, local (if applicable) regulatory and/or pertinent local reimbursement approval.

In case of intolerance or for safety reasons, and as per investigator's discretion, a daily dose of filgotinib 200 mg could be decreased to 100 mg per day, and later returned to 200 mg per day after the reasons for decreasing the dose were resolved. arm 2: Participants from Study GLPG0634-CL-204 (NCT01894516) were rolled-over to receive oral dose of filgotinib tablet at 200 mg once daily (q.d) in this extension study. Treatment was administered until marketing, local (if applicable) regulatory and/or pertinent local reimbursement approval.

Participants started the study with the same dose level (filgotinib 200 mg per day) and in case of intolerance or safety reasons and as per investigator's discretion, the daily dose of filgotinib was decreased to 100 mg q.d and was returned to 200 mg per day after the reasons for decreasing the dose had resolved and at the investigator's discretion.
Interventions: intervention 1: Filgotinib
Intervention descriptions: intervention 1: Administered as Oral Tablets

Protocol documents:
Prot_000.pdf: 
Generaal De Wittelaan L11 A3
2800 Mechelen
Belgium
PROTOCOL AMENDMENT SUMMARY OF CHANGES
PROTOCOL AMENDMENT 4
STUDY GLPG0634-CL-205
A multicenter, open-label, long-term follow-up safety and efficacy study of GLPG0634 
treatment in subjects with moderately to severely active rheumatoid arthritis
Original Protocol Date:
23 August 2013
Amendment 1 Date:
13 March 2014
Amendment 2 Date:
07 October 2016
Amendment 3 Date:
15 March 2018
Amendment 4 Date:
13 May 2021
Rationale:
Herein is a summary of the major changes made to the Protocol 
Amendment 3, dated 15 March 2018 and reflected in the Protocol 
Amendment 4, dated 13 May 2021.
The purpose of Protocol Amendment 4, dated 13 May 2021 is as follows:

To change sponsorship from Gilead Sciences, Inc. to Galapagos NV
Additional formatting and grammatical updates and corrections were made 
throughout the document, which are not explicitly outlined in the changes 
below. New and updated text is indicated by bold italicization and deleted 
text by strikethrough.


Jyseleca® (filgotinib)
Protocol GLPG0634-CL-205
Final
Galapagos NV
Amendment 4 Summary of Changes
CONFIDENTIAL
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13 May 2021
Global 
Changes:

Contact details have been updated due to changes in Medical Monitor, 
Study Personnel, and the contract research organization 
 

Safety monitoring components, including information for the Data Safety 
Monitoring Board, were updated to align with current practices and 
safety standards.

Clarification was made to a study drug discontinuation criterion 
regarding serious infections.

Information regarding packaging, labelling, and distribution was updated 
to align with change in sponsorship.

Administrative, editorial, and formatting updates, changes, corrections, 
and clarifications were made, where appropriate, throughout the protocol.
Section:
Section 6.5 Risk/Benefit Assessment for the Study, Section 8.5 Data Safety 
Monitoring Board, Section 8.9.1.5 Interim Analyses
Original 
Text:
A Data Safety Monitoring Board (DSMB) consisting of independent experts 
will be convened to periodically review the accumulating safety data for the 
study and provide a recommendation on study continuation or early 
termination in case there is a concern regarding safety. The specific 
responsibilities and composition of the DSMB are outlined in a separate 
document, the DSMB Charter. Also the details of timing of the meetings and 
outputs provided for the meetings are referenced in this separate DSMB 
Charter.
Revised Text:
A Data Safety Monitoring Board (DSMB) consisting of independent experts 
will be was convened to periodically review the accumulating safety data for 
the study and provide a recommendation on study continuation or early 
termination in case there is a concern regarding were safety concerns. The 
specific responsibilities and composition of the DSMB are were outlined in a 
separate document, the DSMB Charter. Also As of 01 April 2021, the details 
of timing independent DSMB reviews were discontinued as ongoing review 
of the meetings safety and outputs provided for efficacy data by the 
sponsor’s clinical study team was considered sufficient by the meetings are 
referenced in this separate DSMB Charter sponsor, based on the current 
development status of filgotinib and the open-label design of the study..
Rationale:
Text was added to clarify that the DSMB have performed their final review 
and the DSMB reviews were discontinued.












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3
Synopsis
Protocol Number:
GLPG0634-CL-205
Title:
A multicenter, open-label, long-term follow-up safety and 
efficacy study of filgotinib treatment in subjects with 
moderately to severely active rheumatoid arthritis
Test Drug/Investigational 
Product:
Filgotinib (GS-6034, GLPG0634)
Number of Study 
Centers:
International multicenter. 116 sites.
Phase:
2
Objectives:
The primary objective is to evaluate the long-term safety 
and tolerability of filgotinib for the treatment of 
rheumatoid arthritis (RA).
The secondary objectives are to evaluate the long-term 
efficacy of filgotinib and to evaluate the long-term 
effects of filgotinib administration on subject’s disability, 
fatigue, and quality of life.
Study Design:
This will be an open-label, long-term follow-up safety and 
efficacy study in subjects with RA. Subjects will be 
enrolled in the study after they have completed one of the 
2 core 
studies 
(GLPG0634-CL-203 
or 
GLPG0634-CL-204) if, in the opinion of the investigator, 
they will continue to benefit from treatment in the 
extension study. Subjects will start the study at the same 
dose level (filgotinib 200 mg per day), administered in the 
same dosing regimen (frequency of intake of active IMP) 
as during the preceding core study (200 mg once daily 
[q.d.] or 100 mg twice daily [b.i.d.]). 
Number of Subjects: 
739 subjects 


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Treatment:
All subjects will start the study at the same dose level 
(filgotinib 200 mg per day) either as 200 mg q.d. or as 
100 mg b.i.d. The investigator may decide to decrease 
the daily dose of filgotinib to 100 mg q.d. in case of 
intolerance or for safety reasons. Subjects will return to 
filgotinib 200 mg per day after the reasons for decreasing 
the dose have resolved, and at the investigator’s 
discretion. Subjects can also continue filgotinib 100 mg 
q.d. when deemed necessary by the investigator.
Study Duration:
Ongoing until marketing, local (if applicable) regulatory 
and/or pertinent local reimbursement approval.
Study Population:
Main inclusion criteria: 

Male or female subjects who are ≥18 years of age, 
having completed one of the qualifying core studies 
(GLPG0634-CL-203 or GLPG0634-CL-204) and, 
who in the opinion of the investigator, will continue to 
benefit from treatment in the extension study.
Main exclusion criteria: 

Subjects who have been prematurely withdrawn from 
one of the 2 core studies (GLPG0634-CL-203 and 
GLPG0634-CL-204), for any reason including 
fulfilling the individual stopping criteria. 

Subjects who are deemed not to be benefiting from 
the 
study 
medication 
based 
upon 
lack 
of 
improvement or worsening of their symptoms. Local 
guidelines for subject treatment to be followed. 

Subjects with persistent abnormal laboratory values 
associated with the use of the study medication 
(including but not limited to hematology, liver and 
renal function values) during one of the 2 core 
studies (GLPG0634-CL-203 or GLPG0634-CL-204), 
according to the investigator’s clinical judgment.

Subjects with diagnosis since the inclusion to 
GLPG0634-CL-203 or GLPG0634-CL-204 core 
studies of rheumatic autoimmune disease or 
inflammatory joint disease other than RA, except for 
secondary Sjögren’s syndrome.
Primary Endpoint:
Safety and tolerability of long-term dosing of filgotinib 
200 mg q.d. and 100 mg b.i.d.


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Secondary Endpoints:
Evolution in the percentage of subjects achieving 
American College of Rheumatology (ACR)20, ACR50, 
ACR70, and ACR-N responses; European League 
Against Rheumatism (EULAR) responses; ACR/EULAR 
remission, clinical disease activity index (CDAI), 
simplified disease activity index (SDAI), and the 
disease-activity score based on 28 joints (DAS28 c-
reactive protein [CRP]) every 12 weeks or until the Final 
Visit or the Early Discontinuation Visit (EDV). Change 
from Baseline in the Quality of Life (functional 
assessment of chronic illness therapy [FACIT] fatigue 
scale and 36-item short form health survey [SF-36] 
scores) every 48 weeks or until the Final Visit or the EDV.
Safety Analysis:
The safety analysis will be performed for all subjects who 
used the study medication at least once in this study. 
Assessment of treatment-emergent adverse events, and 
of changes from Baseline in laboratory parameters, vital 
signs, physical examination, and electrocardiograms.
Efficacy Analysis:
ACR20, ACR50, ACR70, ACR-N, EULAR response, and 
ACR/EULAR remission, DAS28(CRP), components of 
the ACR, and DAS28, CDAI, SDAI, and Quality of Life 
data (FACIT fatigue scale and SF-36 questionnaire) at 
each post dosing visit (as appropriate) will be analyzed 
descriptively. Changes from Baseline will be examined to 
check for evolution over time in treatment effect. 


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4
Table of Contents
1
Protocol Approval Signatures........................................................................2
2
Study Personnel ..............................................................................................3
3
Synopsis...........................................................................................................4
4
Table of Contents ............................................................................................7
LIST OF TABLES ...........................................................................................................9
5
List of Abbreviations and Definition of Terms............................................10
6
Introduction....................................................................................................12
6.1
Rheumatoid Arthritis.....................................................................................12
6.2
Background on Filgotinib.............................................................................13
6.3
Background - Pre-clinical Studies ...............................................................13
6.3.1
Physical, Chemical and Pharmaceutical Properties and 
Formulations ...................................................................................13
6.3.2
Nonclinical Pharmacology ..............................................................14
6.3.2.1
Primary and Secondary Pharmacology ..........................................14
6.3.2.2
Safety Pharmacology......................................................................14
6.3.3
Nonclinical Pharmacokinetics and Product Metabolism .................14
6.3.4
Nonclinical Toxicology ....................................................................15
6.4
Clinical Trials of Filgotinib............................................................................15
6.5
Risk/Benefit Assessment for the Study ......................................................20
6.6
Rationale for the Study .................................................................................21
6.7
Rationale of Choice of the Dose and Dosing Interval................................22
7
Study Objectives ...........................................................................................24
7.1
Primary Objective..........................................................................................24
7.2
Secondary Objectives...................................................................................24
8
Investigational Plan.......................................................................................25
8.1
Overall Study Design and Plan ....................................................................25
8.2
Discussion of Study Design.........................................................................26
8.3
Selection of Study Population......................................................................27
8.3.1
Number of Planned Subjects ..........................................................27
8.3.2
Inclusion Criteria .............................................................................27
8.3.3
Exclusion Criteria............................................................................27


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8.4
Criteria for Interruption or Discontinuation of Study Treatment ..............28
8.4.1
Study Drug Interruption Considerations:.........................................28
8.4.2
Study Drug Discontinuation Considerations: ..................................29
8.5
Data Safety Monitoring Board......................................................................31
8.5.1
Cardiovascular Endpoint Adjudication Committee..........................32
8.6
Investigational Products...............................................................................32
8.6.1
Investigational Products Administered............................................32
8.6.2
Identity of Investigational Products.................................................32
8.6.3
Packaging, Labelling and Distribution.............................................33
8.6.4
Method of Assigning Subjects to Treatment Groups ......................33
8.6.5
Selection of Doses in the Study......................................................34
8.6.6
Selection and Timing of Dose for Each Subject .............................34
8.6.7
Blinding ...........................................................................................34
8.6.8
Prior and Concomitant Therapy......................................................34
8.6.9
Treatment Compliance and Drug Accountability ............................37
8.7
Study Procedures..........................................................................................37
8.7.1
Pre-treatment..................................................................................37
8.7.1.1
Entry Visit (Extension Visit 1, Day -1) .............................................37
8.7.2
Treatment Period ............................................................................38
8.7.2.1
Quarterly Evaluation Visit (QEV) ....................................................38
8.7.2.2
Annual Visit (AV).............................................................................39
8.7.2.3
Final Visit or Early Discontinuation Visit (EDV)...............................39
8.7.3
Follow-up Visit ................................................................................40
8.7.4
Duration of Treatment.....................................................................41
8.8
Efficacy and Safety Variables.......................................................................41
8.8.1
Efficacy and Safety Measurements Assessed and Flow 
Chart ...............................................................................................41
8.8.1.1
Efficacy Assessments.....................................................................41
8.8.1.2
Safety Assessments .......................................................................43
8.8.1.3
Flow Chart ......................................................................................50
8.8.2
Appropriateness of Measurements.................................................52
8.9
Statistical Methods........................................................................................52
8.9.1
Statistical and Analytical Plans .......................................................52
8.9.1.1
Datasets or Populations Analyzed..................................................52
8.9.1.2
Demographic and Other Baseline Characteristics..........................52
8.9.1.3
Safety Variables..............................................................................52
8.9.1.4
Efficacy Variables ...........................................................................53
8.9.1.5
Interim Analyses .............................................................................56
8.9.2
Determination of Sample Size ........................................................56
8.10 Quality Assurance and Quality Control.......................................................56
8.10.1
Audit and Inspection .......................................................................56
8.10.2
Monitoring .......................................................................................56


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8.10.3
Data Management and Coding.......................................................57
9
Records and Supplies...................................................................................58
9.1
Drug Accountability ......................................................................................58
9.2
Financing and Insurance ..............................................................................58
10
Ethics..............................................................................................................59
10.1 Independent Ethics Committee or Institutional Review Board.................59
10.2 Regulatory Authorities..................................................................................59
10.3 Ethical Conduct of the Study .......................................................................59
10.4 Informed Consent..........................................................................................59
10.5 Subject Confidentiality..................................................................................59
11
Reporting and Publication, Including Archiving ........................................61
12
References .....................................................................................................62
13
Appendices ....................................................................................................63
13.1 Investigator Signature Page.........................................................................63
13.2 66/68 Joint Count...........................................................................................64
13.3 Patient’s Global Assessment of Disease Activity Questionnaire.............65
13.4 Physician’s Global Assessment of Disease Activity 
Questionnaire ................................................................................................66
13.5 Health Assessment Questionnaire - Disability Index (HAQ-DI) ................67
13.6 FACIT Fatigue Scale......................................................................................69
13.7 36-Item Short-Form Health Survey (SF-36) .................................................70
13.8 Pregnancy Precautions, Definition for Female of Childbearing 
Potential, and Contraceptive Methods ........................................................76
LIST OF TABLES
Table 6-1.
Summary and analysis of ACR20/50/70 response at Weeks 12 and 24 
(NRI [ITT Population]), GLPG0634-CL-203 ...................................................................................16
Table 6-2.
Summary and analysis of ACR20/50/70 response at Weeks 12 and 24 
(NRI [ITT Population]); GLPG0634-CL-204 ...................................................................................19


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5
List of Abbreviations and Definition of Terms
Abbreviations
ACR
=
American College of Rheumatology
AE
=
adverse event
ALT
=
alanine aminotransferase
AST
=
aspartate aminotransferase
ATP
=
adenosine triphosphate
AUC
=
area under the concentration-time curve
AUC0-24
=
area under the concentration-time curve from 0 to 24 hours
b.i.d.
=
bis in die (twice daily)
CD
=
Crohn’s disease
CDAI
=
clinical disease activity index
CES
=
carboxylesterases
CIA
=
collagen-induced arthritis
eCRF
=
electronic case report form
CNS
=
central nervous system
CrCl
=
Creatinine Clearance
CRP
=
c-reactive protein
CYP
=
cytochrome P450
DAS28
=
disease-activity score based on 28 joints
DMARD
=
disease-modifying anti-rheumatic drug
DSMB
=
Data Safety Monitoring Board
ECG
=
electrocardiogram
EDC
=
electronic data capture
EDV
=
early discontinuation visit
EULAR
=
European League Against Rheumatism
FACIT
=
functional assessment of chronic illness therapy
FDA
=
Food and Drug Administration
FSH
=
follicle stimulating hormone
GCP
=
Good Clinical Practice
GH
=
general health
GI
=
gastrointestinal
HAQ-DI
=
health assessment questionnaire – disability index
HCl
=
hydrochloride
HDL
=
high-density lipoprotein
HDPE
=
high density polyethylene
HR
=
heart rate
IB
=
investigator’s brochure
ICF
=
informed consent form
ICH
=
International Council for Harmonisation
IEC
=
Independent Ethics Committee
IL
=
interleukin 
IRB
=
Institutional Review Board
IXRS
=
interactive voice/web response system
JAK
=
janus kinase
LDL
=
low-density lipoprotein


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LH
=
luteinizing hormone
Ln
=
natural logarithm
MTX
=
methotrexate
NOAEL
=
no-observed-adverse-effect-level
NOEL
=
no-observed-effect-level
NSAID
=
non-steroidal anti-inflammatory drug
PD
=
pharmacodynamic
PK
=
pharmacokinetic
PRL
=
prolactin
q.d.
=
quaque die (once daily)
RA
=
rheumatoid arthritis
RBC
=
red blood cell
SAE
=
serious adverse event
SDAI
=
simplified disease activity index
SF-36
=
36-item short-form health survey
SJC
=
swollen joint count
SMPC
=
Summary of Product Characteristics
SQRT
=
square root
STAT
=
signal transducer and activator of transcription
t1/2
=
terminal half-life
TB
=
tuberculosis
TEAE
=
treatment-emergent adverse event
TJC
=
tender joint count
tmax
=
time to maximum plasma concentration
TNF
=
tumor necrosis factor
TYK
=
tyrosine kinase
UGT
=
uridine 5’-diphosphate glucuronosyltransferase
VAS
=
visual analog scale
WBC
=
white blood cell
Cockroft-Gault CrCl Formula = [(140-age) x (Wt in kg) x (0.85 if female)]/(72 x Cr)
Wt = Weight in Kilograms
Cr = Creatinine in mg/dL


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6
Introduction
6.1
Rheumatoid Arthritis 
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory and joint degenerative 
disease that affects almost 1% of the adult population worldwide, with onset classically 
between the ages of 30 and 50, and a higher prevalence in women. The disease is 
characterized by pain, stiffness, and restricted mobility due to a persistent symmetrical 
inflammation of the synovial membrane of multiple joints that ultimately results in 
irreversible damage of the joint cartilage and bone.1,2,3
Development of the disease involves an inflammatory response of the synovial 
membrane that is accompanied by infiltration of a variety of immune cells, which leads 
to the build-up and maintenance of a cytokine network. One of the cytokines central to 
this network is tumor necrosis factor-α (TNF-α), as is clearly demonstrated by the clinical 
success of the TNF-α blockers in treating RA. TNF-α and other proinflammatory 
cytokines contribute to cartilage and bone erosion by inducing release of degradative 
enzymes such as the matrix metalloproteinases and stimulating the release of receptor 
activator for nuclear factor κ B Ligand, which triggers differentiation of hematopoietic 
cells into bone resorbing osteoclasts. When left untreated, the disease leads to 
significant disability associated with high economic costs.
In recent years, the therapeutic management of subjects with RA has seen a major 
revolution. A considerable advance in the treatment of RA came from the introduction of 
the biological therapeutics like etanercept, infliximab, adalimumab or more recently, 
certolizumab pegol, which neutralize TNF-α. Spurred by their therapeutic success, more 
biologicals aimed at targeting other molecules involved in RA pathology are being 
developed. An anti-CD20 antibody (rituximab) directed at depleting B cells, a fusion 
protein targeting T-cell co-stimulation (abatacept), and tocilizumab, targeting the 
interleukin (IL)-6 receptor have all recently been approved for the treatment of RA.4
Despite these advances a need still exists for less expensive and orally active drugs. 
Hence, various companies are pursuing the development of small-molecule inhibitors, 
including janus kinase (JAK) inhibitors.
In November 2012, tofacitinib (Xeljanz) became the first JAK inhibitor to receive Food 
and Drug Administration (FDA) approval for the treatment of adult patients with RA. 
Tofacitinib is a small molecule suitable for oral administration, has strong binding affinity 
for JAK1 and JAK3, and weaker affinity for JAK2. The extensive pre-clinical and phase 
1, 2, and 3 clinical development programs demonstrated its mechanisms of action via 
anti-inflammatory and immunosuppressive effects. The drug proved to be efficacious in 
treating the signs and symptoms of RA and was well tolerated. Overall, the side-effects 
and risk profiles of tofacitinib are similar to those of several conventional antirheumatic 
agents with cytopenias, elevated levels of liver function enzymes, increased level of low-
density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol5, and a small 
increased risk for infections including serious and opportunistic infections seen during 
the studies. Baricitinib, a molecule with strong binding affinity for JAK1 and 2, has been 
through extensive phase 1 and 2 testing and is currently undergoing large scale phase 


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3 studies. In phase 2 clinical studies, VX-509 specifically targets JAK3. Both these 
molecules have demonstrated efficacy roughly similar to tofacitinib with an equally 
manageable side-effect profile. 
6.2
Background on Filgotinib 
JAKs are intracellular cytoplasmic tyrosine kinases (TYKs) that transduce cytokine 
signaling from membrane receptors to the nucleus of cells. JAK inhibitors block the 
signaling of various cytokines, growth factors and hormones, including the 
pro-inflammatory cytokine IL-6. Four different types of JAKs are known which 
(co-)interact with different sets of membrane receptors: JAK1, JAK2, JAK3 and TYK2. 
Inhibition of JAKs is a promising therapeutic option for a range of inflammatory conditions 
including RA and Crohn’s disease (CD).
GLPG0634, now referred to as filgotinib (GS-6034) is a potent and selective inhibitor of 
JAK1 and is being co-developed by Galapagos NV and Gilead Sciences, Inc. (Gilead). 
The compound is currently in phase 3 development for RA and CD and has shown good 
preliminary efficacy in RA patients. The anticipated therapeutic daily dose range is 100 to 
200 mg.
Filgotinib is metabolized to form one major active metabolite, GS-829845 
(formerly G254445). Though the potency of this metabolite is lower than the parent 
molecule, the overall exposure and peak plasma concentration in humans is higher. 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.
More information on the study medication along with references to support the cited data 
is presented in the Investigator’s Brochure (IB).6 A summary is provided hereafter.
6.3
Background - Pre-clinical Studies
6.3.1
Physical, Chemical and Pharmaceutical Properties and Formulations
The chemical name of filgotinib hydrochloride (HCl) trihydrate or GS-6034-01 is 
N-(5-(4-((1,1-dioxidothiomorpholin-4-yl)methyl)phenyl)-[1,2,4]triazole[1,5-a]pyridin-2-yl)
cyclopropanecarboxamide hydrochloride trihydrate.
The 
chemical 
name 
of 
filgotinib 
maleate 
or 
GS-6034-02 
is 
N-(5-{4-[(1,1-dioxidothiomorpholin-4-yl) methyl]phenyl}[1,2,4]triazolo[1,5-a]pyridin-2-yl) 
cyclopropanecarboxamide (2Z)-but-2-enedioate.
Two clinical tablet formulations are currently available: (1) a film-coated tablet 
(25-100 mg per tablet) of the HCl salt of filgotinib and (2) a film-coated tablet (100 mg 
per tablet) of the maleate salt of filgotinib.


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6.3.2
Nonclinical Pharmacology
6.3.2.1
Primary and Secondary Pharmacology
Filgotinib is an adenosine triphosphate (ATP)-competitive inhibitor of JAK1. It is highly 
selective for inhibition of JAK1 among 451 unique kinase gene products tested in vitro. 
In cellular assays, it inhibits biological processes involving JAK1 from 179 nM onwards, 
with a 30-fold selectivity over JAK2 in human whole blood. A high potency is observed 
in the rat collagen-induced arthritis (CIA) model.
Metabolite GS-829845 exhibits a similar JAK1 selectivity profile while being 
approximately 10-fold less potent as compared to parent filgotinib in vitro. In the rat CIA 
model, while being less potent than the parent molecule, GS-829845 displays a good 
curative effect against established arthritis.
6.3.2.2
Safety Pharmacology
Filgotinib and GS-829845 had no effects on the respiratory system and central nervous 
system (CNS) up to respectively 40- and 5-fold the human exposure in RA patients at 
200 mg q.d. filgotinib.
Filgotinib and GS-829845 had no relevant effects on cardiovascular parameters 
(human ether-a-go-go [hERG] and dog telemetry studies), apart from a slight 
non-adverse increase in heart rate (HR) and arterial pressure with GS-829845 at 
exposures approximately 7-fold that of RA patients treated with 200 mg q.d. filgotinib. 
There were no relevant effects on electrocardiogram (ECG) and QT.
6.3.3
Nonclinical Pharmacokinetics and Product Metabolism
Filgotinib shows a good oral bioavailability in mice, rats, dogs and minipigs but less in 
monkeys. Plasma protein binding is low (<70%) in all species, including humans.
The pharmacokinetics (PK) of filgotinib is essentially dose proportional without gender 
differences. No accumulation occurs with repeated dosing. The mean terminal half-life 
after oral administration is 4 and 5 hours in rats and dogs, respectively.
Filgotinib showed a rapid and even distribution throughout the body in the rat. High 
concentrations were only observed in the gastrointestinal (GI) tract and urinary bladder. 
Filgotinib does not penetrate into the CNS tissues. Filgotinib distribution indicates some 
affinity of the test compound for melanin-containing tissues. 
Excretion is nearly complete within 24 hours post-dosing. Fecal and urinary excretion 
accounted for 40% and 53% of the administered dose, respectively, with a bile secretion 
of about 15%.
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).


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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 glucuronosyltransferases (UGTs) and no relevant inhibition of key drug 
transporters, including the organic anion transporters (OATs) involved in the renal 
elimination of MTX, by filgotinib or GS-829845.
6.3.4
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 is 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. A dose of 200 mg/day of filgotinib 
results in an estimated mean clinical AUC of 2.80 μg•h/mL in RA subjects, which 
represents an exposure margin of 2.3, 1.8, and 3.4-fold when considering the mean AUC 
in male dogs at the no-observed-effect-levels (NOELs) in the 26 week and 39 week 
chronic toxicity studies, and the 39 week targeted exposure toxicity study, respectively.
GS-829845-related findings in general repeat dose toxicity studies were 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 at exposures similar to the human exposure at 200 
mg q.d. of filgotinib in subjects with RA.  Administration of filgotinib did not affect female 
fertility but impaired fertility was observed in male rats at exposures approximately 15-
fold the human exposure at 200 mg of filgotinib in subjects with RA. 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.
6.4
Clinical Trials of Filgotinib
Comprehensive data from the Phase 1 and 2 programs are available to support 
development into Phase 3. In general, filgotinib has been safe and well tolerated in all 
populations studied. A detailed description of all clinical studies can be found in the IB. 
Phase 2b GLPG0634-CL-203, filgotinib with MTX in RA
In GLPG0634-CL-203, subjects with active RA on stable dose of MTX were 
randomized to receive either placebo or one of three total daily doses of filgotinib 
(50 mg, 100 mg, or 200 mg) on a once or twice daily schedule for 24 weeks. The 


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primary objective of the study was to evaluate the efficacy of different doses and dose 
regimens of filgotinib compared to placebo at Week 12.
The percentage of American College of Rheumatology (ACR) 20 responders was 
statistically significantly higher in the 100 mg and 200 mg once daily, and 100 mg 
twice daily dose groups at Week 12 and in the 100 mg and 200 mg once daily, and 
50 mg and 100 mg twice daily dose groups at Week 24. The percentage of ACR50 
responders was statistically significantly higher compared with placebo across all 
filgotinib dose groups and regimens at both Weeks 12 and 24 (Table 6-1). The 
percentage of ACR70 responders was statistically significantly higher in the filgotinib 
200 mg once daily and 100 mg twice daily dose groups compared with placebo at 
Week 12 and across all filgotinib dose groups and regimens at Week 24. A 
dose-response was observed for all three parameters. In addition, the ACR20 
response appeared to plateau at Week 8 in the majority of filgotinib treatment groups 
and was maintained up to Week 24. At Week 24, the ACR50 response was maintained 
and the ACR70 response continued to increase compared with Week 12.
Starting at week 2 response was observed for ACR20 and ACR50. No statistically 
significant difference was found between the once and twice daily regimens. 
Table 6-1.
Summary and analysis of ACR20/50/70 response at Weeks 12 and 24 
(NRI [ITT Population]), GLPG0634-CL-203
filgotinib once daily Dose Groups
filgotinib twice daily Dose Groups
Placebo
N=86
50 mg
N=82
100 mg
N=85
200 mg
N=86
25 mg
N=86
50 mg
N=85
100 mg
N=84
Parameter
Time
Point
n (%)
W12
38 (44.2)
46 (56.1)
54 (63.5)*
59 (68.6)**
49 (57.0)
51 (60.0)
66 (78.6)***
ACR20
W24
36 (41.9)
45 (54.9)
52 (61.2)* 63 (73.3)***
48 (55.8)
51 (60.0)*
67 (79.8) ***
W12
13 (15.1)
27 (32.9)*
32 (37.6)** 37 (43.0)*** 24 (27.9)*
29 (34.1)*
46 (54.8)***
ACR50
W24
14 (16.3)
29 (35.4)** 40 (47.1)*** 43 (50.0)*** 30 (34.9)**
30 (35.3)** 46 (54.8)***
W12
7 (8.1)
13 (15.9)
18 (21.2)
21 (24.4)*
12 (14.0)
16 (18.8)
26 (31.0)**
ACR70
W24
8 (9.3)
18 (22.0)*
28 (32.9)** 25 (29.1)**
18 (20.9)*
20 (23.5)*
33 (39.3)***
Note 1: p-values were based on a pairwise comparisons of each group vs. the placebo group using a 
logistic regression model with factors treatment group, geographical region, and prior use of biologics; 
Hommel-corrected p-value. Note 2: The denominator for the percentage calculations = the total number of 
subjects per group with a response (yes or no) at that time point
Note 3: Subjects who switched treatment at Week 12 were handled as if they discontinued at Week 12.
*
p< 0.05; ** p< 0.01; *** p < 0.001
ACR=American College of Rheumatology; ITT=Intent-to-treat; NRI=non-responder imputation; W=week
Source: GLPG0634-CL-203
At Weeks 12 and 24 the mean decrease in Disease Activity Score for 28 joint count 
using c-reactive protein ( DAS28[CRP]) was statistically significantly greater across 
all filgotinib dose groups and regimens compared with placebo. A dose-response was 
observed. No statistically significant difference was apparent between the once and 


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twice daily regimens. At Weeks 12 and 24, the mean decrease in Simplified 
Diagnostic Activity Index ( SDAI) and Clinical Disease Activity Index (CDAI) score was 
statistically significantly greater across all filgotinib dose groups and regimens 
compared with placebo (with the exception of filgotinib 50 mg once daily dose group at 
Week 12). In addition, the mean SDAI and CDAI scores were maintained after 
Week 12 in the 50 mg daily dose groups and continued to improve up to Week 24 
in the 100 mg and 200 mg daily dose groups.
No unexpected safety findings were noted. Overall, no differences were observed in 
the incidence of treatment emergent adverse events (TEAEs) reported for subjects in 
any of the dosing groups, including placebo, for the duration of the study. TEAEs were 
reported for 51.2% of “All Placebo Exposed” subjects (ie, all subjects combined who 
received placebo during either the entire 24 weeks or only during the first 12 weeks) 
and 51.5% of “All filgotinib Exposed” subjects (ie, all subjects combined who received 
filgotinib during either the entire 24 weeks or only during the last 12 weeks, irrespective 
of dose).
A total of 15 subjects had ≥1 serious TEAE; 4 subjects in the placebo group (4.7%) and 
11 subjects (2.0%) in one of the filgotinib groups. One of these subjects with ≥1 serious 
TEAE, who received filgotinib 100 mg twice daily with concurrent MTX, died during the 
second 12 weeks of the study period due to pneumonia and septic shock. Out of the 
15 subjects with a serious TEAE, 11 subjects had a serious TEAE due to which the 
study medication was stopped, and the subject discontinued the study. A total of 
23 subjects had ≥1 AE leading to permanent discontinuation of the study medication 
and the study; 2 subjects (2.3%) in the placebo group and 21 subjects (3.9%) in one of 
the filgotinib groups (including a subject in the filgotinib 100 mg q.d. group who had a 
pre-dosing AE which was ongoing throughout the study, for which the study medication 
was permanently discontinued). Most of the serious TEAEs and the AEs leading to 
discontinuation (by preferred term) were experienced by a single subject.
For the duration of the study, the most common (≥10%) TEAEs reported by SOC in 
subjects from both the placebo and filgotinib dosing groups, were Infections and 
Infestations and Gastrointestinal disorders. There were no differences between 
subjects who received placebo or filgotinib in the severity of TEAEs (most TEAEs were 
mild or moderate; severe TEAEs were observed in 1.2% of “All Placebo Exposed” 
subjects and in 2.2% of “All filgotinib Exposed” subjects). Treatment-related TEAEs 
were generally reported more often for subjects in the filgotinib dosing groups than in 
the placebo group (9.3% with placebo and 20.3% with filgotinib); however, within the 
different filgotinib dosing groups, no clear dose relationships were observed.
Six serious infections were reported (1 in placebo arm, 5 in filgotinib arm). All 6 serious 
and one additional non-serious infection in the filgotinib group led to dosing 
discontinuation. Up to Week 24, herpes zoster infections were observed in 5 subjects 
(1 placebo treated patient and 4 filgotinib). No cases of tuberculosis, opportunistic 
infections, lymphoma, or cancer were reported throughout the 24-week dosing period.
Laboratory data were consistent with prior phase 2 studies and no new safety findings 
were observed from laboratory data. A summary of laboratory findings of interest, 


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including hemoglobin, neutrophil, lymphocyte, creatinine, lipid, and hormone data are 
summarized below. 
Up to Week 12, small increases were observed in mean hemoglobin concentrations in 
the filgotinib 200 mg daily dose groups (increase of 4.4 g/L from baseline in the 
filgotinib 100 mg bid group). Thereafter, hemoglobin mean concentrations appeared to 
plateau and remain stable until Week 24 (increase of 4.9 g/L from baseline in the 
filgotinib 100 mg bid group). 
Up to Week 4, dose-dependent decreases were observed in mean absolute neutrophil 
counts in the filgotinib treatment groups. Mean absolute neutrophil counts appeared to 
plateau and remained stable until Week 24. No decreases in mean absolute 
lymphocyte counts were observed, including lymphocyte subsets. 
Up to Week 4, dose-dependent decreases were observed in mean absolute platelet 
counts in the filgotinib treatment groups. Mean absolute platelet counts appeared to 
plateau and remained stable. Dose-dependent increases in the filgotinib groups were 
observed in mean creatinine concentrations during the first 4 weeks of the study for 
most filgotinib treatment groups (up to Week 8 for the filgotinib 100 mg bid group) that 
subsequently plateaued and remained stable up to Week 24. 
Up to Week 4, dose-dependent increases were observed in mean concentrations of 
total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and 
triglycerides in all filgotinib treatment groups. All these lipid parameters further 
increased up to Week 8 in the filgotinib 200 mg daily dose groups. Thereafter, these 
increases appeared to plateau and maintained at stable mean concentrations up to 
Week 24. At Week 24, mean increases were observed of 0.7 mmol/L in total 
cholesterol, 0.3 mmol/L in LDL cholesterol, 0.3 mmol/L in HDL cholesterol, and 
0.1 mmol/L in triglycerides in the filgotinib 100 mg bid group.
In male subjects, small non dose-dependent increases were observed in total and free 
testosterone during the study (at Week 24, mean increases were 3.4 nmol/L for total 
and 51.7 pmol/L for free testosterone in the filgotinib 100 mg bid group). For FSH, 
inhibin B, LH, and prolactin, small changes (both increases and decreases) were 
observed during the study, without any trends of larger changes in male subjects of 
one or more of the different treatment groups.
GLPG0634-CL-204, Filgotinib administered as monotherapy in RA Subjects
The primary objective of study GLPG0634-CL-204 was to evaluate the efficacy of 
three doses of filgotinib q.d. compared to placebo at Week 12.
As shown in Table 6-2 the percentage of ACR20 and ACR50 responders at week 12 
was statistically significantly higher across all filgotinib dose groups compared with 
placebo. The percentage of ACR70 responders in the filgotinib 100 mg and 200 mg 
once daily dose groups was statistically significantly higher compared with placebo. 
At Week 24, the ACR50 response was maintained and the ACR70 response showed 
continued improvement. An early onset of response was observed for ACR20 


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(from Week 1 in the filgotinib 200 mg once daily dose group and Week 4 across all 
other dose groups), ACR50 (from Week 2 in the filgotinib 200 mg once daily dose 
group and Week 4 across all other filgotinib dose groups), and ACR70 (Week 4 in the 
filgotinib 200 mg once daily dose group). The time to ACR20/50/70 response was 
shorter in all filgotinib dose groups compared with placebo.
Table 6-2.
Summary and analysis of ACR20/50/70 response at Weeks 12 and 24 
(NRI [ITT Population]); GLPG0634-CL-204
Placebo
filgotinib once daily Dose Groups
Parameter
Time
Point
N=72
50 mg
N=72
100 mg
N=70
200 mg
N=69
n (%)
W12
21 (29.2)
48 (66.7)***
46 (65.7)***
50 (72.5)***
ACR20
W24
Not applicable
41 (56.9)
55 (78.6)
46 (66.7)
W12
8 (11.1)
25 (34.7)***
26 (37.1)***
30 (43.5)***
ACR50
W24
Not applicable
24 (33.3)
27 (38.6)
31 (44.9)
W12
2 (2.8)
6 (8.3)
13 (18.6)**
9 (13.0)*
ACR70
W24
Not applicable
14 (19.4)
18 (25.7)
17 (24.6)
Note 1: p-values were based on a pairwise comparisons of each group vs. the placebo group using a 
logistic regression model with factors treatment group, geographical region, and prior use of biologics; 
Hommel-corrected p-value.
Note 2: The denominator for the percentage calculations = the total number of subjects per group with a 
response (yes or no) at that time point
Note 3: Subjects who switched treatment at Week 12 were handled as if they discontinued at Week 12.
*
p< 0.05; ** p< 0.01; *** p < 0.001
ITT=Intent-to-treat; NRI=non-responder imputation; W=week
Source: GLPG0634-CL-204
At Week 12, the mean decrease in DAS28(CRP) was statistically significantly greater 
across all filgotinib dose groups compared with placebo. At Week 24, the mean 
decrease in DAS28(CRP) was maintained in the 50 m g  once daily dose group and 
showed a small improvement in the highest dose groups. In addition, at Week 12, the 
percentage of subjects with DAS28(CRP) remission was higher across all filgotinib 
dose groups compared with placebo. Differences vs. placebo were not statistically 
significant for any of the filgotinib dose groups. The number of subjects with 
DAS28(CRP) < 2.6 and < 3.2 were higher across all filgotinib dose groups 
compared with placebo at Week 12; differences vs. placebo were statistically 
significant for the filgotinib 200 mg once daily dose group.
Safety data revealed no differences in the incidence of TEAEs reported for subjects in 
any of the treatment groups, including placebo, during both the first 12 weeks of 
treatment and the full 24 weeks of treatment. TEAEs were reported for 38.9% of “All 
Placebo Exposed” subjects (ie, all subjects combined who received placebo during the 
first 12 weeks) and 41.3% of “All filgotinib Exposed” subjects (ie, all subjects combined 


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who received filgotinib during either the entire 24 weeks or only during the last 
12 weeks, irrespective of dose).
No deaths were reported and a total of 9 subjects had a serious TEAE; 1 subject 
(1.4%) during placebo dosing and 8 subjects (2.9%) during filgotinib dosing. No serious 
TEAE (by preferred term) was experienced by more than 1 subject, and all subjects 
recovered from their serious TEAEs. Out of the 9 subjects with a serious TEAE, 
3 subjects had a serious TEAE for which the study medication was stopped, and the 
subject discontinued the study. There were no differences in incidences of AEs leading 
to discontinuation among all the different dosing groups, including placebo. A total of 
11 subjects had ≥1 TEAE leading to discontinuation of the study medication; 4 subjects 
(5.6%) during placebo dosing and 7 subjects (2.5%) during filgotinib dosing.
During the whole study, the most common TEAEs reported by System Organ Class in 
subjects from both the placebo and filgotinib treatment groups, were ‘Infections and 
Infestations’ and ‘Gastrointestinal disorders’. There were no differences between 
subjects who received placebo or filgotinib in the severity of TEAEs (most TEAEs were 
mild or moderate; severe TEAEs were observed in 1.4% of “All Placebo Exposed” 
subjects and in 1.1% of “All filgotinib Exposed” subjects). Treatment-related TEAEs 
were generally reported more often for subjects in the filgotinib treatment groups than 
in the placebo group (9.7% with placebo and 16.7% with filgotinib); however, within the 
different filgotinib treatment group, no clear dose relationships were observed.
Low numbers of infections were reported as serious (4 subjects with filgotinib) or led to 
discontinuation of the study medication (2 serious infections; ie, cellulitis and 
pneumonia) were observed during the study. Up to Week 24, 1 subject (filgotinib 50 mg 
q.d. group) had a herpes zoster infection. No cases of tuberculosis, opportunistic 
infections, lymphoma, or cancer were reported throughout the 24-week treatment 
period.
Laboratory data were consistent with prior studies and no new safety findings were 
observed.
Please refer to the IB for additional data regarding efficacy and safety.
6.5
Risk/Benefit Assessment for the Study
A detailed description of all clinical studies can be found in the IB.
Nonclinical studies in rats and dogs identified the testes and lymphoid tissue as target 
organs for filgotinib in long term repeat-dose toxicity studies. In both species, 
histopathological changes 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 rats. The dog was determined to be the most sensitive species. A dose of 
200 mg/day of filgotinib results in an estimated mean clinical AUC of 2.8 μg•h/mL, 
which represents an exposure margin of 2.3, 1.8, and 3.4-fold when considering the 
mean AUC in male dogs at the no-observed-effect-levels (NOELs) in the 26 week and 
39 week chronic toxicity studies, and the 39 week targeted exposure toxicity study, 


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respectively. Decreased lymphocytes observed in nonclinical studies have not been 
shown in clinical studies. 
Filgotinib has shown an increased risk of embryofetal malformations at exposures 
similar to human doses; the use of highly effective contraception in the subject 
population will be implemented in the study to mitigate this risk.
No clinically relevant impact on cardiovascular parameters (including vital signs and 
ECG), respiratory or neurologic function has been observed in Phase 1 and 2 trials of 
filgotinib.  Across phase 2 trials in RA, filgotinib was well tolerated. In the RA studies 
(including this study), infections were reported more commonly in the filgotinib groups, 
including serious infections leading to hospitalization, and even death. The most 
common system organ classes (SOC) with AEs were infections and infestations, and 
gastrointestinal disorders. Dose dependent decreases in the phase 2b studies were 
observed in mean neutrophil counts and platelet counts (but mean changes in both 
remained within normal laboratory reference ranges), and there were no decreases in 
lymphocytes or lymphocyte subsets. Hemoglobin levels slightly improved (increased) 
with filgotinib treatment, confirming that no anemia was induced. Mild and clinically 
insignificant serum creatinine increases were noted in both Phase 2b studies, with 
stabilization by Week 24.  Neutrophil decreases (in the RA population) and a potential 
increased risk of infection may be considered risks consistent with the mechanism of 
JAK inhibition.  
Overall clinical findings and laboratory changes are consistent with selective JAK1 
inhibition and based on Phase 2 data the expected benefit of using filgotinib as 
proposed in this study is considered to outweigh any associated risks.
As of 01 April 2021, the independent data safety monitoring board (DSMB) reviews were 
discontinued as ongoing review of safety and efficacy data by the sponsor’s clinical study 
team was considered sufficient by the sponsor, based on the current development status 
of filgotinib and the open-label design of the study.
The overall risk:benefit balance of this study is considered favorable. For additional 
information about the risks of filgotinib, reference is made to the investigator brochure.
6.6
Rationale for the Study
Over the last decade changes in RA treatment strategies, accompanied with advances 
in drug development and the addition of targeted biological therapies, have greatly 
improved the outcome of patients with RA. Despite these developments, therapeutic 
challenges have remained, since current conventional and biological DMARDs 
sometimes fail or produce only a partial response. Therefore, there is still a need for 
orally administered novel therapies with a different mechanism of action that can 
effectively modify the disease course and are safe and well tolerated.  
Filgotinib is a small molecule for oral daily administration that has shown promising 
results as a potentially safe and effective RA treatment. Study GLPG0634-CL-205 is a 
therapeutic open-label phase 2 extension study to assess the long-term safety and 
efficacy of a stable dose (200 mg q.d. or 100 mg b.i.d.) of filgotinib up to marketing of the 


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compound in subjects with established RA. The aim of the current study is to evaluate 
the long-term safety and tolerability of a stable filgotinib dose, the efficacy of filgotinib 
administration, and to evaluate the long-term effects of filgotinib administration on the 
subject’s disability, fatigue, and quality of life.
As a follow-up study, which will begin following the subject’s completion of either of the 
previous core phase 2b studies (GLP0634-CL-203 and GLP0634-CL-204), data will be 
gathered up to the submission of the compound to regulatory authorities and enable 
assessment of the long-term effects of filgotinib administration. 
The study’s primary endpoint is to assess the long-term safety and tolerability of filgotinib 
and will focus on the changes in safety parameters in order to detect any 
treatment-emergent effect related to the long-term daily administration of a stable 
200 mg dose (200 mg q.d. or 100 mg b.i.d.) of filgotinib. 
The secondary endpoints will focus on the efficacy over a long-term period and to 
evaluate the long-term effects on the subject’s disability, fatigue, and quality of life. The 
efficacy assessments will be the same as for the previous core studies and will focus on 
the changes in efficacy parameters in order to detect any effects related to the long-term 
daily administration of a stable 200 mg daily dose of filgotinib, given as q.d. or divided 
b.i.d. The ACR criteria for 20%, 50%, and 70% improvement in disease activity (ACR20, 
ACR50, and ACR70) responses and the disease-activity score based on 28 joints 
(DAS28) are considered reliable measures of response to treatment and disease activity, 
respectively. Assessment of the ACR criteria will allow for a straightforward interpretation 
of a positive clinically meaningful result and has been shown to achieve high 
discriminatory capacity and is therefore considered an adequate efficacy endpoint for 
long-term studies. Evaluation of continuous outcome measures of DAS28 and ACR-N 
as secondary endpoints enables the demonstration of improvement and magnitudes of 
benefit for study subjects. The European League Against Rheumatism (EULAR) 
response criteria that classify subjects as non-, moderate, or good responders are 
dependent on the extent of change and the level of disease activity reached. These 
criteria are useful when describing clinically meaningful therapeutic targets. Quality of 
Life (functional assessment of chronic illness therapy [FACIT] and 36-item short-form 
health survey [SF-36]) assessed during the course of study treatment, provides further 
insight into the effects on modifying the disease course and its impact on everyday life.  
6.7
Rationale of Choice of the Dose and Dosing Interval
For the current study, all enrolled subjects will start the study at the filgotinib 200 mg q.d. 
or 100 mg b.i.d. dose depending on their dose regimen in GLPG0634-CL-203 or 
GLPG0634-CL-204. At subsequent visits, the investigator will be allowed to decrease 
the dose in subjects to 100 mg q.d. in case of intolerance or safety reasons and allowed 
to return to the 200 mg q.d. or 100 mg b.i.d. dose after the reasons for decreasing the 
dose have been resolved, and at the investigator’s discretion. Subjects can also continue 
filgotinib 100 mg q.d. when deemed necessary by the investigator.


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Ten-day dose regimens up to 450 mg q.d. have been shown to be well tolerated and 
safe in healthy volunteers. Four weeks of treatment with doses up to 300 mg q.d. was 
well tolerated by RA subjects in the 2 phase 2a studies. 
The results from the 2 phase 2a clinical studies have revealed that a high level of efficacy 
is achieved with a 200 mg daily dose and there is no added value administering higher 
(300 mg) doses. In the initial proof-of-concept study, ACR20 at Week 4 was achieved by 
92%, 75% and 33% of subjects in the 100 mg b.i.d., 200 mg q.d., and placebo groups, 
respectively. In the second completed phase 2a study, ACR20 by Week 4 was achieved 
by 65% of subjects in the 300 mg daily dose group compared to 41% for placebo. 
Thus 200 mg daily was chosen as the dose to be administered to give optimal efficacy 
while maintaining appropriate safety margins based on the preclinical evaluation. To 
gather data on long-term safety and efficacy on both q.d. and b.i.d. treatment regimens 
with filgotinib, subjects will remain on the same treatment regimen as during the 
preceding core study (GLPG0634-CL-203: either q.d. or b.i.d.; GLPG0634-CL-204: q.d.).


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7
Study Objectives
7.1
Primary Objective
The primary objective of the study is to evaluate the long-term safety and tolerability of 
filgotinib for the treatment of rheumatoid arthritis.
7.2
Secondary Objectives
The secondary objectives of the study are:

To evaluate the long-term efficacy of filgotinib.

To evaluate the long-term effects of filgotinib administration on subjects’ disability, 
fatigue, and quality of life. 


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8
Investigational Plan
8.1
Overall Study Design and Plan
This is a multicenter, open-label, long-term follow-up study in subjects with RA. An 
approximate total of 600 subjects will be enrolled in the study after they have completed 
one of the previous 2 core studies (GLPG0634-CL-203 or GLPG0634-CL-204). All 
subjects will start the study at the same dose level (filgotinib 200 mg daily, administered 
either as 200 mg q.d. or as 100 mg b.i.d., depending on the dosing regimen [frequency 
of intake of active IMP] that was administered during the preceding core study). The 
investigator may decide to decrease the daily dose of filgotinib to 100 mg q.d. in case of 
intolerance or safety reasons. Subjects will return to the 200 mg GLPG0634 daily dose 
after the reasons for decreasing the dose have resolved, and at the investigator’s 
discretion. Subjects can also continue filgotinib 100 mg q.d. when deemed necessary by 
the investigator. Subjects coming from the GLPG0634-CL-204 study will be allowed to 
start MTX treatment, if deemed necessary according to the investigator’s clinical 
judgment. 
Subjects have entered the study at Entry Visit on Day -1, which occurred on the same 
day as the last visit from the previous core study (GLPG0634-CL-203 or 
GLPG0634-CL-204). Subjects participating in the study have been requested to attend 
Quarterly Evaluation Visits (QEVs) every 12 weeks. If necessary, unscheduled visits can 
occur in between the scheduled study visits, for instance, in case the dose of study 
medication is to be adapted. In case of early withdrawal, an Early Discontinuation Visit 
(EDV) will be scheduled. 
The duration of the participation and treatment for any subject in this study is expected 
to last for several years (from Entry visit to Follow-up Visit) and will be determined by the 
sponsor based on the following: 

Open label period (approximately 96 months).

Marketing Application Approval/Withdrawal in Country of Residence.

Applicable local reimbursement procedures are in place.
Sites will be notified once these criteria are met. 
Following marketing, local (if applicable) regulatory and/or pertinent local reimbursement 
approval of the study medication, subjects should return to their next quarterly scheduled 
study visit as specified in the protocol. This visit will serve as a Final Visit and the subjects 
will be considered as having completed the treatment part of the study. At the end of the 
study, subjects will be requested to attend a Follow-up Visit approximately 2 weeks after 
the Final Visit.


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The design of the study is presented in the following table.
Study 203
Week 1 – 12 
Week 13 – 24
Roll over to Study 205
Half of them are 
rerandomized to 200 mg q.d.
Responders(*) remain on placebo
Half of them are 
rerandomized to 100 mg 
b.i.d.
Nonresponders: half of them are 
rerandomized to 100 mg q.d.
Assigned to 200 mg q.d.
Randomized to placebo
Nonresponders: half of them are 
rerandomized to 50 mg b.i.d.
Assigned to 100 mg b.i.d.
Responders remain on 50 mg q.d.
Assigned to 200 mg q.d.
Randomized to 50 mg q.d.
Nonresponders assigned to 100 mg 
q.d.
Assigned to 200 mg q.d.
Responders remain on 25 mg b.i.d.
Assigned to 100 mg b.i.d.
Randomized to 25 mg b.i.d.
Nonresponders assigned to 50 mg 
b.i.d.
Assigned to 100 mg b.i.d.
Randomized to 100 mg q.d.
Remain on 100 mg q.d.
Assigned to 200 mg q.d.
Randomized to 50 mg b.i.d.
Remain on 50 mg b.i.d.
Assigned to 100 mg b.i.d.
Randomized to 200 mg q.d.
Remain on 200 mg q.d.
Remain on 200 mg q.d.
Randomized to 100 mg 
b.i.d.
Remain on 100 mg b.i.d.
Remain on 100 mg b.i.d.
Study 204
Week 1 – 12 
Week 13 – 24
Roll over to Study 205
Randomized to placebo q.d.
All assigned to 100 mg q.d.
Assigned to 200 mg q.d.
Responders remain on 50 mg q.d.
Assigned to 200 mg q.d.
Randomized to 50 mg q.d.
Nonresponders assigned to 100 mg 
q.d.
Assigned to 200 mg q.d.
Randomized to 100 mg q.d.
Remain on 100 mg q.d.
Assigned to 200 mg q.d.
Randomized to 200 mg q.d.
Remain on 200 mg q.d.
Remain on 200 mg q.d.
(*)
responder: having a decrease of at least 20% in tender joint count (TJC)68 and swollen joint 
count (SJC)66 versus Baseline.
8.2
Discussion of Study Design
The discussion of study design is presented in Section 6.7.


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8.3
Selection of Study Population
8.3.1
Number of Planned Subjects 
739 subjects were enrolled from the previous core studies (GLPG0634-CL-203 or 
GLPG0634-CL-204) into this long-term follow-up study. Details of the statistical 
considerations for the number of subjects are presented in Section 8.8.2.
8.3.2
Inclusion Criteria
To be eligible for study entry subjects must fulfill all of the following criteria:
1.
Male or female subjects who are ≥18 years of age, having completed one of the 
qualifying core studies GLPG0634-CL-203 or GLPG0634-CL-204 and, who in the 
opinion of the investigator, will continue to benefit from treatment in the extension 
study.
2.
Female subjects of childbearing potential who engage in heterosexual intercourse 
must agree to use protocol specified method(s) of contraception and agree to refrain 
from egg donation and in vitro fertilization as described in Appendix 13.8. 
3.
Fertile male subjects who engage in heterosexual intercourse must agree to use 
protocol specified method(s) of contraception and agree to refrain from sperm 
donation as described in Appendix 13.8. 
4.
Able and willing to sign the informed consent as approved by the Independent Ethics 
Committee (IEC)/Institutional Review Board (IRB), prior to the Entry visit and agree 
to the schedule of assessments.
8.3.3
Exclusion Criteria
Subjects will be excluded from the study if one or more of the following statements are 
applicable:
1.
Subjects who had been prematurely withdrawn from one of the 2 core studies 
(GLPG0634-CL-203 or GLPG0634-CL-204), for any reason, including fulfilling the 
individual stopping criteria. 
2.
Subjects who are deemed not to be benefiting from the study medication based upon 
lack of improvement or worsening of their symptoms. Local guidelines for subject 
treatment need to be followed. 
3.
Subjects with persistent abnormal laboratory values, associated with the use of the 
study medication (including but not limited to hematology, liver and renal function 
values) 
during 
one 
of 
the 
2 
core 
studies 
(GLPG0634-CL-203 
and 
GLPG0634-CL-204), according to the investigator’s clinical judgment. 
4.
Subjects who require immunization with live/live attenuated vaccine.


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5.
Subjects 
with 
diagnosis 
since 
the 
inclusion 
to 
GLPG0634-CL-203 
or 
GLPG0634-CL-204 core studies of rheumatic autoimmune disease or inflammatory 
joint disease other than RA, except for secondary Sjögren’s syndrome. 
6.
Subjects with symptoms suggestive of moderate to severe congestive heart failure 
or major cerebrovascular event since the inclusion to GLPG0634-CL-203 and 
GLPG0634-CL-204 core studies. 
7.
Subjects with symptoms suggestive of GI tract ulceration and/or active diverticulitis 
since the inclusion to GLPG0634-CL-203 and GLPG0634-CL-204 core studies. 
8.
Subjects with symptoms suggestive of possible lymphoproliferative disease including 
lymphadenopathy or splenomegaly since the inclusion to GLPG0634-CL-203 and 
GLPG0634-CL-204 core studies. 
9.
Subjects with symptoms suggestive of malignancy since the inclusion to GLPG0634-
CL-203 and GLPG0634-CL-204 core studies. 
10. If applicable to national or local legislation: history of being admitted to an institution 
under administrative or court order since the inclusion to GLPG0634-CL-203 and 
GLPG0634-CL-204 core studies. 
11. History of drug and alcohol abuse since the inclusion to GLPG0634-CL-203 and 
GLPG0634–CL-204 core studies. 
12. Any condition or circumstances which, in the opinion of the investigator, may make 
a subject unlikely or unable to complete the study or comply with study procedures 
and requirements. 
8.4
Criteria for Interruption or Discontinuation of Study Treatment
8.4.1
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.   


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
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.

Subjects with newly positive (converted) QuantiFERON® [or equivalent] TB test 
should be evaluated for active TB. Subjects who are diagnosed with latent TB 
(including chest X ray evaluation), should interrupt study drug dosing and initiate an 
adequate course of prophylaxis as per local standard of care; study drug is not to be 
resumed until after TB treatment has been initiated, as per local standard of care. 
Subjects may resume study drug only after investigator’s written consultation with 
the medical monitor.

QuantiFERON® tests with indeterminate results may be repeated one time via the 
central lab. If the repeat result is also indeterminate, the result will be considered 
positive for the purposes of this study. 
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.
8.4.2
Study Drug Discontinuation Considerations:
The medical monitor should be consulted prior to study drug discontinuation when 
medically feasible. 
Study medication should be permanently discontinued in the following instances:

Any opportunistic infection 

Any subject with active TB

Any serious infection that requires parenteral/intravenous antimicrobial therapy or 
hospitalization, or any infection that meets SAE reporting criteria. 

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

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


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
Treatment failure deemed by the investigator as lack of improvement or worsening 
of the disease symptoms or occurrence of intolerable AEs.

Subject request to discontinue for any reason

Subject noncompliance

Pregnancy during the study (Section 8.8.1.2.1.5 and Appendix 13.8)

Discontinuation of the study at the request of Galapagos, 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.

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 5 days (except for creatinine, which should be retested 7-14 days 
later, unless medically indicated sooner).  
2 sequential white cell counts <2000 cells/mm3 (SI: <2.0 x 109 cells/L)
2 sequential neutrophil counts <1000 neutrophils/mm3 (SI: <1.0 x 109 cells/L) 
2 sequential lymphocyte counts <750 lymphocytes/mm3 (SI: <0.75 x 109 cells/L)
2 sequential hemoglobin <8.0 g/dL (SI: <80 g/L)
2 sequential platelet counts <75,000 platelets/mm3 (SI: <75.0 x 109 cells/L)
2 sequential aspartate aminotransferase (AST) or ALT elevations >3 times the 
upper limit of normal with at least one total Bilirubin value >2 times the upper 
limit of normala;
2 sequential AST or ALT elevations >3 times the upper limit of normal 
accompanied by symptoms consistent with hepatic injurya;
2 sequential AST or ALT elevations >3 times the upper limit of normal 
accompanied by elevated INR;
2 sequential AST or ALT elevations >5 times the upper limit of normal, 
regardless of total Bilirubin or accompanying symptomsa;
2 sequential values for estimate creatinine clearance <35mL/min based on the 
Cockcroft Gault formulab; 


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2 sequential decreases from the baseline (of the core studies 
[GLPG0634-CL-203 or GLPG0634-CL-204]) of inhibin B by 50% with clinically 
relevant concurrent increase in FSHc per investigator judgment. Note that this 
study drug discontinuation criterion applies only to subjects with baseline 
hormone levels within normal limits;
2 sequential decreases from the baseline (of the core studies 
[GLPG0634-CL-203 or GLPG0634-CL-204]) of testosterone by 50% with 
clinically relevant concurrent increase in LH, per investigator judgment c. Note 
that this study drug discontinuation criterion applies only to subjects with 
baseline hormone levels within normal limits. 
a In each case, there is a need for additional investigations, such as review of ethanol, recreational drug 
and dietary supplement consumption; testing for acute hepatitis A, B or C infection and biliary tract 
imaging should be promptly discussed with the medical monitor.
b If Creatinine Clearance has not been centrally reported, use the following: 2 sequential increases in 
serum creatinine>50% over the averaged of screening and baseline value (of the core studies 
[GLPG0634-CL-203 or GLPG0634-CL-204]).
c In each case, hormones in male subjects should be monitored monthly and if no positive dynamics is 
seen after 3 months from stopping filgotinib, referral to an andrologist should be considered.
Subjects withdrawing from the study will be encouraged to complete the same final 
evaluations as subjects completing the study according to the protocol (please refer to 
Section 8.7.2.3 Final Visit or EDV), particularly safety evaluations in the subject’s 
interest. The aim is to record data in the same way as for subjects who completed the 
study. 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).
Reasonable efforts will be made to contact subjects who are lost to follow-up. These 
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.
8.5
Data Safety Monitoring Board
A DSMB consisting of independent experts was convened to periodically review the 
accumulating safety data for the study and provide a recommendation on study 
continuation or early termination in case there were safety concerns. The specific 
responsibilities and composition of the DSMB were outlined in a separate document, the 
DSMB Charter. As of 01 April 2021, the independent DSMB reviews were discontinued 
as ongoing review of safety and efficacy data by the sponsor’s clinical study team was 
considered sufficient by the sponsor, based on the current development status of 
filgotinib and the open-label design of the study.


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8.5.1
Cardiovascular Endpoint Adjudication Committee
A Cardiovascular Endpoint Adjudication Committee (CV-EAC) consisting of at least 2 
cardiologists and governed by a Charter will be set up to perform adjudication of Major 
Adverse Cardiovascular Events occurring during the study. The adjudication of these 
events will be performed in a blinded fashion for the purposes of data analysis, and not 
for monitoring of subject safety. 
8.6
Investigational Products
8.6.1 Investigational Products Administered
The study medication is provided as 100 mg strength tablets of filgotinib for oral 
administration. Study medication was initially provided as 100 mg tablets containing the 
HCl salt. Patients have now been switched to 100 mg tablets containing the maleate salt.  
A separate Phase 1 study in healthy volunteers demonstrated that the bioavailability of 
filgotinib was similar when given as either the HCl salt tablet or as the maleate salt tablet 
(GS-US-417-3900, see IB6 for details).  This switch to the tablets containing the maleate 
salt will not occur in a specific country/study center until the required approvals from both 
the Competent Authorities and IECs/IRBs have been received and the new tablets are 
available at the study center. Subjects currently taking the HCl salt tablets will switch to 
the maleate salt tablets at their next planned visit after the maleate salt tablets are 
available at their study center.
The following doses will be evaluated:

Filgotinib 200 mg q.d.: 2 tablets of 100 mg filgotinib in the morning.

Filgotinib 100 mg b.i.d.: 1 tablet of 100 mg filgotinib in the morning and 1 tablet of 
100 mg filgotinib in the evening.

Filgotinib 100 mg q.d.: 1 tablet of 100 mg filgotinib in the morning, for subjects 
decreasing the dose to 100 mg q.d. in the case of intolerance or safety reasons. 
Subjects can return to the 200 mg daily dose after the reasons for decreasing the 
dose have resolved, and at the investigator’s discretion. Subjects can continue 
filgotinib 100 mg q.d. when deemed necessary by the investigator.
8.6.2
Identity of Investigational Products
The filgotinib study medication is provided as 100 mg strength tablets. Filgotinib HCl salt 
tablets are presented as an oral film-coated tablet containing filgotinib as HCl salt 
equivalent to 100 mg of filgotinib, microcrystalline cellulose, crospovidone, colloidal 
silicon dioxide and glycerol dibehenate. The tablets are coated with a nonfunctional 
film-coating using Opadry® II coating powder.


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Filgotinib maleate salt tablets, 100 mg are beige, debossed with “GSI” on one side and 
“100” on the other, capsule-shaped, biconvex, film-coated tablets for clinical use. Each 
tablet contains the equivalent of 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/PEG 3350, 
polyvinyl alcohol, talc, titanium dioxide, iron oxide yellow, and iron oxide red. 
8.6.3
Packaging, Labelling and Distribution
Filgotinib 100 mg HCl salt tablets are packaged in high density polyethylene (HDPE) 
bottles with a polypropylene closure and grouped in a carton box for shipment.
Filgotinib 100 mg maleate salt tablets are packaged in white, 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, aluminium-faced liner. 
Study drugs to be distributed to centers in the US and other participating countries shall 
be labeled to meet applicable requirements of the United States Food and Drug 
Administration (FDA), EU Guideline to Good Manufacturing Practice – Annex 13 
(Investigational Medicinal Products), and/or other local regulations.
Filgotinib 100 mg tablets should be stored at controlled room temperature of 25°C (77°F); 
excursions are permitted between 15°C and 30°C (59°F to 86°F). Storage conditions are 
specified on the label.
In case of temperature excursions (outside the permitted range mentioned above), the 
sponsor should immediately be contacted for evaluation of the excursion and further use 
of the study drug.
Until dispensed to the subjects, all drug products should be stored in a securely locked 
area, accessible only to authorized site personnel. To ensure the stability of the study 
drug and to ensure proper product identification, the drug product should not be stored 
in a container other than the container in which it is 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.
8.6.4
Method of Assigning Subjects to Treatment Groups
Following completion of one of the previous core studies (GLPG0634-CL-203 or 
GLPG0634-CL-204), subjects who are deemed by the investigator to benefit from 
continued therapy with study medication, will be offered the option to enter this Long-term 
Follow-up study. All subjects who opt to roll over into this study will be enrolled and will 
start the study at the same dose (filgotinib 200 mg daily, administered as either 200 mg 
q.d. or as 100 mg b.i.d., depending on the q.d./b.i.d. regimen of the preceding core 
study). Subjects who were on 24 weeks of placebo during the core study 


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GLPG0634-CL-203 will be randomly assigned to either 100 mg b.i.d. or 200 mg q.d. All 
other subjects will switch to 200 mg daily, keeping the same regimen (q.d. or b.i.d.) they 
had in the preceding core study.
This will be done according to a pre-specified randomization scheme prepared by an 
independent statistician within
. Upon qualification for the study, subjects 
will be randomized using a computerized interactive voice/web response system (IXRS) 
to filgotinib 200 mg q.d. 
or 100 mg b.i.d. in a 1:1 ratio.
For each subject at each visit, the clinic will contact the IXRS system and will be given 
the appropriate kit number to be dispensed. The kit will contain the relevant study 
medication until the next visit.
8.6.5
Selection of Doses in the Study
Details of the selection of doses in the study are presented in Section 6.7.
8.6.6
Selection and Timing of Dose for Each Subject
The study medication will be administered once daily (in the morning) with a glass of 
water for q.d. dosing, and twice daily (in the morning and evening) with a glass of water 
for b.i.d. dosing.
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, subjects should be cautioned not to double the next dose 
with the missed dose of study drug under any circumstances. In those cases, the missed 
dose should be returned to the study drug bottle.
Dose reduction during the study is allowed in the case of intolerance or safety reasons, 
where investigators will be allowed to decrease the dose from 200 mg q.d. to 100 mg q.d. 
or from 100 mg b.i.d. to 100 mg q.d. Subjects will then be allowed to return to the full 
dose of filgotinib (200 mg q.d. or 100 mg b.i.d. as appropriate) after the reasons for 
decreasing the dose have resolved, and at the investigator’s discretion. Subjects can 
continue filgotinib 100 mg q.d. when deemed necessary by the investigator.
Further dose reductions during the study are not allowed. Instead, the subject should 
either temporarily or permanently stop the study drug in accordance with Section 8.4).
8.6.7
Blinding
This is an open-label study. 
8.6.8
Prior and Concomitant Therapy 
Concomitant therapies taken for the long-term treatment of pre-existing conditions can 
continue during the study provided they were in accordance with the inclusion and 


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exclusion criteria of the previous core studies. It is preferred that these medications be 
continued without variation of dose or regimen during the study, as much as possible. 
At each study visit, the site will capture any and all medications taken by the subject 
since the last visit or during the visit (as applicable). Concomitant medications include 
prescription, non-prescription medications, therapies, dietary supplements, and 
minerals.
Subjects coming from the GLPG0634-CL-204 study will be allowed to restart MTX 
treatment, if deemed necessary according to the investigator’s clinical judgment.
In case new (non-prohibited) therapies need to be administered during the study, the 
risk/benefit to the subject should be carefully assessed and consideration given to the 
timing of any necessary introduction of new medications.
Permitted concomitant medications in the previous core studies and continuing during 
this study include: 

Non-steroidal anti-inflammatory drugs (NSAIDs) provided that the dose was stable 
and, if possible, is kept constant during this study; 

Subjects entering the open-label follow-up study had to be on a stable dose of 
≤10 mg/day oral prednisone or its equivalent during one of the 2 core studies. The 
dose of the oral steroid can be reduced or tapered off during this open-label follow-up 
study based on the investigator’s discretion;

Analgesics, other than NSAIDs, up to the maximum recommended doses may be 
used for pain as required. However, subjects must not take analgesics within 
24 hours before a visit where clinical efficacy assessments are performed and 
recorded.
If subjects were taking folic acid in the previous GLPG0634-CL-203 study as a preventive 
measure for MTX toxicity, this should be continued at a stable dose for the duration of 
the study. For those subjects in the previous GLPG0634-CL-204 study who are restarting 
MTX therapy, folic acid may should be given at >5 mg/week total dose or as per local 
clinical practice and maintained at a stable dose throughout the study. All local standard-
of-care practices for the administration of MTX, including laboratory testing, follow-up 
care and contraindications should be performed according to local standards of care 
throughout the study. The concomitant use of csDMARDs and medicines with known 
drug-drug interactions, such as the increased risk of hepatotoxicity and/or nephrotoxicity 
when MTX is administered with NSAIDs, salicylates, or folate antagonists, should be 
avoided, as much as possible, in accordance with clinical practice.
Males, and female subjects of childbearing potential, need to continue to use highly 
effective birth-control methods as outlined in Appendix 13.8. The use of hormonal 
contraceptives will be recorded in the Concomitant Therapy section of the eCRF. 
Applicable procedures and treatment guidance based on package inserts will be 
respected. 


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Hormone replacement therapy will be allowed in post-menopausal women if it was 
ongoing in the previous core studies, or if there is a new diagnosis of menopause. The 
use of hormone replacement therapy will be recorded in the Concomitant Therapy 
section of the eCRF. Applicable procedures and treatment guidance based on package 
inserts will be respected.
Vitamin, mineral or herbal supplementations are permitted during the study per 
judgment of investigator and should be kept at a stable dose and regimen, as much as 
possible.
Prohibited concomitant medications while on study drug include: 

Any DMARDs, other than background MTX, including oral or injectable gold, 
sulfasalazine, azathioprine, D penicillamine, cyclosporine, and leflunomide. 
Subjects in the previous GLPG0634-CL-204 study who were on a stable dose of 
antimalarials can continue with the same treatment.

Any cytotoxic agent, including chlorambucil, cyclophosphamide, nitrogen mustard, 
and other alkylating agents.

Use of any JAK inhibitor or other small molecule immunomodulator

Increases in dosage or dosing regimen of, or initiation of, potent P-gp inducers 
(e.g. rifampin, phenytoin, carbamazepine, and St. John’s wort). Subjects already on 
stable doses should continue per investigator judgment. 
Subjects may receive a maximum of 3 intra-articular injections of corticosteroid every 
12 months while participating in this open-label extension study. The dose of 
corticosteroid injected should not exceed the anti-inflammatory equivalent dose of 
prednisone 40 mg suspension. The dose and volume should be adjusted downward as 
appropriate to the size of the joint. For the analysis of the TJC68 and SJC66, these joints 
will be considered “not assessable” for 3 months from the time of the intra-articular 
injection.
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 
6 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:


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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.
8.6.9
Treatment Compliance and Drug Accountability
The investigator or designated study personnel will maintain a log of all drug dispensed 
and returned. Drug supplies for each subject will be inventoried and accounted for 
throughout the study.
Subjects with a poor compliance (<80% or >120%) will be retrained by the study site. If 
study drug compliance remains <80% or >120% between study visits, or if the subject 
missed more than 2 visits, the subject will be evaluated for potential discontinuation. Any 
discontinuation should be done in consultation with the medical monitor.
8.7
Study Procedures
All planned study assessments are presented in the flow chart in Section 8.8.1.3.
8.7.1
Pre-treatment
Written informed consent will be obtained before any study-related procedures and/or 
assessments are performed. 
8.7.1.1
Entry Visit (Extension Visit 1, Day -1)
The Entry Visit (Visit 1) will take place on Day -1 relative to the start of the study 
medication intake. There will be no gap between the core studies and the open-label 
extension study.

Subjects will be assessed for eligibility against the inclusion and exclusion criteria.

Entry Visit data will be those collected at the Week 24 visit from the previous core 
study 
in 
which 
the 
subject 
has 
participated 
(GLPG0634-CL-203 
or 
GLPG0634-CL-204) for physical examination, 12-lead ECG, vital signs, clinical 
laboratory tests (including serum pregnancy test), SJC66, TJC68, Physician’s Global 
Assessment, Patient’s Global Assessment, health assessment questionnaire – 
disability index (HAQ-DI), FACIT fatigue scale, and SF-36 questionnaire. Data on 
demographics, baseline characteristics, and medical history will be retrieved from the 


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Screening visit of the previous core studies. Data will not be re-entered in the 
GLPG0634-CL-205 eCRF but will be retrieved from the preceding core study 
database during statistical programming.

Urine (dipstick) pregnancy test for females of childbearing potential.

Tuberculosis (TB) blood test (QuantiFERON-TB gold testa) will be performed.

Any new AEs that have occurred since signing the informed consent form (ICF) will 
be documented.

Any ongoing or unresolved AEs and concomitant medications from the preceding 
core study will be documented on the GLPG0634-CL-205 AE and concomitant 
medication pages of the eCRF, respectively.

IXRS call.
a In case of a positive or confirmed indeterminate result for QuantiFERON-TB gold test: 1.) Permanent 
withdrawal of the subject from the study; 2.) Consultation with the local infectious disease specialist is 
highly recommended to investigate if the patient has active or latent TB or no TB
When all the Entry Visit procedures have been performed and the investigator has 
confirmed the subject’s eligibility for the study, the study medication will be dispensed to 
the subject. The subject will start taking the study medication on Day 1 and subsequent 
visits will be scheduled.
8.7.2
Treatment Period
In addition to the procedures noted below, urine pregnancy tests will be done for female 
subjects of childbearing potential every 4 weeks during study participation through the 
follow-up visit using home urine pregnancy tests that will be provided to the subject. The 
site will call the subject every 4 weeks to obtain results of these pregnancy tests and will 
record the information in the source documents and CRF. If a positive urine pregnancy 
test is reported, the subject will be asked to return to the clinic for a confirmatory serum 
pregnancy test. Refer to Appendix 13.8 for more information.
8.7.2.1
Quarterly Evaluation Visit (QEV) 
A QEV visit will take place every 12 weeks ±1 week relative to the start of the study 
medication intake.

Subjects will be assessed for eligibility against the withdrawal criteria.

Any remaining study medication as well as empty study medication containers will 
be returned to the investigator and an accountability check performed.

A physical examination will be performed.

Weight is measured at all visits.


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
A 12-lead ECG will be performed.

Any AEs that have occurred since signing the ICF will be documented and any 
changes in concomitant medication reported.

Vital signs will be measured.

Hematology, clinical chemistry, hormones (for male subjects only), and urinalysis 
(dipstick and, in case of abnormal dipstick result, microscopy) tests will be performed 
on samples collected at this visit. A urine pregnancy test will be performed on females 
of childbearing potential.

Serum CRP will be measured.

SJC66 and TJC68 evaluations will be performed.

Physician’s and Patient’s Global Assessments of Disease Activity will be completed.

The subject will complete the HAQ-DI.

IXRS call.
When all of these procedures have been performed, the study medication will be 
dispensed, and the date of the next visit confirmed.
8.7.2.2
Annual Visit (AV) 
An annual visit (AV) will take place at 48 weeks ±1 week relative to the start of the study 
medication intake. All of the procedures as outlined in the QEV will be performed. In 
addition, the following will be performed:

A serum pregnancy test will be performed on females of childbearing potential (ie, no 
urine pregnancy test will be performed).

TB blood test (QuantiFERON-TB gold test) will be performed.

Weight is measured. 

The subject will complete the FACIT fatigue scale and SF-36 questionnaire.
When all of the procedures have been performed, the study medication will be 
dispensed, and the date of the next visit confirmed.
8.7.2.3
Final Visit or Early Discontinuation Visit (EDV)
Following marketing, local (if applicable) regulatory and/or pertinent local reimbursement 
approval of the study medication, subjects should return to their next quarterly scheduled 


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study visit as specified in the protocol. This visit will serve as a Final Visit and the subjects 
will be considered as having completed the treatment part of the study.

Any remaining study medication as well as empty study medication containers will 
be returned to the investigator and an accountability check performed.

A physical examination will be performed.

Weight is measured. 

A 12-lead ECG will be performed.

Any AEs that have occurred since signing the ICF will be documented and any 
changes in concomitant medication reported.

Vital signs will be measured.

Hematology, clinical chemistry, hormones (for male subjects only), and urinalysis 
(dipstick and, in case of abnormal dipstick result, microscopy) tests will be performed 
on samples collected at this visit. A serum pregnancy test will be performed on 
females of childbearing potential.

Serum CRP will be measured.

SJC66 and TJC68 evaluations will be performed.

Physician’s and Patient’s Global Assessments of Disease Activity will be completed.

The subject will complete the HAQ-DI.

The subject will complete the FACIT fatigue scale and SF-36 questionnaire.
8.7.3
Follow-up Visit 
A Follow-up Visit will take place 2 weeks (+/- 4 days) after the Final Visit or the EDV.

A physical examination will be performed.

Weight is measured. 

A 12-lead ECG will be performed.

Any AEs that have occurred since signing the ICF will be documented and any 
changes in concomitant medication reported.

Vital signs will be measured.


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
Hematology, clinical chemistry (without CRP), hormones (for male subjects only), 
and urinalysis (dipstick and, in case of abnormal dipstick result, microscopy) tests 
will be performed on samples collected at this visit. A serum pregnancy test will be 
performed on females of childbearing potential.
8.7.4
Duration of Treatment
Subjects participating in the study will be requested to attend a series of visits throughout 
the study, including: an Entry Visit (Day -1 [Extension Visit 1]), QEVs every 12 weeks, a 
Final Visit, and a Follow-up Visit approximately 2 weeks after the Final Visit. In case of 
early withdrawal, an EDV will be scheduled. Home urine pregnancy testing will also be 
required for female subjects of childbearing potential every 4 weeks during study 
participation through the follow-up visit using home urine pregnancy tests provided to the 
subject (refer to Appendix 13.8).
The duration of the participation and treatment for any subject in this study is expected 
to last for several years (from Entry visit to Follow-up Visit) and will be determined by the 
sponsor based on the following:

Open label period (approximately 96 months).

Marketing Application Approval/Withdrawal in Country of Residence.

Applicable local reimbursement procedures are in place.
Sites will be notified once these criteria are met.
Following marketing, local (if applicable) regulatory and/or pertinent local reimbursement 
approval of the study medication, subjects should return to their next quarterly scheduled 
study visit as specified in the protocol. This visit will serve as a Final Visit and the subjects 
will be considered as having completed the treatment part of the study. A Follow-up Visit 
will take place approximately 2 weeks after the Final Visit or the EDV.
8.8
Efficacy and Safety Variables 
The flow chart in Section 8.8.1.3 shows the planned study assessments.
8.8.1
Efficacy and Safety Measurements Assessed and Flow Chart 
8.8.1.1
Efficacy Assessments
8.8.1.1.1 Evaluation of Disease Activity
Efficacy assessments (excluding FACIT and SF-36) will be carried out at every visit, 
except the Follow-up Visit. FACIT and SF-36 will be carried out at the AV and the 
Final Visit/EDV.


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Each of 68 joints will be evaluated for tenderness, and each of 66 joints will be evaluated 
for swelling, except upon receipt of an intra-articular injection of corticosteroid in the 
previous 3 months, where joints will be classed as not assessable (Appendix 13.2). 
A joint assessor with adequate training and experience in performing joint assessments 
will be designated at each study site to perform all joint assessments. The joint assessor 
should preferably be a rheumatologist; however, if a rheumatologist is not available, it 
should be a health care worker with at least one years’ experience in performing joint 
assessments. The assessor should remain the same throughout the study per subject, 
as much as possible. It is required that the designated joint assessor identify an 
appropriate back up assessor to provide coverage if the designated joint assessor is 
absent.
8.8.1.1.2 Patient’s Global Assessment of Disease Activity
The Patient’s Global Assessment of Disease Activity will be recorded on a 0 to 100 visual 
analog scale (VAS), with 0 indicating “very well” and 100 indicating “very poor” to the 
question “Considering all the ways arthritis affects you, how well are you doing today?” 
(Appendix 13.3).
8.8.1.1.3 Physician’s Global Assessment of Disease Activity
The Physician’s Global Assessment of Disease Activity will be recorded on a 0 to 
100 mm VAS, with 0 indicating “no disease activity” and 100 indicating “extreme disease 
activity”. The evaluating physician and the subject must complete the global 
assessments independently of each other (Appendix 13.4).
8.8.1.1.4 Health Assessment Questionnaire – Disability Index (HAQ-DI)
The functional status of the subject will be assessed using the HAQ-DI. This 20-question 
instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 
domains (dressing, arising, eating, walking, hygiene, reaching, gripping and 
errands/chores). Responses are scored on a 4-point Likert scale from 0 indicating no 
difficulty to 3, indicating inability to perform a task in that area. The need for aids/devices 
or help from another person will also be recorded. The HAQ-DI total score ranges from 
0 to 3 with higher scores indicating greater dysfunction (Appendix 13.5).
As part of the HAQ-DI, subjects will be asked to assess their average pain during the 
last week on a 0 to 100 mm VAS, with 0 indicating “no pain” and 100 indicating “severe 
pain”. This assessment should be completed before the joint examination. This pain 
score will be used to derive the ACR20/50/70.
8.8.1.1.5 FACIT Fatigue Scale
The FACIT fatigue scale (version 4) measures an individual’s level of fatigue during their 
usual daily activities over the past week. It consists of 13 questions with a 7-day recall 
period on a 5-point Likert scale, with 0 indicating “not at all” and 4 indicating “very much”. 
The total score ranges from 0 to 52. The higher the score, the better the quality of life 
(Appendix 13.6).


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8.8.1.1.6 36-Item Short-form Health Survey (SF-36)
The health–related quality of life of the subject will be assessed using the SF-36 (version 
2) with a 4-week recall period. This consists of 36 questions belonging to 8 domains in 2 
components:

Physical well-being: 4 domains: physical functioning (10 items), role physical 
(4 items), bodily pain (2 items), and general health (GH) perceptions (5 items).

Mental well-being: 4 domains: vitality (4 items), social functioning (2 items), 
role emotional (3 items), and mental health (5 items).
The remaining item (health transition) is not part of the above domains but is kept 
separately (Appendix 13.7).
These scales will be rescaled from 0 to 100 (converting the lowest possible score to 
0 and the highest possible score to 100), with higher scores indicating a better quality of 
life.
8.8.1.2
Safety Assessments
8.8.1.2.1 Adverse Event Definitions and Reporting
8.8.1.2.1.1 Definitions
ICH, FDA and European guidance will be followed for AE reporting.
Adverse Event
An AE is any untoward medical occurrence in a clinical study subject administered a 
medicinal (investigational or non-investigational) product. An AE does not necessarily 
have a causal relationship with the treatment. An AE can therefore be any unfavorable 
and unintended sign (including an abnormal finding), symptom, or disease temporally 
associated with the use of a medicinal (investigational or non-investigational) product, 
whether or not related to that medicinal (investigational or non-investigational) product.
Serious Adverse Event
An SAE is any untoward medical occurrence that at any dose meets any of the following 
conditions:

results in death.

is life-threatening: the subject is at risk of death at the time of the event. It does not 
refer to an event that hypothetically might cause death if it were more severe.

requires inpatient hospitalization or prolongation of existing hospitalization.

results in persistent or significant disability/incapacity.


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
is a congenital anomaly/birth defect.

is a medically significant event that 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 listed in the definitions above.
Unexpected Adverse Event/Reference Safety Information
An AE is considered unexpected if the nature or intensity is not consistent with the 
applicable product reference safety information. For GLPG0634, the expectedness of 
AEs will be determined by whether or not it is an ADR listed in the IB.
Intensity of an Adverse Event
Each AE must be rated on a 3-point scale of increasing intensity:

Mild: Transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required.

Moderate: Mild to moderate limitation in activity; some assistance may be needed; 
no or minimal medical intervention/therapy required.

Severe: Marked limitation in activity; some assistance usually required; medical 
intervention/therapy required; hospitalization possible.
If there is a change in intensity of an ongoing AE, it must be recorded as a separate 
event.
Causality Assessment
The following decision choice will be used by the investigator to describe the causality 
assessment between the reported event and the investigational medicinal product. 

Unrelated: No relationship between the AE and the administration of investigational 
product; related to other etiologies such as concomitant medications or subject’s 
clinical state.

Unlikely: Event or laboratory test abnormality, with a time to study medication intake 
that makes a relationship improbable (but not impossible). Disease or other drugs 
provide plausible explanations.

Possible: Event or laboratory test abnormality, with reasonable time relationship to 
study medication intake which could also be explained by disease or other drugs. 
Information on drug withdrawal may be lacking or unclear.

Probable: Event or laboratory test abnormality, with reasonable time relationship to 
study medication intake. Event unlikely to be attributed to disease or other drugs. 
Response to withdrawal is clinically reasonable and rechallenge not required.


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
Certain: Event or laboratory test abnormality, with plausible time relationship to study 
medication intake which cannot be explained by disease or other drugs. Response 
to withdrawal is plausible (pharmacologically, pathologically). Event definitive 
pharmacologically or phenomenologically (ie, an objective and specific medical 
disorder or a recognized pharmacological phenomenon). Rechallenge satisfactory, if 
necessary.
Action Taken Regarding Investigational Product
The action taken must be described by choosing among:

Dose not changed: In case no action is taken regarding the study medication.

Study medication permanently withdrawn: In case a subject is permanently 
withdrawn from the study.

Study medication temporarily withdrawn: In case the study medication is temporarily 
withdrawn.

Dose reduction: If a subject’s daily dose is adjusted from 200 mg to 100 mg 
(q.d., once daily in the morning).

Not applicable: Other situations (eg, in case an AE started after the last study 
medication administration).
Outcome
Each AE must be rated by choosing among:

Recovered/Resolved.

Recovered/Resolved with sequelae.

Not recovered/Not resolved.

Fatal.

Recovering/Resolving.

Unknown.
8.8.1.2.1.2 Recording Adverse Events
AEs will be recorded from the signature of ICF until the final Follow-up Visit. In case an 
AE is ongoing at that time, it will be followed up until resolution or until stabilization by 
the investigator’s medical judgment.






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Clinical Chemistry
Creatinine, 
blood 
urea 
nitrogen, 
aspartate 
aminotransferase, 
ALT, 
gamma-glutamyltransferase, alkaline phosphatase, total bilirubin, amylase, lipase, 
albumin, total protein, sodium, potassium, chloride, glucose, uric acid, total cholesterol, 
HDL- and LDL-cholesterol, triglycerides, calcium, and phosphorus.
Serum CRP will be measured at every visit except the Follow-up Visit.
Serum pregnancy test for females of childbearing potential is performed at the AV, Final 
Visit/EDV and the Follow-up Visit.
Hormone tests (for male subjects only)
Testosterone (total and free), LH, FSH, PRL, and inhibin B.
Urinalysis
pH, glucose, ketone bodies, indicators of blood and WBC, and protein (quantitative).
Urine pregnancy test for females of childbearing potential is performed at Entry Visit and 
QEV, and also performed every 4 weeks during the dosing period through 35 days after 
their last dose of study drug using home pregnancy tests that will be provided to them. 
Refer to Appendix 13.8 for details.
Other
TB blood (QuantiFERON-TB Gold) test at Entry Visit and AV. 
8.8.1.2.3 Vital Signs
Vital signs (blood pressure [systolic and diastolic] and HR) will be recorded as described 
in the flow chart in a standardized manner, ie, after the subject has rested in the sitting 
position for 5 minutes. 
8.8.1.2.4 Physical Examination
A physical examination will be performed at times as described in the flow chart. Any 
changes will be recorded. 
8.8.1.2.5 Other Safety Assessments 
12-Lead ECG
A resting 12-lead ECG will be performed at times presented in the flow chart.
Subjects should rest for at least 5 minutes in the supine position before ECG evaluation.


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Parameters to be recorded in the eCRF include: HR, RR, QRS, uncorrected QT, 
morphology, and rhythm analysis. QTcF will be derived during the statistical analysis. 
ECGs will be interpreted by the investigator for clinical significance and results will be 
entered into the eCRF.


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8.8.1.3
Flow Chart
Event
Entry Visit
Treatment perioda
FUV
Study scheduleb
D -1c
QEV (q12 weeks)
AV (q48 weeks)
FV/EDV
FV + 2 weeks
Or
EDV + 2 weeks
Informed consent
X
Inclusion/
exclusion criteria
X
Withdrawal criteria
X
X
Physical examination
X
X
X
X
Pregnancy testd
X
X
X
X
X
12-Lead ECG
X
X
X
X
Vital signse
X
X
X
X
TB blood test
X
X
Clinical laboratory testsf
X
X
X
X
IXRS call
X
X
X
X
Study medication dosing
Serum CRP
X
X
X
SJC66
X
X
X
TJC68
X
X
X
Physician’s global assessment
X
X
X


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Event
Entry Visit
Treatment perioda
FUV
Study scheduleb
D -1c
QEV (q12 weeks)
AV (q48 weeks)
FV/EDV
FV + 2 weeks
Or
EDV + 2 weeks
Patient’s global assessment
X
X
X
HAQ-D
X
X
X
FACIT fatigue scale
X
X
SF-36 questionnaire
X
X
AE assessment
Concomitant medications
a.
During the treatment period, a visit time window of ±1 week is allowed for each quarterly visit.
b.
QEV=Quarterly Evaluation Visit every 12 weeks; AV=Annual Visit every 48 weeks; FV=Final Visit; EDV=Early Discontinuation Visit; 
FUV=Follow-Up Visit.
c.
Entry Visit data are those collected at the last visit from the previous core study in which the subject has participated (GLPG0634-CL-203 or 
GLPG0634-CL-204) for physical examination, 12-lead ECG, vital signs, clinical laboratory tests (including serum CRP and serum 
pregnancy test), SJC66, TJC68, Physician’s Global Assessment, Patient’s Global Assessment, HAQ-DI, FACIT fatigue scale, and SF-36 
questionnaire, with the exception of demographics, baseline disease characteristics, and medical history. 
d.
For female subjects of childbearing potential only. Urine pregnancy test will be performed at Entry Visit and QEV and serum pregnancy test 
will be performed at AV, Final Visit/EDV and Follow-up Visit. In addition, home urine pregnancy testing will be performed every 4 weeks 
using home testing kits provided to the subject, as described in Appendix 13.8.
e.
Vital signs are defined as heart rate and blood pressure (systolic and diastolic).
f.
Refer to Section 8.8.1.2.2.


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8.8.2
Appropriateness of Measurements
The safety and efficacy assessments are widely used and generally recognized as 
reliable, accurate, and relevant to the disease condition.
8.9
Statistical Methods
8.9.1
Statistical and Analytical Plans
A detailed statistical analysis plan will be created and finalized prior to database lock.
8.9.1.1
Datasets or Populations Analyzed
All subjects who received at least one dose of study medication in the 
GLPG0634-CL-205 study will be included in the safety analysis.
All subjects who received at least one dose of study medication in the 
GLPG0634-CL-205 study will be included in the efficacy analysis.
As it is optional that MTX is restarted for subjects rolling over from the 
GLPG0634-CL-204 study, the analysis tables may keep subjects with/without MTX 
background therapy separated as well as pooled.
Other subgroups may be studied separately, when the sample size is considered to be 
of relevant size.
8.9.1.2
Demographic and Other Baseline Characteristics
Demographic characteristics will be listed. Demographic and baseline clinical 
characteristics; trial termination reasons; concomitant medications; and drug exposure 
will be summarized using appropriate descriptive statistics, as applicable.
8.9.1.3
Safety Variables
Clinical safety will be evaluated by assessing treatment-emergent AEs (TEAEs), physical 
examinations, laboratory assessments, ECG results, and vital signs results. The safety 
analysis may combine the data of all 3 studies (GLPG0634-CL-203, GLPG0634-CL-204, 
and GLPG0634-CL-205). 
A treatment-emergent analysis of AEs will be done, based on the start date of the AE. 
TEAE (AE and SAE) preferred terms, intensity, frequency, relationship to study 
medication, dose reductions, and temporary/permanent treatment stops will all be 
tabulated. An additional analysis based on patient-years of exposure may be added 
when deemed useful.
Original results and changes from baseline will be summarized for all laboratory, vital 
signs, and ECG parameters, intended to detect any changes in safety parameters that 
could be attributed to GLPG0634 dosing. No imputations will be done for safety data in 
cases where subjects discontinued the study prematurely. 


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Further subgroup analyses (e.g., a selection of TEAEs with an onset date during the first 
weeks or months, or a division according to the mean actual dose) and exploratory 
analyses may be added when deemed appropriate.
8.9.1.4
Efficacy Variables
The efficacy analysis may combine the data of all 3 studies (GLPG0634-CL-203, 
GLPG0634-CL-204, and GLPG0634-CL-205).
Definition of Efficacy Endpoints
ACR20
The ACR response is a measurement of improvement in multiple disease assessment 
criteria. The ACR20 response is defined as:
≥20% improvement from Baseline in SJC66 and TJC68
AND
≥20% improvement from Baseline in at least 3 of the following 5 assessments:

Pain (VAS) in cm (from HAQ-DI).

Patient’s Global Assessment of Disease Activity (VAS) in cm.

Physician’s Global Assessment of Disease Activity (VAS) in cm.

Patient’s Assessment of Physical Function as measured by HAQ-DI.

CRP in mg/dL or mg/L.
ACR50 and ACR70
ACR50 and ACR70 are similarly defined as ACR20, except the improvement threshold 
from Baseline is 50% and 70%, respectively. 
ACR-N
The ACR-N7 is the smallest percentage improvement in swollen and tender joints and 
the median of the remaining 5 core parameters, and is expected to be more sensitive to 
change than the ACR20, ACR50, or ACR70.
ACR-N = MIN [%improvement in TJC68, 
%improvement in SJC66, 
MED %improvement in (Patient’s Global Assessment, Physician’s
Global Assessment, patient’s assessment of pain, HAQ-DI, CRP)]


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ACR/EULAR Remission
A subject’s disease activity status can be defined as being in remission:
when scores on the TJC28, SJC28, CRP (actual value in mg/dL), and Patient Global 
Assessment of Disease Activity (cm) are all ≤1.
Simplified Disease Activity Index (SDAI)
The SDAI9 is the numerical sum of 5 outcome parameters: TJC28, SJC28, Patient’s 
Global Assessment of Disease Activity (in cm), Physician’s Global Assessment of 
Disease Activity (in cm), and CRP (mg/dL).
SDAI = TJC28 + SJC28 + Patient’s Global Assessment of Disease Activity (VAS in cm) 
+ Physician’s Global Assessment of Disease Activity (VAS in cm) + CRP (mg/dL)
The SDAI can be categorized:

High disease activity: SDAI >26

Moderate disease activity: [11,26]

Low disease activity: [3.3,11]

Remission: ≤3.3 
Clinical Disease Activity Index (CDAI)
The CDAI9 is the SDAI modified to exclude CRP.
CDAI = TJC28 + SJC28 + Patient’s Global Assessment of Disease Activity (VAS in cm) 
+ Physician’s Global Assessment of Disease Activity (VAS in cm)
The CDAI can also be categorized:

High disease activity: >22

Moderate disease activity: [10,22]

Mild disease activity: [2.8,10]

Remission: ≤2.8
Disease Activity Score 28 Joints Corrected for CRP (DAS28[CRP])
The DAS28(CRP)10 is a statistically derived index combining tender joints (28 joints), 
swollen joints (28 joints), CRP, and the Patient’s Global Assessment of Disease Activity 
(GH). DAS28(CRP) is defined as follows:


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DAS28(CRP) = 0.56 x SQRT(TJC28) + 0.28 x SQRT(SJC28) + 0.36 x Ln(CRP+1) + 
0.014 x GH + 0.96,
Where:
TJC28 is 28 joint count for tenderness
SJC28 is 28 joint count for swelling. 
Ln(CRP+1) is the natural logarithm of (CRP value [mg/L] + 1)
SQRT is square root
GH is the Patient’s Global Assessment of Disease Activity on a 100 mm VAS 
Categorization of the DAS28(CRP) scores:
High disease activity: >5.1
Moderate disease activity: [3.2,5.1]
Low disease activity: [2.6,3.2]
Remission: <2.6
EULAR Response
A second categorization of the DAS28(CRP) will be done according to the following 
table11:
Improvement in DAS28(CRP) from Baseline:
Actual DAS28(CRP)
>1.2
>0.6 and ≤1.2
≤0.6
≤3.2
Good
Moderate
None
>3.2 and ≤5.1
Moderate
Moderate
None
>5.1
Moderate
None
None
Quality of Life - FACIT Fatigue Scale and SF-36
Quality of life will be assessed using the FACIT fatigue scale and the SF-36 
questionnaire. The appropriate (sub)totals will be derived according to the scale’s scoring 
algorithm.
Methods of Analysis
Efficacy data (ACR20, ACR50, ACR70, ACR-N, DAS28(CRP), EULAR response, and 
ACR/EULAR remission, components of the ACR, SDAI, and CDAI, and the quality of life 
data (FACIT fatigue scale and SF 36 questionnaire)) will be analyzed descriptively. 
Details on the analysis will be specified in the statistical analysis plan. A descriptive 
sensitivity analysis by country and geographic region may be performed for the ACR 
criteria response rates.
Further exploratory analyses may be added when deemed useful to understand the data.


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Graphical presentations may be added to facilitate the overall interpretation of the study 
results.
8.9.1.5
Interim Analyses
Safety data will be reviewed by the sponsor on an ongoing basis. Details are presented 
in Section 8.5.
Interim analyses of efficacy and/or safety data may be added when such data are needed 
(e.g., when the integrated safety and efficacy analyses will be performed for the 
registration file). If such an interim analysis would be done, no correction for multiplicity 
will be applied because all analyses will be mainly descriptive.
8.9.2
Determination of Sample Size
It is expected that around 70% of the subjects in the previous core studies 
GLPG0634-CL-203 
(N=595, 
approximately) 
and 
GLPG0634-CL-204 
(N=280, 
approximately) will roll over into this study, corresponding to a sample size of roughly 
600 subjects: 0.7 x (595 subjects in study 203 + 280 subjects in study 204) = 612.
8.10 Quality Assurance and Quality Control 
8.10.1
Audit and Inspection
Study centers and study documentation may be subject to Quality Assurance audit 
during the course of the study by 
, the sponsor, or its nominated 
representative. In addition, inspections may be conducted by regulatory authorities at 
their discretion.
8.10.2
Monitoring
Data for each subject will be recorded on an eCRF. Data collection must be completed 
for each subject who signs an ICF and is administered study medication.
In accordance with GCP and ICH guidelines, the study monitor will carry out source 
document verification at regular intervals to ensure that the data collected in the eCRF 
are accurate and reliable. The frequency of monitoring visits will be determined by the 
rate of subject recruitment. 
The following will be reviewed at these visits:

Compliance with the protocol.

Consent procedure.

Source documents.

AE procedures.

Storage and accountability of materials.


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The monitoring visits also provide the sponsor with the opportunity to ensure the 
investigator’s obligations and all applicable ICH or health authority regulation 
requirements are being fulfilled.
The investigator must permit the monitor, the IEC/IRB, the sponsor’s internal auditors, 
and representatives from regulatory authorities’ direct access to all study-related 
documents and pertinent hospital or medical records for confirmation of data contained 
within the eCRFs. Subject confidentiality will be protected at all times.
8.10.3
Data Management and Coding
 will be responsible for activities associated with the data management of 
this study. This will include setting up a relevant database and data transfer mechanisms, 
along with appropriate validation of data and resolution of queries. Data generated within 
this clinical study will be handled according to the relevant standard operating 
procedures of the data management and biostatistics departments of 
.
Study centers will enter data directly into the electronic data capture (EDC) system by 
completing the eCRF via a secure internet connection. Data entered into the eCRF must 
be verifiable against source documents at the study center. Data to be recorded directly 
on the eCRF (without prior written or electronic record) will be identified and the eCRF 
will be considered the source document. Any changes to the data entered into the EDC 
system will be recorded in the audit trail and will be FDA Code of Federal Regulations 
(CFR) 21 Part 11 compliant.
Data entered into the eCRF will be validated as defined in the data validation plan. 
External data checks will be programmed where appropriate (eg, for laboratory data, 
ECGs) as well as for cross table checking between eCRFs (eg, AE and concomitant 
medication forms). 
Medical coding will use Medical Dictionary for Regulatory Activities for concomitant 
diseases and AEs and World Health Organization Drug dictionary for medications.
Missing or inconsistent data will be queried in writing to the investigator for clarification. 
Subsequent modifications to the database will be documented.


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9
Records and Supplies
9.1
Drug Accountability
On receipt of the study medication, the investigator (or deputy) will conduct an inventory 
of the supplies and verify that study medication supplies are received intact and in the 
correct amounts before completing a supplies receipt. The investigator will retain a copy 
of this receipt at the study center and return the original receipt to the study monitor. The 
inventory of supplies at each study center may be checked at any time during the study 
by the monitor.
It is the responsibility of the study monitor to ensure that the investigator (or deputy) has 
correctly documented the pharmaceutical formulation (tablets) and the amount received, 
dispensed, and returned of the study medication on the dispensing log that will be 
provided. A full drug accountability log will be maintained at the study center at all times. 
The study monitor will arrange collection/destruction of unused study medication 
returned by the subject as needed throughout the study. The study monitor will also 
perform a final inventory of study medication at the close-out visit in the study center. All 
discrepancies must be accounted for and documented.
9.2
Financing and Insurance
Financing and insurance of this study will be outlined in a separate agreement between 
 and the sponsor.


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10 Ethics
10.1 Independent Ethics Committee or Institutional Review Board
Before initiation of the study at each study center, the protocol, the ICF, other written 
material given to the subjects, and any other relevant study documentation will be 
submitted to the appropriate IEC/IRB. Written approval of the study and all relevant study 
information must be obtained before the study center can be initiated or the study 
medication is released to the investigator. Any necessary extensions or renewals of 
IEC/IRB approval must be obtained for changes to the study such as modification of the 
protocol, the ICF, or other study documentation. The written approval of the IEC/IRB 
together with the approved ICF must be filed in the study files.
The investigator will report promptly to the IEC/IRB any new information that may 
adversely affect the safety of the subjects or the conduct of the study. The investigator 
will submit written summaries of the study status to the IEC/IRB as required. On 
completion of the study, the IEC/IRB will be notified that the study has ended.
10.2 Regulatory Authorities
The protocol, name, and study center of the investigators, the votes of the IEC(s)/IRB(s), 
as well as other relevant study documentation will be submitted to the Regulatory 
Authorities of the participating countries, according to local/national requirements, for 
review and approval before the beginning of the study. On completion of the study, the 
Regulatory Authorities will be notified that the study has ended.
10.3 Ethical Conduct of the Study
The investigator(s) and all parties involved in this study should conduct the study in 
adherence to the ethical principles based on the Declaration of Helsinki, GCP, 
ICH guidelines, and the applicable national and local laws and regulatory requirements.
10.4 Informed Consent
The investigator is responsible for obtaining written informed consent from each 
individual participating in this study after adequate explanation of the aims, methods, 
objectives, and potential hazards of the study and before undertaking any study-related 
procedures. The study investigator must ensure that the potential risk of infertility is 
discussed with all male subjects during the informed consent process.  The investigator 
must use the most current IRB/IEC approved consent form for documenting written 
informed consent. Each informed consent (or assent as applicable) will be appropriately 
signed and dated by the subject and the person conducting the consent discussion, and 
also by an impartial witness if required by IRB/ IEC or local requirements. 
10.5 Subject Confidentiality
Monitors, auditors, and other authorized agents of the sponsor and/or its designee, the 
IEC(s)/IRB(s) approving this research, and the United States FDA, as well as that of any 
other applicable agency(ies) in other countries, will be granted direct access to the study 


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subjects’ original medical records for verification of clinical study procedures and/or data, 
without violating the confidentiality of the subjects to the extent permitted by the law and 
regulations. In any presentations of the results of this study or in publications, the 
subjects’ identity will remain confidential.


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11 Reporting and Publication, Including Archiving
The name of the coordinating investigator will be documented separately. During the 
study, the sponsor will contact some of the participating investigators and assess their 
interest in taking up the role of the coordinating investigator. Once selected the 
coordinating investigator will help review and sign-off the final clinical study report.
Essential documents are those documents that individually and collectively permit 
evaluation of the study and quality of the data produced. After completion of the study, 
all documents and data relating to the study will be kept in an orderly manner by the 
investigator in a secure study file. This file will be available for inspection by the sponsor 
or its representatives. Essential documents should be retained for 2 years after the final 
marketing approval in an ICH region or for at least 2 years since the discontinuation of 
clinical development of the test drug/investigational product or according to local 
regulation if they state otherwise. It is the responsibility of the sponsor to inform the study 
center of when these documents no longer need to be retained. The investigator must 
contact the sponsor before destroying any study related documentation. In addition, all 
subject medical records and other source documentation will be kept for the maximum 
time permitted by the hospital, institution, or medical practice.
The sponsor must review and approve any results of the study or abstracts for 
professional meetings prepared by the investigator(s). Published data must not 
compromise the objectives of the study. Data from individual study centers in multi-center 
studies must not be published separately.


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12 References
1.
Smolen JS, Steiner G, Therapeutic strategies for rheumatoid arthritis. Nat Rev 
Drug Discov. 2003;2:473-488.
2.
Smolen JS et al., New therapies for treatment of rheumatoid arthritis. Lancet. 
2007;370:1861-1874.
3.
Firestein GS, Evolving concepts of rheumatoid arthritis. Nature. 2003;15;423:356 
361.
4.
EMEA website: http://www.emea.europa.eu/htms/human/epar/a.htm.
5.
Nature Biotechnology, 2011, Volume 29, 467-468.
6.
Filgotinib Investigator’s Brochure. Edition 11, 03 July 2016. 
7.
Jeffrey N. Siegel, Bo-Guang Zhen, Arthritis & Rheumatism. 2005 Jun. 52; 
6:1637-1641.
8.
American College of Rheumatology/European League Against Rheumatism 
Provisional Definition of Remission in Rheumatoid Arthritis for Clinical Trials David 
T. Felson, Josef S. Smolen, George Wells, et al. Arthritis & Rheumatism. 2011 
Mar. 63; 3:573–586.
9.
The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity 
Index (CDAI): A review of their usefulness and validity in rheumatoid arthritis D. 
Aletaha, J. Smolen. Clin Exp Rheumatol. 2005; 23 (Suppl. 39):S100-S108.
10.
Modified disease activity scores that include twenty-eight-joint counts. 
Development and validation in a prospective longitudinal study of patients with 
rheumatoid arthritis. Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van 
de Putte LB, van Riel PL. Arthritis Rheum. 1995 Jan;38(1):44-8.
11.
The Disease Activity Score and the EULAR response criteria. J. Fransen, P.L.C.M. 
van Riel. Clin Exp Rheumatol 2005; 23 (Suppl. 39):S93-S99.


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13 Appendices
13.1 Investigator Signature Page
Protocol Title:
A multicenter, open-label, long-term follow-up safety and efficacy 
study of GLPG0634 treatment in subjects with moderately to 
severely active rheumatoid arthritis
Protocol Number:
GLPG0634-CL-205
Investigator Statement
I have read the protocol, including all appendices, and I agree that it contains all 
necessary details for me and my staff to conduct this study as described. I will conduct 
this study as outlined herein and will make a reasonable effort to complete the study 
within the time designated.
I will provide all study personnel under my supervision copies of the protocol and 
access to all information provided by Galapagos NV. I will discuss this material with 
them to ensure that they are fully informed about the drugs and the study.
Principal Investigator Name (Printed)
Signature
Date
Site Number


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13.2 66/68 Joint Count
Joints Assessed (left and right)
Temporomandibular 
Sternoclavicular 
Acromioclavicular 
Shoulder 
Elbow
Wrist
Metacarpophalangeal 
First 
Second 
Third 
Fourth 
Fifth 
Proximal interphalangeal 
First
Second
Third 
Fourth
Fifth 
Distal interphalangeal
Second 
Third 
Fourth 
Fifth 
Hip # 
Knee 
Ankle 
Tarsus 
Metatarsophalangeal 
First 
Second 
Third 
Fourth 
Fifth 
Proximal interphalangeal (toe)
First 
Second 
Third 
Fourth 
Fifth 
#Assessed for tenderness only
Joints will not be assessed if an intra-articular injection of corticosteroid has been given 
in the previous 3 months, where joints will be classed as not assessable.


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13.3 Patient’s Global Assessment of Disease Activity Questionnaire
Instructions:
Considering all the ways arthritis affects you, how well are you doing today? 
Please indicate by making a vertical line (I) through the line below.
0
100
Very Well
Very Poor
Note: The VAS Scale must be 100 mm long.


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13.4 Physician’s Global Assessment of Disease Activity Questionnaire
Instructions:
Please indicate your assessment of the subject’s overall disease activity by marking a 
vertical line (I) through the line below.
0
100
No Disease Activity 
Extreme Disease Activity
Note: The VAS Scale must be 100 mm long.


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13.5 Health Assessment Questionnaire - Disability Index (HAQ-DI)


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13.6 FACIT Fatigue Scale


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13.7 36-Item Short-Form Health Survey (SF-36)


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13.8 Pregnancy Precautions, Definition for Female of Childbearing Potential, and 
Contraceptive Methods
The administration of filgotinib in embryo-fetal animal development studies resulted in 
decreased numbers of viable rat fetuses, increased resorptions, and visceral and 
skeletal malformations. Similar effects were noted in the rabbit. A safety margin relative 
to human exposure has not been identified.  Pregnancy is contraindicated during use of 
filgotinib.
For participation in this study, all subjects of childbearing potential must agree to the 
use of highly effective contraception as outlined below. In addition, women of 
childbearing potential should have a urine pregnancy test every 4 weeks during the 
study.
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. In addition, women of any age with amenorrhea ≥12 months may 
also be considered postmenopausal if their FSH level is in the postmenopausal range 
at Screening and they are not using hormonal contraception or hormonal replacement 
therapy.
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 sterile 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 


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drug-drug interaction study of filgotinib and hormonal contraceptives demonstrated that 
filgotinib does not alter the pharmacokinetics of representative hormonal contraceptives 
levonorgestrel/ethinyl estradiol. 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 investigator’s brochure 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 
from Week 24 for the previous core study they participated in and a negative urine 
pregnancy test at the Entry Visit. Urine pregnancy tests will be performed at each 
Quarterly Evaluation Visit and Serum pregnancy tests will be performed at each Annual 
Visit and the Final Visit or Early Discontinuation Visit. In addition, urine pregnancy tests 
will also be performed every 4 weeks during study participation through the follow-up 
visit using home pregnancy urine tests that will be provided to them. The site will call 
the subject every 4 weeks to obtain results of these pregnancy tests and will record the 
information in the source documents and CRF. If a positive urine pregnancy test is 
reported, the subject will be asked to interrupt study drug and return to the clinic for a 
confirmatory serum pregnancy test. 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 
the Entry Visit until 35 days following the last dose of study drug, or for at least 6 
months following the last dose of study drug for females of childbearing potential who 
were taking concurrent MTX therapy, as indicated by the SmPC of MTX.

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 at least 3 months after 
procedure, with documentation of sperm-free ejaculate)
Female subjects who wish to use a hormonally based method must agree to use it in 
conjunction with a barrier method (used either by the female subject or by her male 
partner).  Female subjects who utilize a hormonal contraceptive as one of their birth 


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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 (subject must agree to use with a barrier method, preferably, 
with a male condom)
Oral contraceptives (either combined estrogen/progestin or progesterone only)
Injectable progesterone
Implants of levonorgestrel
Transdermal contraceptive patch
Contraceptive vaginal ring

Barrier methods (subject must agree to use 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 agree to refrain from egg donation and in vitro 
fertilization during study participation and for at least 35 days after the last study 
drug dose, or for at least 6 months for female subjects of childbearing potential who 
were taking concurrent MTX therapy, as indicated by the SmPC of MTX. 
Participants and their providers must agree to adhere to the respective SmPC for 
concomitant csDMARDs used by the subject during the study. For example, 
if methotrexate is used as concomitant background medication during the clinical trial, 
subjects and investigators must agree to adhere to the methotrexate SmPC: “Women 
must not become pregnant during and at least 6 months after treatment with 
methotrexate and must therefore practice an effective form of contraception.”
3)
Contraception for Male Subjects
It is theoretically possible that a relevant systemic concentration 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 agree to use condoms 
during study participation and for 90 days after the last study drug dose, or for at least 
6 months for subjects who were taking concurrent MTX therapy, as indicated by the 
SmPC of MTX.  Female partners of male study subjects should consider using one of 
the above methods of contraception as well. Male subjects must also agree to refrain 
from sperm donation during treatment and until at least 90 days after the end of dosing, 
or for at least 6 months for subjects who were taking concurrent MTX therapy, as 
indicated by the SmPC of MTX.


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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 35 days of last study drug dose, or 
within at least 6 months for subjects who were taking concurrent MTX therapy, as 
indicated by the SmPC of MTX.  Subjects who become pregnant or who suspect that 
they are pregnant during the study must report the information to the investigator and 
discontinue all study drug and background therapy 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 8.8.1.2.1.5.

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN
Study Title:
A multicenter, open-label, long-term follow-up safety and 
efficacy study of filgotinib treatment in subjects with moderately 
to severely active rheumatoid arthritis
Name of Test Drug:
Filgotinib 
Study Number:
GLPG0634-CL-205
Protocol Version (Date):
Amendment 3: 15 March 2018
Analysis Type:
Final Analysis
Analysis Plan Version:
2.0
Analysis Plan Date:
24 January 2019
Analysis Plan Author(s):
CONFIDENTIAL AND PROPRIETARY INFORMATION


Filgotinib
GLPG0634-CL-205
Statistical Analysis Plan – Final Analysis
Version 2.0
CONFIDENTIAL
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24 January 2019
TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................3
LIST OF ABBREVIATIONS........................................................................................................................................4
1.
INTRODUCTION ................................................................................................................................................6
1.1.
Study Objectives ......................................................................................................................................6
1.2.
Study Design............................................................................................................................................6
1.3.
Sample Size and Power............................................................................................................................8
2.
TYPE OF PLANNED ANALYSIS ......................................................................................................................9
2.1.
Data Monitoring Committee Analyses.....................................................................................................9
2.2.
Pharmacovigilance & Epidemiology (PVE) Analysis..............................................................................9
2.3.
Interim Analysis for Conference..............................................................................................................9
2.4.
Week 156 Analysis ..................................................................................................................................9
2.5.
Final Analysis ..........................................................................................................................................9
3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES............................................................................10
3.1.
Analysis Sets..........................................................................................................................................10
3.1.1.
Full Analysis Set ..................................................................................................................10
3.1.2.
Safety Analysis Set...............................................................................................................10
3.2.
Subject Grouping ...................................................................................................................................10
3.3.
Missing Data and Outliers......................................................................................................................11
3.3.1.
Missing Data ........................................................................................................................11
3.3.2.
Outliers.................................................................................................................................11
3.4.
Data Handling Conventions and Transformations .................................................................................11
3.5.
Analysis Visit Window ..........................................................................................................................12
3.5.1.
Definition of Study Day .......................................................................................................12
3.5.2.
Analysis Visit Windows.......................................................................................................12
3.5.3.
Selection of Non-Efficacy Data in the Event of Multiple Records in an 
Analysis Visit Window ........................................................................................................15
4.
SUBJECT DISPOSITION ..................................................................................................................................17
4.1.
Subject Enrollment and Disposition.......................................................................................................17
4.2.
Extent of Filgotinib Exposure ................................................................................................................17
4.3.
Protocol Deviations................................................................................................................................18
5.
BASELINE CHARACTERISTICS....................................................................................................................19
5.1.
Demographics and Other Core Baseline Characteristics........................................................................19
5.2.
Core Baseline Disease Characteristics ...................................................................................................19
5.3.
Medical History......................................................................................................................................20
6.
EFFICACY ANALYSES ...................................................................................................................................21
6.1.
General Considerations ..........................................................................................................................21
6.2.
Efficacy Endpoints.................................................................................................................................22
6.3.
Definition of Efficacy Endpoints ...........................................................................................................23
6.3.1.
Tender/Swollen Joint Counts (TJC/SJC)..............................................................................23
6.3.2.
Global Assessment of Disease Activity................................................................................24
6.3.3.
Health Assessment Questionnaire Disability Index (HAQ-DI)............................................24
6.3.4.
ACR20..................................................................................................................................24
6.3.5.
ACR50 and ACR70..............................................................................................................25


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GLPG0634-CL-205
Statistical Analysis Plan – Final Analysis
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CONFIDENTIAL
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6.3.6.
DAS28(CRP)........................................................................................................................25
6.3.7.
SDAI and CDAI...................................................................................................................25
6.3.8.
ACR-N .................................................................................................................................26
6.3.9.
EULAR Response ................................................................................................................26
6.3.10.
ACR/EULAR remission.......................................................................................................26
6.3.11.
Health-Related Quality of Life (HRQoL) ............................................................................26
6.4.
Analysis of the Efficacy Endpoint..........................................................................................................27
7.
SAFETY ANALYSES........................................................................................................................................28
7.1.
Adverse Events and Deaths....................................................................................................................28
7.1.1.
Adverse Event Dictionary ....................................................................................................28
7.1.2.
Adverse Event Severity........................................................................................................28
7.1.3.
Relationship of Adverse Events to Study Drug....................................................................28
7.1.4.
Serious Adverse Events........................................................................................................28
7.1.5.
Treatment-Emergent Adverse Events...................................................................................28
7.1.6.
Summaries of Adverse Events and Deaths...........................................................................29
7.1.7.
Adverse Events of Special Interest.......................................................................................30
7.2.
Laboratory Evaluations ..........................................................................................................................32
7.2.1.
Summaries of Numeric Laboratory Results .........................................................................32
7.2.2.
Graded Laboratory Value.....................................................................................................34
7.2.3.
Laboratory Evaluations of Special Interest ..........................................................................35
7.3.
Body Weight and Vital Signs.................................................................................................................36
7.4.
Concomitant Medications ......................................................................................................................37
7.5.
Electrocardiogram Results .....................................................................................................................38
7.5.1.
Investigator Electrocardiogram Assessment ........................................................................38
7.6.
Other Safety Measures ...........................................................................................................................38
7.7.
Changes From Protocol-Specified Safety Analyses...............................................................................38
8.
REFERENCES ...................................................................................................................................................39
9.
SOFTWARE.......................................................................................................................................................40
10.
SAP REVISION..................................................................................................................................................41
11.
APPENDIX.........................................................................................................................................................42
Appendix 1.
Lists of RA Medications.........................................................................................................42
Appendix 2.
Health Assessment Questionnaire Disability Index (HAQ-DI)..............................................44
Appendix 3.
Corticosteroids........................................................................................................................46
LIST OF IN-TEXT TABLES
Table 3-1.
Analysis Visit Windows for Efficacy Data (SF-36 and FACIT-Fatigue Excluded) in 
the Core Studies......................................................................................................................13
Table 3-2.
Analysis Visit Windows for SF-36 and FACIT-Fatigue in the Core Studies.........................13
Table 3-3.
Analysis Visit Windows for Efficacy Data (SF-36 and FACIT-Fatigue Excluded) in 
GLPG0634-CL-205................................................................................................................14
Table 3-4.
Analysis Visit Windows for SF-36 and FACIT-Fatigue in GLPG0634-CL-205 ...................14
Table 3-5.
Analysis Visit Windows for Non-Efficacy Data ....................................................................14
Table 6-1.
Composition of the 28 Joints..................................................................................................23
Table 6-2.
EULAR Response Criteria .....................................................................................................26


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LIST OF ABBREVIATIONS
ACR
American College of Rheumatology
ACR20/50/70
American College of Rheumatology 20/50/70% improvement
AE
adverse event
AESIs
adverse events of special interest
ALP
alkaline phosphatase
ALT
alanine aminotransferase
AST
aspartate aminotransferase
ATC
anatomical therapeutic chemical drug class
bDMARD
biological disease modifying anti-rheumatic drug
b.i.d.
bis in die (twice a day)
BMI
body mass index
CBC
complete blood count
CCP
cyclic citrullinated peptide
CDAI
clinical disease activity index
CRF
case report form
CRP
c-reactive protein
CSR
clinical study report
CTCAE
Common Toxicity Criteria for Adverse Events
DAS28
disease activity score for 28 joint count
DMC
data monitoring committee
ECG
electrocardiogram
EULAR
European League Against Rheumatism
FACIT-Fatigue
Functional Assessment of Chronic Illness Therapy-Fatigue
FAS
full analysis set
GI
Gastrointestinal 
HAQ-DI
health assessment questionnaire-disability index
HLGT
high-level group term
HLT
high-level term
HRQoL
health-related quality of life
ID
identification
LLT
lower-level term
LOQ
limit of quantitation
MedDRA
Medical Dictionary for Regulatory Activities
MST
MedDRA search listing
MTX
methotrexate
NRI
non-responder imputation
OC
observed case
PGA
physician’s global assessment 


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PT
preferred term
PTM
placebo to match
PVE
pharmacovigilance & epidemiology department
Q1, Q3
first quartile, third quartile
q.d.
quaque die (each day)
RA
rheumatoid arthritis
RF
rheumatoid factor
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SDAI
simplified disease activity index
SF-36
36-item short form survey
SGA
subject's global assessment 
SJC
swollen joint count
SMQ
standardized MedDRA query
SOC
system organ class
TEAE
treatment-emergent adverse event
TFLs
tables, figures, and listings
TJC
tender joint count
ULN
upper limit of normal
VAS
visual analog scale
WBC
white blood cell
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) in the clinical study report (CSR) 
for study GLPG0634-CL-205. This SAP is based on the study protocol amendment 3 dated
15 March 2018 and the electronic case report form (eCRF). The SAP will be finalized before 
database finalization. Any changes made after the finalization of the SAP will be documented in 
the CSR.
1.1.
Study Objectives
The primary objective of this study is as follows:

To evaluate the long term safety and tolerability of filgotinib for the treatment of rheumatoid 
arthritis (RA)
The secondary objectives of this study are as follows:

To evaluate the long-term efficacy of filgotinib

To evaluate the long-term effects of filgotinib administration on subjects’ disability, fatigue, 
and quality of life
GLPG0634-CL-205 data and the most current GLPG0634-CL-203 and GLPG0634-CL-204 data 
will be used in the analyses.
1.2.
Study Design
This is a multicenter, open-label, long-term follow-up study in subjects with RA. An 
approximate total of 600 subjects will be enrolled in the study after they have completed one of 
the previous 2 core studies: (GLPG0634-CL-203 or GLPG0634-CL-204). All subjects will start 
the study at the same dose level (filgotinib 200 mg daily, administered either as 200 mg q.d. or as 
100 mg b.i.d., depending on the dosing regimen (frequency of intake of active IMP) that was 
administered during the preceding core study). US males were limited to dosing with filgotinib 
100 mg q.d. due to an FDA requirement based on a non-clinical testicular toxicity signal.
The investigator may decide to decrease the daily dose of filgotinib to 100 mg q.d. in case of 
intolerance or safety reasons. Subjects will return to the 200 mg filgotinib daily dose after the 
reasons for decreasing the dose have resolved, and at the investigator’s discretion. Subjects can 
also continue on filgotinib 100 mg q.d. when deemed necessary by the investigator. Subjects 
coming from the GLPG0634-CL-204 study will be allowed to start MTX treatment, if deemed 
necessary according to the investigator’s clinical judgment.
Subjects will enter the study at Entry Visit on Day -1, which will occur on the same day as the 
last visit from the previous core study (GLPG0634-CL-203 or GLPG0634-CL-204). Subjects 


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participating in the study will be requested to attend Quarterly Evaluation Visits (QEVs) every 
12 weeks. If necessary, unscheduled visits can occur in between the scheduled study visits, for 
instance, in case the dose of study medication is to be adapted. In case of early withdrawal, an 
Early Discontinuation Visit (EDV) will be scheduled.
The duration of the participation and treatment for any subject in this study is expected to last for 
several years (from Entry visit to Follow-up Visit) and will be determined by the sponsor based 
on the following:

Open label period (approximately 96 months).

Marketing Application Approval/Withdrawal in Country of Residence.

Applicable local reimbursement procedures are in place.
Sites will be notified once these criteria are met.
Following marketing, local (if applicable) regulatory and/or pertinent local reimbursement 
approval of the study medication, subjects should return to their next quarterly scheduled study 
visit as specified in the protocol. This visit will serve as a Final Visit and the subjects will be 
considered as having completed the treatment part of the study. At the end of the study, subjects 
will be requested to attend a Follow-up Visit approximately 2 weeks after the Final Visit.


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The design of the study is presented in the following table:
Study 203
Roll over to Study 205
Week 1-12
Week 13-24
Randomized to placebo
Responders(*) remain on placebo
Half of them are rerandomized 
to 200 mg q.d.
Half of them are rerandomized 
to 100 mg b.i.d.
Nonresponders: half of them are
rerandomized to 100 mg q.d.
Assigned to 200 mg q.d.
Nonresponders: half of them are
rerandomized to 50 mg b.i.d.
Assigned to 100 mg b.i.d.
Randomized to 50 mg q.d.
Responders remain on 50 mg q.d.
Assigned to 200 mg q.d.
Nonresponders assigned to 100 mg q.d.
Assigned to 200 mg q.d.
Randomized to 25 mg b.i.d.
Responders remain on 25 mg b.i.d.
Assigned to 100 mg b.i.d.
Nonresponders assigned to 50 mg b.i.d.
Assigned to 100 mg b.i.d.
Randomized to 100 mg q.d.
Remain on 100 mg q.d.
Assigned to 200 mg q.d.
Randomized to 50 mg b.i.d.
Remain on 50 mg b.i.d.
Assigned to 100 mg b.i.d.
Randomized to 200 mg q.d.
Remain on 200 mg q.d.
Assigned to 200 mg q.d.
Randomized to 100 mg b.i.d.
Remain on 100 mg b.i.d.
Assigned to 100 mg b.i.d.
Study 204
Roll over to Study 205
Week 1-12
Week 13-24
Randomized to placebo q.d.
All assigned to 100 mg q.d.
Assigned to 200 mg q.d.
Randomized to 50 mg q.d.
Responders remain on 50 mg q.d.
Assigned to 200 mg q.d.
Nonresponders assigned to 100 mg q.d.
Assigned to 200 mg q.d.
Randomized to 100 mg q.d.
Remain on 100 mg q.d.
Assigned to 200 mg q.d.
Randomized to 200 mg q.d.
Remain on 200 mg q.d.
Remain on 200 mg q.d.
(*)  responder: having a decrease of at least 20% in tender joint count (TJC)68 and swollen joint count (SJC)66 versus Baseline.
1.3.
Sample Size and Power
It is expected that around 70% of the subjects in the previous core studies GLPG0634-CL-203 
(N=595, approximately) and GLPG0634-CL-204 (N=280, approximately) will roll over into this 
study, corresponding to a sample size of roughly 600 subjects: 0.7 x (595 subjects in study 203 + 
280 subjects in study 204) = 612.


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2.
TYPE OF PLANNED ANALYSIS
2.1.
Data Monitoring Committee Analyses
An external multidisciplinary Data Monitoring Committee (DMC) will review the progress of 
the study and perform interim reviews of safety data in order to protect subject welfare and 
preserve study integrity. To ensure the best interests of the participants, the DMC will 
recommend to the sponsor if the nature, frequency, and severity of adverse effects associated 
with the study treatment warrant the early termination of the study, the continuation of the study, 
or the continuation of the study with modifications.
The initial review has been conducted approximately 3 months after the DMC organizational 
meeting. The 2nd and 3rd DMC meetings have been conducted approximately 3 months after the 
previous meeting. Subsequent DMC meetings will be scheduled at approximately 12 months 
intervals following the 3rd DMC meeting.
The DMC’s role and responsibilities and the scope of analysis to be provided to the DMC are 
provided in a mutually agreed upon charter, which defines the DMC membership, meeting 
logistics, and meeting frequency.
2.2.
Pharmacovigilance & Epidemiology (PVE) Analysis
The Pharmacovigilance & Epidemiology (PVE) analysis may be conducted periodically as 
needed in order to review emerging safety data from GLPG0634-CL-205.
2.3.
Interim Analysis for Conference
A subset of efficacy and safety data may be analyzed periodically as needed for the purpose of 
possible publication.
2.4.
Week 156 Analysis
A planned Week 156 analysis will be conducted after all subjects have either completed their 
Week 156 visit or prematurely discontinued from the study.
2.5.
Final Analysis
After all subjects have completed the study, outstanding data queries have been resolved or 
adjudicated as unresolvable, and the data have been cleaned, the final analysis of the data will be 
performed.


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3.
GENERAL CONSIDERATIONS FOR DATA ANALYSES
Analysis results will be presented using descriptive statistics. For categorical variables, 
the number and percentage of subjects in each category will be presented; for continuous 
variables, the number of subjects (n), mean, standard deviation (SD) or standard error (SE), 
median, first quartile (Q1), third quartile (Q3), minimum, and maximum will be presented.
By-subject listings will be presented for all subjects in the Safety Analysis Set and sorted by 
subject identification (ID) number, visit date, and time (if applicable). Data collected on log 
forms, such as AEs, will be presented in chronological order within the subject. The treatment 
group to which subjects were randomized or assigned will be used in the listings, as well as age, 
sex at birth, race, and ethnicity.
3.1.
Analysis Sets
Analysis sets define the subjects to be included in an analysis. Analysis sets and their definitions 
are provided in this section. The analysis set will be identified and included as a subtitle of each 
TFL.
For each analysis set, the number and percentage of subjects eligible for inclusion, as well as the 
number and percentage of subjects who were excluded and the reasons for their exclusion, 
will be summarized by treatment group.
3.1.1.
Full Analysis Set
The Full Analysis Set (FAS) includes all subjects who enrolled in GLPG0634-CL-205 and 
received at least one dose of study drug in GLPG0634-CL-205. This is the primary analysis set 
for efficacy analyses.
The study drug in GLPG0634-CL-205 is filgotinib. The study drugs in the core studies are
filgotinib and placebo to match (PTM).
3.1.2.
Safety Analysis Set
The Safety Analysis Set includes all subjects who enrolled in GLPG0634-CL-205 and received 
at least one dose of study drug in GLPG0634-CL-205. This is the primary analysis set for safety 
analyses.
3.2.
Subject Grouping
For analyses based on the FAS subjects will be grouped according to the treatment to which they 
were randomized or assigned in GLPG0634-CL-205. For analyses based on the Safety Analysis 
Set, subjects will be grouped according to actual treatment received in GLPG0634-CL-205. The 
actual treatment received will differ from the randomized treatment only when their actual 
treatment differs from randomized treatment for the entire GLPG0634-CL-205 treatment 
duration. 


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Subjects will be presented by the following groups:

Filgotinib with MTX

Filgotinib monotherapy
The filgotinib with MTX group includes subjects who were from GLPG0634-CL-203 and 
randomized or assigned to filgotinib 100 mg q.d., filgotinib 100 mg b.i.d. or filgotinib 200 mg 
q.d. in GLPG0634-CL-205. The filgotinib monotherapy group includes subjects who were from 
GLPG0634-CL-204 and randomized or assigned to filgotinib 100 mg q.d., filgotinib 100 mg 
b.i.d. or filgotinib 200 mg q.d. in GLPG0634-CL-205.
3.3.
Missing Data and Outliers
3.3.1.
Missing Data
In general, missing data will not be imputed unless methods for handling missing data are 
specified. Exceptions are presented in this document.
For missing last dosing date of study drug, imputation rules are described in Section 4.2. For 
partial date of initial RA diagnosis, imputation rules are described in Section 5.2. The handling 
of missing or incomplete dates for AE onset is described in Section 7.1.5.2. The handling of 
missing or incomplete dates for prior medications is described in Section 5.2. and for
concomitant medications in Section 7.4. Imputation rules adopted in the efficacy analyses are 
specified in Section 6.1. 
3.3.2.
Outliers
Outliers will be identified during the data management and data analysis process, but no 
sensitivity analyses will be conducted. All data will be included in the data analyses.
3.4.
Data Handling Conventions and Transformations
In general, age (in years) on the date of the first dose of study drug in the core studies will be 
used for analyses and presentation in listings. If an enrolled subject was not dosed with any study 
drug in the core studies, the randomization date will be used instead of the first dosing date of 
study drug. For the screen failures in the core studies, the date the last informed consent was 
signed in the core studies will be used for age calculation. If only birth year is collected on the 
CRF, “01 July” will be used for the unknown birth day and month for the purpose of age 
calculation. 
Non-PK Data that are continuous in nature but are less than the lower limit of quantitation
(LOQ) or above the upper LOQ will be imputed as follows:

A value that is 1 unit less than the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “x” (where x is considered the LOQ). For example, if the 
values are reported as < 50 and < 5.0, values of 49 and 4.9, respectively, will be used to 


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calculate summary statistics. An exception to this rule is any value reported as < 1 or < 0.1, 
etc. For values reported as < 1 or < 0.1, a value of 0.9 or 0.09, respectively, will be used for 
calculate summary statistics.

A value that is 1 unit above the LOQ will be used to calculate descriptive statistics if the 
datum is reported in the form of “> x” (where x is considered the LOQ). Values with decimal 
points will follow the same logic as above.

The LOQ will be used to calculate descriptive statistics if the datum is reported in the form of 
“≤ x” or “≥ x” (where x is considered the LOQ).
3.5.
Analysis Visit Window
3.5.1.
Definition of Study Day 
The first dose date of individual study drug will be calculated separately for each study drug in a 
treatment group. Study Day 1 is defined as the first dose date of any study drug, which is the 
minimum of the first dose dates of individual study drugs in a treatment group.
The last dose date of individual study drug will be calculated separately for each study drug in a 
treatment group. The last dose date of any study drug will be defined as the maximum of the last 
dose dates of individual study drugs in a treatment group.
The first dose date of individual study drug in GLPG0634-CL-205 is identified by the first drug 
dispense date + 1 day. The last dose date of individual study drug in GLPG0634-CL-205 is 
identified by the Final Visit date or the Early Discontinuation Visit date.
Study Day will be calculated from the Reference Date and derived as follows:

For postdose study days: Assessment date – Reference Date + 1

For days prior to the first dose: Assessment date – Reference Date
Reference Date is defined as follows:

For efficacy data in the core studies: Study Day 1 in the core studies

For efficacy data in GLPG0634-CL-205: Study Day 1 in GLPG0634-CL-205

For safety data: The first dose date of filgotinib in the core studies or GLPG0634-CL-205
3.5.2.
Analysis Visit Windows
Subject visits may not occur on protocol-specified days. Therefore, for the purpose of analysis, 
observations will be assigned to analysis windows for efficacy data in the core studies (Table 3-1
and Table 3-2) and GLPG0634-CL-205 (Table 3-3 and Table 3-4), and for non-efficacy data 
(Table 3-5). The analysis visit windows for non-efficacy data will be applied up to the last dose 
date of any study drug.


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The baseline value is defined as follows:
Efficacy data:

Core baseline: The last nonmissing value on or prior to the first dose date of study drug in the 
core studies

Extension baseline: The last nonmissing value on or prior to the first dose date of study drug 
in GLPG0634-CL-205, and no earlier than the core study nominal Week 24 visit date
Safety data:

Filgotinib baseline: The last nonmissing value on or prior to the first dose date of filgotinib in 
the core studies or GLPG0634-CL-205
Table 3-1.
Analysis Visit Windows for Efficacy Data (SF-36 and FACIT-Fatigue
Excluded) in the Core Studies
Analysis Visit
Nominal Study Day
Lower Limit
Upper Limit
Core Baseline 
1
(none)
1
Core Week 1
8
2
11
Core Week 2
15
12
22
Core Week 4
29
23
43
Core Week 8
57
44
71
Core Week 12
85
72
99
Core Week 16
113
100
127
Core Week 20
141
128
155
Core Week 24
169
156
≥169
Table 3-2.
Analysis Visit Windows for SF-36 and FACIT-Fatigue in the Core 
Studies
Analysis Visit
Nominal Study Day
Lower Limit
Upper Limit
Core Baseline 
1
(none)
1
Core Week 4
29
2
57
Core Week 12
85
58
127
Core Week 24
169
128
≥169


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Table 3-3.
Analysis Visit Windows for Efficacy Data (SF-36 and FACIT-Fatigue
Excluded) in GLPG0634-CL-205
Analysis Visit
Nominal Study Day
Lower Limit
Upper Limit
Extension Baseline
1
(none)
1
Extension Week 12
85
2
127
Extension Week 24
169
128
211
Extension Week 36
253
212
295
Extension Week 48
337
296
379
Extension Week 60
421
380
463
Extension Week 72
505
464
547
Extension Week 84
589
548
631
Extension Week W
7xW+1
7xW–40
7xW+43
Table 3-4.
Analysis Visit Windows for SF-36 and FACIT-Fatigue in GLPG0634-
CL-205
Analysis Visit
Nominal Study Day
Lower Limit
Upper Limit
Extension Baseline
1
(none)
1
Extension Week 48
337
2
505
Extension Week 96
673
506
841
Extension Week W
7xW+1
7xW–166
7xW+169
Table 3-5.
Analysis Visit Windows for Non-Efficacy Data
Analysis Visit
Nominal Study Day
Lower Limit
Upper Limit
Filgotinib Baseline
1
(none)
1
Week 12
85
2
127
Week 24
169
128
211
Week 36
253
212
295
Week 48
337
296
379
Week 60
421
380
463
Week 72
505
464
547
Week 84
589
548
631
Week W
7xW+1
7xW–40
7xW+43


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CRP measured on or after nominal follow up visit will not be assigned analysis window and 
summarized, but will be included in the listing.
Vital signs, ECG, and safety laboratory data collected in the follow up period will also be 
summarized. The analysis window for the post-treatment follow-up period is defined as from 
(last dose date of filgotinib + 1 day) to (last dose date of filgotinib + 30 days). If multiple valid, 
nonmissing measurements exist in the post treatment follow-up visit window, the latest record 
will be selected for analysis. If the chronological order cannot be determined, for any given 
subject, the value with the worst severity will be selected for categorical variable, and the 
average will be taken for continuous variable. Data obtained after last dose date plus 30 days will 
be excluded from the summaries, but will be included in the listings.
3.5.3.
Selection of Non-Efficacy Data in the Event of Multiple Records in an 
Analysis Visit Window
Depending on the statistical analysis method, single values may be required for each analysis 
window. For example, change from baseline by visit usually requires a single value, whereas a 
time-to-event analysis would not require 1 value per analysis window.
If multiple valid, nonmissing, continuous measurements exist in an analysis window, 
records will be chosen based on the following rules if a single value is needed:

In general, the filgotinib baseline value will be the last nonmissing value on or prior to the 
first dose date of filgotinib in the core studies or GLPG0634-CL-205, unless otherwise 
specified. If multiple measurements occur on the same day, the last nonmissing value prior to 
the time of first dose of filgotinib in the core studies or GLPG0634-CL-205 will be 
considered as the filgotinib baseline value. If these multiple measurements occur at the same 
time or the time is not available, the average of these measurements (for continuous data) 
will be considered the filgotinib baseline value.

For postbaseline visits:
The record closest to the nominal day for that visit will be selected.
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.
If there is more than 1 record on the selected day, the average will be taken, 
unless otherwise specified.
If multiple valid, nonmissing, categorical measurements exist in an analysis window, 
records will be chosen based on the following rules if a single value is needed:

For filgotinib baseline, the last available record on or prior to the date of the first dose of 
filgotinib in the core studies or GLPG0634-CL-205 will be selected. If there are multiple 
records with the same time or no time recorded on the same day, the value with the lowest
severity will be selected (eg, normal will be selected over abnormal for safety ECG findings).


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
For postbaseline visits:
The record closest to the nominal day for that visit will be selected.
If there are 2 records that are equidistant from the nominal day, the later record will be 
selected.
If there is more than 1 record on the selected day, the value with the worst severity will 
be selected (eg, abnormal will be selected over normal for safety ECG findings), 
unless otherwise specified.
The rules for selecting efficacy data in the event of multiple records in an analysis visit window 
are specified in Section 6.1.


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4.
SUBJECT DISPOSITION
4.1.
Subject Enrollment and Disposition
A summary of subject enrollment will be provided by treatment group for each country within 
each geographic region, and investigator within a country. The summary will present the number 
and percentage of subjects enrolled. For each column, the denominator for the percentage 
calculation will be the total number of subjects analyzed for that column.
The randomization schedule used for the study will be provided in a listing and used as an 
appendix to the CSR.
A summary of subject disposition will be provided by treatment group. This summary will 
present the number of subjects in each of the categories listed below:

Safety Analysis Set

Full Analysis Set

Continuing study

Completed study

Did not complete study with reasons for premature discontinuation from the study
For the status of study completion and reasons for premature discontinuation, the number and 
percentage of subjects in each category will be provided. The denominator for the percentage 
calculation will be the total number of subjects in the Safety Analysis Set corresponding to that 
column.
A by-subject listing of reasons for premature study discontinuation will be provided by subject 
identification (ID) number in ascending order to support the above summary tables.
4.2.
Extent of Filgotinib Exposure
Total duration of exposure to filgotinib will be defined as (last dose date of filgotinib in 
GLPG0634-CL-205 - first dose date of filgotinib in the core studies or GLPG0634-CL-205 + 1), 
regardless of any temporary interruptions in administration and will be expressed in weeks using 
up to 1 decimal place (eg, 4.5 weeks). 
If the last filgotinib dosing date is missing, the latest date among the clinical visit date and 
laboratory sample collection date that occurred during the on-treatment period will be used.
If subjects are continuing on study drug, The data cutoff date will be used to impute the last 
dosing date for the calculation of the duration of exposure to filgotinib.


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The total duration of exposure to filgotinib will be summarized using descriptive statistics and 
using the number (ie, cumulative counts) and percentage of subjects exposed for filgotinib 
baseline and every 12 weeks afterwards. 
Summaries will be provided by treatment group for the Safety Analysis Set. No formal statistical 
testing is planned.
4.3.
Protocol Deviations 
Subjects who did not meet the eligibility criteria for study entry, but enrolled in the study will be 
summarized regardless of whether they were exempted by the sponsor or not. The summary will 
present the number and percentage of subjects who did not meet at least 1 eligibility criterion and 
the number of subjects who did not meet specific criteria by treatment group based on the Safety 
Analysis Set. A by-subject listing will be provided for those subjects who did not meet at least 
1 eligibility (inclusion or exclusion) criterion. The listing will present the eligibility criterion 
(or criteria if more than 1 deviation) that subjects did not meet and related comments, if 
collected.
Protocol deviations occurring after subjects entered the study are documented during routine 
monitoring. The number and percentage of subjects with important protocol deviations by 
deviation reason (eg, nonadherence to study drug, violation of select inclusion/exclusion criteria) 
will be summarized by treatment group for the Safety Analysis Set. A by-subject listing will be 
provided for those subjects with important protocol deviation.


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5.
BASELINE CHARACTERISTICS
5.1.
Demographics and Other Core Baseline Characteristics
Subject demographic and other core baseline characteristics variables will be summarized by 
treatment group and overall using descriptive statistics for continuous variables, and using 
number and percentage of subjects for categorical variables. The summary of demographic and 
other core baseline characteristics data will be provided for the Safety Analysis Set for the 
following:

Age (on the first dose date of any study drug in the core studies)

Sex at birth (male, female)

Race 

Ethnicity (Hispanic or Latino, not Hispanic or Latino)

Geographic region and country (Region 1: Latin America; Region 2: Central and Eastern 
Europe, EU; Region 3: Central and Eastern Europe, non-EU; Region 4: West and Asia Pac)

Weight (kg)

Height (cm)

Body mass index (BMI; in kg/m2)
A by-subject demographic and other core baseline characteristics listing, including the informed 
consent date, will be provided by subject ID number in ascending order.
5.2.
Core Baseline Disease Characteristics
Core baseline disease characteristics include:

Duration from RA diagnosis (years)
Calculated as ((first dose date of study drug in the core studies) – (date of initial diagnosis) + 
1 day) / 365.25. If the date of initial diagnosis is incomplete, then the following rules will be 
applied: 
missing day: use the first of the month
missing month: use January

Presence of RF (Yes/No)
Positive presence of RF is defined as RF value > ULN


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
Presence of anti-CCP (Yes/No)
Positive presence of anti-CCP is defined as anti-CCP value > ULN

Prior exposure to bDMARDs (Yes/No)
Prior exposure to bDMARDs (Please refer to Appendix 1 for a list of bDMARDs) are 
defined as any bDMARDs taken before a subject took the first study drug in the core studies.
A subject reporting the same bDMARDs more than once will be counted only once when 
calculating the number and percentage of subjects who received bDMARDs.
For the purposes of analysis, any bDMARDs with a start date prior to the first dosing date of 
any study drug in the core studies will be counted regardless of when the stop date is. If a 
partial start date is entered the bDMARDs will be considered prior unless the month and year 
(if day is missing) or year (if day and month are missing) of the start date are after the first
dosing date in the core studies. bDMARDs with a completely missing start date will be 
counted, unless otherwise specified.

Concurrent oral corticosteroids use on the first dosing date (Yes/No)
Oral corticosteroids dose, mg/day, expressed as prednisone-equivalent dose, mean (SD)

Concurrent MTX use on the first dosing date (Yes/No)
MTX dose, mg/week, mean (SD)
These core baseline disease characteristics will be summarized by treatment group and overall 
using descriptive statistics for continuous variables and using number and percentage of subjects 
for categorical variables. The summary of core baseline characteristics will be provided for the 
Safety Analysis Set. 
A by-subject listing of core baseline disease characteristics will be provided by subject ID 
number in ascending order.
5.3.
Medical History
Medical history collected at Screening in the core studies will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA) Version 21.0.
Medical history will be summarized by system organ class (SOC), preferred term (PT), treatment
group, and overall. Subjects who report 2 or more medical history items that are coded to the 
same SOC and/or PT will be counted only once by the unique coded term in the summary. The 
summary will be provided for the Safety Analysis Set. No formal statistical testing is planned.
A by-subject listing of medical history will be provided by subject ID number.


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6.
EFFICACY ANALYSES
6.1.
General Considerations
The primary analysis set for efficacy analyses will be the FAS, defined in Section 3.1.1.
If multiple valid, nonmissing efficacy measurements exist in an analysis window, records will be 
chosen based on the following rules if a single value is needed:

The record closest to the nominal day for that visit will be selected

If there are 2 records that are equidistant from the nominal day, or more than 1 record (with 
time known) on the selected day, the latest record will be taken

If chronological order cannot be determined (eg, more than 1 record on the same day with 
time missing), for any given subject, the worst outcome will be selected.
For the calculation of composite endpoints including DAS28(CRP), ACR20/50/70, ACR-N, 
SDAI, CDAI and ACR/EULAR remission, we use the following steps unless otherwise 
specified:

Step 1: Assign individual components to analysis visit windows defined in Section 3.5.2.

Step 2: Within each analysis visit window, select the component-level data based on the rules 
for selecting efficacy data as above

Step 3: Calculate the composite endpoint based on the selected component-level data in 
Step 2.
Below are the descriptions for the imputation methods that will be used throughout the efficacy 
analyses:

Observed case (OC): Missing values remain missing. For the categorical composite 
endpoints, in the case that some components are missing, the composite endpoint assessment 
will be derived based on the non-missing components.  If non-missing components are not 
sufficient to determine final composite endpoint, then the composite endpoint will be set as 
missing. For continuous composite endpoints (including ACR-N), if any components are 
missing, the composite endpoints will be set as missing.

Non-responder imputation (NRI): For all binary response measurements, starting from OC, 
all missings will be set as non-responders.
If a subject only has core baseline measurements, OC analyses will not include this subject.  
But this subject will be treated as non-responder in NRI analyses.


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For a specific visit if both regular CRP and high-sensitive CRP are available, only regular CRP will 
be used.
6.2.
Efficacy Endpoints
The efficacy endpoints include: 

The proportion of subjects who achieve an American College of Rheumatology 20% 
improvement response (ACR20) over time

The proportion of subjects who achieve an American College of Rheumatology 
50% improvement response (ACR50) over time

The proportion of subjects who achieve an American College of Rheumatology 
70% improvement response (ACR70) over time

Actual value and change from core baseline in individual components of the ACR response
over time

Actual value and change from core baseline in Disease Activity Score for 28 Joint Count 
using CRP (DAS28[CRP)]) over time

The proportion of subjects who achieve DAS28(CRP) ≤ 3.2 over time

The proportion of subjects who achieve DAS28(CRP) < 2.6 over time

Actual value and change from core baseline in Clinical Disease Activity Index (CDAI) over 
time

Actual value and change from core baseline in Simplifed Disease Acitivity Index (SDAI)
over time

ACR-N over time

European League Against Rheumatism (EULAR) response over time.

The proportion of subjects who achieve ACR/EULAR remission over time

Actual value and change from core baseline in SF-36 over time

Actual value and change from core baseline in FACIT-Fatigue over time


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6.3.
Definition of Efficacy Endpoints
6.3.1.
Tender/Swollen Joint Counts (TJC/SJC)
Tender joint count based on 68 joints (TJC68) and swollen joint count based on 66 joints
(SJC66) will be collected during the course of the study. The assessment for each joint will be 
from the following selections: Tender Only, Swollen Only, Tender and Swollen, Joint 
Non-Evaluable or Missing, or Not Tender or Swollen.
Individual joint with missing assessment will not be imputed. If at least half of the joints are 
assessd at a given visit, the prorated tender and swollen joint counts will be calculated using the 
following formula:
68 =

  
  

68 −( 
 
 
  
 
 
 68 
) × 68
 66 =

  
 !
 

66 −( 
 
 
  
 
 
 66 
) × 66
If less than half of joints are assessed at a given visit, joint counts are treated as missing for that 
visit.
A more abbreviated assessment considering 28 joints as listed in Table 6-1 for both tenderness 
and swelling will also be conducted (as part of the TJC68 and SJC66 assessment), denoted as 
TJC28 and SJC28, respectively.
Table 6-1.
Composition of the 28 Joints 
Joints 
Number
Shoulder Joints (Left and Right)
2
Elbow Joints (Left and Right)
2
Wrist Joints (Left and Right)
2
Metacarpophalangeal Joints I-V (Left and Right)
10
Hand Proximal Interphalangeal Joints I-V (Left and Right)
10
Knee Joints (Left and Right)
2
If there exist non-evaluable or missing joints among the 28 joints, similar prorated tender and 
swollen joint counts will be calculated as follows:
28 =

  
  

28 −( 
 
 
  
 
 
 28 
) × 28
 28 =

  
 !
 

28 −( 
 
 
  
 
 
 28 
) × 28


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If less than half of the 28 joints are assessed at a given visit, TJC28 and SJC28 are treated as 
missing for that visit.
6.3.2.
Global Assessment of Disease Activity
Subject’s Global Assessment of Disease Activity (SGA) and Physician’s Global Assessment of 
Disease Activity (PGA) based on a 0-100 mm visual analog scale (VAS) will be recorded during 
the study, with 0 indicating “no disease activity” and 100 indicating “maximum disease activity” 
(or similar description of disease severity). 
6.3.3.
Health Assessment Questionnaire Disability Index (HAQ-DI)
The HAQ-DI score is defined as the average of the scores of eight functional categories (dressing 
and grooming, arising, eating, walking, hygiene, reach, grip, and other activities), reported by the 
patient. Responses in each functional category are collected as: without any difficulty; with some 
difficulty; with much difficulty; unable to do a task in that area and with or without aids or 
devices. The HAQ-DI score ranges from 0 (no disability) to 3 (completely disabled), when 6 or 
more categories are non-missing. Detailed algorithm for calculating HAQ-DI score is described 
in Appendix 2.
HAQ-DI also includes a separate pain assessment and subject will be requested to mark the 
severity of the pain in the past week on a 0-100 mm VAS, with 0 indicating “no pain” and 
100 indicating “severe pain”.
6.3.4.
ACR20
A subject achieves ACR20 response when this subject has

≥ 20% improvement from core baseline in TJC68, AND

≥ 20% improvement from core baseline in SJC66, AND

≥ 20% improvement from core baseline in at least 3 of the following 5 items:
1) PGA
2) SGA
3) Subject’s pain assessment
4) HAQ-DI score
5) CRP
Percent improvement from core baseline at a postbaseline visit is calculated as follows for all 7 
components mentioned above:
% improvement = baseline value - postbaseline value
baseline value
× 100


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If the core baseline value is 0 then the percent improvement from core baseline is set to missing.
In the case that some ACR20 components are missing, the ACR20 assessment will be based on 
the non-missing components.  If non-missing components are not sufficient to determine ACR20
response, then the ACR20 response will be considered as missing.
6.3.5.
ACR50 and ACR70
ACR50 and ACR70 are similarly defined as ACR20 (see Section 6.3.4.), except the 
improvement threshold from core baseline is 50% and 70%, respectively
6.3.6.
DAS28(CRP)
The DAS28(CRP) score is calculated as follows:
DAS28(CRP) = 0.56-TJC28 + 0.28-SJC28 + 0.36 ln(CRP + 1) + 0.014 × SGA + 0.96,
where 
CRP = CRP measurement (mg/L)
SGA = subject’s global assessment of disease activity on a 0-100 mm VAS
Higher DAS28(CRP) value indicates more severe disease activity.
No component-level imputation will be performed for the calculation of DAS28(CRP) for the 
primary analyses.  If any components are missing, the DAS28(CRP) will be set as missing.
6.3.7.
SDAI and CDAI
Simplifed Disease Acitivity Index (SDAI) is a composite measure that sums the TJC28, SJC28, 
the SGA on a 0-10 cm scale, the PGA on a 0-10 cm scale, and the CRP (mg/dL). SDAI is scored 
as follow {Aletaha 2005}:
SDAI = TJC28 + SJC28 + SGA + PGA + CRP 
Higher SDAI score indicates more severe disease activity status.
Clinical Disease Activity Index (CDAI) is a further simplification of the SDAI that excludes the 
CRP, which is calculated using the following formula {Aletaha 2005}:
CDAI = TJC28 + SJC28 + SGA + PGA 
CDAI can range from 0 to 76, with higher score indicating more severe disease activity status.
No component-level imputation will be performed for the calculation of both SDAI and CDAI.  
If any components are missing, the SDAI and CDAI will be set as missing.


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6.3.8.
ACR-N
ACR-N is defined as the smallest percentage improvement from core baseline in swollen joints, 
tender joints and the median of the following 5 items (PGA, SGA, Patient pain assessment, 
HAQ-DI score and CRP). It has a range between 0 and 100%. In particular,
ACR-N = min {improvement in TJC68 (%), improvement in SJC66 (%), median [improvement 
in SGA (%), improvement in PGA (%), improvement in pain assessment (%), improvement in 
HAQ-DI (%), improvement in CRP (%)]}.
If this calculation results in a negative value, then the ACR-N is set to 0. If any components are 
missing, the ACR-N will be set as missing.
6.3.9.
EULAR Response
Subject’s response will be categorized according to the following table based on the 
DAS28(CRP).
Table 6-2.
EULAR Response Criteria
DAS28(CRP) at Visit
DAS28(CRP) Improvement from Core Baseline
> 1.2
> 0.6 and ≤ 1.2
≤ 0.6
≤ 3.2
Good Response
Moderate Response
No Response
> 3.2 and ≤ 5.1
Moderate Response
Moderate Response
No Response
> 5.1
Moderate Response
No Response
No Response
6.3.10.
ACR/EULAR remission
ACR/EULAR remission is achineved when TJC28 ≤ 1 and SJC28 ≤ 1 and CRP ≤ 1 mg/dL and 
SGA ≤ 1 (on a 0-10 cm scale). ACR/EULAR remission is not achieved when at least 1 of the 4 
components has a value > 1. 
In case that some components are missing, ACR/EULAR remission is not achieved if at least 
1 of the non-missing components has a value > 1. If non-missing components are not sufficient 
to determine ACR/EULAR remission, then ACR/EULAR remission will be considered as 
missing.
6.3.11.
Health-Related Quality of Life (HRQoL)
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SF-36
TThe SF-36 is a 36-item, self-reported, generic, comprehensive, and health-related quality of life 
questionnaire that yields an 8 health domains (physical functioning, role-physical, bodily pain, 
general health, vitality, social functioning, role-emotional, and mental health). Each domain is 
scored by summing the individual items and transforming the scores into a 0 to 100 scale with 
higher scores indicting better health status or functioning, In addition, 2 summary scores, the 
physical component summary (PCS) score and the mental component summary (MCS) score 
will be evaluated based on the 8 SF-36 domains.
FACIT-Fatigue
The FACIT-Fatigue scale is a brief, 13-item, symptom-specific questionnaire that specifically 
assesses the self-reported severity of fatigue and its impact upon daily activities and functioning 
in the past 7 days. The FACIT-Fatigue uses 0 (“not at all”) to 4 (“very much”) numeric rating 
scales. Negatively stated items are reversed by subtracting the response from “4” before being 
added to obtain a total score. FACIT-Fatigue ranges from 0 to 52 with higher score indicating 
less fatigue. In the case of missing response for some items in the questionnaire, if at least half of 
the items (ie, ≥ 7 of 13 items) were answered at a given visit, the prorated score will be 
calculated and used in the analysis.
6.4.
Analysis of the Efficacy Endpoint
For binary efficacy endpoints both OC and NRI data will be summarized using descriptive 
statistics (counts and proportions of subjects) by treatment and visit. For continuous efficacy 
endpoints, OC data will be summarized using descriptive statistics (sample size, mean, SD, 
median, Q1, Q3, minimum and maximum) by treatment and visit. No formal statistical testing is 
planed.
Plots of proportions of subjects for categorical endpoints and mean ± SD for continuous 
endpoints will be presented over time by treatment and by visit.
6.5.
Changes From Protocol-Specified Efficacy Analyses
There are no deviations from the protocol-specified efficacy analyses.


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7.
SAFETY ANALYSES
7.1.
Adverse Events and Deaths
7.1.1.
Adverse Event Dictionary
Clinical and laboratory adverse events (AEs) will be coded using the MedDRA Version 21.0.
System organ class (SOC), high-level group term (HLGT), high-level term (HLT), preferred 
term (PT), and lower-level term (LLT) will be provided in the AE dataset.
7.1.2.
Adverse Event Severity
Adverse events are graded by the investigator as Mild, Moderate and Severe according to 
toxicity criteria specified in the protocol. The severity grade of events for which the investigator 
did not record severity will be categorized as “missing” for tabular summaries and data listings.
The missing category will be listed last in summary presentation.
7.1.3.
Relationship of Adverse Events to Study Drug
Related AEs are those for which the investigator selected “Possible”, “Probable” or “Certain” on 
the AE CRF to the question of “Causality”. However, the investigator’s original answer to the 
question will be showed in the by-subject data listings. Relatedness will always default to the 
investigator’s choice, not that of the Medical Monitor. Events for which the investigator did not 
record causality will be considered related to study drug for summary purposes. However, by-
subject data listings will show the relationship as missing.
7.1.4.
Serious Adverse Events
Serious adverse events (SAEs) will be identified and captured as SAEs if AEs met the definitions 
of SAE that were specified in the study protocol. SAEs captured and stored in the clinical 
database will be reconciled with the SAE database from the Gilead Pharmacovigilance & 
Epidemiology (PVE) Department before data finalization.
7.1.5.
Treatment-Emergent Adverse Events
7.1.5.1.
Definition of Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as any AEs with an onset date on or 
after the filgotinib start date in the core studies or GLPG0634-CL-205, and no later than 30 days 
after permanent discontinuation of filgotinib in GLPG0634-CL-205.
7.1.5.2.
Incomplete Dates
If the onset date of the AE is incomplete and the AE stop date is not prior to the first dosing date 
of filgotinib in the core studies or GLPG0634-CL-205, then the month and year (or year alone if 
month is not recorded) of onset determine whether an AE is treatment emergent. The event is 
considered treatment emergent if both of the following 2 criteria are met:

The AE onset is the same as or after the month and year (or year) of the first dosing date of 
filgotinib in the core studies or GLPG0634-CL-205, and

The AE onset date is the same as or before the month and year (or year) of the date 
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An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dosing date of filgotinib in the core studies or GLPG0634-CL-205, will 
be considered to be treatment emergent. In addition, an AE with the onset date missing and 
incomplete stop date with the same or later month and year (or year alone if month is not 
recorded) as the first dosing date of filgotinib in the core studies or GLPG0634-CL-205 will be 
considered treatment emergent.
7.1.6.
Summaries of Adverse Events and Deaths
Treatment-emergent AEs will be summarized based on the Safety Analysis Set.
7.1.6.1.
Summaries of AE incidence in Combined Severity Grade Subsets 
The number and percentage of subjects who experienced at least 1 TEAE will be provided and 
summarized by SOC, HLT, PT, and treatment group. For other AEs described below, summaries 
will be provided by SOC, PT, and treatment group:

TEAEs of Grade severe

TEAEs of Grade moderate or higher

All TE treatment-related AEs

TE Treatment-related AEs of Grade severe

TE Treatment-related AEs of Grade moderate or higher

All TE SAEs

All TE treatment-related SAEs 

All TEAEs leading to premature discontinuation of any study drug

All TEAEs leading to premature discontinuation of study

All TEAEs leading to temporary interruption of any study drug

All TE SAEs leading to death (ie, outcome of death)
A brief, high-level summary of AEs described above will be provided by treatment group and by 
the number and percentage of subjects who experienced the above AEs. All deaths reported in 
the study will be also included in this summary.
Multiple events will be counted only once per subject in each summary. Adverse events will be 
summarized and listed first in alphabetic order of SOC and HLT within each SOC (if applicable), 
and then by PT in descending order of total frequency within each SOC. For summaries by 


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severity grade, the most severe grade will be used for those AEs that occurred more than once in 
an individual subject during the study. 
In addition to the above summary tables, all TEAEs and TE treatment-related AEs will be 
summarized by PT only, in descending order of total frequency.
In addition, data listings will be provided for the following:

All AEs, indicating whether the event is treatment emergent

All AEs of Grade severe

All AEs of Grade moderate or higher

SAEs

Deaths

All SAEs leading to death (ie, outcome of death)

AEs leading to premature discontinuation of any study drug

AEs leading to premature discontinuation of study

AEs leading to temporary interruption of any study drug
7.1.7.
Adverse Events of Special Interest
Events of interest will be identified by the use of either SMQs or MSTs. However, should 
additional cases not detected by the predefined search term listings be identified during the 
clinical review process, these cases will also be reported by respective category.
7.1.7.1.
Adjudication Committee for MACE 
An independent cardiovascular safety endpoint adjudication committee (CVEAC) will be formed 
to periodically review and adjudicate all potential major cardiovascular adverse events (MACE) 
events. MACE events are defined as cardiovascular death, non-fatal myocardial infarction and 
non-fatal stroke.
To identify the MACE event, the following potential cases will be adjudicated:

All deaths

Cardiovascular events  (meeting serious criteria)

Myocardial infarction (Narrow)


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
Unstable angina (meeting serious or hospitalization criteria)

Transient ischemic attack

Stroke

Cardiac failure (meeting serious or hospitalization criteria)

Percutaneous coronary intervention
Potential MACE will be identified using MedDRA search listing (MST) searches. 
The CVEAC will review those potential MACE and related clinical data to determine whether a 
MACE has occurred. 
The CVEAC’s role and responsibilities and the data to be provided to the CVEAC are described 
in a mutually agreed upon CVEAC charter. The CVEAC charter defines the CVEAC 
membership, adjudication process, meeting logistics, and meeting frequency. 
The number and percentage of subjects with positively adjudicated MACE will be summarized 
by treatment group using the PT term.
A by-subject listing for all patients who have potential MACE at any time will be provided.
7.1.7.2.
Other Adverse Events of Special Interest
In addition to general safety parameters and MACE, safety information on other adverse events 
of special interest (AESIs) will also be analyzed. AESIs will be identified by either laboratory 
results, standardized MedDRA queries (SMQs), or sponsor defined MSTs, or a combination of 
these methods as indicated below.

All infections (defined as all PTs in the Infections and Infestations SOC)

Serious infections (defined as all PTs in the Infections and Infestations SOC that are SAEs)

Infections of special interest as defined below
a) Herpes zoster
b) Active tuberculosis 
c) Opportunistic infections 
d) Hepatitis B or C infections 

Deep vein thrombosis (DVT) and pulmonary embolism (PE) 


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
Malignancy (including lymphoma; not including nonmelanoma skin cancer)

Nonmelanoma skin cancer

Gastrointestinal (GI) perforations
The number and percentage of patients with aforementioned events of special interest will be 
provided by the PT term for each AE of special interests.
A by-subject listing for all patients having AE of special interests at any time will be provided 
for each AE of special interests.
7.2.
Laboratory Evaluations
Laboratory collected during the study will be analyzed and summarized using both quantitative 
and qualitative methods. Summaries of laboratory data will be provided for the Safety Analysis 
Set and will include data collected up to the last dose of filgotinib plus 30 days for subjects who 
have permanently discontinued filgotinib in GLPG0634-CL-205, or all available data at the time 
of the database snapshot for subjects who were ongoing at the time of an interim analysis. The 
analysis will be based on values reported in conventional units. When values are below the LOQ, 
they will be listed as such, and the closest imputed value will be used for the purpose of 
calculating summary statistics as specified in Section 3.4. 
A by-subject listing for laboratory test results will be provided by subject ID number and visit in 
chronological order for hematology, serum chemistry, and urinalysis separately. Values falling 
outside of the relevant reference range and/or having a severity grade of 1 or higher on the 
CTCAE severity grade will be flagged in the data listings, as appropriate.
No formal statistical testing is planned.
7.2.1.
Summaries of Numeric Laboratory Results
Descriptive statistics of filgotinib baseline values, values at each postbaseline visit and change 
from filgotinib baseline at each post baseline visit will be provided by treatment group for the 
following laboratory tests:

Hematology
Hematocrit
Hemoglobin
Platelet count
Red blood cell count
White blood cell (WBC) count


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Lymphocytes
Monocytes
Neutrophils
Eosinophils
Basophils

Chemistry
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Alkaline phosphatase (ALP)
Total bilirubin
Serum creatinine
Creatinine clearance by Cockcroft-Gault formula
Glucose

Lipid
Triglycerides
Total cholesterol
HDL
LDL
LDL/HDL ratio

Hormone in male subjects
Follicle stimulating hormone 
Inhibin B
Luteinizing hormone  
Testosterone


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A filgotinib baseline laboratory value will be defined as the last measurement obtained on or 
prior to the date/time of first dose of filgotinib in the core studies or GLPG0634-CL-205. Change 
from filgotinib baseline to a postbaseline visit will be defined as the visit value minus the 
filgotinib baseline value. The mean, median, Q1, Q3, minimum, and maximum values will be 
displayed to the reported number of digits; SD values will be displayed to the reported number of 
digits plus 1.
Median (Q1, Q3) of the observed values for the laboratory tests specified above will be plotted 
using a line plot by treatment group and visit.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.5.3.
7.2.2.
Graded Laboratory Value
The CTCAE Version 4.03 will be used to assign toxicity grades to laboratory results for analysis. 
Grade 0 includes all values that do not meet the criteria for an abnormality of at least Grade 1. 
For laboratory tests with criteria for both increased and decreased levels, analyses for each 
direction (ie, increased, decreased) will be presented separately. 
7.2.2.1.
Treatment-Emergent Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are defined as values that increase at least 
1 toxicity grade from filgotinib baseline at any postbaseline time point, up to and including the 
date of last dose of filgotinib plus 30 days for subjects who permanently discontinued filgotinib
in GLPG0634-CL-205, or the last available date in the database snapshot for subjects who were 
still on treatment at the time of an interim analysis. 
If the relevant filgotinib baseline laboratory value is missing, any abnormality of at least Grade 1 
observed within the time frame specified above will be considered treatment emergent.
7.2.2.2.
Treatment-Emergent Marked Laboratory Abnormalities
Treatment-emergent marked laboratory abnormalities are defined as values that increase from 
filgotinib baseline by at least 3 toxicity grades at any postbaseline time point, up to and including 
the date of the last dose of filgotinib plus 30 days for subjects who permanently discontinued 
filgotinib in GLPG0634-CL-205 or the last available date in the database snapshot for subjects 
who were still on treatment at the time of an interim analysis.
If the relevant filgotinib baseline laboratory value is missing, any Grade 3 or higher values 
observed within the time frame specified above will be considered treatment-emergent marked 
abnormalities.


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7.2.2.3.
Summaries of Laboratory Abnormalities
Laboratory data that are categorical will be summarized using the number and percentage of 
subjects in the study with the given response at filgotinib baseline and each scheduled 
postbaseline visit.
The following summaries (number and percentage of subjects) for treatment-emergent laboratory 
abnormalities will be provided by lab test and treatment group; subjects will be categorized 
according to the most severe postbaseline abnormality grade for a given laboratory test:

Graded laboratory abnormalities

Grade 3 or higher laboratory abnormalities

Marked laboratory abnormalities
For all summaries of laboratory abnormalities, the denominator is the number of subjects with 
nonmissing postbaseline values up to 30 days after last dosing date of filgotinib in 
GLPG0634-CL-205.
A by-subject listing of treatment-emergent Grade 3 or higher laboratory abnormalities and 
marked laboratory abnormalities will be provided separately by subject ID number and visit in 
chronological order. These listings will include all test results that were collected throughout the 
study for the laboratory test of interest, with all applicable severity grades or abnormal flags 
displayed.
7.2.3.
Laboratory Evaluations of Special Interest
7.2.3.1.
Liver-Related Laboratory Evaluations
Liver-related abnormalities after initial study drug dosing will be examined and summarized 
using the number and percentage of subjects who were reported to have the following laboratory 
test values for postbaseline measurements:

AST: (a) > 3 times of the upper limit of reference range  (ULN); (b) > 5 x ULN; 
(c) > 10 x ULN; (d) > 20 x ULN

ALT: (a) > 3 x ULN; (b) > 5 x ULN; (c) > 10 x ULN; (d) > 20 x ULN

AST or ALT > 3 x ULN and total bilirubin > 2 x ULN
The summary will include data from all postbaseline visits up to 30 days after the last dose of 
filgotinib in GLPG0634-CL-205. For individual laboratory tests, subjects will be counted once 
based on the most severe postbaseline values. For both the composite endpoints of AST or ALT 
and total bilirubin, subjects will be counted once when the criteria are met at the same 
postbaseline visit date. The denominator is the number of subjects in the Safety Analysis Set who 


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have nonmissing postbaseline values of all relevant tests at the same postbaseline visit date. A 
listing of subjects who met at least 1 of the above criteria will be provided.
7.2.3.2.
Complete Blood Count-Related Laboratory Evaluations
Complete blood count (CBC)-related abnormalities such as anemia, leucopenia, neutropenia, 
lymphopenia, and thrombocytopenia after initial study drug dosing will be examined and 
summarized using the number and percentage of subjects who were reported to have the 
following laboratory test values for postbaseline measurements:

Hemoglobin: (a) any postbaseline worsening CTCAE grade from filgotinib baseline; 
(b) filgotinib baseline value of less than Grade 3 and increase to Grade 3 or higher at worst 
postbaseline; (c) filgotinib baseline value of less than Grade 3 and increase to Grade 4 at 
worst postbaseline

WBC count: (a) any postbaseline worsening CTCAE grade from filgotinib baseline; 
(b) filgotinib baseline value of less than Grade 3 and increase to Grade 3 or higher at worst 
postbaseline; (c) filgotinib baseline value of less than Grade 3 and increase to Grade 4 at 
worst postbaseline

Absolute neutrophil count: (a) any postbaseline worsening CTCAE grade from filgotinib 
baseline; (b) filgotinib baseline value of less than Grade 3 and increase to Grade 3 or higher 
at worst postbaseline; (c) filgotinib baseline value of less than Grade 3 and increase to 
Grade 4 at worst postbaseline

Lymphocyte count: (a) any postbaseline worsening CTCAE grade from filgotinib baseline; 
(b) filgotinib baseline value of less than Grade 3 and increase to Grade 3 or higher at worst 
postbaseline; (c) filgotinib baseline value of less than Grade 3 and increase to Grade 4 at 
worst postbaseline

Platelet count: (a) any postbaseline worsening CTCAE grade from filgotinib baseline; 
(b) filgotinib baseline value of less than Grade 3 and increase to Grade 3 or higher at worst 
postbaseline; (c) filgotinib baseline value of less than Grade 3 and increase to Grade 4 at 
worst postbaseline
The summary will include data from all postbaseline visits up to 30 days after the last dose of 
filgotinib.
7.3.
Body Weight and Vital Signs
Descriptive statistics will be provided by treatment group for body weight, BMI and vital signs
(systolic and diastolic blood pressures [mmHg], pulse [beats/min] ) as follows:

Filgotinib baseline value

Values at each postbaseline visit

Change from filgotinib baseline at each postbaseline visit


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A filgotinib baseline value will be defined as the last available value collected on or prior to the 
date/time of first dose of filgotinib in the core studies or GLPG0634-CL-205. Change from 
filgotinib baseline to a postbaseline visit will be defined as the postbaseline value minus the 
filgotinib baseline value. Body weight and vital signs measured at unscheduled visits will be 
included for the filgotinib baseline value selection.
In the case of multiple values in an analysis window, data will be selected for analysis as 
described in Section 3.5.3. No formal statistical testing is planned.
A by-subject listing of vital signs (systolic and diastolic blood pressure [mmHg], pulse 
[beats/min]) will be provided by subject ID number and visit in chronological order. In the same 
manner, a by-subject listing of body weight, height, and BMI will be provided separately.
7.4.
Concomitant Medications
Medications collected during the study will be coded using the World Health Organization 
(WHO) Drug dictionary version BSEP17.
Concomitant medications are defined as medications taken while a subject took study drug in 
GLPG0634-CL-205. Use of concomitant medications will be summarized by ATC drug class 
preferred name using the number and percentage of subjects for each treatment group. A subject 
reporting the same medication more than once will be counted only once when calculating the 
number and percentage of subjects who received that medication. The summary will be provided
by preferred name in descending overall frequency. For drugs with the same frequency, sorting 
will be done alphabetically.
For the purposes of analysis, any medication with a start date prior to or on the first dosing date 
of filgotinib in GLPG0634-CL-205 and continued to take after the first dosing date, or started 
after the first dosing date but prior to or on the last dosing date of filgotinib in 
GLPG0634-CL-205 will be considered concomitant medications. Medications started and 
stopped on the same day as the first dosing date or the last dosing date of filgotinib in 
GLPG0634-CL-205 will also be considered concomitant. Medications stopped on the same day 
as the first dosing date of filgotinib in GLPG0634-CL-205 will be considered concomitant. 
Medications with a stop date prior to the date of first dosing date of filgotinib in 
GLPG0634-CL-205 or a start date after the last dosing date of filgotinib in GLPG0634-CL-205
will be excluded from the concomitant medication summary. If a partial stop date is entered, any 
medication with the month and year (if day is missing) or year (if day and month are missing) 
prior to the date of first filgotinib administration in GLPG0634-CL-205 will be excluded from 
the concomitant medication summary. If a partial start date is entered, any medication with the 
month and year (if day is missing) or year (if day and month are missing) after the filgotinib stop 
date in GLPG0634-CL-205 will be excluded from the concomitant medication summary. 
GLPG0634-CL-205 medications with completely missing start and stop dates will be included in 
the concomitant medication summary, unless otherwise specified. 
Summaries will be based on the Safety Analysis Set. No formal statistical testing is planned.


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All GLPG0634-CL-205 concomitant medications (other than per-protocol study drugs) will be 
provided in a by-subject listing sorted by subject ID number and administration date in 
chronological order.
7.5.
Electrocardiogram Results
7.5.1.
Investigator Electrocardiogram Assessment
A shift table of the investigators’ assessment of ECG results at each visit compared with 
filgotinib baseline values will be presented by treatment group using the following categories: 
normal; abnormal (not clinically significant); abnormal (clinically significant); or missing. The 
number and percentage of subjects in each cross-classification group of the shift table will be 
presented. Subjects with a missing value at filgotinib baseline or postbaseline will not be 
included in the denominator for percentage calculation. 
No formal statistical testing is planned.
A by-subject listing for ECG assessment results will be provided by subject ID number and visit
in chronological order.
7.6.
Other Safety Measures
A data listing will be provided for subjects who have positive or borderline urine or serum
pregnancy test result during the study.
7.7.
Changes From Protocol-Specified Safety Analyses
There are no deviations from the protocol-specified safety analyses.


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8.
REFERENCES
Aletaha D, Nell VP, Stamm T, Uffmann M, Pflugbeil S, Machold K, et al. Acute phase reactants 
add little to composite disease activity indices for rheumatoid arthritis: validation 
of a clinical activity score. Arthritis research & therapy 2005;7 (4):R796-806.


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9.
SOFTWARE
SAS® Software Version 9.4. SAS Institute Inc., Cary, NC, USA.


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10.
SAP REVISION
Revision Date
(DD MMM YYYY)
Section
Summary of Revision
Reason for Revision
24 JAN 2019
Section 2.2 
and 2.3
Update analysis frequency
Administrative change
24 JAN 2019
Section 
6.3.11
Update physical component score
(PCS) to physical component 
summary (PCS), and mental
component score (MCS) to mental 
component summary (MCS)
Administrative change
24 JAN 2019
Section 5.2
Update Oral systemic 
corticosteroids to Oral 
corticosteroids
Administrative change


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11.
APPENDIX
Appendix 1.
Lists of RA Medications
1. List of of bDMARDs and Investigational bDMARDs (WHO Preferred Terms)

ABATACEPT

ADALIMUMAB

ANAKINRA

BAMINERCEPT

BELIMUMAB

BIMEKIZUMAB

CABIRALIZUMAB

CERTOLIZUMAB

CERTOLIZUMAB PEGOL

CLAZAKIZUMAB

DENOSUMAB

EPRATUZUMAB

ETANERCEPT

GOLIMUMAB

INFLIXIMABINTERLEUKIN-2

OCRELIZUMAB

REMTOLUMAB

RITUXIMAB

SARILUMAB

SECUKINUMAB

SIRUKUMAB

TABALUMAB

TILDRAKIZUMAB

TOCILIZUMAB

TREGALIZUMAB

Other investigational bDMARDs


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2. List of Oral Corticosteroid (WHO Preferred Terms)

BETAMETHASONE

BETAMETHASONE DIPROPIONATE

BETAMETHASONE SODIUM PHOSPHATE

CORTISONE

DEXAMETHASONE

DEXAMETHASONE PALMITATE

DEXAMETHASONE SODIUM PHOSPHATE

MEPREDNISONE

METHYLPREDNISOLONE

METHYLPREDNISOLONE ACETATE

METHYLPREDNISOLONE SODIUM SUCCINATE

MOMETASONE FUROATE

PREDNISOLONE

PREDNISOLONE FARNESYLATE

PREDNISOLONE SODIUM SUCCINATE

PREDNISONE
3. List of Methotrexate (WHO Preferred Terms)

METHOTREXATE

METHOTREXATE SODIUM


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Appendix 2.
Health Assessment Questionnaire Disability Index (HAQ-DI)
The HAQ-DI score is defined as the average of the scores of eight functional categories (dressing 
and grooming, arising, eating, walking, hygiene, reach, grip, and other activities), usually 
administered by the patient.  Responses in each functional category are collected as 0 (without 
any difficulty) to 3 (unable to do a task in that area), with or without aids or devices. 
The highest score for questions in each category (range 0 to 3) determines the score for the 
category, unless aids or devices are required. Dependence on equipment or physical assistance 
increases a lower score (ie, scores of 0 or 1) to the level of 2 to more accurately represent 
underlying disability. The eight category scores are averaged into an overall HAQ-DI score on a 
scale from 0 (no disability) to 3 (completely disabled) when 6 or more categories are 
non-missing.  If more than 2 categories are missing, the HAQ-DI score is set to missing. The 
HAQ-DI can be treated as a continuous measure. 
The HAQ-DI score using aids (and/or devices) is computed by taking the maximum score of the 
questions in each category (range: [0, 3]) and whether or not aids/devices are used (0 or 1):
A = max(dressing & grooming category questions, 2*aids indicator) +
max(rising category questions, 2*aids indicator) +
max(eating category questions, 2*aids indicator) +
max(walking category questions, 2*aids indicator) +
max(hygiene category questions, 2*aids indicator) +
max(reach category questions, 2*aids indicator) +
max(grip category questions, 2*aids indicator) +
max(usual activities category questions, 2*aids indicator)
HAQ-DI = A/(total number of categories with at least 6 non-missing)


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The following table shows the contribution of the 43 questions used to calculate the HAQ-DI:
HAQ-DI Category:
Category questions:
At least 6 categories must have scores to 
compute the HAQ-DI.
HAQ-DI Category Score with 
Aids/Devices Calculation:
Category Questions
Aids/Devices Indicators
Dressing/Grooming
HAQ0101, HAQ0102
(DRESS, HAIR)
HAQ0114, HAQ0119
(DRSG, GROOM)
Using each question with a scale of 
0-3, calculate the category score as 
the maximum of the category 
questions.
If the Aids/Devices indicator is 
“No”, no need to adjust the category 
score.
If the Aids/Devices indicator is 
“Yes” and the category score is <2, 
then the category score with the 
Aids/Devices is set to 2.
If the Aids/Devices indicator is 
“Yes” and the category score is ≥2, 
then the category score with 
Aids/Devices is the calculated 
category score without adjustment.
For example:
The Dressing/Grooming category 
score is 2 if subject answered 1 for 
both questions 1 and 2 and “Yes” for 
both question 14 and 18. 
In the HAQ-DI score calculation, 
questions on other device/aids will 
not be used.
Arising
HAQ0103, HAQ0104
(STAND, BED)
HAQ0116, HAQ0120
(CHAIR, ARISING)
Eating
HAQ0105,HAQ0106, 
HAQ0107
(MEAT, LIFT,MILK)
HAQ0115, HAQ0121
(UTENSIL, EAT)
Walking
HAQ0108, HAQ0109
(WALK, STEPS)
HAQ0110, HAQ0111, 
HAQ0112, HAQ0113, 
HAQ0122
(CANE, WALKER, 
CRUTCH, WHEEL, 
WALKING)
Hygiene
HAQ0123, HAQ0124, 
HAQ0125
(WASH, BATH, 
TOILET)
HAQ0134, HAQ0135, 
HAQ0137, HAQ0139, 
HAQ0142
(RAISEAT, BATHBAR, 
BATHSEAT, 
LONGBATH, 
HYGIENE)
Reach
HAQ0126, HAQ0127
(REACH, BEND)
HAQ0138, HAQ0143
(LONGRCH, REACH)
Grip
HAQ0128, HAQ0129, 
HAQ0130
(OPENCAR, JAR, 
FAUCET)
HAQ0136, HAQ0144
(JAROPEN, GRIP)
Activity
HAQ0131, HAQ0132, 
HAQ0133
(SHOP, INCAR, 
CHORES)
HAQ0145
(ERRAND)
Handling Missing Data: If no more than 2 categories have missing category scores, then the 
HAQ-DI is the mean of the non-missing category scores. Otherwise, the HAQ-DI score is set to 
missing.
If any of the category questions are missing, but the aids/device indicator is non-missing, the 
category score can still be computed.  However, if all category questions and its aids/device 
indicators are missing, then the category score is considered missing. 


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Appendix 3.
Corticosteroids
The following table will be used for converting non-prednisone medications to prednisone 
equivalent:
Example: Subject is taking 8 mg of Methylprednisolone orally daily. To get the equivalent dose 
of prednisone: 8 mg Methylprednisolone = (5*8)/ 4 = 10 mg prednisone. 
Corticosteroids Name
Equivalent Dose (mg) to 5 mg Prednisone
Betamethasone 
0.75
Betamethasone Dipropionate
0.75
Betamethasone Sodium Phosphate
0.75
Cortisone
20
Dexamethasone 
0.75
Dexamethasone Palmitate
0.75
Dexamethasone Phosphate
0.75
Dexamethasone Sodium Phosphate
0.75
Hydrocortisone 
20
Meprednisone
4
Methylprednisolone 
4
Methylprednisolone Acetate
4
Methylprednisolone Sodium Succinate
4
Prednisone 
5
Prednisolone 
5
Prednisolone Farnesylate
5
Prednisolone Sodium Succinate
5
Triamcinolone 
4