A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of GLPG3970, Administered Orally for 6 Weeks in Adult Subjects With Moderately to Severely Active Rheumatoid Arthritis and an Inadequate Response to Methotrexate
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Sponsor: Galapagos NV

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Confidentiality Statement 
The information contained in this document is privileged and confidential. It is the property of Galapagos NV and 
may not be used, disclosed, reproduced or otherwise disseminated within your organization or communicated to any 
third parties without the express written authorization of Galapagos NV. 
 
CLINICAL STUDY PROTOCOL 
Project Number: 
GLPG3970 
 
 
Study Number: 
GLPG3970-CL-209 
 
 
Study Title: 
A randomized, double-blind, placebo-controlled, multicenter study to evaluate 
the safety, tolerability, efficacy and pharmacokinetics of GLPG3970, 
administered orally for 6 weeks in adult subjects with moderately to severely 
active rheumatoid arthritis and an inadequate response to methotrexate  
Short Study Title: 
A study evaluating the effects of GLPG3970 given as an oral treatment for 6 
weeks in adults with moderately to severely active rheumatoid arthritis and 
an inadequate response to methotrexate 
Clinical Study 
Phase: 
2 
Protocol Version:  
1.0 
Date: 
29-May-2020 
Status: 
Final 
 
 
EudraCT No: 
2020-000658-83 
CT.gov No: 
to be confirmed 
IND No: 
not applicable 
Sponsor: 
Galapagos NV, Generaal De Wittelaan L11 A3, 2800 Mechelen, Belgium 
Clinical Scientist: 
 
Translational 
Medicine Leader: 
 
 
General Protocol 
 

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TABLE OF CONTENTS 
EMERGENCY CONTACT INFORMATION ........................................................................... 2 
TABLE OF CONTENTS ........................................................................................................ 3 
CLINICAL STUDY PROTOCOL HISTORY ............................................................................ 7 
SUMMARY OF CHANGES ................................................................................................... 8 
LIST OF TABLES .................................................................................................................. 9 
LIST OF FIGURES ................................................................................................................ 9 
LIST OF APPENDICES ......................................................................................................... 9 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS..................................................10 
1. 
CLINICAL STUDY PROTOCOL SYNOPSIS .................................................................17 
2. 
INTRODUCTION ...........................................................................................................22 
2.1. 
Background - Nonclinical Studies .......................................................................23 
2.1.1. 
Nonclinical Pharmacokinetics .............................................................23 
2.1.2. 
Safety Pharmacology ..........................................................................23 
2.1.3. 
General Toxicology .............................................................................23 
2.1.4. 
Genotoxicity ........................................................................................24 
2.1.5. 
Embryo-fetal Development Toxicity .....................................................24 
2.1.6. 
Phototoxicity .......................................................................................24 
2.2. 
Background - Clinical Studies ............................................................................24 
3. 
CLINICAL STUDY OBJECTIVES ..................................................................................25 
3.1. 
Primary Objectives .............................................................................................25 
3.2. 
Secondary Objective ..........................................................................................25 
3.3. 
Other Objectives ................................................................................................25 
4. 
ENDPOINTS .................................................................................................................25 
4.1. 
Primary Endpoints..............................................................................................25 
4.2. 
Secondary Endpoints .........................................................................................25 
4.3. 
Other Endpoints .................................................................................................26 
5. 
INVESTIGATIONAL PLAN ............................................................................................26 
5.1. 
Clinical Study Design .........................................................................................26 
5.2. 
Start and End of Study Definition .......................................................................27 
5.3. 
Clinical Study Rationale .....................................................................................27 
5.4. 
Dosing Rationale ...............................................................................................28 
5.5. 
Potential Risks and Benefits ..............................................................................28 
6. 
CLINICAL STUDY POPULATION .................................................................................30 
6.1. 
Inclusion Criteria ................................................................................................30 

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9. 
STATISTICAL METHODS .............................................................................................57 
9.1. 
Determination of Sample Size ............................................................................57 
9.2. 
Population for Analyses .....................................................................................57 
9.2.1. 
All Screened Subjects .........................................................................57 
9.2.2. 
All Randomized Subjects ....................................................................58 
9.2.3. 
Full Analysis Set .................................................................................58 
9.2.4. 
Safety Analysis Set .............................................................................58 
9.3. 
Statistical Analyses ............................................................................................58 
9.3.1. 
General Statistical Considerations ......................................................58 
9.3.2. 
Interim Analysis ..................................................................................58 
9.3.3. 
Analyses of Demographics and Baseline Characteristics ....................59 
9.3.4. 
Analyses of Efficacy Parameters .........................................................59 
9.3.4.1. 
Analysis for Primary Efficacy Endpoint...............................59 
9.3.4.2. 
Analyses for Other Efficacy Endpoints ...............................59 
9.3.5. 
Analyses of Safety Data ......................................................................59 
9.3.5.1. 
Extent of Exposure ............................................................60 
9.3.5.2. 
Adverse Events .................................................................60 
9.3.5.3. 
Clinical Laboratory Evaluations ..........................................60 
9.3.5.4. 
Physical Examinations .......................................................60 
9.3.5.5. 
Vital Signs .........................................................................60 
9.3.5.6. 
12-Lead Electrocardiogram ................................................61 
9.3.6. 
Pharmacokinetic Analyses ..................................................................61 
 
 
9.3.8. 
Additional Statistical Considerations ...................................................61 
10. DATA MONITORING .....................................................................................................61 
10.1. 
Data Safety Monitoring Committee ....................................................................61 
11. SAFETY REPORTING ..................................................................................................62 
11.1. 
Definitions of Adverse Events, Serious Adverse Events and Special 
Situations ...........................................................................................................62 
11.1.1. 
Adverse Events ...................................................................................62 
11.1.2. 
Serious Adverse Events ......................................................................62 
11.1.3. 
Unlisted (Unexpected) Adverse Events/ Reference Safety 
Information ..........................................................................................63 
11.1.4. 
Adverse Events of Special Interest .....................................................63 
11.1.5. 
Clinical Laboratory Abnormalities and Other Abnormal 
Assessments as Adverse Events or Serious Adverse Events .............63 
11.1.6. 
Special Situations ...............................................................................63 
11.2. 
Assessment of Adverse Events and Serious Adverse Events ............................64 
11.2.1. 
Assessment of Causality .....................................................................64 
11.2.2. 
Assessment of Severity ......................................................................65 
11.2.3. 
Action Taken Regarding Investigational Product .................................66 
11.2.4. 
Outcome .............................................................................................66 
11.3. 
Investigator Requirements and Instructions for Reporting Adverse Events, 
Serious Adverse Events, Pregnancies, and Other Special Situations to the 
Sponsor .............................................................................................................66 

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11.3.1. 
Adverse Events ...................................................................................66 
11.3.2. 
Serious Adverse Events ......................................................................67 
11.3.3. 
Pregnancy ..........................................................................................67 
11.3.4. 
Reporting of Special Situations (Other Than Pregnancy) and 
Associated Adverse Events ................................................................68 
11.4. 
Sponsor Reporting Requirements ......................................................................68 
12. SPONSOR’S AND INVESTIGATOR’S RESPONSIBILITIES .........................................68 
12.1. 
Sponsor’s Responsibilities .................................................................................69 
12.1.1. 
Regulatory Authority Approval ............................................................69 
12.1.2. 
Clinical Study Closure Considerations ................................................69 
12.1.3. 
Indemnification ....................................................................................69 
12.1.4. 
Insurance ............................................................................................70 
12.1.5. 
Archiving .............................................................................................70 
12.1.6. 
Reporting ............................................................................................70 
12.1.7. 
Publication ..........................................................................................70 
12.2. 
Investigator’s Responsibilities ............................................................................71 
12.2.1. 
Source Data and Data Capture ...........................................................71 
12.2.2. 
Archiving .............................................................................................71 
12.2.3. 
Participation Cards ..............................................................................71 
12.3. 
Confidentiality ....................................................................................................71 
12.4. 
Ethical Considerations .......................................................................................72 
12.4.1. 
Independent Ethics Committee / Institutional Review Board ...............72 
12.4.2. 
Informed Consent ...............................................................................73 
12.5. 
Data Quality Control/Assurance .........................................................................74 
12.5.1. 
Monitoring ...........................................................................................74 
12.5.2. 
Audit and Inspection ...........................................................................74 
13. REFERENCES ..............................................................................................................75 
14. APPENDICES ...............................................................................................................77 
SIGNATURE PAGE – SPONSOR ........................................................................................88 
SIGNATURE PAGE – INVESTIGATOR ...............................................................................89 
 
 

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CLINICAL STUDY PROTOCOL HISTORY 
Clinical Study Protocol (CSP) / 
Amendment # 
Date 
Main Rationale 
General / Country-Specific 
CSP Version 1.0 
29-May-2020 
Initial CSP Version 
General  
 
 

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SUMMARY OF CHANGES 
Not applicable because this is the initial clinical study protocol (CSP). 
 
 
 

 
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviations 
 
 
ACR 
American College of Rheumatology 
ADL 
Activities of Daily Living 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUC 
area under the plasma concentration-time curve 
BCRP 
Breast cancer resistance protein 
bDMARD 
biologic disease-modifying anti-rheumatic drug 
bpm 
beats per minute 
BMI 
body mass index 
 
 
CI 
confidence interval 
CIA 
collagen-induced arthritis 
CL 
clearance 
CLCr 
creatinine clearance 
CL/F 
apparent total clearance 
Cmax 
maximum observed plasma concentration 
CRF 
case report form 
CRP 
C-reactive protein 
CRO 
contract research organization 

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HDL 
high-density lipoprotein 
hERG 
human ether-a-go-go related gene 
HIV 
human immunodeficiency virus 
HOMA-IR 
Homeostatic model assessment of insulin resistance 
hsCRP 
high sensitivity C-reactive protein 
IB 
investigator’s brochure 
IC50 
half maximum inhibitory concentration 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IgG 
immunoglobulin G 
IL 
interleukin 
IP 
investigational product 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IXRS 
interactive voice/web response system 
JAK 
Janus kinase 
LDL 
low-density lipoprotein 
LFT 
liver function test 
LPS 
lipopolysaccharide 
LRV 
lower reference value 
MMRM 
mixed models for repeated measures 
mRNA 
messenger ribonucleic acid 
MTX 
methotrexate 

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NOAEL 
no-observed-adverse-effect level 
NSAID 
non-steroidal anti-inflammatory drug 
P1NP 
serum N terminal propeptide type I collagen 
PBMC 
peripheral blood mononuclear cells 
 
 
PK 
pharmacokinetic 
pop-PK 
population pharmacokinetics 
q.d. 
once daily 
QTcF 
QT interval corrected for the heart rate using Fridericia’s formula 
QTv 
QT interval corrected by heart rate using the van de Water formula 
RA 
rheumatoid arthritis 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SBP 
systolic blood pressure 
SD 
standard deviation 
 
 
SIK 
salt-inducible kinase 
SJC66 
swollen joint count evaluated in 66 joints 
SOC 
System Organ Class 
SUSAR 
suspected unexpected serious adverse reaction 
t1/2 
elimination half-life 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse event 
TJC68 
tender joint count evaluated in 68 joints 

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TNF 
tumor necrosis factor 
TNFi 
tumor necrosis factor inhibitor 
TV 
target value 
ULN 
upper limit of normal 
VAS 
visual analog scale 
Vss 
volume of distribution at steady state 
WOCBP 
women of childbearing potential 
 
 

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1. 
CLINICAL STUDY PROTOCOL SYNOPSIS 
Title of Study 
A randomized, double-blind, placebo-controlled, multicenter study to evaluate the safety, 
tolerability, efficacy and pharmacokinetics of GLPG3970, administered orally for 6 weeks in 
adult subjects with moderately to severely active rheumatoid arthritis and an inadequate 
response to methotrexate 
Short Title of Study 
A study evaluating the effects of GLPG3970 given as an oral treatment for 6 weeks in adults 
with moderately to severely active rheumatoid arthritis and an inadequate response to 
methotrexate 
Phase of Development: Phase 2 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary  
 
To evaluate the effect of GLPG3970 compared to 
placebo on the signs and symptoms of rheumatoid 
arthritis (RA) in subjects with moderately to 
severely active RA and an inadequate response to 
methotrexate (MTX). 
Change from baseline in DAS28 (C-reactive protein 
[CRP]) at Week 6. 
Secondary 
 
To evaluate the safety and tolerability of 
GLPG3970 compared to placebo in subjects with 
moderately to severely active RA and an inadequate 
response to MTX. 
Number, incidence and severity of treatment-
emergent adverse events (TEAEs). 
To characterize the pharmacokinetics (PK) of 
GLPG3970 in subjects with moderately to severely 
active RA and an inadequate response to MTX. 
Observed GLPG3970 plasma trough concentrations 
(Ctrough). 

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The study is planned to randomize 25 subjects in a 3:2 ratio (15 subjects planned to receive 
GLPG3970 and 10 subjects planned to receive placebo). 
Study Design 
This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter parallel-group 
study evaluating GLPG3970 in adult subjects with moderately to severely active RA and an 
inadequate response to MTX. In this study, subjects will receive 1 dose level of GLPG3970 
(400 mg once daily [q.d.]) or placebo on top of their stable dose and dosing regimen of MTX. 
The study will consist of 3 study periods: 
− 
Screening period: up to 3 weeks with 1 study visit.  
− 
Double-blind treatment period: 6 weeks with 4 study site visits (Days 1, 15, 29, and 43) 
and 1 telephone call (Day 8). 
− 
Follow-up (FU) period: 2 weeks with 1 study visit. 
A schematic diagram of clinical study design, procedures, and stages is provided below. 
Study Duration 
Subjects will participate in the study for a maximum of 11 weeks (screening to FU) and will 
receive oral GLPG3970 or placebo, as a reconstituted oral solution, q.d. for 6 weeks. 

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Main Criteria for Inclusion and Exclusion 
Main Inclusion Criteria 
1. Male or female subject ≥18 and <65 years of age, on the date of signing the informed 
consent form (ICF). 
2. A body mass index (BMI) between 18–32 kg/m2, inclusive. 
3. Diagnosis of RA ≥6 months prior to screening AND meeting the 2010 ACR/ EULAR 
criteria of RA AND ACR functional class I-III. 
4. Have ≥6 swollen joints (from a SJC66) AND ≥8 tender joints (from a TJC68) at screening 
and at the baseline visit (Visit 1) prior to the first IP dosing. 
5. DAS28 (CRP) >3.2 (moderate disease) at screening. 
6. Screening serum high sensitivity CRP (hsCRP) > upper limit of normal (ULN, central 
laboratory reference: ≤ 5.0 mg/L). 
7. Inadequate response to MTX, i.e. treatment-experienced subjects who demonstrated 
inadequate clinical response during treatment with MTX. 
8. Have received MTX for ≥6 months and on stable dose (10 to 20 mg/week) of MTX for at 
least 4 weeks prior to screening and willing to continue on their current stable dose and 
dosing regimen for the duration of the study. 
9. If taking systemic steroids, prednisone equivalent at a dose of ≤10 mg/day and stable for 
at least 4 weeks prior to the first IP dosing. 
Main Exclusion Criteria 
1. Current therapy with any conventional disease-modifying anti-rheumatic drug (DMARD) 
other than MTX, including 
a. 
 oral or injectable gold, sulfasalazine, antimalarials, azathioprine, or D-penicillamine 
within 4 weeks prior to screening,  
b. cyclosporine within 8 weeks prior to screening, and  
c. 
leflunomide within 3 months prior to screening or a minimum 4 weeks prior to 
screening if after 11 days of standard cholestyramine therapy. 
2. Current or previous treatment with a biologic DMARD (bDMARD). Except for subjects 
who received bDMARDs only in a single clinical study setting: 
a. 
For whom the last dose of bDMARD ≥6 months prior to screening (12 months for 
rituximab or other lymphocyte depleting agents), AND; 
b. For whom the bDMARD was effective, without being discontinued due to lack of 
efficacy. 
3. Subjects who received an intra-articular or parenteral corticosteroid injection within 4 
weeks prior to screening. 
4. Subjects who received a prior surgical intervention within 12 weeks prior to screening or 
likely requirement for surgery during the study. 
5. Subject has a history of tuberculosis (TB) diagnosis or evidence of active or latent 
infection with Mycobacterium tuberculosis as defined by one of the following 
assessments: 
a. 
Positive QuantiFERON-TB Gold test result at screening, OR 

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b. Chest radiograph (posterior anterior view) taken within 12 weeks prior to screening, 
read by a qualified radiologist or pulmonologist, with evidence of current active TB 
or old inactive TB. 
6. Subject has any active systemic infection within the last 2 weeks prior to first IP dosing, 
or poorly controlled chronic cardiac, pulmonary, or renal disease. 
7. Subject has a known or suspected history of or a current immunosuppressive condition, or 
a history of invasive opportunistic infections (e.g. human immunodeficiency virus [HIV] 
infection, histoplasmosis, listeriosis, coccidiodmycosis, pneumocystosis, aspergillosis). 
8. Subject has a chronic hepatitis B virus (HBV) infection, as defined by persistent HBV 
surface antigen (HBsAg) positivity. Subject has hepatitis C virus (HCV) infection, as 
defined by positive HCV antibody at screening and detectable HCV viremia. Subjects 
with positive HCV antibody must undergo reflex HCV RNA testing, and subjects with 
HCV RNA positivity will be excluded. Subjects with positive HCV antibody and negative 
HCV RNA are eligible. 
9. Subject testing positive at screening for SARS-CoV-2 infection as detected by real time 
polymerase chain reaction (RT-PCR), subjects presenting any signs or symptoms as 
detected at baseline following careful physical examination (e.g. cough, fever, headaches, 
fatigue, dyspnea, myalgia, anosmia, dysgeusia, anorexia, sore throat, others) or reporting 
any signs and symptoms for the 2 preceding weeks, or subjects who have been exposed to 
individuals with confirmed or suspected diagnosis of SARS-CoV-2 within 2 weeks prior 
to baseline. In addition, any other locally applicable standard diagnostic criteria may also 
apply to rule out SARS-CoV-2 infection. 
Treatment and Treatment Schedule 
 
Investigational Medicinal Product, Dosage, and Mode of Administration 
GLPG3970 will be provided as a powder and solvent for oral solution, to be reconstituted 
prior to use. The final dosage form for administration is an oral solution containing 400 mg of 
the active pharmaceutical ingredient G1567970 (G1567970 is the compound code for 
Key selection criteria
• Inadequate response to
MTX
• Age ≥18 and <65 years
• RA diagnosis by ACR/EULAR 
criteria 
• ≥6 swollen joints from 
SJC66 and ≥8 tender joints 
from TJC68, CRP > ULN, 
DAS28 (CRP) > 3.2
Double-blind Treatment Period
Day 1 (Baseline) to Week 6
Follow-up Period
2 Weeks following  
end of Treatment
Screening
Up to 3 weeks
3:2 RANDOMIZATION
Group B (Placebo, n=10)
Group A (GLPG3970 400 mg q.d., n=15)
Key Outcome Measures
• Rate and severity TEAEs
• DAS28 (CRP)
• PK
•

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2. 
INTRODUCTION 
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory and joint degenerative disease 
that affects almost 1% of the adult population worldwide. The onset of RA classically occurs 
around 40 years of age (Oton & Carmona, 2020) and RA has 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 (Smolen, Aletaha, Koeller, Weisman, & Emery, 2007). 
The treatment of RA aims to reduce synovial inflammation, relieve pain, prevent joint damage 
and deterioration of physical function and the final goal is to achieve remission or at least low 
disease activity for all patients. To date, monotherapy with methotrexate (MTX), a disease-
modifying anti-rheumatoid drug (DMARD), is the recommended first-line treatment for patients 
with RA. Many patients fail to respond or don’t achieve disease remission with MTX 
(Chatzidionysiou & Sfikakis, 2019; Köhler, Günther, & Kaudewitz, 2019). In clinical trials, 
remission rates with MTX (with or without corticosteroids) range from 15% to 50.8% in subjects 
with early RA (disease duration <1 year) and from 7.6% to 28% in subjects with RA disease 
duration >1 year (Chatzidionysiou & Sfikakis, 2019). For patients with moderate or high disease 
activity despite DMARD therapy, it is recommended to use a combination of DMARDs with a 
tumor necrosis factor inhibitor (TNFi), or a non-TNF biologic and, in the case of established RA, 
a Janus kinase (JAK) inhibitor can be used (Smolen, et al., 2020). Glucocorticoids are often used 
in combination during acute disease flares to relieve pain and swelling fast and to gain control of 
the inflammation. A number of pro-inflammatory cytokines including TNF and interleukin-6 (IL-
6) are involved in the pathophysiology of RA and thus, biologic DMARDs (bDMARDs), 
targeting those cytokines and cells of the immune system have been approved for the treatment of 
RA (such as adalimumab, etanercept, infliximab, abatacept, rituximab, tocilizumab etc.). Due to 
the inconvenience of parenteral administration, safety, and tolerability issues (e.g. increased risk 
for infection and potential immunogenicity), and failure or only partial response to biologicals, 
there is still a need for safer, better tolerable, and orally active drugs with a different mechanism 
of action that can effectively modify the disease course. Oral, small-molecule inhibitors of 
intracellular kinases might bring therapeutic benefit in a wide range of inflammatory diseases and 
could address this need. More recently, JAK inhibitors demonstrated good efficacy in patients 
with RA. Even though many efficient drugs are currently available for the treatment for RA, 
many patients still suffer from ongoing symptoms and don’t achieve the final goal which is 
sustained disease remission and drug-free remission (Ajeqanova & Huizinga, 2017). Thus, there 
is still unmet medical need for patients with RA. 
GLPG3970 has a dual mechanism of action with the potential to improve upon the currently 
available treatments, via the induction of immunoregulatory mechanisms in addition to its anti-
inflammatory properties. GLPG3970 is an oral, selective, small-molecule serine/threonine salt-
inducible kinase (SIK) 2 and 3 inhibitor. These kinases provide a molecular switch in the control 
of pro- and anti-inflammatory cytokine production. Inhibition of these targets blocks the 
production of pro-inflammatory cytokines (TNFα, IL-12) and increases IL-10 levels, which has a 
tolerogenic effect, by activated macrophages and dendritic cells, thereby, converting the 
inflammatory state of these cells toward regulatory and tolerogenic phenotypes. In a mouse 
model of RA, treatment with GLPG3970 reduced disease activity. 

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Refer to the Schedule of Activities (Section 8.11) for further details.  
A schematic diagram of clinical study design, procedures and stages is provided in Figure 1. 
 
Figure 1 
Schematic Diagram 
For detailed information regarding dosage form, packaging and labeling of the investigational 
product (IP) refer to Section 7.2, “Dosage and Administration” and Section 7.3, “Packaging, 
Labeling and Distribution”. 
5.2. 
Start and End of Study Definition 
The study start is defined when the first informed consent form (ICF) is signed. The end of the 
study is reached when the last FU visit, as planned according to the Schedule of Activities 
(Section 8.11), for the last subject is performed. 
5.3. 
Clinical Study Rationale 
Published data showed that RA results from a breakdown of immune tolerance (Smolen, Aletaha, 
Koeller, Weisman, & Emery, 2007). GLPG3970 displays a unique dual mode of action with an 
anti-inflammatory component (reduction of pro-inflammatory cytokines by activated monocytes, 
macrophages, dendritic cells and T cells) coupled with a robust induction of immunoregulatory 
mechanisms (induced production of IL-10) in activated monocytes, macrophages and dendritic 
cells. The mouse collagen-induced arthritis (CIA) model is one of the most widely used models 
for the study of new therapeutic treatment options in RA and mimics the characteristics of human 
RA. GLPG3970 has demonstrated therapeutic potential in this model at the highest dose of 
60 mg/kg b.i.d. tested, similar to anti-TNFα treatment used as active comparator in the model. 
Treatment with GLPG3970 showed a significant effect on protection against bone erosion 
(Larsen score) and significantly reduced the production of total immunoglobulin G (IgG) levels, 
quantified in plasma as a measure of the autoreactive B cell state in the arthritic CIA model. 
These data provide strong rationale for the evaluation of GLPG3970 in subjects with RA. 
The double-blind, placebo-controlled, randomized, parallel-group design is a standard design for 
a first study of GLPG3970 in subjects with RA. 
Key selection criteria
• Inadequate response to
MTX
• Age ≥18 and <65 years
• RA diagnosis by ACR/EULAR 
criteria 
• ≥6 swollen joints from 
SJC66 and ≥8 tender joints 
from TJC68, CRP > ULN, 
DAS28 (CRP) > 3.2
Double-blind Treatment Period
Day 1 (Baseline) to Week 6
Follow-up Period
2 Weeks following  
end of Treatment
Screening
Up to 3 weeks
3:2 RANDOMIZATION
Group B (Placebo, n=10)
Group A (GLPG3970 400 mg q.d., n=15)
Key Outcome Measures
• Rate and severity TEAEs
• DAS28 (CRP)
• PK
•

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may be performed during a SARS-CoV-2 pandemic, the age limit of participants was set to 65 
years of age and appropriate measures should be taken to minimize the risk of SARS-CoV-2 
infection for subjects participating in the study as well as study site personnel. Local guidelines to 
prevent SARS-CoV-2 infection should be adhered to and a leaflet should be made available for 
all subjects detailing the SARS-CoV-2 safety measures to be taken.  
In case a randomized subject is not available to attend a scheduled study visit on site due to 
SARS-CoV-2 travel restrictions, a phone call or a televisit may be conducted instead. It is 
strongly recommended to conduct planned study assessments for the applicable visit as per 
protocol as much as possible. If possible and if local regulations allow and the subject agrees, 
trained study staff or trained personnel are encouraged to collect study assessments at the study 
subjects’ home or a local facility if social distancing and hygiene rules can be applied.  
Only staff trained in conducting the protocol planned assessments are authorized to perform 
home or local facility visit assessments and the alternative arrangements need to be adequately 
documented. Direct to patient (DTP) shipments are possible if needed. Subjects presenting with 
signs and symptoms of infection, including SARS-CoV-2 infection should immediately contact 
the site investigator, who should inform the sponsor’s medical responsible as soon as possible, 
and SARS-CoV-2 testing should be performed. 
6. 
CLINICAL STUDY POPULATION 
6.1. 
Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to be eligible for participation in this 
study: 
1. Male or female subject ≥18 and <65 years of age, on the date of signing the ICF. 
2. A body mass index (BMI) between 18–32 kg/m2, inclusive. 
3. Diagnosis of RA ≥6 months prior to screening AND meeting the 2010 ACR/EULAR criteria 
of RA AND ACR functional class I-III. 
4. Have ≥6 swollen joints (from a SJC66) AND ≥8 tender joints (from a TJC68) at screening 
and at the baseline visit (Visit 1) prior to the first IP dosing. 
5. DAS28 (CRP) >3.2 (moderate disease) at screening. 
6. Screening serum high sensitivity CRP (hsCRP) > upper limit of normal (ULN, central 
laboratory reference: ≤ 5.0 mg/L). 
7. Inadequate response to MTX, i.e. treatment-experienced subjects who demonstrated 
inadequate clinical response during treatment with MTX. 
8. Have received MTX for ≥6 months and on stable dose (10 to 20 mg/week) of MTX for at 
least 4 weeks prior to screening and willing to continue on their current stable dose and 
dosing regimen for the duration of the study.  
9. If taking systemic steroids, prednisone equivalent at a dose of ≤10 mg/day and stable for at 
least 4 weeks prior to the first IP dosing. 
10. If taking non-steroidal anti-inflammatory drugs (NSAIDs), these must be at a stable dose for 
at least 2 weeks prior to first IP dosing. 
11. Female subjects of childbearing potential must have a negative highly sensitive (serum beta 
human chorionic gonadotropin) pregnancy test at screening. Female subjects of non-

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childbearing potential must have a negative FSH test at screening or must be at least 6 
months permanently surgically sterile (bilateral oophorectomy, i.e. surgical removal of 
ovaries, bilateral salpingectomy or hysterectomy, i.e. surgical removal of uterus).  
12. Female subject of child bearing potential or male subject must agree to use highly effective 
contraception/preventive exposure measures (as described in Section 6.3.1).  
13. Able and willing to comply with the CSP requirements (e.g. opening and reconstituting the 
IP formulation) and must sign and date the ICF as approved by the Independent Ethics 
Committee (IEC) / Institutional Review Board (IRB), prior to any screening evaluations. 
14. Able and willing to comply with restrictions on prior and concomitant medication as 
described in Section 6.3.2. 
6.2. 
Exclusion Criteria 
Subjects meeting one or more of the following criteria cannot be enrolled in this clinical study: 
1. Current therapy with any conventional DMARD other than MTX, including 
a. 
Oral or injectable gold, sulfasalazine, antimalarials, azathioprine, or D-penicillamine 
within 4 weeks prior to screening,  
b. Cyclosporine within 8 weeks prior to screening, and  
c. 
Leflunomide within 3 months prior to screening or a minimum 4 weeks prior to 
screening if after 11 days of standard cholestyramine therapy. 
2. Current or previous treatment with a bDMARD. Except for subjects who received 
bDMARDs only in a single clinical study setting: 
a. 
For whom the last dose of bDMARD ≥6 months prior to screening (12 months for 
rituximab or other lymphocyte depleting agents), AND; 
b. For whom the bDMARD was effective, without being discontinued due to lack of 
efficacy. 
3. Subjects who received an intra-articular or parenteral corticosteroid injection within 4 weeks 
prior to screening. 
4. Subjects who received a prior surgical intervention within 12 weeks prior to screening or 
likely requirement for surgery during the study. 
5. Subject has a history of tuberculosis (TB) diagnosis or evidence of active or latent infection 
with Mycobacterium tuberculosis as defined by one of the following assessments: 
a. 
Positive QuantiFERON-TB Gold test result at screening, OR 
b. Chest radiograph (posterior anterior view) taken within 12 weeks prior to screening, read 
by a qualified radiologist or pulmonologist, with evidence of current active TB or old 
inactive TB. 
6. Subject has any active systemic infection within 2 weeks prior to first IP dosing, or poorly 
controlled chronic cardiac, pulmonary, or renal disease. 
7. Subject has a known or suspected history of or a current immunosuppressive condition, or a 
history of invasive opportunistic infections (e.g. HIV infection, histoplasmosis, listeriosis, 
coccidiodmycosis, pneumocystosis, aspergillosis). 
8. Subject has a chronic hepatitis B virus (HBV) infection, as defined by persistent HBV 
surface antigen (HBsAg) positivity. Subject has hepatitis C virus (HCV) infection, as defined 

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by positive HCV antibody at screening and detectable HCV viremia. Subjects with positive 
HCV antibody must undergo reflex HCV RNA testing, and subjects with HCV RNA 
positivity will be excluded. Subjects with positive HCV antibody and negative HCV RNA 
are eligible. 
9. Subject testing positive at screening for SARS-CoV-2 infection as detected by real time 
polymerase chain reaction (RT-PCR), subjects presenting any signs or symptoms as detected 
at baseline following careful physical examination (e.g. cough, fever, headaches, fatigue, 
dyspnea, myalgia, anosmia, dysgeusia, anorexia, sore throat, others) or reporting any signs 
and symptoms for the 2 preceding weeks, or subjects who have been exposed to individuals 
with confirmed or suspected diagnosis of SARS-CoV-2 within 2 weeks prior to baseline 
(BMJ, 2020) (BMJ, 2020). In addition, any other locally applicable standard diagnostic 
criteria may also apply to rule out SARS-CoV-2 infection. 
10. Investigator or other study staff or relative thereof who is directly involved in the conduct of 
the study. 
11. Subject has any condition or circumstances that, in the opinion of the investigator, may make 
a subject unlikely or unable to complete the study or comply with study procedures and 
requirements. 
12. Subject has a known hypersensitivity to IP ingredients or history of a significant allergic 
reaction to IP ingredients as determined by the investigator. 
13. Subject has any illness, judged by the investigator as relevant for participation in the study, 
in the 3 months prior to the first dose of the IP. 
14. Subject has presence or sequelae of gastrointestinal, liver, kidney (creatinine clearance 
[ClCr] ≤90 mL/minute, for elderly ≤60 mL/minute, using the Cockcroft-Gault formula: if 
calculated result is ≤90 mL/minute, for elderly ≤60 mL/minute, if applicable, a 24-hour urine 
collection can be used) or other conditions known to interfere with the absorption, 
distribution, metabolism, or excretion of drugs. 
15. Subject has a history of malignancy within the past 5 years prior to screening with the 
exception of excised and curatively treated non-metastatic basal cell carcinoma or squamous 
cell carcinoma of the skin or carcinoma in situ cervix which is considered cured with 
minimal risk of recurrence. 
16. Subject concurrently participates or participated in a drug, drug/device or biologic 
investigational research study within 3 months or 5 half-lives of the IP, whichever is longer, 
prior to screening. 
17. Subject has a history or presence of clinically significant abnormalities detected on 12-lead 
ECG of either rhythm or conduction e.g. known long QT syndrome or a QTcF >450 ms 
(male), >460 ms (female) detected on the 12-lead ECG. A first-degree atrioventricular block 
will not be considered as a significant abnormality. 
18. Female subject is breast feeding or intending to become pregnant or breastfeed during the 
study. 
19. Subject was vaccinated with a live vaccine within 60 days prior to screening. 

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6.3. 
Prohibition and Restrictions 
6.3.1. 
Precautions for Sexual Intercourse 
Highly effective contraceptive measures for both males and females of childbearing potential 
must be documented in the source documents. 
6.3.1.1. 
Female Subjects 
Female subjects are considered of non-childbearing potential if they meet one of the following 
criteria: 
− 
No menses for 12 or more months without an alternative medical cause. A high follicle 
stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or hormonal replacement 
therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is 
insufficient. 
− 
Permanently surgically sterile (bilateral oophorectomy, i.e. surgical removal of ovaries, 
bilateral salpingectomy or hysterectomy, i.e. surgical removal of uterus). 
All other female subjects are considered to be of childbearing potential (WOCBP) and must use 
one of the following highly effective methods of birth control prior to the first dose of IP, during 
the clinical study and for at least 35 days after the last dose of IP: 
− 
Combined (estrogen and progesterone containing) (oral, intravaginal, transdermal) hormonal 
contraception associated with inhibition of ovulation plus a barrier method. 
− 
Progesterone-only hormonal (oral, injectable, implantable) contraception associated with 
inhibition of ovulation plus a barrier method. 
− 
Intrauterine device. 
− 
Intrauterine hormone-releasing system plus a barrier method. 
− 
Bilateral tubal occlusion. 
− 
Sexual abstinence defined as refraining from heterosexual intercourse during the entire 
period of risk associated with the study treatments. The reliability of sexual abstinence needs 
to be evaluated in relation to the duration of the clinical study and the preferred and usual 
lifestyle of the subject. 
Periodic abstinence (e.g. calendar, symptothermal, post-ovulation methods), declaration of 
abstinence for the duration of a clinical study, withdrawal, spermicides only, and lactational 
amenorrhea method are not acceptable as methods of contraception. 
In case a WOCBP has a vasectomized partner, provided that partner is the sole sexual partner of 
the WOCBP clinical study participant and that the vasectomized partner has received medical 
assessment of the surgical success, then she is not required to use an additional form of 
contraception. 

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Within these limits, the specific forms of contraception employed are left to the discretion of the 
subject, the investigator, and/or the subject’s physician. 
The safety of GLPG3970 during breastfeeding is unknown. Nursing women are not allowed to 
take part in this clinical study. 
6.3.1.2. 
Male Subjects 
Non-vasectomized male subjects with female partners of childbearing potential must be willing 
to use a condom from the time of the first dose of IP, during the clinical study and for at least 
7 days after the last dose of IP, in addition to having their female partner use one of the following 
forms of contraception: 
− 
Combined (estrogen and progesterone containing) (oral, intravaginal, transdermal) hormonal 
contraception associated with inhibition of ovulation. 
− 
Progesterone-only hormonal (oral, injectable, implantable) contraception associated with 
inhibition of ovulation. 
− 
Intrauterine device. 
− 
Intrauterine hormone-releasing system. 
 
Sexual abstinence defined as refraining from heterosexual intercourse is considered a highly 
effective contraceptive measure only if it is the preferred and usual lifestyle of the subject. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical 
study. 
Periodic abstinence (e.g. calendar, symptothermal and post-ovulation methods), declaration of 
abstinence for the duration of a clinical study, withdrawal, spermicides only and lactational 
amenorrhea method are not acceptable methods of contraception. 
In a case where the female partner of a male subject has undergone documented surgical 
sterilization that was performed more than one year before screening, then the subject is not 
required to use an additional form of contraception. 
Vasectomized male subjects with female partners of childbearing potential are not required to use 
an additional form of contraception providing that surgical sterilization has been successful 
(documented azoospermia by semen analysis). 
No sperm donation is allowed from the first dose of IP during the clinical study until 7 days after 
the last dose of IP. 
6.3.2. 
Prior and Concomitant Medications 
Prior and concomitant therapies taken for long term treatment of pre-existing conditions are 
allowed, provided they are in accordance with the inclusion and exclusion criteria (see 
Section 6.1 and Section 6.2, respectively) and with the prohibitions and restrictions listed below. 

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Information on previous inadequate response on MTX therapy for RA within 2 years prior to 
screening should be recorded with approximate dates of use (year, duration in months) and dose. 
In case additional concomitant medications need to be administered or dose adjustments for pre-
existing conditions (except for RA) are needed during the study, the risk/benefit to the subject 
should be carefully assessed by the study physician and consideration given to the timing of any 
necessary introduction of new medications. 
If during the study, the subject’s condition necessitates the use of prohibited medication, the use 
of IP may be interrupted, preferably after consultation with the sponsor’s medical responsible. 
Re-introduction of IP can be considered after the treatment course with the prohibited medication 
has been stopped and after consultation with the sponsor’s medical responsible.  
During the study, subjects will be instructed to record any change in concomitant medication in a 
diary (see Section 8.8.1). 
Permitted Medications 
Permitted medications at screening and during the study include: 
− 
NSAIDs, provided that the dose is stable for at least 2 weeks prior to first IP dosing and, if 
possible, is kept constant during the study. 
− 
Analgesics, other than NSAIDs, up to the maximum recommended doses may be used for 
pain as required.  
− 
Oral steroids, provided that the dose is stable, at a dose of ≤10 mg/day prednisone or 
equivalent (see Appendix 7 for prednisolone conversion table) for at least 4 weeks prior to 
first IP dosing, and is kept stable for the study duration.  
− 
Medications prescribed for the treatment of comorbidities and which are not described as 
prohibited medications. 
Prohibited Medications 
Prohibited medications during the study include any DMARDs, other than background MTX, 
including: 
− 
Oral or injectable gold, sulfasalazine, antimalarials, azathioprine, or D-penicillamine within 
4 weeks prior to screening, 
− 
cyclosporine within 8 weeks prior to screening, 
− 
leflunomide within 3 months prior to screening or within 4 weeks prior to screening if after 
11 days of standard cholestyramine therapy. 
Current or previous treatment with a bDMARD. Except for subjects who received bDMARDs in 
a single clinical study setting: 
− 
For whom the last dose of bDMARD ≥6 months prior to screening (12 months for rituximab 
or other lymphocyte depleting agents), AND; 
− 
For whom the bDMARD was effective, without being discontinued due to lack of efficacy. 

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documents, and the subject will be asked to complete the ED visit and FU visit for safety 
assessments. 
Treatment with IP should be discontinued by the investigator (who may consult the sponsor’s 
medical responsible) for any of the following conditions: 
− 
Life-threatening adverse event (AE) or a serious adverse event (SAE) that places the subject 
at immediate risk. 
− 
Serious infections deemed related to study treatment by the investigator, and requiring 
parenteral antimicrobial therapy and/or hospitalization. 
− 
Confirmed pregnancy or lactation. 
− 
Arrhythmia or conduction abnormality, including but not limited to prolonged QT interval 
corrected for the heart rate using Fridericia’s formula (QTcF), where the severity is 
categorized as Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 
higher (QTcF >500 ms on at least 2 separate ECGs) or clinically significant arrhythmia of 
any grade. 
− 
Liver enzyme increase (see also Appendix 8)  
• 
AST and/or ALT ≥8x the ULN. 
• 
AST and/or ALT elevations ≥3x ULN with signs of liver damage (i.e. with the 
appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, 
rash and/or eosinophilia [>5%], and/or total bilirubin ≥2.0x ULN or international 
normalized ration [INR] >1.5) 
• 
In addition, a dose interruption or reduction (if applicable) should be considered if AST 
and/or ALT ≥3x ULN and <5x ULN and dosing with IP should be interrupted if AST 
and/or ALT ≥5 and <8x ULN. 
− 
Subjects presenting with signs and symptoms of SARS-CoV-2 infection should immediately 
contact the site investigator, who should inform the sponsor’s medical responsible as soon as 
possible, and report an AE/SAE as applicable. In case of suspected SARS-CoV-2 infection 
RT-PCR and serology tests should be performed to confirm the infection. The investigator, 
preferably after consultation with the sponsor’s medical responsible, must discontinue the 
subject from the study. The subject could be tested for SARS-CoV-2 in facilities outside the 
study site and if so, the subject should be instructed to immediately inform the study 
investigator if the test is positive and test results should be shared with the investigator as 
soon as possible. 
 
For subjects having: 
• 
AST or ALT ≥8xULN 
• 
AST or ALT ≥3xULN with signs of liver damage (i.e. with the appearance of fatigue, 
nausea, vomiting, right upper quadrant pain or tenderness, fever, rash and/or 
eosinophilia [>5%], and/or total bilirubin ≥1.5xULN or INR >1.5) 
 
The following steps will need to be performed by the investigator: 
 

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• 
The site should immediately contact the subject and require the subject to discontinue IP 
immediately. The subject should be asked to return to the site within a 48-hour window 
from awareness of the result.  
• 
A full evaluation of various causes of hepatitis should be conducted (i.e. infectious, 
alcohol, medications, anatomical).  
• 
An assessment of other concomitant medications and standard of care should be made. 
The investigator should consider whether it is in the best interest of the subject to 
stop/interrupt concomitant medications and standard of care treatment.  
• 
A detailed history including relevant information on alcohol use, recreational drug use, 
supplement consumption, any herbal remedies, family history, sexual history, travel 
history, history of contact with a jaundiced subject, surgery, occupational history, blood 
transfusion, history of liver or allergic disease, and any other potential causes of 
attributable to a liver insult should be collected.  
• 
A detailed assessment of the subject’s clinical condition and repeat laboratory tests for 
liver function tests (LFT), including albumin, creatine kinase, total bilirubin (direct and 
indirect), gamma-glutamyl transferase (GGT), INR, and alkaline phosphatase should be 
done. 
• 
Further testing for hepatitis A, B, and C, and for autoimmune hepatitis should be done. 
Other causes of viral hepatitis (cytomegalovirus or Eppstein Barr virus etc) should be 
excluded. Liver imaging should be considered.  
• 
Referral to a hepatologist or gastroenterologist should be requested. 
• 
All these cases should be reported as SAEs. 
If during the study, the subject’s condition necessitates the use of prohibited medication, the use 
of IP may be interrupted, preferably after consultation with the sponsor’s medical responsible. 
Re-introduction of IP can be considered after the treatment course with the prohibited medication 
has been stopped and after consultation with the sponsor’s medical responsible.  
Every effort should be made to keep subjects in the study and on treatment. However, the 
investigator, who may consult the sponsor’s medical responsible, can consider stopping the study 
treatment in case of concerns about the subject’s safety, serious or severe AEs or worsening of 
the disease condition, which in the investigator’s opinion needs an alternative treatment approach 
not being covered in the clinical study (e.g. rescue medication). If IP treatment is interrupted due 
to an SAE, IP could be restarted, as per the investigator’s judgment and after consultation with 
the sponsor’s medical responsible.  
When study treatment is discontinued, the subject will be requested to complete the assessments 
for the ED visit and return for the FU visit. Reason for discontinuation must be documented in 
the case report form (CRF). 
Subjects will be informed prior to clinical study entry that they are allowed to withdraw from the 
clinical study. At any time and for any reason, a subject’s participation in the clinical study may 
terminate at his/her request without prejudice to his/her future medical care. The subject will be 
encouraged to share the reason(s) for withdrawal so this can be documented in the source 

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documents, and to complete the ED visit and FU visit for safety assessments, but will not be 
obliged to do so. 
Subjects who withdraw from the clinical study without contact with the site (lost-to-FU) should 
be contacted by the site so that their health status can be assessed and documented in the source 
documents. The site should make every effort to understand whether the subject is alive, 
including checking the medical records and contacting general practitioner or relatives, if 
necessary. All attempts must be documented in the source documents.  
The sponsor has the right to terminate the clinical study at any time and for any reason. In this 
event, the investigator(s) and relevant authorities will be informed of the reason for clinical study 
termination. 
6.5. 
Measures to Minimize Bias 
6.5.1. 
Randomization 
At screening, subjects will be assigned a subject identification number. When a subject is 
confirmed to be eligible for the clinical study, the subject will be randomized. Allocation of each 
subject to a given treatment will be done using a centralized electronic system (interactive 
voice/web response system [IXRS]). Subjects will be randomized in a 3:2 ratio to GLPG3970 or 
placebo. 
6.5.2. 
Blinding and Unblinding 
This is a randomized, double-blind clinical study. The subjects and the entire clinical study team, 
including the investigators, clinical study coordinators, and sponsor personnel are blinded to 
treatment assignment. 
Blinded and packaged medication will be provided to the site. All IP formulations will be 
identical in appearance, shape, smell and taste, and will be packaged in the proper proportion to 
assure desired dosages and maintenance of the blinding.  
The blind can be broken by the investigator for the safety of a subject. The investigator is 
encouraged to discuss considerations to break the blind with the sponsor’s medical responsible, 
whenever possible and where the situation allows. However, the responsibility to break the 
treatment code in emergency situations resides solely with the investigator. The investigator is 
not required to discuss unblinding beforehand if he or she feels rapid emergency unblinding is 
necessary, but is required to inform the sponsor within 24 hours after unblinding has occurred. 
The blind can be broken via IXRS by the investigator. 
If the blind is broken for any reason during the course of the clinical study, the moment on which 
the blind was broken and all other relevant information will be documented by the site. The 
reason for breaking the blind will be indicated and justified in the source documentation. 

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Subjects will receive powder and solvent to take home. The total content of the oral solution, 
reconstituted from the whole amount of powder and solvent, will need to be drunk. Detailed 
instructions for preparing and storing the applicable doses will be provided to the subject via 
on-site training on dummy kits and via a patient leaflet. 
If a subject misses a dose (e.g. because he/she forgot to take the medication), he/she should take 
the missed dose within 12 hours after the planned intake time. If IP is not taken within 12 hours 
after the planned time, the missed dose should be skipped. For each dose taken at home, the time 
and date should be recorded in the subject’s diary. 
7.3. 
Packaging, Labeling and Distribution 
IP packages will be labeled with clinical study-specific details, including storage conditions. 
All manufacturing, packaging and labeling operations will be performed according to Good 
Manufacturing Practice for Medicinal Products and the relevant regulatory requirements. 
Each medication kit will be identified with a unique kit number. Multiple kits can be provided to 
a subject at each visit, providing the subject with sufficient IP to cover the period until the next 
scheduled visit. 
The distribution of IP to the site will only occur after the required local documentation is 
obtained, including clinical study approval by Competent Authorities and the IECs/IRBs, 
documentation on which the assessment of the investigator’s qualifications was based (e.g. 
curriculum vitae), and the signed and dated study agreement and financial agreement. 
To ensure study subjects maintain dosing per protocol requirements during this study special 
delivery services through DTP shipments of IP from the investigational site to the subject can be 
implemented in case of SARS-CoV-2 restrictions. DTP should only be used in case of emergency 
where on-site IP dispensation is not possible, and if allowed per local regulations. Local 
guidelines must be followed and regulatory approval or notification of authorities may be 
required. Agreement of the subject to receive IP at home is required prior to the shipment of IP 
from the investigational site to the subject’s home. The DTP process used will be reviewed and 
approved by the sponsor, but the DTP shipments will be coordinated by the investigational site(s) 
in collaboration with the local CRO without the involvement of the sponsor to ensure clinical 
study integrity in case of SARS-CoV-2 restrictions. 
7.4. 
Storage 
Sites are to store IP supplies in a secure area until dispensed. Powder and solvent for oral solution 
at room temperature (below 30 °C), should not be refrigerated or frozen and protected from light 
and stored in the original packaging.  
Sites will be required to monitor the storage temperature by using at least a min-max 
temperature-recording device and to keep a minimum to maximum temperature log, which must 
be completed each working day in order to establish a record of compliance with these storage 
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The investigator will instruct subjects on how the IP should be stored at home. Storage conditions 
to be taken into account by the subject when taking IP home, are described in the patient leaflet. 
7.5. 
Treatment Compliance and Drug Accountability 
The investigator should discuss treatment compliance with the subject prior to the start of the 
study. Missed doses should be discussed to try to ascertain the reason(s). Every effort should be 
made to ensure the proper subject dose. Subjects with poor compliance will be retrained by the 
site. IP administration as indicated by the subject (amounts as well as periods) will be recorded 
on the CRF. 
The pharmacist or designated clinical study personnel will maintain a documentation of the total 
amount of IP received at site, amount dispensed to the subject, and the amount of IP returned by 
the subject to the site. IP supplies for each subject will be inventoried and accounted for 
throughout the clinical study. At the end of the treatment period, these records will be checked 
against the inventory by the study monitor. All clinical supplies will be stored in locked and 
access controlled facilities. Subjects will record IP administration at home in a subject diary. 
Subjects will return any unused IP and empty IP packages at each study visit and/or ED visit. 
Upon sponsor approval, all unused IP and empty IP packages are to be returned from the sites 
and/or any vendor involved in the clinical study supplies management activities to the agreed 
location (depot), if possible. All returns and destruction must be properly documented.  
8. 
CLINICAL STUDY ASSESSMENTS 
Every effort should be made to ensure that CSP-required tests and procedures are completed as 
described in the Schedule of Activities (see Section 8.11). To avoid inter-observer variability, 
every effort should be made to ensure that all safety and efficacy evaluations are completed by 
the same individual who made the initial baseline determinations. In case study assessments are 
not performed for reasons related to SARS-CoV-2 pandemic restrictions, this should be 
documented in the medical records and e-CRF.  
In case a randomized subject is not available to attend a scheduled study visit on site due to of 
SARS-CoV-2 travel restrictions, a phone call or a televisit may be conducted instead. It is 
strongly recommended to conduct planned study assessments for the applicable visit as per 
protocol as much as possible. If possible and if local regulations allow and the subject agrees, 
trained study staff or trained personnel are encouraged to collect study assessments at the study 
subjects’ home or a local facility if social distancing and hygiene rules can be applied.  
Only staff trained in conducting the protocol planned assessments are authorized to perform 
home or local facility visit assessments and the alternative arrangements need to be adequately 
documented. Direct to patient shipments are possible if needed. Subjects presenting with signs 
and symptoms of infection, including SARS-CoV-2 infection should immediately contact the site 
investigator, who should inform the sponsor’s medical responsible as soon as possible, and 
SARS-CoV-2 testing should be performed. 

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− 
For QuantiFERON –TB Gold test with indeterminate result (the subject is not eligible if 
retest result is indeterminate or positive).  
− 
During screening or later during the study, retesting (resampling) of clinical laboratory safety 
tests or SARS-CoV-2 RT-PCR tests is allowed once, only for technical or transport reasons 
(e.g. sample hemolyzed, out of stability, late arrival at laboratory impacting sample quality, 
loss, or destruction of the sample before analysis). 
8.1.2. 
Rescreening of Subjects 
If a subject is a screening failure, it is allowed to rescreen the subject once, if the reason for 
failure is temporary and expected to resolve, as judged by the investigator. When a subject is 
rescreened, the subject needs to be reconsented and all screening assessments need to be 
repeated. The subject will be assigned a new subject identification number. The time in between 
2 screening attempts could vary depending on the screening failure reason. 
The following data will be collected for screening failure subjects: ICF signed data, 
demographics, failed inclusion or exclusion criteria, and AEs. 
8.2. 
Unscheduled Visits 
Additional visits can be performed at other time points for any safety assessments, if clinically 
indicated. These unscheduled visits and outcomes of additional assessments need to be recorded 
in the source and, if performed before the subject’s last visit per CSP, also in the CRF. 
8.3. 
Initial Subject and Disease Characteristics 
Subjects will be asked to attend the study site for a screening assessment. After giving written 
informed consent, demographic data (year of birth, age, sex, ethnicity and race) will be collected 
and medical history will be taken, including RA disease history and treatment history. RA disease 
history will capture the duration of disease, clinical symptoms, and medication used to treat the 
disease. A physical examination will be performed, including measurement of weight and height. 
The subject’s diagnosis of RA will be confirmed based on 2010 ACR/EULAR criteria 
(documented diagnosis) and classified as ACR functional class I-III.  
Vital signs (systolic and diastolic blood pressure, pulse, oral/tympanic body temperature, the 
same method of measuring body temperature to be used throughout the study) will be measured 
and a 12-lead ECG will be recorded. Subjects should rest for at least 5 minutes in the supine 
position before the ECG recording, blood pressure and pulse measurement. 
The inclusion and exclusion criteria will be checked to assess eligibility for the study. All 
screening tests will be reviewed to confirm eligibility before randomization and the first IP dose. 
A serum pregnancy test will be done for all female subjects as well as an FSH test for 
postmenopausal female subjects.  

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presenting such symptoms at screening/baseline should not be included/randomized in the study 
(see Section 6.2). Developing such symptoms during the study, should be managed as per Section 
8.5.6. 
8.5.4. 
Vital Signs 
Vital signs (systolic and diastolic blood pressure taken at the same arm for each measurement, 
pulse  and oral/tympanic body temperature, the same method of measuring body temperature to 
be used throughout the study) will be recorded in a standardized manner (i.e. after the subject has 
rested in a supine position for at least 5 minutes) at visits specified in the Schedule of Activities 
in Section 8.11 (see also Section 8.1, “Timing of Assessments”). Clinically significant abnormal 
values should be recorded as AEs. 
8.5.5. 
12-lead Electrocardiogram 
At the time points specified in the Schedule of Activities (see Section 8.11 and also Section 8.1, 
“Timing of Assessments”), a triplicate 12-lead ECG will be recorded and results will be sent for 
central reading.  
12-lead ECG recordings will be performed before blood sampling and after subjects rested for at 
least 5 minutes in supine position. In case an indwelling catheter is used, ECGs may be recorded 
after blood sampling, provided that there is at least 30 minutes between catheter insertion and the 
ECG recording. When catheter insertion would fail, the 12-lead ECG needs to be taken before the 
venipuncture and at least 30 minutes after the failed attempt. Triplicate ECGs will be performed 
within a time span of 10 minutes, with an approximate 3-minute interval between ECGs.  
The following parameters need to be recorded: heart rate, RR interval, PR interval, QRS interval, 
uncorrected QT interval, morphology and rhythm analysis (QTcF will be derived). QTcF will be 
considered as normal if ≤450 ms (male) and ≤460 ms (female), while a prolongation of QTcF to 
>500 ms or an increase from baseline >60 ms will be considered a threshold of concern.  
Immediately after recording, the ECG will be reviewed by the investigator on clinical significant 
abnormalities. This immediate review during the visit needs to be documented in the subject’s 
source. After receipt of the central report, also all flagged ECG abnormalities need to be assessed 
by the investigator on clinical relevance. Clinically significant abnormal findings should be 
recorded as AEs. 
8.5.6. 
Other Safety Assessments 
SARS-CoV-2 infection will be assessed at screening by RT-PCR and at baseline through careful 
physical examination to exclude any potential signs and symptoms of infection, e.g. cough, fever, 
headaches, fatigue, dyspnea, myalgia, anosmia, dysgeusia, anorexia, sore throat, etc. 
Additional RT-PCR and serology testing will be repeated at baseline for documentation and 
throughout the study as needed. The subject could be tested for SARS-CoV-2 in facilities outside 
the study site and if so, the subject should be instructed to immediately inform the study 

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8.11. 
Schedule of Activities 
For detailed instructions on the clinical study procedures, please see referred sections and Section 8.1, “Timing of Assessments”. 
EVENT 
SCREENING 
PERIOD 
TREATMENT PERIOD1,2 
FOLLOW-UP 
PERIOD2 
Study visit 
S 
1 
2 
3 
4 
5 
ED3 
FU Visit 
Study Weeks  
 
Baseline 
1 
2 
4 
6 
 
 
Study Day (D) ± Days  
-21 to -1 
1 
8 ± 2 
15 ± 2 
29 ± 2 
43 ± 2 
Early treatment 
discontinuation 
57 ± 3  
On site visit 
✓ 
✓ 
 
✓ 
✓ 
✓ 
✓ 
✓ 
Telephone call 
 
 
✓ 
 
 
 
 
 
Informed consent  
✓ 
 
 
 
 
 
 
 
Inclusion/exclusion criteria  
✓ 
✓ 
 
 
 
 
 
 
Demographics  
✓ 
 
 
 
 
 
 
 
Medical history  
✓ 
 
 
 
 
 
 
 
FSH test (postmenopausal 
women) 
✓ 
 
 
 
 
 
 
 
                                                 
1 On dosing days, all assessments are to be performed within 3 hours pre-dose, unless otherwise specified. 
2 Subjects must come for the study visits 1, 3 and 5 in the morning in a fasting state (no food intake for at least 8 hours). For Visit 1 (predose measurements) and for 2 post 
dose visits (Visit 3, 4 or 5) all attempts should be made to plan the visit within 2 days following MTX intake. 
3 Subjects who discontinue treatment early will be requested to return for an early discontinuation (ED) visit to complete all Visit 5 assessments and to return for a follow-up 
(FU) visit 14 ± 3 days after last IP administration. 
 

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EVENT 
SCREENING 
PERIOD 
TREATMENT PERIOD1,2 
FOLLOW-UP 
PERIOD2 
Study visit 
S 
1 
2 
3 
4 
5 
ED3 
FU Visit 
Study Weeks  
 
Baseline 
1 
2 
4 
6 
 
 
Study Day (D) ± Days  
-21 to -1 
1 
8 ± 2 
15 ± 2 
29 ± 2 
43 ± 2 
Early treatment 
discontinuation 
57 ± 3  
Pregnancy test4  
✓ 
✓ 
 
 
✓ 
✓ 
✓ 
 
Physical examination  
✓ 
✓ 
 
 
 
✓ 
✓ 
✓ 
Vital signs  
✓ 
✓ 
 
✓ 
✓ 
✓ 
✓ 
✓ 
Body weight and height 5 
✓ 
✓ 
 
✓ 
✓ 
✓ 
✓ 
✓ 
12-lead triplicate ECG  
✓ 
✓ 
 
✓ 
✓ 
✓ 
✓ 
✓ 
Serology  
✓ 
 
 
 
 
 
 
 
QuantiFERON-TB Gold test  
✓ 
 
 
 
 
 
 
 
SARS-CoV-2 RT-PCR test6 
✓ 
✓ 
As needed 
SARS-CoV-2 serology test6 
 
✓ 
As needed 
Randomization  
 
✓ 
 
 
 
 
 
 
Clinical safety blood samples  
✓ 
✓7 
 
✓7 
✓ 
✓7 
✓ 
✓ 
                                                 
4 Serum beta human chorionic gonadotropin at screening, baseline (Visit 1), Visit 4 and Visit 5, or at the ED visit, if applicable (all female subjects). 
5 Height only to be measured at screening. 
6 RT-PCR from a nasal swab sample at screening and RT-PCR from a nasal swab sample and serology testing at baseline (Visit 1), and as needed when subject presents signs 
and symptoms of SARS-CoV-2 infection. 
7 Fasted glucose, fasted insuline and HOMA-IR only at Visit 1, 3 and 5 and the ED visit, if applicable. 
 

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9. 
STATISTICAL METHODS 
All statistical methods shall be detailed in a statistical analysis plan (SAP) that will be finalized 
prior to the database lock and unblinding. All relevant data collected in this clinical study will be 
documented using summary tables, figures, and subject data listings. 
Any deviations from the CSP are to be justified in the SAP. 
9.1. 
Determination of Sample Size 
The operating characteristics of the chosen decision framework at a sample size of 15 subjects 
(GLPG3970) + 10 subjects (placebo) are represented in the following graphical output and table, 
and were deemed acceptable. A common standard deviation (SD) of 1.3 for placebo and 
GLPG3970 was assumed based on previous experience with RA studies.  
Lower Reference Value and Target Value for the decision framework were determined based on 
the published studies and the therapies in development or on the market. They were identified by 
the project team as the lowest delta of possible interest and the best case scenario for efficacy 
outcome respectively. 
A dropout rate of 20% was taken into account to allow a minimum of 20 subjects to complete the 
study. In case of drop-outs due to SARS-CoV-2 infection, additional subjects may be randomized 
on top of the planned sample size. The number of additional subjects randomized will not exceed 
the number of subjects dropping out of the study in relation to SARS-CoV-2. Randomization of 
additional subjects will ultimately be decided by the sponsor before any study lock or related 
unblinding has occurred. 
 
Probability 
Reference 
value 
Outcome 
0.852 
-1.6 
Signal detected 
0.043 
-1.6 
No conclusion 
0.105 
-1.6 
No signal 
detected 
0.192 
-0.6 
Signal detected 
0.091 
-0.6 
No conclusion 
0.717 
-0.6 
No signal 
detected 
 
 
 
9.2. 
Population for Analyses 
9.2.1. 
All Screened Subjects 
All subjects who signed and dated an ICF. 

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received. Clinical safety will be addressed by assessing AEs, laboratory assessments, physical 
examinations, vital signs, and 12-lead ECGs. 
9.3.5.1. 
Extent of Exposure 
A subject’s extent of exposure to the IP will be generated from the IP administration page of the 
CRF. Exposure data will be summarized by treatment group. Duration of exposure to the IP will 
be expressed as the number of days between the first and last dose of IP, inclusive, regardless of 
temporary interruptions in IP administration and summarized by treatment group. 
9.3.5.2. 
Adverse Events 
Clinical and laboratory AEs will be coded using the latest version of the Medical Dictionary for 
Regulatory Activities. System Organ Class (SOC), High-Level Group Term, High-Level Term, 
Preferred Term, and Lower-Level Term will be attached to the clinical database. 
The following AEs will be considered as TEAEs: 
Any AE with an onset date on or after the IP start date and no later than 14 days after last dose of 
IP, or any worsening of any AE on or after the IP start date. Investigators are not obliged to 
actively seek SAEs after the CSP-defined FU period. However, if the investigator is informed 
about an SAE that occurs at any time after the subjects post-treatment FU visit and the event is 
deemed relevant to the use of IP, they should promptly document and report the event to the 
sponsor by using the SAE form. 
Summaries (number and percentage of subjects) of TEAEs per subject by SOC and Preferred 
Term will be provided by treatment group. TEAEs will also be summarized by causal 
relationship to the IP and severity. In addition, TEAEs leading to ED of the IP will be 
summarized and listed. Also, all SAEs, including the non-treatment-emergent SAEs, will be 
listed. 
9.3.5.3. 
Clinical Laboratory Evaluations 
Laboratory assessments will be analyzed descriptively. Changes from baseline and treatment-
emergent shifts, according to normal ranges as well as CTCAE version current at the time of the 
assessment, will be presented. Analyses will be done per treatment group.  
9.3.5.4. 
Physical Examinations 
Only abnormal post-baseline physical examination results will be listed, when available. 
9.3.5.5. 
Vital Signs 
Vital signs will be analyzed descriptively. Changes from baseline will be presented as well. 
Analyses will be done per treatment group. 

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experts (such as an expert in the field of RA and an infectious diseases expert) to support data 
interpretation. The Committee will review unblinded safety data and assess any potential safety 
issues arising during the conduct of the clinical study, including (but not limited to) any potential 
issues in the context of the SARS-CoV-2 pandemic. The process is described in a separate 
‘Internal Safety Monitoring Committee Charter’. 
11. 
SAFETY REPORTING 
11.1. 
Definitions of Adverse Events, Serious Adverse Events and 
Special Situations 
11.1.1. 
Adverse Events 
An AE is any untoward medical occurrence, new or worsening of any pre-existing condition, in a 
clinical study subject administered a medicinal product and which does not necessarily have to 
have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (e.g. an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal product, whether 
or not considered related. AEs may also include pre- or post-treatment complications that occur 
as a result of CSP-specified procedures, worsening of the targeted disease, overdose, drug 
abuse/misuse reports, or occupational exposure. Pre-existing conditions that increase in severity 
or change in nature during or as a consequence of participation in the clinical study will also be 
considered AEs. 
11.1.2. 
Serious Adverse Events 
An SAE is defined as an AE that: 
− 
Results in death; 
− 
Is life-threatening (Note: The term ‘life-threatening’ in the definition of ‘serious’ refers to an 
event in which the subject was at risk of death at the time of the event; it does not refer to an 
event that hypothetically might have caused death if it were more severe.); 
− 
Requires in-patient hospitalization or prolongation of existing hospitalization; 
− 
Results in persistent or significant disability/incapacity; 
− 
Is a congenital anomaly / birth defect; 
− 
Is medically significant (medical and scientific judgment should be exercised in deciding 
whether other situations should be considered serious such as important medical events that 
might not be immediately life-threatening or result in death or hospitalization but might 
jeopardize the subject or might require intervention to prevent one of the other outcomes 
listed in the definition above). 

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11.1.3. 
Unlisted (Unexpected) Adverse Events/ Reference Safety Information 
An AE is considered unlisted if the nature or intensity is not consistent with the applicable 
product reference safety information. For an IP, the expectedness of an AE will be determined by 
whether or not it is listed in the reference safety information part of the IB. 
11.1.4. 
Adverse Events of Special Interest 
Not applicable. 
11.1.5. 
Clinical Laboratory Abnormalities and Other Abnormal Assessments as 
Adverse Events or Serious Adverse Events 
Laboratory abnormalities without clinical significance based on the investigator’s judgment are 
not considered AEs or SAEs. However, laboratory abnormalities (e.g. clinical chemistry, 
hematology, and urinalysis) or other abnormal (clinical study-specific) assessments (e.g. ECG, 
radiography, vital signs) that require medical or surgical intervention, are associated with signs 
and/or symptoms, and/or lead to IP interruption, modification or discontinuation must be 
recorded as an AE or SAE if they meet the definition as described in Sections 11.1.1 and 11.1.2, 
respectively. If the laboratory abnormality is part of a syndrome, the syndrome or diagnosis is to 
be reported (e.g. anemia instead of decreased hemoglobin). 
The following liver enzyme elevations should be reported as SAEs: 
− 
AST or ALT ≥8xULN. 
− 
AST or ALT ≥3xULN with signs of liver damage (total bilirubin >2xULN OR international 
normalized ratio >1.5, and/or with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash and/or eosinophilia [>5%]). 
11.1.6. 
Special Situations 
Special situations are situations that have a possible impact on the safe use of the IP. These 
situations might be or might not be associated with AEs. 
− 
Pregnancy 
− 
Abuse or misuse of IP 
Abuse of IP is defined as the persistent or sporadic, intentional excessive use of the IP, which 
is accompanied by harmful physical or psychological effects. 
Misuse of IP is defined as a situation where the IP is intentionally and inappropriately used 
not in accordance with the product information. 
− 
Drug interaction or food interaction with IP 
A drug interaction with IP is defined as a situation in which there is evidence or a suspicion 
that the IP interacts with another drug when both are administered together. 
A food interaction with IP is defined as a situation in which there is evidence or a suspicion 
that the IP interacts with a food when taken together. 
− 
Medication error with IP 

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A medication error with IP is defined as an unintended failure in the drug treatment process 
that leads to, or has the potential to lead to, harm to the subject. 
− 
Occupational exposure to IP 
Occupational exposure to IP is defined as an exposure to the IP as a result of one’s 
professional or non-professional occupation. 
− 
Overdose with IP 
An overdose of IP is defined as the administration of a quantity of the IP given per 
administration or cumulatively, which is above the dose of IP given during this study. 
− 
Product complaint or quality defect of IP 
Product complaint or quality defect of IP is defined as complaints or defects of the IP arising 
from potential deviations in the manufacture, packaging, or distribution of the IP. 
11.2. 
Assessment of Adverse Events and Serious Adverse Events 
The investigator is responsible for assessing AEs and SAEs for causality and severity. This is the 
basis for the sponsor’s final review and confirmation of accuracy and completeness of event 
information and causality assessments. 
11.2.1. 
Assessment of Causality 
The investigator is responsible for assessing the causal relationship to IP(s) administration or 
study procedures (e.g. invasive procedures such as venipuncture) based on her/his clinical 
judgment. The following decision choice will be used by the investigator to describe the causality 
assessment between the reported event or laboratory test abnormality and the IP. 
− 
Unrelated: 
Time relationship to IP intake is improbable. Related to other etiologies such as concomitant 
medications or subject's clinical state. 
− 
Unlikely: 
Time relationship to IP intake is improbable (but not impossible). Concomitant disease or 
other drugs provide plausible explanations. 
− 
Possible: 
Time relationship to IP intake is reasonable. Event or laboratory test abnormality could also 
be explained by disease or other drugs. Information on IP withdrawal may be lacking or 
unclear. 
− 
Probable: 
Time relationship to IP intake is reasonable. Unlikely to be attributed to concurrent disease 
or other drugs. Response to withdrawal is clinically reasonable and rechallenge not required. 

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− 
Certain: 
Time relationship to IP intake is plausible. Cannot be explained by concomitant disease or 
other drugs. Response to withdrawal is plausible (pharmacologically, pathologically). Event 
definitive pharmacologically or phenomenologically (i.e. an objective and specific medical 
disorder or a recognized pharmacological phenomenon). Rechallenge satisfactory, if ethical 
and necessary. 
 
It should be emphasized that ineffective treatment (worsening of the disease) should not be 
considered as causally related in the context of AE reporting. 
11.2.2. 
Assessment of Severity 
The severity of AEs should be graded using the CTCAE version current at the time of 
assessment. If a CTCAE criterion does not exist, the investigator should use the grade or 
adjectives: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening) or 
Grade 5 (fatal) to describe the maximum intensity of the AE. For purposes of consistency with 
the CTCAE, these intensity grades are defined in the table below. 
Table 1 
Grading of AE Severity 
Grade  
Adjective  
Description  
Grade 1  
Mild 
Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated  
Grade 2  
Moderate 
Local or noninvasive intervention indicated; limiting age-appropriate 
instrumental ADL*  
Grade 3  
Severe 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care ADL**  
Grade 4  
Life-threatening 
Urgent intervention indicated  
Grade 5  
Death 
Death-related AE  
* 
Instrumental Activities of Daily Living (ADL) refer to preparing meals, shopping for groceries or clothes, using the 
 
telephone, managing money, etc. 
** 
Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
 
bedridden. 
For AEs associated with laboratory abnormalities, the event should be graded on the basis of the 
clinical severity in the context of the underlying conditions; this may or may not be in agreement 
with the grading of the laboratory abnormality. This is upon the investigator’s assessment. 
If there is a change in intensity (worsening or improvement) of an AE, it must be recorded. 

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11.2.3. 
Action Taken Regarding Investigational Product 
The action taken must be described by choosing from: 
− 
Dose not changed: In case no action is taken regarding the IP. 
− 
IP permanently discontinued: In case a subject is permanently discontinued from treatment 
or withdrawn from the study by the investigator (who may consult the sponsor’s medical 
monitor). 
− 
IP temporarily discontinued: In case the IP is temporarily discontinued by the investigator 
(who may consult the sponsor’s medical monitor). 
− 
Not applicable: Other situations (e.g. in case an AE started after the last IP administration). 
11.2.4. 
Outcome 
Each AE must be rated by choosing among: 
− 
Recovered/resolved; 
− 
Recovered/resolved with sequelae; 
− 
Recovering/resolving; 
− 
Not recovered/not resolved; 
− 
Fatal; 
− 
Unknown. 
11.3. 
Investigator Requirements and Instructions for Reporting Adverse 
Events, Serious Adverse Events, Pregnancies, and Other Special 
Situations to the Sponsor 
11.3.1. 
Adverse Events 
The AE reporting period for safety surveillance begins when the subject signs the ICF and ends at 
the subject’s last FU visit (the last FU visit after the last dose of IP). In this period, all new AEs, 
regardless of cause or relationship, derived by spontaneous, unsolicited reports of subjects, by 
observation and by routine open questioning (such as “How do you feel?”) need to be recorded in 
the source and in the CRF. 
In case an AE is ongoing at the time of the last FU visit, the investigator needs to FU on the 
subject until AE resolution or reasonable stabilization and to document in the subject’s source 
documentation. No related updates or additional data on the AE should be reported in the CRF. 
If a subject is documented as lost-to-FU, ongoing/unknown outcome AEs will not be followed-
up. 
If the AE meets the criteria for seriousness, the SAE form must be completed and sent to the 
sponsor within 24 hours (see Section 11.3.2). 

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11.3.2. 
Serious Adverse Events 
Subjects experiencing an SAE or an emergency situation will be examined by a physician as soon 
as possible. The subject will remain under observation as long as medically indicated. 
Appropriate laboratory tests will be performed until all parameters return to normal or are 
otherwise explained or stable. 
All SAEs, whether or not deemed IP related, must be recorded in the CRF and on the SAE form. 
The investigator must report each SAE immediately, and under no circumstances should this 
exceed 24 hours following the knowledge of the SAE, as is indicated on page 2 under 
“Emergency Contact Information”. 
The SAE form should at least contain identifiers of the subject and the reporter, SAE term and 
statement of relatedness to the IP, and at a later stage if not yet available within 24 hours, the 
form needs to be completed with a clearly written narrative describing signs, symptoms, and 
treatment of the event, diagnostic procedures, as well as any relevant laboratory data and any 
sequelae. 
Follow-up and outcomes should be reported and documented in the source documents for all 
subjects that experience an SAE. It is important that the information provided on the SAE form 
matches the information recorded on the CRF for the same event. 
Copies of additional laboratory tests, consultation reports, post-mortem reports, hospital case 
reports, autopsy reports, and other documents should be sent when requested and available. Only 
subject identifiers (subject number) should appear on the copies, and all names and initials should 
be blackened and rendered illegible. Follow-up reports relative to the subject’s subsequent course 
must be submitted until the event has subsided or, in case of permanent impairment, until the 
condition stabilizes. 
Any SAEs that occur after the post-treatment FU visit but within 30 days of the last dose of IP(s), 
regardless of causality, should also be reported (Emergency Contact Information on page 2). 
Investigators are not obligated to actively seek SAEs after the CSP-defined FU period. However, 
if the investigator is informed about an SAE that occurs at any time after the subjects’ post-
treatment FU visit and the event is deemed relevant to the use of IP(s), he/she should promptly 
document and report the event to the sponsor by using the SAE form. 
11.3.3. 
Pregnancy 
All initial reports of pregnancy in female subjects and pregnancies in partners of male subjects 
included in the clinical study must be recorded and documented in the source documents and on 
the pregnancy form. The investigator must report each pregnancy immediately, and under no 
circumstances should this exceed 24 hours following the knowledge of the pregnancy, as is 
indicated on page 2 under “Emergency Contact Information”.  
All pregnancies should be followed-up until delivery or pregnancy interruption. The investigator 
will contact the subject or partner of the subject after giving consent, at the expected time of 
delivery for FU and for information regarding the outcome of the newborn. Abnormal pregnancy 

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and/or abnormal newborn outcomes are considered SAEs and must be reported using the SAE 
form. 
11.3.4. 
Reporting of Special Situations (Other Than Pregnancy) and Associated 
Adverse Events 
In case a special situation is not associated with an AE, the special situation should be reported 
within 24 hours by using the Special Situations form as is indicated on page 2 under “Emergency 
Contact Information”. 
In case a special situation is associated with an AE, the special situation should be reported 
within 24 hours by using the Special Situations form and the associated AE should be reported as 
specified in Section 11.3.1. 
In case a special situation is associated with an SAE, the special situation should be reported 
within 24 hours by using the SAE form (and not the Special Situations form) and the associated 
SAE should be reported as specified in Section 11.3.2. 
11.4. 
Sponsor Reporting Requirements 
Depending on relevant local legislation or regulations, including the applicable United States 
Federal Drug Administration Code of Federal Regulations, the EU Clinical Trials Directive 
(2001/20/EC) and relevant updates, and other country-specific legislation or regulations, the 
sponsor may be required to expedite reports of SAEs and serious adverse drug reactions or 
suspected unexpected serious adverse reactions (SUSARs) to worldwide regulatory authorities. 
The sponsor or a specified designee will notify worldwide regulatory authorities and the relevant 
IEC/IRB in concerned Member States of applicable SUSARs as outlined in current regulations. 
Assessment of expectedness for SAEs will be determined using the reference safety information 
section in the IB or relevant local label as applicable. 
All concerned investigators will receive a safety letter notifying them of relevant SUSAR reports 
associated with any IP(s). The investigator should notify the IEC/IRB of SUSAR reports as soon 
as is practical, where this is required by local regulatory agencies, and in accordance with the 
local institutional policy. 
12. 
SPONSOR’S AND INVESTIGATOR’S RESPONSIBILITIES 
This clinical study is conducted in accordance with the current applicable regulations, ICH-GCP 
Guideline E6 and its updates, and local ethical and legal requirements. 
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording and reporting studies that involve the participation of human subjects. 
Compliance with this standard provides public assurance that the rights, safety and well-being of 
clinical study subjects are protected, consistent with the principles that have their origin in the 
Declaration of Helsinki, and that the clinical study data are credible. 

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The name and address of each third party vendor (e.g. CRO) used in this study and the sponsor’s 
study team members will be maintained in the investigator’s and sponsor’s files as appropriate. 
12.1. 
Sponsor’s Responsibilities 
12.1.1. 
Regulatory Authority Approval  
Prior to clinical study start, this CSP together with all relevant documentation needs to be 
submitted to the respective regulatory authorities for review and approval in compliance with 
current regulations before the study can start. 
12.1.2. 
Clinical Study Closure Considerations 
The sponsor reserves the right to close the investigational site or end the clinical study at any 
time for any reason. In case of an early termination of the clinical study or temporary halt by the 
sponsor, the IEC/IRB and health authority will be notified within 15 calendar days, unless 
otherwise specified by the sponsor, the IEC/IRB or health authority, including a detailed written 
explanation of the reasons for the termination/halt. 
Reasons for the closure of an investigational site may include, but are not limited to: 
− 
Successful completion of the clinical study at the center. 
− 
The overall required number of subjects for the clinical study has been recruited. 
− 
Failure of the investigator to comply with the CSP, ICH-GCP guidelines or local 
requirements. 
− 
Inadequate recruitment of subjects by the investigator. 
 
Reasons for early termination of a clinical study by the sponsor may include, but are not limited 
to: 
− 
Safety concerns. 
− 
Sufficient data suggesting lack of efficacy. 
 
The end of clinical study declaration will be submitted to the regulatory authorities and IEC/IRB 
after the complete clinical study has ended in all participating centers, in all countries. This 
notification will also be submitted according to local requirements of the end of the clinical study 
in a given country/member state. 
12.1.3. 
Indemnification 
Under the conditions of a contract concluded between investigator, site and sponsor or designee, 
which shall prevail, the sponsor shall, except in case of gross negligence or willful misconduct, 
indemnify and hold harmless the investigator and his/her medical staff from any claim arising 
from the clinical study activities carried out in compliance with the CSP, sponsor’s instructions 
and applicable local regulations. 

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The investigator must notify the sponsor immediately upon notice of any claims or lawsuits. 
12.1.4. 
Insurance 
The sponsor shall maintain insurance coverage that is sufficient to cover its obligations and that 
is consistent with human clinical study local regulations. Provided that the subject has been 
treated according to the CSP and sponsor’s instructions, any injury caused to a subject which is 
the direct result of his/her participation to the clinical study shall be covered by the sponsor’s 
insurance, except in case of gross negligence or willful misconduct by the investigator. 
12.1.5. 
Archiving 
The sponsor will archive the content of the Trial Master File (TMF) for at least 25 years after the 
end of the clinical study. 
12.1.6. 
Reporting 
Where required by IEC/IRB per local requirements, at least once a year the investigator will 
provide the IEC/IRB with a progress report to allow review of the clinical study (see 
Section 12.4.1). At the end of the clinical study, the results of the clinical study will be reported 
in a CSR. The pop-PK analysis data, disease and/or drug-related biomarker data and mRNA data 
may be reported separately from the main CSR. A summary or full report, depending on the 
requirements, will be provided to the investigators, to the applicable regulatory authorities, and 
IECs/IRBs (if required by the applicable regulatory requirements) within one year, or 6 months 
for pediatric studies, after the end of the clinical study. 
12.1.7. 
Publication 
It is understood by the investigator that the sponsor shall be free to use the compound-related 
information, which is generated during the clinical study and may disclose it to other clinical 
investigators and to regulatory agencies. As a consequence, the investigator agrees to provide all 
clinical study results and data generated during this clinical study to the sponsor. 
The investigator shall not be authorized to submit the results of this clinical study and any data 
for public disclosure (e.g. publication or presentation) without the prior written approval of the 
sponsor, which shall not be unreasonably withheld. 
However, it is understood and agreed by the investigators that their results and/or findings shall 
not be authorized for publication prior to sponsor’s publication of the overall clinical study 
results. The investigator agrees that prior to the publication of any results, he/she shall provide 
the sponsor with a draft copy of the intended publication. The sponsor shall have the right to 
review it and to make any comments. In accordance with generally accepted scientific 
collaboration principles, co-authorship with any staff member sponsor involved in the clinical 
study, will be discussed and mutually agreed upon before submission of any manuscript to a 
publisher. 

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12.2. 
Investigator’s Responsibilities 
12.2.1. 
Source Data and Data Capture 
The nature and location of all source documents need to be identified and documented to ensure 
that all sources of original data required to complete the CRF are known and are accessible for 
verification by the monitor. 
Source data may be directly captured from devices transferred from third partners (e.g. laboratory 
data) or entered manually into the CRF. The CRF completion guidelines will be provided to each 
investigational site. 
It is recommended that the author of an entry in the source documents should be identifiable. 
Following ICH-GCP guidelines, direct access to sponsor’s representatives to source documents 
must be granted for the purpose of verifying that the data recorded on the CRF are consistent 
with the original source data. 
12.2.2. 
Archiving 
Unless local legislation requires archiving for a longer period, the investigator shall archive the 
content of the clinical investigator site file (ISF) for at least 25 years after the end of the clinical 
study. However, the medical files of subjects shall be archived in accordance with national law. 
The investigator should take measures to prevent accidental or premature destruction of these 
documents. 
Under no circumstance shall the investigator relocate or dispose any clinical study documents 
before having obtained a written approval of the sponsor. 
If it becomes necessary for the sponsor or the appropriate Regulatory Authority to review any 
documentation relating to this clinical study, the investigator must permit access to such reports. 
The subject is granting access to his/her source data by signing the ICF. 
Any difficulty in storing original documents must be discussed with the monitor prior to the 
initiation of the clinical study. 
12.2.3. 
Participation Cards 
If the subjects are not under 24-hour supervision of the investigator or site staff, they must be 
provided with a subject participation card indicating the name of the IP, the clinical study 
number, the investigator's name, and the site’s 24-hour emergency contact number. The subject 
should be advised to keep the participation card in his/her wallet at all times. 
12.3. 
Confidentiality 
The subject will receive all information as required by the EU General Data Protection 
Regulation, namely the identity and contact details of the controller, the contact details of the data 
protection officer, the clinical research purposes, the legal basis for the processing, the recipients 

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of the personal data, the transfer of the personal data to third countries and respective safeguards, 
the retention periods, the fair processing of his data, and all his/her data subject’s rights. All 
details are listed in the ICF. 
All information concerning the product and the sponsor’s operations (such as patent applications, 
formulas, manufacturing processes, basic scientific data, or formulation information supplied to 
the investigator by the sponsor and not previously published) is considered confidential and 
should not be disclosed by the investigator to any third party without the sponsor’s prior written 
approval. The investigator agrees to use this information only in accomplishing the clinical study 
and will not use it for other purposes. 
In order to permit easy identification of the individual subject during and after the clinical study, 
the investigator is responsible for keeping an updated Subject Identification Code List. The 
monitor will review this document for completeness. However, the investigator must guarantee 
the subject’s anonymity will be maintained. Therefore, in order to ensure subject confidentiality, 
the Subject Identification Code List must remain at the center and no copy will be made. 
12.4. 
Ethical Considerations 
12.4.1. 
Independent Ethics Committee / Institutional Review Board  
This clinical study can only be undertaken after IEC/IRB approval of this CSP together with all 
relevant documentation. This approval document must be dated and clearly identify the clinical 
study and the related clinical study documents being approved, including the subject 
compensation programs, if applicable. 
During the course of the clinical study, at least the following documents will be submitted to the 
IEC/IRB, per local requirements: 
− 
Changes to the IB 
− 
Reports of AEs that are serious, unlisted, and associated with the IP (in compliance with 
IEC/IRB, per local requirements) 
− 
CSP amendments 
− 
ICF amendments 
 
After the subject has completed the study, the subject will receive a financial compensation, or 
depending on the country, the study physician may offer the option of a course of post-study 
medication approved for the treatment of RA, at no cost and for a duration of up to 6 months.  
Subjects will be eligible for compensation in case a subject received at least 1 dose of IP and 
completed the study, or discontinued early for e.g. safety reasons. In case a subject withdraws 
from the study early compensation will be pro rata, unless the reason for withdrawal from the 
study is noncompliance, then no compensation will be provided. Any form of compensation and 
conditions for compensation will require approval by an IEC and documented in the ICF.  
The IEC/IRB is responsible for continuous review of the clinical study. Where required by 
IEC/IRB, per local requirements, at least once a year the investigator will provide the IEC/IRB 

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with a progress report to allow review of the clinical study. Additional progress reports should be 
provided according to local legal requirements. These requests and (re-)approvals, if applicable, 
should be documented in writing. 
12.4.2. 
Informed Consent 
The investigator or designated personnel must explain the clinical study and the implications of 
participation (e.g. objectives, methods, anticipated benefits, possible risks) to potential subjects 
according to applicable regulations prior to any clinical study-related activity. Subjects will be 
informed that their participation is voluntary and that they may withdraw from the clinical study 
at any time. They will be informed that choosing not to participate or to withdraw from the 
clinical study will not have an impact on the care the subject will receive for the treatment of 
his/her disease. 
The subject will be given sufficient time to read the ICF and to ask additional questions. After 
this explanation and before entry in the clinical study, the subject’s consent should be 
appropriately recorded by means of the subject's personally dated signature and by the 
investigator’s dated signature. In case the subject is unable to read and/or write, oral consent in 
the presence of at least one impartial witness who was also included when the affected person 
was being informed, may be given. The witness may not be anyone working at the site nor a 
member of the investigating team. The orally given consent shall be documented in writing, dated 
and signed by the witness. After having obtained the consent, a copy of the signed and dated ICF 
must be given to the subject. 
If new information becomes available relevant to the subject’s willingness to participate in the 
clinical study, the subject will be informed in a timely manner by means of an amended ICF. This 
amended ICF will be signed and dated by the subject (or, if applicable, by an independent 
witness) and the investigator to document the willingness of the subject to continue with the 
clinical study. 
This signed and dated amended version will be filed together with the initial signed and dated 
ICF. 
A pregnant partner, who agrees that information will be gathered about her pregnancy and the 
birth, will be asked to sign a specific ICF to participate in the data collection. Data about the 
health of the baby will be collected if the parent(s)/legal guardian(s) agree with the data 
collection and sign a specific ICF. 
Subjects who agree to participate in the study and who have signed informed consent, will be 
given the option to provide additional (and optional) informed consent for the long term storage 
of left over samples and associated data, collected during the study, for future scientific research.  

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12.5. 
Data Quality Control/Assurance 
12.5.1. 
Monitoring 
Data quality will be assured through Risk-Based Monitoring, medical monitoring, and other 
relevant activities as described in the Data Management Plan or Medical Review Plan and 
monitoring plans available in the TMF. This clinical study will be monitored by sponsor 
representatives according to their current standard operating procedures.  
To guarantee adequate protection of the subjects and to guarantee the quality of the data, the 
sponsor will ensure oversight of any clinical study-related duties and functions carried out on its 
behalf, including clinical study-related duties and functions that are subcontracted to another 
party by the sponsor’s contracted CRO(s).  
A risk-based Quality Management Plan (QMP) is prepared for the study that evaluates potential 
risks in relation to rights, safety, and well-being of the study subjects as well as the data integrity. 
The QMP describes and evaluates all involved stakeholder interfaces having potential critical 
impact on the above. Risks are considered at both the system level (e.g. standard operating 
procedures, computerized systems, personnel, and vendors) and study level (e.g. IP, study design, 
data collection, informed consent process and recording). 
12.5.2. 
Audit and Inspection 
To ensure compliance with relevant regulations, an independent quality assurance representative, 
regulatory authorities and/or IECs/IRBs may review this clinical study. This implies that 
auditors/inspectors will have the right to inspect the clinical study center(s) at any time during 
and/or after completion of the clinical study and will have access to the data generated during the 
clinical study, source documents, and subject's files. By participating in this clinical study, 
investigators agree to this requirement. 
 

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13. 
REFERENCES 
Ajeqanova, S., & Huizinga, T. (2017). Sustained remission in rheumatoid arthritis: latest 
evidence and clinical considerations. Ther Adv Musculoskel Dis, 9(10):249-262. 
BMJ, B. M. (2020, May 13). British Medical Journal Best Practice. Retrieved from 
Coronavirus disease 2019 (COVID-19) Diagnostic guidelines: 
https://bestpractice.bmj.com/topics/en-gb/3000168/history-exam 
BMJ, B. M. (2020, May 13). British Medical Journal Best Practice. Retrieved from 
Coronavirus disease 2019 (COVID-19) History and exam: 
https://bestpractice.bmj.com/topics/en-gb/3000168/history-exam 
Chatzidionysiou, K., & Sfikakis, P. (2019). Low rates of remission with methotrexate 
monotherapy in rheumatoid arthritis: review of randomised controlled trials could point 
towards a paradigm shift. RMD Open, 5(2):e000993. 
 
Frewer, P., Mitchell, P., Watkins, C., & Matcham, J. (2016). Decision-making in early clinical 
drug development. Pharmaceut. Statist., 15:255-263. 
Köhler, B., Günther, J., & Kaudewitz, D. L. (2019). Current therapeutic options in the 
treatment of rheumatoid arthritis. pii: E938. doi: 10.3390/jcm8070938. J Clin Med, 
8(7), pii: E938. 
 
 
Oton, T., & Carmona, L. (2020). The epidemiology of established rheumatoid arthritis. Best 
Practice & Research Clinical Rheumatology, 
https://doi.org/10.1016/j.berh.2019.101477. 
Siegel, J. N., & Zhen, B. (2005). Use of the American College of Rheumatology N (ARC-N) 
Index of Improvement in Rheumatoid Arthritis. Arthritis & Rheumatism, 52(6):1637-
1641. 
Smolen, J. S., Aletaha, D., Koeller, M., Weisman, M., & Emery, P. (2007). New therapies for 
treatment of rheumatoid arthritis. Lancet, 370:1861-1874. 
 
 
 

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Steriod Conversion Calculator. (n.d.). Retrieved from https://www.mdcalc.com/steroid-
conversion-calculator, accessed 26 November 2019. 
 
 
 

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Appendix 7: Prednisolone Conversion Table 
Glucocorticoid Name 
Dose Equivalent to 5 mg Prednisolone 
Prednisone 
5 mg  
Betamethasone 
0.6 mg 
Cortisol (hydrocortisone) 
20 mg 
Cortisone 
25 mg 
Deflazacort 
7.5 mg 
Dexamethasone 
0.75 mg 
Methylprednisolone 
4 mg 
Methylprednisolone Acetate 
4 mg 
Methylprednisolone Sodium Succinate 
4 mg 
Paramethasone 
2 mg 
Prednisolone 
5 mg 
Triamcinolone 
4 mg 
Beclometasone Dipropionate 
1.25 mg 
Budesonide 
1.5 mg 
Hydrocortisone Sodium Succinate 
20 mg 
 (Steriod Conversion Calculator) 
 

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Appendix 8: Algorithm for Elevated Liver Function Tests 
 
AST or ALT increase to 
Value Range 
≥1.5x to 
3xULN 
≥3x to <5xULN 
≥5x to <8xULN 
≥3xULN with signs 
of liver damage1 
≥8xULN 
IP Action 
Continue as 
planned 
Reduce or 
interrupt IP for 
at least 2 weeks 
Close 
observation2  
Interrupt IP for 
at least 2 weeks 
Close 
observation2 
Discontinue IP2 
Discontinue IP2 
 
 
 
 
↙ ↘ 
 
After at least 
2 weeks 
AST and ALT <3xULN 
 
AST or ALT ≥3xULN 
  
Weekly LFTs for the first 2 weeks 
(biweekly for the following 
weeks, or more frequently at 
investigator’s discretion) 
 
Discontinue IP 
Report SAE and complete liver event page for any of 
abnormalities listed below3: 
- 
AST/ALT increase ≥8xULN 
- 
AST/ALT increase ≥3xULN with signs of liver 
damage1  
 
1 Signs of liver damage: 
 
total bilirubin ≥2.0xULN OR international normalized ratio >1.5, and/or 
 
symptoms: appearance of fatigue, nausea, vomiting, right upper abdominal quadrant pain or tenderness, fever, rash and/or eosinophilia (>5%)  
2 Close observation recommendations:  
 
Monitor 2 to 3 times per week all of the following parameters: ALT, AST, ALP, total bilirubin, eosinophils, INR. If local regulations allow, 
home visits can be performed if subjects cannot come to the clinical study center. 
 
Frequency of retesting can be reduced to once a week or less if abnormalities stabilize or the IP has been discontinued; however, monitoring 
might still be needed more frequently taking into consideration the standard of care and/or changes to this. 
 
Based upon investigator’s discretion gastroenterology or hepatology consultations, additional serology testing, imaging, and pathology 
assessments may be required. 
 
Re-query history of symptoms, prior and concurrent diseases, concomitant medication and non-prescription medicines, herbal, dietary 
supplements, alcohol use, recreational drug use, special diets. 
 
Rule out all of the following: acute viral hepatitis, autoimmune hepatitis, alcoholic hepatitis, non-alcoholic fatty hepatitis, hypoxic/ischemic 
hepatitis, biliary tract disease, and cholestasis. 
 
Re-query exposure to environmental chemical agents. 
3 The following steps should be followed: 
 
The site should immediately contact the subject and require the subject to discontinue IP immediately. The subject should be asked to return 
to the site within a 48-hour window from awareness of the result.  
 
A full evaluation of various causes of hepatitis should be conducted (i.e. infectious, alcohol, medications, anatomical).  

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− 
An assessment of other concomitant medications and standard of care should be made. The investigator should consider to whether is in the 
best interest of the subject to stop/interrupt concomitant medications and SOC treatment.  
− 
A detailed history including relevant information on alcohol use, recreational drug use, supplement consumption, any herbal remedies, family 
history, sexual history, travel history, history of contact with a jaundiced subject, surgery, occupational history, blood transfusion, history of 
liver or allergic disease, and any other potential causes of attributable to a liver insult should be collected.  
− 
A detailed assessment of the subject’s clinical condition and repeat laboratory tests for LFT, including albumin, creatine kinase, total bilirubin 
(direct and indirect), GGT, INR, and ALP should be done. 
− 
Further testing for Hepatitis A, B, and C, and for autoimmune hepatitis should be done. Other causes of viral hepatitis (cytomegalovirus or 
Epstein-Barr virus etc) should be excluded. Liver imaging should be considered.  
− 
Referral to a hepatologist or gastroenterologist should be requested. 
− 
All these cases should be reported as SAEs. 
 
 
 

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Appendix 9: 66/68 Joint Count 
Joints Assessed (left and right) for Swelling (66 Joints) and/or Tenderness (68 joints) 
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 
 

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SIGNATURE PAGE – SPONSOR 
Study Title: 
A randomized, double-blind, placebo-controlled, multicenter study to 
evaluate the safety, tolerability, efficacy and pharmacokinetics of 
GLPG3970, administered orally for 6 weeks in adult subjects with 
moderately to severely active rheumatoid arthritis and an inadequate 
response to methotrexate 
CSP Version: 
1.0 
Date: 
 
 
This clinical study protocol has been reviewed and approved by the sponsor to ensure compliance 
with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use (ICH) guidelines for Good Clinical Practices (GCP) and applicable regulatory 
requirements. 
 
 
 
  
  
Scientific Leader 
 Signature 
 Date 
 
 
 

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SIGNATURE PAGE – INVESTIGATOR 
Study Title: 
A randomized, double-blind, placebo-controlled, multicenter study to 
evaluate the safety, tolerability, efficacy and pharmacokinetics of 
GLPG3970, administered orally for 6 weeks in adult subjects with 
moderately to severely active rheumatoid arthritis and an inadequate 
response to methotrexate  
CSP Version: 
1.0 
Date: 
 
 
I, the undersigned, have read this clinical study protocol and will conduct the study as described 
in compliance with the clinical study protocol, in accordance with International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines 
for Good Clinical Practices (GCP) and applicable regulatory requirements. 
 
 
 
  
  
Investigator Name 
 Signature 
 Date